(Address, Including Zip Code, and Telephone Number, Including Area Code, of Registrant’s Principal Executive Offices)

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐☒ No ☒☐

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Securities Act. Yes ☐ No ☒

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to the filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated ~~filer”,~~filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act.) Yes ☐ No ☒

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☒

As of June 30, ~~2019,~~2021, the last day of the registrant’s most recently completed second fiscal quarter, the aggregate market value of the Common Stock held by non-affiliates of the registrant was approximately ~~$208.3~~$833.4 million, based on the closing price of the registrant’s common stock on June 30, ~~2019.~~2021. Shares of the registrant’s common stock held by each officer and director and stockholders that the registrant has concluded are affiliates of the registrant. This determination of affiliate status is not a determination for other purposes.

As of ~~March 4, 2020,~~February 25, 2022, there were ~~30,240,838~~55,012,245 shares of common stock outstanding.

Portions of the registrant’s definitive proxy statement for its ~~2020~~2022 Annual Meeting of Stockholders, which the registrant intends to file pursuant to Regulation 14A with the Securities and Exchange Commission not later than 120 days after the registrant’s fiscal year ended December 31, ~~2019,~~2021, are incorporated by reference into Part III of this Annual Report on Form 10-K.

This Annual Report on Form 10-K contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are “forward-looking statements” for purposes of this Annual Report on Form 10-K. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “could,” “estimate,” “expects,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative or plural of those terms, and similar expressions.

Factors that may cause actual results to differ materially from current expectations include, among other things, those set forth in Part I, Item 1A, “Risk Factors,” below and for the reasons described elsewhere in this Annual Report on Form 10-K. Any forward-looking statement in this Annual Report on Form 10-K reflects our

current view with respect to future events and is subject to these and other risks, uncertainties and assumptions. Given these uncertainties, you should not rely on these forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, our information may be incomplete or limited and we cannot guarantee future results. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future.

This Annual Report on Form 10-K also contains estimates, projections and other information concerning our industry, our business and the markets for certain drugs and consumer products, including data regarding the estimated size of those markets, their projected growth rates and the incidence of certain medical conditions. Information that is based on estimates, forecasts, projections or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, we obtained these industry, business, market and other data from reports, research surveys, studies and similar data prepared by third parties, industry, medical and general publications, government data and similar sources and we have not independently verified the data from third party sources. In some cases, we do not expressly refer to the sources from which these data are derived.

In this Annual Report on Form 10-K, unless otherwise stated or as the context otherwise requires, references to “Syndax,” “the Company,” “we,” “us,” “our” and similar references refer to Syndax Pharmaceuticals, Inc. and its wholly owned subsidiaries. This Annual Report on Form 10-K also contains references to our trademarks and to trademarks belonging to other entities. Solely for convenience, trademarks and trade names referred to, including logos, artwork and other visual displays, may appear without the ® or TM symbols, but such references are not intended to indicate, in any way, that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. We do not intend our use or display of other companies’ trade names or trademarks to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

We are a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Our two lead product ~~candidate,~~candidates are SNDX-5613 and SNDX-6352, or axatilimab. We are developing SNDX-5613, targeting the binding interaction of menin with the mixed lineage leukemia 1, or MLL1, protein for the treatment of MLL-rearranged, or MLLr, acute leukemias and nucleophosmin 1, or NPM1, mutant acute myeloid leukemia, or AML, as well as axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1, or CSF-1 receptor. We have deprioritized the development of entinostat, ~~is a~~our once-weekly, oral, small molecule, Class I HDAC inhibitor, ~~currently being evaluated in the Phase 3 E2112 registrational clinical trial in combination~~to focus resources on advancing our existing pipeline and expanding it with exemestane for advanced hormone receptor positive, or HR+, human epidermal growth factor receptor 2 negative, or HER2-, breast cancer, an indication for which entinostat has been granted breakthrough therapy designation from the U.S Food and Drug Administration, or FDA. We continue to anticipate that the Phase 3 E2112 clinical trial will reach 410 death events in the second quarter of 2020, triggering the final overall survival, or OS, analysis. The Phase 3 E2112 clinical trial design was informed by the Phase 2b ENCORE 301 clinical trial, the results of which led to entinostat’s breakthrough therapy designation from the FDA in HR+ breast cancer, in which patients receiving the entinostat/exemestane combination demonstrated a clinically meaningful OS benefit over treatment with exemestane alone.

Our second clinical-stage product candidate, SNDX-5613, is our orally available, small molecule inhibitor of the interaction of menin with the mixed lineage leukemia protein, or MLL. We are developing SNDX-5613 as a targeted therapy to potentially treat two genetically defined acute leukemias: (i) mixed lineage leukemia-rearranged, or MLLr, a genetically-defined subset of acute leukemias with chromosomal rearrangements in the MLL gene; and (ii) acute myeloid leukemia, or AML, with a mutated nucleophosmin 1, or NPM1, characterized by a somatic mutation in the NPM1 gene, or NPM1c. We anticipate presenting initial clinical data from a Phase 1/2 open-label AUGMENT-101 clinical trial of orally administered SNDX-5613 in the fourth quarter of 2020. The Phase 1 dose escalation portion of AUGMENT-101 is enrolling adults with relapsed/refractory acute leukemias, including patients with MLL-rearrangements and NPM1c mutations, to establish a recommended dose for the Phase 2 portion of the trial. The Phase 2 portion will evaluate efficacy, as defined by Complete Response rate (per International Working Group response criteria), across three expansion cohorts: MLL-r acute lymphoblastic leukemia, AML and NPM1 mutant AML.

We are also developing SNDX-6352, a monoclonal antibody targeting the colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In many cancers, inhibition of CSF-1R will reduce the number of immunosuppressive tumor-associated macrophages, or TAMs, and enable an immune response against tumors. In December 2019, we presented clinical proof-of-concept data from a Phase 1 clinical trial in which we observed the effects of SNDX-6352 for the treatment of chronic Graft Versus Host Disease, or cGVHD. We are initiating a Phase 2 expansion cohort based on this evidence of clinical efficacy at all dosage levels to date and expect to present Phase 1 and 2 results in the second half of 2020.

new assets. We plan to continue to leverage the technical and business expertise of our management team and scientific collaborators to ~~opportunistically~~ license, acquire and develop additional ~~cancer therapies~~therapeutics to expand our pipeline.

Our clinical-stage pipeline includes SNDX-5613, a highly selective inhibitor of the menin–MLL binding interaction, axatilimab, a monoclonal antibody that blocks the CSF-1 receptor, and entinostat, a Class I HDAC inhibitor.

We are developing ~~entinostat,~~ SNDX-5613 in acute leukemias and ~~SNDX-6352~~axatilimab for use in ~~multiple cancer~~cGVHD and potentially other ~~indications~~fibrotic-macrophage driven diseases as single agents and in combination with ~~complementary~~approved drugs. We have deprioritized the development of entinostat but may opportunistically explore potential disease areas where entinostat could play an important therapeutic ~~drugs and potentially as single agents.~~role. Key elements of our strategy include:

Develop SNDX-6352 as monotherapy and in combination in one or more tumor types. We are conducting a Phase 1/2 trial of SNDX-6352 as a monotherapy in patients with cGVHD and are currently looking to establish a recommended Phase 2 dose for use of SNDX-6352 as a monotherapy. In 2019, we established a recommend Phase 2 dose for use of SNDX-6352 as a combination agent in solid tumors.

~~Entinostat is our oral, small molecule~~Our first clinical-stage product candidate, that has direct effects on both cancer cells and immune regulatory cells, potentially enhancing the body’s immune response to tumors. The favorable safety profile of entinostat has been demonstrated in clinical trials in more than 1,200 cancer patients. The long half-life of entinostat allows for once weekly dosing while also providing continuous exposure to therapy potentially resulting

in positive efficacy benefits. Based on entinostat’s ability to reverse hormone resistance, alter cancer stem cells, and modulate immunosensitivity, we believe entinostat may have broad applications in tumor types which have become resistant to hormone and/or immunotherapy.

Entinostat has also been shown to enhance the immune system’s ability to identify and target tumor cells. It is now widely accepted that many tumors have the ability to evade the immune system either through direct cellular interactions and recruitment of immuno-suppressive cells to the area surrounding the tumor, or through parallel evasion-mechanisms focused on the interaction between the T cell with other immune cells found within the surrounding tumor microenvironment. Entinostat has been observed to decrease the population of immuno-suppressive cells known as myeloid-derived suppressor cells, or MDSCs, and regulatory T cells, or Tregs, which localize in the area surrounding the tumor and block T cells from killing cancer cells, while sparing the cytotoxic T cells. Through blocking the immuno-suppressive effects of MDSCs and Tregs, we believe entinostat has the potential to be used synergistically with therapies such as immune checkpoint inhibitors, resulting in the increased ability of the T cells to attack the tumor.

We are evaluating entinostat in an ongoing Phase 3 clinical trial testing exemestane in combination with entinostat versus exemestane in combination with placebo in patients with advanced HR+, HER2- breast cancer. ECOG-ACRIN Cancer Research Group, or ECOG-ACRIN, is conducting this clinical trial under sponsorship and funding support from the National Cancer Institute, or NCI. The Phase 3 clinical trial was designed to determine whether the addition of entinostat to exemestane improves progression-free survival, or PFS, OS, or both in patients who have previously progressed after treatment with standard-of-care hormonal agents.

To confirm the PFS and OS benefits observed in the Phase 2b clinical trial, we collaborated with ECOG-ACRIN to develop and conduct the Phase 3 clinical trial, E2112. ECOG-ACRIN is conducting the trial under sponsorship and funding support from the NCI. We are providing financial and operational support for the Phase 3 clinical trial under a Cooperative Research and Development Agreement, or CRADA, with theNational Cancer Institute, or NCI, and a separate agreement with ECOG-ACRIN. The trial is a randomized, double-blind, placebo-controlled trial of entinostat in combination with exemestane compared to exemestane and a placebo. The protocol for the Phase 3 clinical trial was reviewed and agreed upon by the FDA under a Special Protocol Assessment, or SPA, agreement with the NCI in January 2014.

Syndax, the NCI and ECOG-ACRIN designed the trial to evaluate whether the addition of entinostat to exemestane improves PFS, OS or both PFS and OS in patients with advanced HR+, HER2- breast cancer who have previously progressed after treatment with standard of care hormonal agents such as NSAIs or Faslodex. In November 2017, ECOG-ACRIN notified us that the Data Safety Monitoring Committee, or DSMC, completed the final PFS analysis and the first interim analysis for OS. The results of this analysis are held confidentially by the ECOG-ACRIN study statistician and the DSMC until the trial completed enrollment.

In October 2018, we announced that enrollment in E2112 concluded, with a total of 608 patients enrolled. ECOG-ACRIN and NCI conducted the primary analysis of PFS after 247 events occurred among the initial 360 patients enrolled and informed us that the trial did not meet the first primary endpoint of improving PFS. Although a positive result on PFS would have provided the earliest regulatory filing opportunity, it does not impact the potential for the trial to achieve the OS endpoint. The trial has now successfully passed five interim OS analyses, all conducted by the trial’s DSMC, continuing until the occurrence of 410 death events, which will trigger the final OS analysis. We expect to achieve this milestone in the second quarter of 2020.

Entinostat in HR+ breast cancer obtained breakthrough therapy designation from the FDA based on positive Phase 2b OS results. Accordingly, any positive OS assessment would enable us to file for full regulatory approval. We continue to actively engage in expanding our commercial and medical affairs activities, to support the planned launch of entinostat in the United States.

We have completed multiple clinical trials of entinostat across a broad range of solid tumors, including breast, non-small cell lung cancer, or NSCLC, melanoma, ovarian and microsatellite stable colorectal carcinoma, or MSS-CRC. We conducted these trials in collaboration with partners, including Merck, Genentech, and Ares Trading, S.A., a subsidiary of Merck KGaA, Darmstadt, Germany, and Pfizer in combination with their anti-PD-(L)1 antibodies.

We designed these trials to test whether entinostat could enhance the activity of PD-1 pathway antagonists across a variety of immunologic environments. NSCLC and melanoma represent settings where the tumors are infiltrated with T cells, MSS-CRC and TNBC are characterized as excluded where the T cells cannot enter the tumor and instead organize around the edges of the tumor, and ovarian cancer which is characterized by having an absence of T-cells. The data that we have received thus far suggest that the addition of entinostat to a PD-1 antagonist can help overcome resistance in patients who have stopped responding to anti-PD-1 therapy in tumors that have been infiltrated with T cells such as NSCLC and melanoma. We presented these results most recently at the 2019 American Association of Cancer Research annual meeting.

In January 2018, we entered into a second clinical collaboration with Genentech to evaluate the combination of entinostat with Tecentriq in patients with HR+, HER2- metastatic breast cancer in a Phase 1b/2, open-label, multicenter, randomized trial that is enrolling patients with metastatic HR+, HER2- breast cancer who have experienced disease progression during or following treatment with a CDK4/6 inhibitor. Genentech is responsible for conducting the trial and has initiated patient enrollment.

Entinostat is also being evaluated in over a dozen ongoing and additional planned investigator-sponsored clinical trials that are designed to provide further validation of entinostat’s immuno-modulatory activity in various other immuno-responsive tumors.

We believe that there may be further opportunities through these and additional collaborations to expand the indications in which entinostat may target immunologic mechanisms of resistance to cancer therapies. In the first quarter of 2019, we completed a full portfolio prioritization assessment and have determined to place the initiation of potential registration trials in non-small cell lung cancer and melanoma on hold until we receive final OS results from E2112.

SNDX-5613, is a potent, orally active inhibitor of the high affinity interaction site on menin with the protein MLL1. This specific interaction is a key driver for two genetically defined acute leukemias: (i) MLLr and (ii) NPM1c AML. Both diseases have a poor ~~prognosis with an unmet need.~~prognosis. In preclinical testing, SNDX-5613 has demonstrated ~~complete tumor regression and profound, dose-dependent and long-lasting survival~~ benefit in leukemic models of disease. Initial clinical evidence with SNDX-5613 also supports the hypothesis that disruption of the menin-MLL interaction can lead to responses in acute leukemias.

We are developing SNDX-5613 as a targeted therapy to potentially treat two genetically defined acute leukemias: (i) a genetically defined subset of acute leukemias with chromosomal rearrangements in the mixed lineage leukemia gene, known as MLLr; and (ii) AML, with a somatic mutation in the nucleophosmin 1, or NPM1, gene, also known as NPM1c. Our near-term focus is to rapidly establish ~~proof of concept~~proof-of-concept that SNDX-5613 is a targeted therapy that can potentially provide meaningful clinical benefit to adult and pediatric leukemia patients having relapsed or refractory MLLr or NPM1c ~~AML.~~acute leukemias. Our investigational new drug, or IND, application for SNDX-5613 ~~was approved by~~took effect with the U.S. Food and Drug Administration, or FDA, in the second quarter of 2019 and we commenced AUGMENT-101, a clinical trial consisting initially of a Phase 1 dose escalation portion to determine the maximum tolerated dose, or MTD, and recommended Phase 2 dose of SNDX-5613 in patients with acute leukemia. ~~Upon completion of~~We are conducting the trial at multiple centers in the United States. We are completing the Phase 1 portion of the trial and ~~identification of~~have initiated the ~~recommended Phase 2 dose, we will initiate the~~pivotal Phase 2 portion of the trial with patients to be enrolled in three

indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of SNDX-5613 in MLLr ALL, MLLr AML and NPM1c AML. ~~We are conducting~~

In September 2021, we participated in a meeting with the ~~trial at multiple centers in~~FDA to discuss the ~~United States and anticipate completing enrollment~~results of the Phase 1 portion inof our AUGMENT-101 trial. At the ~~second half of 2020,~~meeting, the FDA agreed with ~~an expected total enrollment of up to 132 patients for the Phase 1/2 clinical trial.~~

SNDX-6352 is a humanized monoclonal antibody that binds with high affinity to CSF-1R and blocks the binding of the two known CSF-1R ligands CSF-1 and IL-34. CSF-1R is expressed on the surface of specific immune cells known as macrophages and their precursor cells known as monocytes. CSF-1R signaling on these cells has been demonstrated in preclinical studies conducted in animal models of skin and lung cGVHD, to be the key regulatory pathway involved in the expansion and infiltration of the macrophages that mediate the cGVHD disease process. Blocking CSF-1R activity with an experimental CSF-1R antibody in these studies was shown to prevent and treat the symptoms of cGVHD. We are developing SNDX-6352 to bind to CSF-1R and block the ability of CSF-1 and IL-34 to activate CSF-1R signaling. We believe that by inhibiting CSF-1R activation on monocytes and macrophages, that SNDX-6352 has the potential to be used to treat cGVHD.

CSF-1R is also expressed on immuno-suppressive cells (e.g., TAMs) known to play a role in the growth, survival, and metastasis of cancer. Inhibition of CSF-1R is thought to disrupt the activity of TAMs, resulting in a decrease in the immunosuppressive environment immediately surrounding the tumor, or tumor micro-environment. This mode of action is thought to make CSF-1R inhibitors such as SNDX-6352 well suited for use in combination with checkpoint inhibitors, particularly in cancers where there may be limited activity of immune checkpoint inhibitors as monotherapy. We believe that SNDX-6352 has the potential to be used to treat a variety of cancers in combination with entinostat and with other oncology agents, including immune checkpoint inhibitors, radiation, and chemotherapy.

Our near-term focus is to rapidly establish proof of concept that SNDX-6352 can provide meaningful clinical benefit to patients in one or more tumor types when combined with standard of care therapies for a given indication as well as to patients with cGVHD when used as a single agent. We intend to conduct clinical trials in patients with tumor types having clear unmet needs (e.g., NSCLC, TNBC, prostate, melanoma, pancreatic, ovarian, bladder) and in patients with advanced cGVHD where prior therapies are no longer effective.

We are conducting a Phase 1 dose escalation trial of SNDX-6352-502. In addition to assessing safety at increasing doses of SNDX-6352, this trial will provide information on the concentration of SNDX-6352 and levels of CSF-1, IL-34 and non-classical monocytes in the blood. We are conducting the trial at multiple centers in the United States and completed enrollment at the end of 2019, with safety and bioanalytical assessments ongoing and expected to be completed by the end of the first quarter of 2020. We expect to utilize the safety assessment of SNDX-6352 to determine the starting dose for subsequent clinical trials testing multiple doses of SNDX-6352 as a single agent and in combinations.

~~In early 2018, we expanded SNDX-6352-502 to include a Phase 1b dose escalation study evaluating the safety of SNDX-6352 in combination with~~ ~~Imfinzi~~, AstraZeneca’s human monoclonal antibody directed against PD-L1. These cohorts will also provide information on pharmacokinetic and pharmacodynamic effects of the combination. We completed enrollment of the Phase 1b portion and at the end of the second quarter of 2019 we identified the requiredour recommended Phase 2 dose and ~~schedule as 3 mg/kg every~~confirmed that we may initiate the Phase 2 ~~weeks~~registration-directed cohorts of AUGMENT-101. Additionally, the FDA agreed with our proposed statistical design and endpoints for ~~SNDX-6352~~each of the three Phase 2 expansion cohorts.

Additionally, we announced that we will initiate a frontline trial of SNDX-5613 in combination with ~~Imfinzi~~.venetoclax and azacytidine in newly diagnosed AML patients unable to tolerate induction chemotherapy. The trial will be conducted as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial, and SNDX-5613 is the first menin inhibitor to be included in the Beat AML Master Clinical Trial. We also announced that we will initiate a trial to assess the anti-leukemic efficacy of SNDX-5613 in MLLr or NPM1 patients with measurable residual disease progression following anti-leukemic treatment. This trial will be conducted as part of the Australian Leukemia and Lymphoma Group INTERCEPT Master Clinical Trial, a collaborative clinical trial investigating novel therapies to target early relapse and clonal evolution as pre-emptive therapy in AML. SNDX-5613 is the first menin inhibitor to be included in the INTERCEPT AML Master Clinical Trial. Lastly, we announced that we will initiate a new trial to assess the safety, tolerability, and preliminary anti-leukemic efficacy of SNDX-5613 in combination with chemotherapy in patients with relapsed or refractory MLLr or mNPM1 acute leukemias. We expect that the Phase 1b trial, which we refer to as AUGMENT-102, will enroll up to 27 patients.

In December 2021, we presented positive date from the Phase 1 portion of our AUGMENT-101 trial in heavily pretreated patients with MLLr or NPM1c mutations in an oral presentation during the American Society of Hematology (ASH) Virtual Annual Meeting. The following table summarizes select efficacy and safety data that has been presented by us throughout 2021.

In the ~~fourth quarter~~data that we presented at ASH, SNDX-5613 was well tolerated, with no discontinuations due to treatment-related adverse events observed. The only dose limiting toxicity observed was Grade 3 QT prolongation, which occurred in 7% (n=3/43) of ~~2018, we opened enrollment in SNDX-6352-503, a Phase 1 dose escalation trial of SNDX-6352 in~~ patients ~~with cGVHD. The objectives of this trial are to evaluate~~treated at the ~~safety and preliminary efficacy of SNDX-6352 in cGVHD and to identify a required~~four doses that met the study’s pre-defined recommended Phase 2 dose and schedule. The trial remains ongoing with up to 30 patients anticipated to participate in the trial. We anticipate completing enrollment in the second quarter of 2020. Based on emerging data suggesting preliminary activity at 1 mg/kg, we have amended the protocol to add an expansion cohort of approximately 20 patients to further explore this dose level. We anticipate that enrollment in the expansion cohort will be completed by the fourth quarter of 2020.

Patients in the United States with advanced HR+ breast cancer are treated with hormone therapies with the goal to prolong OS and to delay treatment with more toxic chemotherapies. Hormone therapies are designed to inhibit estrogen stimulation of HR-driven breast cancers. Due to limited efficacy of hormone therapies in the advanced HR+ breast cancer setting, multiple lines of treatment are typically used, with each additional line of hormone therapy resulting in a shorter PFS and lower OS. The cause of resistance is multi-factorial and results in tumor progression independent of estrogen stimulation. In 2019, approximately 35,000 patients with HR+ breast cancer were treated with a hormone therapy as second-line or later treatment in the United States. The median OS for advanced HR+ breast cancer in the second-line setting is approximately two years.

~~Over the past decade,~~January 2020, the FDA ~~has approved multiple agents for use in combination with hormone therapy to treat advanced~~granted SNDX-5613 Orphan Drug Designation, or ~~metastatic HR+ breast cancer.~~ ~~Afinitor~~^® ~~(everolimus), an inhibitor of mammalian target of rapamycin, was the first drug approved in combination with hormone therapy, followed by the cyclin-dependent kinase 4 and 6, or CDK4/6, inhibitors,~~ ~~Ibrance~~^® ~~(palbociclib),~~ ~~Kisqali~~^® ~~(ribociclib) and~~ ~~Verzenio~~^® ~~(abemaciclib). More recently~~ ~~Piqray~~^® (alpelisib), an inhibitor of the alpha isoform phosphatidylinositol-3-kinase, became the first agent approved for use in a specific subpopulation of HR+ HER2- mBC, patients with PI3Kalpha mutations, which represent 20 to 40% of the HR+ HER2- mBC population. Notably, all agents have been approved based on their ability to prolong the time to disease progression versus treatment with hormone therapy alone, though ~~Kisqali~~ ~~and~~ ~~Verzenio~~ also showed a survival benefit in treated patients. Based on the significant PFS and OS benefit observed in combination with endocrine therapy, CDK4/6 inhibitors have become a mainstay in the front-line treatment of advanced HR+, HER2- mBC, while Afinitor is more likely to be reserved for second-line treatment or later.

~~While the treatment of advanced HR+ breast cancer is evolving given the introduction of multiple combination therapies~~, ~~we believe physicians will welcome the introduction of a well-tolerated therapy that improves survival, which has not been demonstrated to date for~~ ~~Afinitor~~ or ~~Piqray~~. We believe current data suggests that entinostat could demonstrate an improvement in OS combined with favorable benefit-risk profile and could become a preferred treatment option for patients with advanced HR+ breast cancer who have stopped responding to their first line endocrine-based regimen.

Lung cancer is the leading cause of cancer death among men and women, with more people dying of lung cancer each year than of colon, breast and prostate cancers combined. According to the American Cancer Society, approximately 84% of lung cancers are NSCLC, with an estimated 228,820 new cases of lung cancer and 135,720 deaths from lung cancer expected in the United States in 2020. The five-year survival rate for patients with non-small cell lung cancer is 24% and for patients with Stage IV is approximately 6%, indicating a significant need for new therapies that can prolong OS.

Advanced/metastatic NSCLC is a severe disease with a poor prognosis in the majority of patients. Treatment typically has included a first-line combination chemotherapy followed by a choice of a second-line therapeutic approaches. Though the availability of immune checkpoint inhibitors has brought a significant advancement for NSCLC patients, most patients may still see their disease progress and the proportion of treated patients with low PD-L1 expression who respond to approved regimens is quite low (approximately 10%). We believe with these disease-progressing patients and low response rates, there is significant room to improve upon the benefit of PD-L1 inhibitors through combinations with drugs, like entinostat, that target immune modulation through complementary mechanisms.

The incidence of malignant melanoma in most developed countries has risen faster than any other cancer type since the mid-1950s. In 2011, the average survival duration for patients with Stage IV melanoma, in which the melanoma has metastasized, was only six to ten months; and the five-year survival rate for such patients was 16%.

~~Although this rate had not changed in some time, a major advance for melanoma came with the development and approval of drugs such as~~ ~~Zelboraf~~^® ~~(vemurafenib),~~ ~~Tafinlar~~^® ~~(dabrafenib) and~~ ~~Mekinist~~^® ~~(trametinib),~~ ~~Braftovi~~^®~~(encorafenib) and~~ ~~Mektovi~~^® ~~(binimetinib) for patients with a mutated BRAF gene, which is a human gene that encodes a protein called B Raf.~~

~~Melanoma is a particularly immune-responsive tumor, and thus, immunotherapy of melanoma has developed as a dynamic field for clinical research. To date, immunotherapies such as~~ ~~Yervoy~~^® ~~(ipilmumab),~~ ~~Keytruda~~ ~~and~~ ~~Opdivo~~^® ~~(nivolumab), have been approved~~ODD, for the treatment of ~~malignant melanoma~~adult and pediatric AML and in June 2021, the FDA granted Fast Track Designation to SNDX-5613 for the treatment of adult and pediatric patients with ~~unresectable~~relapsed or ~~metastatic disease. However, in this tumor type as well,~~refractory acute leukemias harboring a MLLr or NPM1 mutation. In December 2021, we announced that the ~~immunotherapies represent a significant advance~~European Commission granted ODD to SNDX-5613 for ~~only a small proportion~~the treatment of patients, leaving significant room to improve upon the benefit of immune checkpoint inhibitors through combinations with drugs, like entinostat, that target immune modulation through a complementary mechanism.AML.

MLLr leukemias arise by rare, spontaneous translocations at the MLL1 locus (11q23). It is estimated that approximately 10% of AML and ALL harbor this MLL-re-arrangement with a worldwide incidence of approximately 5,000 to 7,000 cases per year. These translocations generate oncogenic fusion proteins with more than 90 different MLL fusions currently known. All MLL fusion proteins bind with high affinity to the chromatin associated protein menin through a conserved N-terminal sequence. This specific interaction with menin enables an aberrant transcription program that drives leukemic transformation. In pre-clinical animal models, small molecule inhibitors of the menin-MLL interaction have demonstrated deep and durable single agent treatment effects in multiple leukemic xenografts harboring MLL fusions. Inhibiting the menin-MLL1 interaction represents a novel targeted strategy for the treatment of MLLr leukemias. Today, the first choice therapy for both MLLr AML and MLLr ALL still relies heavily on intensive chemotherapy, if a patient can tolerate such treatment. Despite these patients being routinely diagnosed, there are currently no targeted therapies approved to treat patients with MLLr acute leukemias. Currently there are several other clinical-stage menin-inhibitors in development for the treatment of MLLr AML and MLLr ALL.

NPM1 is among the most frequently mutated genes in AML, found in approximately 30% of AML cases for an incidence of approximately 20,000 cases per year. Mutations in NPM1 lead to the aberrant cytoplasmic localization of the mutants, termed NPM1c. Loss of NPM1c from the nucleus leads to suppression of differentiation and enables a leukemic transcription program that relies critically on the menin-MLL1 complex to drive and maintain the program. As a result, NPM1c harboring cells are sensitive to menin-MLL interaction inhibitors. In NPM1c cells, inhibition of the menin-MLL interaction suppresses the leukemic transcription program, causing growth arrest, terminal differentiation and cell death. In animal models, small molecule inhibitors of the menin-MLL interaction have demonstrated deep and durable single agent treatment effects in multiple NPM1c xenografts. Based on these findings, blocking the menin-MLL1 interaction represents a novel targeted strategy for the treatment of NPM1c AML.

~~SNDX-6352~~Like MLLr, NPM1 is readily diagnosed as part of the standard AML patient work-up today, and yet there are no approved targeted therapies approved to treat patients with a NPM1 mutant AML. There are several additional clinical stage agents currently advancing as potential treatments for NPM1 mutant AML.

We are also developing axatilimab a monoclonal antibody targeting the colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. Axatilimab binds with high affinity to CSF-1R and blocks the binding of the two known CSF-1R ligands CSF-1 and IL-34. CSF-1R is expressed on the surface of specific immune cells known as macrophages and their precursor cells known as monocytes. CSF-1R signaling on these cells has been demonstrated in ~~GVHD~~preclinical studies conducted in animal models of skin and lung chronic graft versus host disease, or cGVHD, to be the key regulatory pathway involved in the expansion and infiltration of the macrophages that mediate fibrosis and the cGVHD disease process. Blocking CSF-1R activity with an experimental CSF-1R antibody in these studies was shown to prevent and treat the symptoms of cGVHD. We believe that by inhibiting CSF-1R activation on monocytes and macrophages, axatilimab has the potential to be used to treat cGVHD as well as other fibrotic diseases where monocyte-derived macrophages have been shown to play a significant role.

Our near-term focus is to rapidly establish that axatilimab can provide meaningful clinical benefit in patients with advanced cGVHD where prior therapies are no longer effective and to establish proof-of-concept of using axatilimab to treat other fibrotic diseases where monocyte-derived macrophages have been shown to play a role.

We announced that following our end of Phase 1 meeting with the FDA, we have aligned on a regulatory path for axatilimab for the treatment of cGVHD. We commenced a pivotal Phase 2 trial, AGAVE-201, to assess the safety and efficacy of different doses and schedules of axatilimab for the treatment of patients with cGVHD. The primary endpoint is the objective response rate based on the 2014 NIH consensus criteria for GVHD with key secondary endpoints including duration of response and improvement in modified Lee Symptom Scale score. We anticipate releasing topline data in 2023. We completed enrollment of the Phase 1/2 trial evaluating axatilimab for the treatment of patients with cGVHD in the second quarter of 2021.

In December 2021, we presented positive data from the Phase 1/2 trial of axatilimab in patients with recurrent or refractory chronic cGVHD despite two or more prior lines of therapy in an oral presentation during the American Society of Hematology at ASH. During the presentation, and in a press release that we issued on the presentation date, we shared that as of October 22, 2021 (data cutoff) a total of 40 patients were treated in the SNDX-6352-503 trial, who received a median of four prior systemic therapies. There were 31 evaluable patients treated at 1mg/kg every 2 weeks or 3mg/kg every 4 weeks, the doses that we are testing in the ongoing AGAVE-201 global pivotal study. Of the evaluable patients, responses were observed in 68% (n=21/31) of patients, with a best ORR (complete response (CR) plus partial response) of 72% (n=18/25) at 1mg/kg every two weeks and 50% (n=3/6) at 3mg/kg every four weeks. Responses observed across a range of organ systems with difficult to treat manifestations such as lung (n=5/15), skin (n=3/28), and joints and fascia (n=16/24). Fifty-three percent of patients (n=16/30) reported clinically meaningful improvement as measured by at least a 7-point decrease in Lee Symptom Scale score. As of data cutoff 43% (n=17/40) of patients remained on treatment.

In the data that we presented at ASH, axatilimab was well-tolerated with a favorable safety profile. The most common observed adverse events were consistent with on-target effects on liver enzyme pharmacology. There was no incidence of cytomegalovirus or other viral reactivation and no apparent increases in risk for infection. Enrollment remains ongoing in the global pivotal Phase 2 AGAVE-201 trial of axatilimab in patients with cGVHD, with topline data expected in 2023.

In March and April of 2021, we announced that the FDA granted Orphan Drug Designation to axatilimab for the treatment of patients with cGVHD and idiopathic pulmonary fibrosis, or IPF. In addition to the ongoing AGAVE-201 trial, we and Incyte expect to initiate additional trials of axatilimab in patients with cGVHD in 2022, including a Phase 2 trial in combination with a JAK inhibitor in patients with steroid-refractory cGVHD. Beyond cGVHD, we plan to commence a Phase 2 proof-of-concept trial of axatilimab in the first half of 2022 in patients with IPF.

cGVHD, an immune response of the donor-derived hematopoietic cells against recipient tissues, is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation, or HSCT, that can last for years. cGVHD is estimated to develop in approximately 40% of transplant recipients and affects approximately 14,000 patients in the United States. cGVHD typically manifests across multiple organ systems, with the skin and mucosa being commonly involved, and is characterized by the development of fibrotic tissue

The first line of therapy for cGVHD is typically corticosteroids, though approximately 50% of patients may require treatment with additional systemic therapies, such as extracorporeal photopheresis, cytostatic agents such as mycophenolate moftetil, methotrexate, and immunmodulators such as rituximab, IL-2. Imbruvica® (ibrutinib), a BTK inhibitor, iswas the ~~only~~first FDA-approved therapy for cGVHD and is indicated for use after one or more lines of therapy. Imbruvica received approval based on Phase 1/2 clinical trial data that showed a 68% overall response rate, with 48% of responses lasting 20 weeks or longer and reduced dependence on steroids for most patients. ~~KD-025 and Ruxolitinib are currently~~While approved agents have shown a benefit in ~~registration-directed clinical trials for patients with steroid refractory cGVHD, with~~

~~results expected in 2020. Still, a significant unmet need remains for these patients as no agent has~~improving symptoms of this disease, none have demonstrated an improvement in long-term ~~outcomes.~~outcomes and a significant unmet medical need still remains for this patient population. Additionally, all currently approved agents are believed to exert their effect through T- and B-cells, with minimal impact on macrophages. By inhibiting the work of monocyte-derived macrophages, Axatilimab, provides a differentiated way to treat cGVHD, which we expect is ultimately expected to have a more pronounced impact on the fibrotic process. We also believe that shifting CSF-1R inhibition earlier in the treatment phase of cGVHD, to minimize formation of fibrotic tissue, could have a meaningful long-term impact on the disease process itself.

~~Clinical Collaborations~~Entinostat is our oral, small molecule product candidate that has direct effects on both cancer cells and immune regulatory cells, potentially enhancing the body’s immune response to tumors. In May 2020, we reported final results of E2112, the Phase 3 clinical trial conducted by ECOG-ACRIN Cancer Research Group and sponsored by the National Cancer Institute, that evaluated the investigational compound entinostat plus exemestane in ~~Immuno-Oncology~~patients with advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer. The trial did not achieve the primary endpoint of demonstrating a statistically significant overall survival benefit over hormone therapy alone.

We have ~~entered into several clinical collaborations in immuno-oncology, as we have further described below. To~~deprioritized the extent that any inventions arise from such a collaboration, each party will solely own inventions relating to its drug alone, and the parties will jointly own any inventions relating to the combination of the two drugs. In most cases, clinical data from the trial will be jointly owned. In general, either party may terminate the applicable collaboration agreement for the other party’s uncured material breach. In addition, either party may terminate the applicable agreement if it determines that the trial may unreasonably affect patient safety, or if a regulatory authority withdraws the approval to conduct a trial or takes an action that prevent such party from supplying its drug, or if the other party or its employees are sanctioned under certain healthcare-related laws, or if such party decides to discontinue development of ~~its drug.~~entinostat, but may opportunistically explore potential disease areas where entinostat could play an important therapeutic role.

In ~~March 2015,~~September 2021, we entered into a ~~clinical trial~~ collaboration and ~~supply~~license agreement, or the Incyte Agreement, with ~~MSD International GmbH, an affiliate~~Incyte for the development and commercialization of ~~Merck, under which we conducted a clinical trial evaluating entinostat~~axatilimab. Additionally, in ~~combination with Merck’s drug~~ ~~Keytruda~~ ~~in patients with NSCLC and melanoma. We were~~September 2021 the ~~sponsor of the clinical trial and Merck supplied~~ ~~Keytruda~~ for use in the clinical trial. Neither party will have any obligation to reimburse any costs incurred by the other party, except that a party may be required to reimburse the manufacturing costs of the other party upon certain early termination events. We remain interested in potentially conducting further studies in NSCLC and melanoma.

~~In August 2015, we~~Company entered into a ~~combination study collaboration~~share purchase agreement with ~~Genentech under which~~Incyte, or Incyte Share Purchase Agreement. Collectively referred to as the Incyte Agreements. Under the terms of the Incyte Agreement, Incyte received exclusive commercialization rights outside of the United States, and we ~~conducted~~and Incyte will, subject to the exercise of our co-promotion option, have co-commercialization rights in the United States, with respect to axatilimab. Incyte is responsible for leading commercialization strategy and booking all revenue from worldwide sales of axatilimab, subject to its royalty payment obligations set forth below. The parties will share equally the profits and losses from the co-commercialization efforts. We and Incyte are co-developing axatilimab and sharing development costs associated with global and U.S.-specific clinical trials, with Incyte responsible for 55% of such costs and we are responsible for 45% of such costs. Each company is responsible for funding any independent development activities. All development costs related to the collaboration are subject to a ~~clinical trial evaluating entinostat in combination with Genentech’s drug~~ ~~Tecentriq~~ ~~in patients with TNBC. In March 2019, we announced that this trial did not meet its primary endpoint~~joint development plan. A joint development committee between us and Incyte will govern future development of ~~statistically significant improvement in PFS for the combination regimen versus~~ ~~Tecentriq~~ ~~monotherapy.~~axatilimab.

In ~~January 2018,~~addition, we and Incyte entered into a ~~combination study~~Letter Agreement memorializing how the parties would work together in the event that the government intervened in the proposed collaboration ~~agreement~~and the parties are forced to terminate and unwind the collaboration. Pursuant to the Letter Agreement, the parties agreed, in part, (i) to permit Incyte to terminate the Incyte Agreement through September 2022 if, prior to March 23, 2022, either party for the

first time receives a formal request from either the Federal Trade Commission or the Department of Justice, Antitrust Division, regarding the Incyte Agreement, which we refer to as the Termination Right, and (ii) to provide the parties with ~~Genentech~~a mechanism to settle any gain or loss related to Incyte’s equity investment in the Company solely in the event that Incyte exercises its Termination Right. If Incyte exercises its Termination Right, (x) we will refund to Incyte the $117 million upfront license fee and any payments made by Incyte for royalties, milestones and development costs and any other amounts paid by Incyte to us under ~~which Genentech~~the Incyte Agreement, and (y) we will ~~conduct~~waive any remaining lock-up restrictions and Incyte may sell may the shares of our common stock that it purchased in connection with its equity investment pursuant to the Incyte Agreement. Following a ~~clinical trial evaluating entinostat~~sale of its shares, Incyte will remit to us any gain that it received, or, alternatively, we will repay Incyte for any loss that it incurred in ~~combination~~each case in connection with ~~Genentech’s drug~~ ~~Tecentriq~~ ~~in patients with HR+, HER2-, metastatic breast cancer. Genentech is~~ the ~~sponsor~~sale of the ~~clinical trial.~~shares. The Termination Right expires if the parties do not receive a formal request before March 23, 2022. To date, the parties have not received any formal request from either the Federal Trade Commission or the Department of Justice, Antitrust Division.

Upon signing the Letter Agreement in December 2021 both the Incyte Agreement and Incyte Share Purchase Agreement became effective. As a result, we received an upfront fee of $117 million and we issued 1,421,523 shares of common stock for an aggregate purchase price of $35 million, or $24.62 per share. We are ~~supplying entinostat for use~~eligible to receive up to $230 million in commercialization milestones as well as tiered royalties ranging in the ~~clinical trial. Each party will perform its obligations under~~mid-teens on sales outside of the ~~agreement at its own expense, including its internal costs.~~

In December 2015, we entered into a clinical trial collaboration and supply agreement with Merck KGaA and Pfizer under which we conducted a clinical trial evaluating entinostat in combination with an investigational monoclonal antibody, ~~Bavencio, in patients with ovarian cancer. In March 2019, we announced that this did not meet its primary endpoint of a statistically significant improvement in PFS for the combination regimen compared with~~ ~~Bavencio~~ ~~monotherapy.~~United States.

Collaborative Research and Development Agreement with the NCI related to Entinostat

Our collaboration with the NCI is governed by a CRADA between us and the NCI. The CRADA was originally signed by Mitsui Pharmaceuticals, Inc., or Mitsui, and was then assigned to Schering AG following Schering AG’s acquisition of Mitsui. In 2007, Schering AG, then known as Bayer Schering Pharma ~~AG),~~AG, agreed to

assign the CRADA to us in connection with the execution of a license, development and commercialization agreement, or the Bayer license agreement, with Bayer.

Under the CRADA, as amended, the NCI sponsors clinical studies on entinostat using researchers at the NCI as well as NCI-funded researchers at other institutions, including ECOG-ACRIN and JHU. In return, we receive access to the data generated in these clinical studies, and we are obligated to supply the clinical trial sites with sufficient quantities of entinostat. Additionally, we are required to make an annual payment to a particular NCI laboratory to help support certain research studies related to this and other clinical trial. We have no other payment obligations under the CRADA.

We own any intellectual property generated in the course of the collaboration with the NCI, or Collaboration IP, to the extent that Collaboration IP is generated by our employees. We also have an exclusive option to obtain an exclusive or non-exclusive commercialization license under Collaboration IP generated by the NCI. With respect to any Collaboration IP that is owned by or licensed to us, we have agreed to grant the United States government a non-exclusive license to practice or have practiced this Collaboration IP throughout the world by or on behalf of the government for research or other government purposes.

Either party may terminate the CRADA either by mutual consent or unilaterally upon advance written notice to the other party. Absent such early termination, the CRADA will expire on May 21, 2023. As we have in the past, we expect to renew the CRADA at that time.

In March 2014, we entered into a clinical trial agreement with Eastern Cooperative Oncology Group, a contracting entity for ECOG-ACRIN, which describes the parties’ obligations with respect to the NCI-sponsored pivotal Phase 3 clinical trial of entinostat. Under the terms of the clinical trial agreement, ECOG-ACRIN is performing this clinical trial in accordance with the clinical trial protocol and a mutually agreed scope of work. In January 2015, we amended the agreement to provide for additional patient site reimbursement funds, which will be paid based on milestone-based payments. We will provide a fixed level of financial support for the clinical trial through an upfront payment of $0.7 million and a series of time- and milestone-based payments of up to $1.0 million each that are comprised of milestone payments through the completion of enrollment and time-based payments through the completion of patient monitoring post-enrollment. In addition, we are obligated to supply entinostat and placebo to ECOG-ACRIN for use in the clinical trial. From the second quarter of 2016 through the fourth quarter of 2018, we have entered into a number of amendments to the agreement to provide for additional study activities resulting in an increase of the contractual obligation of $5.1 million. We have agreed to provide this additional financial support to fund the additional activities required to ensure that the E2112 clinical trial will satisfy FDA registration requirements. As of December 31, 2018, our aggregate payment obligations under this agreement are approximately $24.5 million; and our remaining obligations under this agreement were $9.6 million over an estimated period of approximately three years.

ECOG-ACRIN owns data and inventions from the Phase 3 clinical trial. We have access to the data generated in the clinical trial, both directly from ECOG-ACRIN under the clinical trial agreement, as well as from the NCI through our agreement with it. Additionally, ECOG-ACRIN has granted us a non-exclusive license to any inventions or discoveries that are derived from entinostat as a result of its use during the clinical trial, along with a first right to negotiate an exclusive license to any of these inventions or discoveries.

Either party may terminate the clinical trial agreement in the event of an uncured material breach by the other party or if the FDA or NCI withdraws the authorization to perform the clinical trial in the United States. The parties may jointly terminate the clinical trial agreement if the parties agree that safety-related issues support termination.

Collaborative Research and Development Agreement with the NCI related to ~~Entinostat~~Axatilimab and ~~SNDX-6352~~Entinostat

In September 2016, we entered into aan additional collaboration with the NCI related to both entinostat and ~~SNDX-6352 is governed by a CRADA between us and the NCI.~~axatilimab. Under the CRADA, the NCI sponsors preclinical and clinical studies on entinostat and ~~SNDX-6352~~axatilimab using researchers at the NCI as well as NCI-funded researchers at other institutions. In return, we

receive access to the data generated in these preclinical and clinical studies and we are obligated to supply the laboratories and clinical trial sites with sufficient quantities of entinostat and ~~SNDX-6352.~~axatilimab. Additionally, we are required to make an annual payment to a particular NCI laboratory to help support certain research studies related to this and other preclinical and clinical ~~trial.~~trials. We have no other payment obligations under the CRADA.

We own all intellectual property generated during the collaboration with the NCI, or ~~6352~~Axatilimab Collaboration IP, to the extent that ~~6352~~Axatilimab Collaboration IP is generated by our employees. We also have an exclusive option to obtain an exclusive or non-exclusive commercialization license under ~~6352~~Axatilimab Collaboration IP generated by the NCI. With respect to any ~~6352~~Axatilimab Collaboration IP that is owned by or licensed to us, we have agreed to grant the ~~United States~~U.S. government a non-exclusive license to practice or have practiced this ~~6352~~Axatilimab Collaboration IP throughout the world by or on behalf of the government for research or other government purposes.

We have a license agreement with Vitae Pharmaceuticals, Inc., a subsidiary of AbbVie plc, or the AbbVie License Agreement, under which Vitae granted us an exclusive, sublicenseable, worldwide license to, preclinical, orally-available, small molecule inhibitors of the interaction of menin with the MLL protein, or the Menin Assets. We are solely responsible for the development and commercialization of the Menin Assets.

Subject to the achievement of certain milestone events, we may be required to pay Vitae up to an aggregate of $99 million in one-time development and regulatory milestone payments over the term of the AbbVie License Agreement. In the event that we or any of its affiliates or sublicensees commercializes the Menin Assets, we will also be obligated to pay Vitae low single to low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $70.0 million in potential one-time, sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, we may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with Vitae. In June 2019, we achieved certain development and regulatory milestones resulting in a $4.0 million payment, which was paid with interest in May 2020. In January 2022, we dosed the first patient in our pivotal phase 2 study, consequently completing our phase 1 study. Completion of the phase 1 study requires us to pay AbbVie a $2.0 million development milestone. We anticipate paying this milestone in the first quarter of 2022.

Each party may terminate the AbbVie License Agreement for the other party’s uncured material breach or insolvency; and we may terminate the AbbVie License Agreement at will at any time upon advance written notice to Vitae. Vitae may terminate the AbbVie License Agreement if we or any of its affiliates or sublicensees institutes a legal challenge to the validity, enforceability, or patentability of the licensed patent rights. Unless terminated earlier in accordance with its terms, the AbbVie License Agreement will continue on a country-by-country and product-by-product basis until the later of: (i) the expiration of all of the licensed patent rights in such country; (ii) the expiration of all regulatory exclusivity applicable to the product in such country; and (iii) 10 years from the date of the first commercial sale of the product in such country.

We have a license agreement with UCB, or the UCB license agreement, under which UCB granted us a worldwide, sublicenseable, exclusive license to UCB6352, which the Company refers to as axatilimab. The UCB license agreement permits us to use axatilimab or other licensed products for all human uses, including treatment, prevention and diagnostic uses, in all indications, diseases, conditions or disorders, and we are obligated to use commercially reasonable efforts to develop, obtain regulatory approval and commercialize a certain licensed product. We are solely responsible for the development and commercialization of axatilimab.

Subject to the achievement of certain milestone events, we may be required to pay UCB up to $119.5 million in one-time development and regulatory milestone payments over the term of the UCB license agreement. In the event that we or any of our affiliates or sublicensees commercializes axatilimab, we will also be obligated to pay UCB low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $250.0 million in potential one-time, sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, we may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with UCB. During the year ended December ~~2014,~~31, 2020 and 2021, we ~~entered into~~were required to pay $2.0 million and $4.0 million, respectively, due to the achievement of certain development and regulatory milestones. As of December 31, 2021, $2.0 million is recorded as an accrued expense.

Each party may terminate the UCB license agreement for the other party’s uncured material breach or insolvency; and we may terminate the UCB license agreement at will at any time upon advance written notice to UCB. UCB may terminate the UCB license agreement if we or any of our affiliates or sublicensees institutes a legal challenge to the validity, enforceability, or patentability of the licensed patent rights. Unless terminated earlier in accordance with its terms, the UCB license agreement will continue on a country-by-country and product-by-product basis until the later of: (i) the expiration of all of the licensed patent rights in such country; (ii) the expiration of all regulatory exclusivity applicable to the product in such country; and (iii) 10 years from the date of the first commercial sale of the product in such country.

We have a license agreement with Bayer Pharma AG, or Bayer, pursuant to which we obtained a worldwide, exclusive license to develop and commercialize entinostat and any other products containing the same active ingredient. The Bayer license agreement, as amended, permits us to use entinostat or other licensed products for the treatment of any human disease, and we are obligated to use commercially reasonable efforts to develop, manufacture and commercialize licensed products for all commercially reasonable indications. Initially, Bayer manufactured and supplied our requirements of entinostat, but effective May 2012, manufacturing rights and responsibility for entinostat was transferred to us, by mutual agreement of the parties.

We are obligated to pay up to approximately $50.0 million in the aggregate upon obtaining certain milestones in the development and marketing approval of entinostat, assuming that we pursue at least two different indications for entinostat or any other licensed product. We are also obligated to pay Bayer up to $100.0 million in aggregate sales milestones, and a tiered single-digit royalty on net sales by us, our affiliates and sublicensees of entinostat and any other licensed products under the Bayer license agreement. We are obligated to pay Bayer these royalties on a country-by-country basis for the life of the relevant licensed patents covering such product or 15 years after the first commercial sale of such product in such country, whichever is longer. We cannot determine the date on which our royalty payment obligations to Bayer would expire because no commercial sales of entinostat have occurred and the last-to-expire relevant patent covering entinostat in a given country may change in the future.

The Bayer license agreement will remain in effect until the expiration of our royalty obligations under the agreement in all countries. Upon expiration of the agreement our licenses become fully paid-up and irrevocable. Either party may terminate the Bayer license agreement in its entirety or with respect to certain countries in the event of an uncured material breach by the other party. Either party may terminate the Bayer license agreement if voluntary or involuntary bankruptcy proceedings are instituted against the other party, if the other party makes an assignment for the benefit of creditors, or upon the occurrence of other specific events relating to the insolvency or dissolution of the other party. Bayer may terminate the Bayer license agreement if we seek to revoke or challenge the validity of any patent licensed to us by Bayer under the Bayer license agreement or if we procure or assist a third party to take any such action.

We have a license, development and commercialization agreement with ~~Kyowa Kirin Co., Ltd.,~~Eddingpharm International Company Limited, or ~~KKC,~~Eddingpharm, under which we granted ~~KKC~~Eddingpharm an exclusive license under our intellectual property rights to develop and commercialize entinostat in ~~Japan~~China and ~~Korea.~~certain other Asian countries. This license includes a sublicense under the rights we received under the Bayer license agreement. If we acquire or develop any other anti-cancer drug that, like entinostat, is a selective inhibitor of Class I HDAC, such drug will be included in this license as well. ~~We will manufacture and supply~~Eddingpharm is manufacturing entinostat ~~to KKC~~ during the term of the agreement ~~and such obligation may continue for a longer period if KKC continues to sell entinostat following expiration of the agreement~~ or through termination of the agreement for our breach. During the term of the agreement, subject to certain exceptions, each party is prohibited from commercializing in ~~the Japan~~China and ~~Korea~~certain other Asian countries any other selective inhibitor of Class I HDACs for the same indication as entinostat, with all forms of cancer being treated as the same indication.

We ~~received an upfront license fee of $17.5 million, and KKC purchased 536,049 shares of our Series B-1 Preferred Stock for an aggregate price of approximately $7.5 million. We~~ are eligible to receive up to ~~$50.0~~$10.0 million in development and regulatory milestone payments and up to $25.0 million in sales milestone payments. In October 2017, we announced that KKC dosed the first patient in a randomized, double-blind, placebo-controlled, pivotal Phase 2 trial of entinostat (designated KHK2375 by KKC), in combination with exemestane versus exemestane plus placebo in Japanese patients with advanced or recurrent HR+, HER2- breast cancer. Enrollment of the first patient in this trial triggered a $5 million milestone payment to us from KKC.

~~KKC will pay us a transfer price for the supply of entinostat~~ as well as ~~royalties~~royalty payments based on ~~net sales of entinostat above a specified threshold each calendar year by KKC, its affiliates and sublicensees in the low single digits.~~revenue targets. Royalty payment obligations will be payable in each country in the ~~KKC~~Eddingpharm territory until the later to occur of (i) the date that all valid claims of the last effective license patent in such country expires or is abandoned, withheld or otherwise invalidated and (ii) 15 years from the date of first commercial sale of entinostat in such country. Any payments owed to Bayer as a result of ~~KKC~~ Eddingpharm’s

development ~~and commercialization~~ of entinostat in the ~~KKC~~Eddingpharm territory will be made by us out of the payments we receive from ~~KKC.~~Eddingpharm.

The agreement with ~~KKC~~Eddingpharm will expire with respect to each country in the ~~KKC~~Eddingpharm territory upon the expiration of all royalty payment obligations in such country. In addition, we may terminate the agreement in its entirety upon written notice to ~~KKC~~Eddingpharm if ~~KKC~~Eddingpharm or any affiliate commences any action or proceeding that challenges the validity, enforceability or scope of any licensed patent in the ~~KKC~~Eddingpharm territory. ~~KKC~~Eddingpharm may terminate the agreement in its entirety for convenience at any time upon advance notice to us. Either party may terminate the agreement for the other party’s uncured material breach, or bankruptcy or related actions or proceedings. If we commit an uncured material breach of certain provisions of the agreement, ~~KKC~~Eddingpharm may, instead of terminating the agreement, elect to continue the agreement in full force and effect except certain payments to us will be reduced.

Given our stage of development, we have not yet established a commercial organization or distribution capabilities. We ~~are creating~~intend to build a commercial infrastructure to support sales of our product candidates in the United States. Our targeted sales force will focus on a well-defined group of medical oncologists, primarily in the non-hospital and academic settings, who are responsible for the care and treatment of cancer patients. We expect to manage sales, marketing and distribution through internal resources and third-party relationships. While we may commit significant financial and management resources to commercial activities, we would also consider collaborating with one or more pharmaceutical companies to enhance our commercial capabilities. Outside the United States, we plan to rely on our current partners and may seek additional pharmaceutical partners for sales and marketing activities.

We do not own or operate manufacturing facilities for the production of ~~entinostat, SNDX-6352~~axatilimab, SNDX-5613 or ~~SNDX-5613,~~entinostat, and we do not have plans to develop our own manufacturing operations in the foreseeable future. We currently rely on third-party contract manufacturers for all of our required raw materials, active pharmaceutical ingredients and finished product for our preclinical research and clinical trials. We do not have ~~long-term agreements with any of these third parties. We also do not have~~ any current contractual relationship for the manufacture of commercial supplies. If ~~entinostat, SNDX-6352~~axatilimab, SNDX-5613 or ~~SNDX-5613~~entinostat is approved by any regulatory agency, we intend to enter into agreements with a third-party contract manufacturer and one or more backup manufacturers for the commercial production of such product. Development and commercial quantities of any products that we develop will need to be manufactured in facilities, and by processes, that comply with the requirements of the FDA and the regulatory agencies of other jurisdictions in which we are seeking approval.

Through licensed intellectual property and our owned intellectual property, we seek patent protection in the United States and internationally for our product candidates, their methods of use and processes for their manufacture, as well as for other technologies, where appropriate. Our policy is to actively seek to protect our proprietary position by, among other things, filing patent applications in the United States and abroad claiming our proprietary technologies that are important to the development of our business. We also rely on trade secrets, know-how, continuing technological innovation and in-licensing opportunities to develop and maintain our proprietary position.

We cannot be sure that patents will be granted with respect to any of our owned or licensed pending patent applications or with respect to any patent applications filed by us or our licensors in the future, nor can we be sure that any of our existing owned or licensed patents or any patents that may be granted to us or to our licensors in the future will protect our technology. Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for the technologies that we consider important to our business, defend our patents, preserve the confidentiality of our trade secrets, operate our business without infringing the patents and proprietary rights of third parties, and prevent third parties from infringing our proprietary rights.

We in-licensed from UCB a patent portfolio directed to axatilimab. As of December 31, 2021, the axatilimab composition-of-matter patent portfolio included two granted U.S. patents, seven allowed non-U.S. applications, fourteen granted non-U.S. patents, including a granted EP patent which has been validated in 37 countries, and 19 non-U.S. pending patent applications. The in-licensed granted patents covering axatilimab, and any non-U.S. pending applications should they issue, will expire in August 2034 or later should patent term extension be granted.

Our in-licensed patent portfolio also includes pending U.S. and non-U.S. patent applications directed to methods for the treatment and/or prophylaxis of fibrotic disease by administration of an inhibitor of CSF-1R activity, methods for the treatment and/or prophylaxis of inflammatory bowel disease, or IBD, by administration of an inhibitor of CSF-1R activity, and liquid pharmaceutical compositions of anti-CSF-1R antibodies. If these pending applications were to issue as one or more patents, these patents would expire between November 2024 and February 2036 or later should patent term extension be granted. Further, the in-licensed portfolio includes three non-U.S. patents directed to methods of treating solid tumors by administration of an inhibitor of CSF-1R activity. The three patents expired in October 2020.

Our owned axatilimab patent portfolio includes one pending U.S. patent application and six non-U.S. patent application directed to combinations of entinostat and axatilimab. If any one of these applications were to issue as one or more patents, these patents would expire in May 2038 or later should patent term extension be granted. Our owned axatilimab patent portfolio also consists of one pending international patent application under the Patent Cooperation Treaty, or PCT, directed to the treatment regimens and methods of using axatilimab. If this PCT application were to issue as one or more patents, these patents would expire in December 2040 or later should patent term extension be granted.

We in-licensed from Vitae Pharmaceuticals, Inc., a subsidiary of AbbVie plc, a patent portfolio directed to a series of selective preclinical inhibitors targeting the binding interaction of menin with MLL-r. As of December 31, 2021, the in-licensed portfolio includes two granted U.S. patents, U.S. Patent Nos. 10,683,302 and 10,899,758, six granted non-U.S patents, including a granted European patent, which was validated in 30 member states, two pending U.S. applications and 28 non-U.S. pending patent applications covering composition of matter and methods of treating, e.g., MLL. The granted patents based on the in-licensed applications is expected to expire June 2037 or later should patent term extension be granted. If the in-licensed application were to issue as one or more patents, these patents would expire between June 2037 and September 2037.

Our owned menin patent portfolio consists of one pending international patent application under the Patent Cooperation Treaty, or PCT, directed to combinations of a menin inhibitor and a CYP3A inhibitor for the treatment of various cancers. Our owned menin patent portfolio also consists of two U.S. provisional applications directed to menin inhibitors and combinations with various other compounds. If any applications arising from the PCT or provisional applications were to issue as one or more patents, these patents would expire between April 2041 and May 2042 or later should patent term extension be granted.

We strive to protect entinostat with multiple layers of patents. As of December 31, ~~2019,~~2021, our portfolio included ~~one owned U.S. provisional patent application, five~~four owned pending U.S. non-provisional patent applications, one owned granted U.S. patent, U.S. Patent No. 10,226,472, which expires in August 2032 or later should patent term extension be granted, one allowed U.S. non-provisional patent ~~five~~application directed to methods of treating a patient with combinations of entinostat and

pembrolizumab, eight granted non-U.S. patents (including one Canadian patent jointly owned with The Regents of the University of ~~Colorado)~~Colorado, which will expire in April 2029), and 7149 owned non-U.S. pending patent ~~applications (including one pending international patent application under the Patent Cooperation Treaty, or PCT).~~applications. Also, we have filed national phase applications in the Eurasia Regional Patent Office, Ukraine and Georgia based on our owned PCT application directed to treatment of selected breast cancer patients with a combination of entinostat and exemestane. We have assigned our rights to the application we filed in the Eurasia Regional Patent Office to Domain Russia Investments Limited, or DRI. We have also assigned our rights to the applications we filed in Ukraine and Georgia to NovaMedica LLC, or NovaMedica. We have also filed national phase applications based on our owned PCT application directed to treatment of selected breast cancer patients with the combination of entinostat and exemestane in the U.S. Patent and Trademark Office, or USPTO, the European Patent Office, or EPO,

~~China, India, Australia, Canada, Japan, South Korea, South Africa, Brazil and Mexico.~~ Our owned entinostat patent portfolio includes pending U.S. and ex-U.S. patent applications directed to methods of treating cancer patients by administration of entinostat ~~according to selected dosing regimens,~~and exemestane, methods of treating cancer patients by administration of entinostat in combination with an HER2 inhibitor, ~~and~~ treatments with entinostat combined with anti PD-1 or anti PD-L1 ~~antibodies. Our owned pending PCT applications relate to~~antibodies, entinostat and CSF-1 or CSF-1R combination therapies (also discussed above in the Axatilimab Patent Portfolio) and patient selection for combination therapy comprising entinostat and a second therapeutic ~~agent, respectively.~~agent. If ~~issued, patents based on~~ our owned pending U.S. applications and non-U.S. filings ~~based on our owned PCT applications~~were to issue as one or more patents, these patents would expire between ~~April 2029~~August 2032 and May 2039.

The patent portfolio we licensed from Bayer contains a number of issued U.S. and foreign patents as well as patent applications pending outside the United States. A number of the patents and patent applications we licensed from Bayer are directed to entinostat while other patents and patent applications are directed to compounds other than entinostat. As of December 31, 2019, the portfolio we licensed from Bayer included seven issued U.S. patents, 62 granted non-U.S. patents and 17 patent applications pending in non-U.S. patent offices. For example, the portfolio we licensed from Bayer includes reissue U.S. Patent RE39,754, which covers a genus of benzamide compounds including entinostat or SNDX-275. RE39,754 is a composition of matter patent having an initial term which expired in September 2017.

The portfolio we licensed from Bayer also includes U.S. Patent 7,973,166, or the ’166 patent, which covers a crystalline polymorph of entinostat which is referred to as crystalline polymorph B, the crystalline polymorph used in the clinical development of entinostat. Many compounds can exist in different crystalline forms. A compound which in the solid state may exhibit multiple different crystalline forms is called polymorphic, and each crystalline form of the same chemical compound is termed a polymorph. A new crystalline form of a compound may arise, for example, due to a change in the chemical process or the introduction of an impurity. Such new crystalline forms may be patented. By comparison, the U.S. Patent RE39,754, which expired in September 2017, covers the chemical entity of entinostat and any crystalline or non-crystalline form of entinostat. On March 7, 2014, our licensor Bayer applied for reissue of the ‘166 patent. The reissue application sought to add three additional inventors to the ‘166 patent. The reissue was granted as RE45,499 on April 28, 2015, at which time the original ‘166 patent was surrendered. The reissue patent has the same force and effect as the original ‘166 patent and the same August 2029 expiration date.

Of the 62unexpired foreign-granted patents we licensed from Bayer, 26there are 33 granted foreign counterparts of the ‘166 patent (now RE45,499) that cover crystalline polymorph B, including the European patent and Eurasian patent. The granted European patent comprises 37 national countries that have all been validated, and the granted Eurasian patent comprises nine countries that have all been validated. Likewise, ~~15 of the 17~~there are 3 pending foreign ~~applications are~~ counterparts of the ‘166 crystalline polymorph B patent. Other patents and patent applications in the licensed Bayer portfolio are expired and cover methods of treatment by administration of entinostat. For example, U.S. Patent 7,317,028, which expired in October 2017, covers methods of treating selected cancers by administration of entinostat; U.S. Patent 7,687,525, which also expired in September 2017, covers methods of treating autoimmune disease by administration of entinostat; U.S. Patent 6,320,078, which ~~expires~~expired in July 2019, covers methods of manufacturing entinostat; U.S. Patent No. 8,026,239, which expired in September 2017, covers methods of treating certain malignant tumors by administration of a compound within a subgenus of benzamide compounds including entinostat; U.S. Patent RE40,703, which expired in September 2017, covers a subgenus of benzamide compounds that does not include entinostat; and U.S. Patent 6,794,392, which expired in September 2017, covers a subgenus of benzamide compounds that does not include entinostat.

We have also in-licensed from UCB a patent portfolio directed to SNDX-6352, an IND-ready anti-CSF-1R monoclonal antibody. As of December 31, 2019, the SNDX-6352 composition-of-matter patent portfolio included one granted U.S. non-provisional patent application, two allowed non-U.S. applications, four granted non-U.S. patents and 33 non-U.S. pending patent applications. If issued, patents based on the in-licensed pending U.S. application and non-U.S. applications covering SNDX-6352 would expire in August 2034. Our in-licensed patent portfolio also includes pending U.S. and non-U.S. patent applications directed to methods for the treatment and/or prophylaxis of fibrotic disease by administration of an inhibitor of CSF-1R activity, methods for the treatment and/or prophylaxis of inflammatory bowel disease, or IBD, by administration of an inhibitor of CSF-1R activity, and liquid pharmaceutical compositions of anti-CSF-1R antibodies. If issued, patents based on these pending

applications would expire between November 2024 and February 2036. Further, the in-licensed portfolio includes three non-U.S. patents directed to methods of treating solid tumors by administration of an inhibitor of CSF-1R activity. The three patents will expire in October 2020. Our owned SNDX-6352 patent portfolio consists of a U.S. provisional patent application directed to a method of use. If issued, patents based on this provisional application would expire in December 2040.

We have in-licensed from Vitae Pharmaceuticals, Inc., a subsidiary of Allergan, a patent portfolio directed to a series of selective preclinical inhibitors targeting the binding interaction of menin with MLL-r. As of December 31, 2019, the in-licensed portfolio included two pending U.S. applications and 28 non-U.S. pending patent applications covering composition of matter and methods of treating, e.g., MLL. If issued, patents based on the in-licensed applications would expire between June 2037 and September 2037.

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, the patent term is 20 years from the date of filing the earliest non-provisional application or PCT application.

In the United States, a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the USPTO in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent. The term of a patent that covers an approved drug may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the development and regulatory review process. To obtain a patent extension in the United States, the term of the relevant patent must not have expired before the extension application, the patent cannot have been extended previously under this law, an application for extension must be submitted, the product must be subject to regulatory review prior to its commercialization, and the permission for the commercial marketing or use of the product after such regulatory review period is the first permitted commercial marketing or use of the product. If our future products contain active ingredients which have not been previously approved, we may be eligible for a patent term extension in the United States. In the United States, we expect to seek extension of patent terms under the Drug Price Competition and Patent Term Restoration Act of 1984, which permits a patent term extension of up to five years beyond the expiration of the patent for patent claims covering a new chemical entity. If patent extensions are available to us outside of the United States, we would expect to file for a patent term extension in applicable jurisdictions.

In March 2007, we entered into the Bayer license agreement pursuant to which we obtained a worldwide, exclusive license to develop and commercialize entinostat and any other products containing the same active ingredient. The Bayer license agreement, as amended, permits us to use entinostat or other licensed products for the treatment of any human disease, and we are obligated to use commercially reasonable efforts to develop, manufacture and commercialize licensed products for all commercially reasonable indications. Initially, Bayer manufactured and supplied our requirements of entinostat, but effective May 2012, manufacturing rights and responsibility for entinostat was transferred to us, by mutual agreement of the parties.

In connection with the execution of the Bayer license agreement, we paid Bayer an upfront license fee of $2.0 million. We are also obligated to pay up to approximately $50.0 million in the aggregate upon obtaining certain milestones in the development and marketing approval of entinostat, assuming that we pursue at least two different indications for entinostat or any other licensed product.

We are also obligated to pay Bayer up to $100.0 million in aggregate sales milestones, and a tiered single-digit royalty on net sales by us, our affiliates and sublicensees of entinostat and any other licensed products under the Bayer license agreement. We are obligated to pay Bayer these royalties on a country-by-country basis for the life of

the relevant licensed patents covering such product or 15 years after the first commercial sale of such product in such country, whichever is longer. We cannot determine the date on which our royalty payment obligations to Bayer would expire because no commercial sales of entinostat have occurred and the last-to-expire relevant patent covering entinostat in a given country may change in the future.

In July 2016, we entered into a license agreement with UCB, or the UCB license agreement, under which UCB granted us a worldwide, sublicenseable, exclusive license to UCB6352, which the Company refers to as SNDX-6352, an IND-ready anti-CSF-1R monoclonal antibody. The UCB license agreement permits us to use SNDX-6352 or other licensed products for all human uses, including treatment, prevention and diagnostic uses, in all indications, diseases, conditions or disorders, and we are obligated to use commercially reasonable efforts to develop, obtain regulatory approval and commercialize a certain licensed product.

In consideration for the license grant, we made a nonrefundable upfront payment of $5.0 million to UCB in the third quarter of 2016. Additionally, subject to the achievement of certain milestone events, we may be required to pay UCB up to $119.5 million in one-time development and regulatory milestone payments over the term of the UCB license agreement. In the event that we or any of our affiliates or sublicensees commercializes SNDX-6352, we will also be obligated to pay UCB low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $250.0 million in potential one-time, sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, we may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with UCB. We are solely responsible for the development and commercialization of SNDX-6352, except that UCB is performing a limited set of transitional chemistry, manufacturing and control tasks related to SNDX-6352.

In October 2017, we entered into a license agreement with Vitae Pharmaceuticals, Inc., a subsidiary of Allergan, or the Allergan License Agreement, under which Allergan granted us an exclusive, sublicenseable, worldwide license to, preclinical, orally-available, small molecule inhibitors of the interaction of menin with the MLL protein, or the Menin Assets. We made a nonrefundable upfront payment of $5.0 million to Allergan in the fourth quarter of 2017. Additionally, subject to the achievement of certain milestone events, we may be required to pay Allergan up to an aggregate of $99 million in one-time development and regulatory milestone payments over the term of the Allergan License Agreement. In the event that we or any of its affiliates or sublicensees commercializes the Menin Assets, we will also be obligated to pay Allergan low single to low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $70.0 million in potential one-time, sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, we

may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with Allergan. We are solely responsible for the development and commercialization of the Menin Assets.

Each party may terminate the Allergan License Agreement for the other party’s uncured material breach or insolvency; and we may terminate the Allergan License Agreement at will at any time upon advance written notice to Allergan. Allergan may terminate the Allergan License Agreement if we or any of its affiliates or sublicensees institutes a legal challenge to the validity, enforceability, or patentability of the licensed patent rights. Unless terminated earlier in accordance with its terms, the Allergan License Agreement will continue on a country-by-country and product-by-product basis until the later of: (i) the expiration of all of the licensed patent rights in such country; (ii) the expiration of all regulatory exclusivity applicable to the product in such country; and (iii) 10 years from the date of the first commercial sale of the product in such country.

We require our employees and consultants to execute confidentiality agreements upon the commencement of employment, consulting or collaborative relationships with us. These agreements provide that all confidential information developed or made known during the course of the relationship with us be kept confidential and not disclosed to third parties except in specific circumstances.

In the case of employees, the agreements provide that all inventions resulting from work performed for us, utilizing our property or relating to our business and conceived or completed by the individual during employment shall be our exclusive property to the extent permitted by applicable law. Our consulting and service agreements also provide for assignment to us of any intellectual property resulting from services performed for us.

In the United States, the FDA regulates drugs and biologics under the Federal Food, Drug, and Cosmetic Act, or FDCA, the Public Health Service Act, and related regulations. Drugs and biologics are also subject to other federal, state and local statutes and regulations. The FDA and comparable regulatory agencies in state and local jurisdictions impose substantial requirements upon, among other things, the testing, development, manufacture, quality control, safety, purity, potency, labeling, storage, distribution, record keeping and reporting, approval, import and export, advertising and promotion, and postmarket surveillance of drugs and biologics.

The process required by the FDA before biopharmaceutical products may be marketed in the United States generally involves the following:

Before testing any compounds with potential therapeutic value in humans, the product candidate enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry and formulation, as well as animal studies to assess the potential safety, toxicity profile and activity of the product candidate. The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs.

Prior to commencing the first clinical trial in humans, an IND must be submitted to the FDA, and the IND must become effective. A sponsor must submit preclinical testing results to the FDA as part of the IND and the FDA must evaluate whether there is an adequate basis for testing the drug in humans. The IND automatically becomes effective 30 days after receipt by the FDA unless the FDA within the 30-day time period raises concerns or questions about the submitted data or the conduct of the proposed clinical trial and places the IND on clinical hold. In such case, the IND application sponsor must resolve any outstanding concerns with the FDA before the clinical trial may begin. A separate submission to the existing IND application must be made for each successive clinical trial to be conducted during product development. Further, an independent Institutional Review Board, or IRB, for each site proposing to conduct the clinical trial must review and approve the protocol and informed consent for any clinical trial before it commences at that site. Informed consent must also be obtained from each study subject. Regulatory authorities, an IRB, a data safety monitoring board or the trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the participants are being exposed to an unacceptable health risk.

Human clinical trials are typically conducted in three sequential phases that may overlap:

Post-approval studies, or Phase 4 clinical trials, may be conducted after initial marketing approval. These studies may be required by the FDA as a condition of approval and are used to gain additional experience from the treatment of patients in the intended therapeutic indication. The FDA also has express statutory authority to require post-market clinical studies to address safety issues.

The FDCA permits the FDA and an IND sponsor to agree in writing on the design and size of clinical studies intended to form the primary basis of a claim of effectiveness in an NDA or BLA. An SPA agreement is not a guarantee of product approval by the FDA or approval of any permissible claims about the product. The FDA retains significant latitude and discretion in interpreting the terms of the SPA agreement and the data and results from any study that is the subject of the SPA agreement. In particular, the SPA agreement is not binding on the FDA if previously unrecognized public health concerns later come to light, other new scientific concerns regarding product safety or efficacy arise, the IND sponsor fails to comply with the protocol agreed upon, or the relevant data, assumptions, or information provided by the IND sponsor when requesting an SPA agreement change, are found to be false statements or misstatements, or are found to omit relevant facts. An SPA agreement may not be changed by the sponsor or the FDA after the trial begins except with the written agreement of the sponsor and the FDA, or if the FDA determines that a substantial scientific issue essential to determining the safety or effectiveness of the drug was identified after the testing began.

Some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data monitoring board or committee. This group provides ~~authorization~~recommendations for whether or not a trial may move forward at designated checkpoints based on access to certain data from the study. A sponsor may also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the product candidate as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the drug candidate and, among other things, must include developed methods for testing the identity, strength, quality and purity of the finished product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

In order to obtain approval to market a biopharmaceutical product in the United States, a marketing application must be submitted to the FDA that provides data establishing to the FDA’s satisfaction the safety and effectiveness of the investigational drug for the proposed indication. Each NDA or BLA submission requires a substantial user fee payment unless a waiver or exemption applies. The application includes all relevant data available from pertinent nonclinical studies and clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls and proposed labeling, among other things. Data can come from company-sponsored clinical trials intended to test the safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by investigators.

The FDA will initially review an NDA or BLA for completeness before it accepts it for filing. The FDA has 60 days from its receipt of an application to determine whether the application will be accepted for filing based on the agency’s threshold determination that the application is sufficiently complete to permit substantive review. If it is not, the FDA may refuse to file the application and request additional information, in which case the application must be resubmitted with the supplemental information, and review of the application is delayed. After an NDA or BLA submission is accepted for filing, the FDA reviews the application to determine, among other things, whether the proposed product is safe and effective for its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, strength, quality and purity. The FDA may refer applications for novel drug products or drug products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and, if so, under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Upon the filing of an NDA or BLA, the FDA may grant a priority review designation to a product, which sets the target date for FDA action on the application at 6 months, rather than the standard 10 months. Priority review is given for drug that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. Priority review designation does not change the scientific or medical standard for approval or the quality of evidence necessary to support approval.

Before approving an NDA or BLA, the FDA will inspect the facilities at which the product is manufactured. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA or BLA, the FDA may inspect one or more clinical sites to assure compliance with GCP.

After the FDA completes its initial review of an NDA or BLA, it will communicate to the sponsor that the product is approved, or it will issue a complete response letter to communicate that the application will not be approved in its current form and inform the sponsor of changes that must be made or additional clinical, nonclinical or manufacturing data that must be received before the application can be approved.

Even if a product candidate receives regulatory approval, the approval may be limited to specific disease states, patient populations and dosages, or might contain significant limitations on use in the form of warnings, precautions or contraindications, or in the form of onerous risk management plans, restrictions on distribution, or post-marketing study requirements. For example, the FDA may require Phase 4 testing, which involves clinical trials designed to further assess a drug’s safety and effectiveness and may require testing and surveillance programs to

monitor the safety of approved products that have been commercialized. The FDA may also determine that a risk evaluation and mitigation strategy, or REMS, is necessary to assure the safe use of the drug. If the FDA concludes a REMS is needed, the sponsor of an NDA must submit a proposed REMS, and the FDA will not approve an NDA without an approved REMS, if required.

Among other programs, the FDA may expedite the review of a product candidate designated as a breakthrough therapy, which is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. A sponsor may request the FDA to designate a drug as a breakthrough therapy at the time of, or any time after, the submission of an IND application for the drug. If the FDA designates a drug as a breakthrough therapy, it must take actions appropriate to expedite the development and review of the application, which may include holding meetings with the sponsor and the review team throughout the development of the drug; providing timely advice to, and interactive communication with, the sponsor regarding the development of the drug to ensure that the development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable; involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review; assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor; and taking steps to ensure that the design of the clinical trials is as efficient as practicable, when scientifically appropriate, such as by minimizing the number of patients exposed to a potentially less efficacious treatment. The FDA may rescind a breakthrough therapy designation in the future if further clinical development later shows that the criteria for designation are no longer met.

Breakthrough therapy designation does not change the standards for approval but may expedite the development or review process.

If and when approved, any products manufactured or distributed by us or on our behalf will be subject to continuing regulation by the FDA, including requirements for record-keeping, reporting of adverse experiences and submitting annual reports.

Biopharmaceutical manufacturers are required to register their facilities with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMPs, which impose certain quality processes, manufacturing controls and documentation requirements upon us and our third-party manufacturers in order to ensure that the product is safe, has the identity and strength, and meets the quality and purity characteristics that it purports to have. The FDA and certain states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including technology capable of tracking and tracing product as it moves through the distribution chain. We cannot be certain that we or our present or future suppliers will be able to comply with the cGMP and other FDA regulatory requirements. If our present or future suppliers are not able to comply with these requirements, the FDA may halt our clinical trials, fail to approve any application, shut down manufacturing operations or withdraw approval of an application, or we may recall the product from distribution. Noncompliance with cGMP or other requirements can result in issuance of warning letters, civil and criminal penalties, seizures and injunctive action.

The FDA closely regulates the labeling, marketing and promotion of drugs and biologics. While doctors are free to prescribe any drug approved by the FDA for any use based on the doctor’s independent medical judgement, a company can only make claims relating to safety and efficacy of a drug that are consistent with FDA approval, and the company is allowed to actively market a drug only for the particular use and treatment approved by the FDA. In addition, any claims we make for our products in

advertising or promotion must be appropriately balanced with important safety information and otherwise be adequately substantiated. Failure to comply with these requirements can result in adverse publicity, warning letters, corrective advertising, injunctions and potential civil and criminal penalties. Government regulators recently have increased their scrutiny of the promotion and marketing of drugs.

In both domestic and foreign markets, sales of any products for which we may receive regulatory approval will depend in part upon the availability of coverage and adequate reimbursement to healthcare providers from third-party payors. Such third-party payors include government health programs, such as Medicare and Medicaid, as well as managed care organizations, private health insurers and other organizations. Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are available. Assuming coverage is granted, the reimbursement rates paid for covered products might not be adequate. Even if favorable coverage status and adequate reimbursement rates are attained, less favorable coverage policies and reimbursement rates may be implemented in the future. The marketability of any products for which we may receive regulatory approval for commercial sale may suffer if the government and other third-party payors fail to provide coverage and adequate reimbursement to allow us to sell such products on a competitive and profitable basis. For example, under these circumstances, physicians may limit how much or under what circumstances they will prescribe or administer such products, and patients may decline to purchase them. This, in turn, could affect our ability to successfully commercialize our products and impact our profitability, results of operations, financial condition, and future success.

In the United States, the European Union and other potentially significant markets for our product candidates, government authorities and third-party payors are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative products and therapies. Such pressure, along with the increased emphasis on managed healthcare in the United States and on country and regional pricing and reimbursement controls in the European Union, will likely put additional downward pressure on product pricing, reimbursement and usage, which may adversely affect our future product sales and results of operations. These pressures can arise from rules and practices of managed care groups, judicial decisions, governmental laws and regulations related to government healthcare programs, healthcare reform, and pharmaceutical coverage and reimbursement policies.

The market for any product candidates for which we may receive regulatory approval will depend significantly on the degree to which these products are listed on third-party payors’ drug formularies or lists of medications for which third-party payors provide coverage and reimbursement to the extent products for which we may receive regulatory approval are covered under a pharmacy benefit or are otherwise subject to a formulary. The industry competition to be included on such formularies often leads to downward pricing pressures on pharmaceutical companies. Also, third-party payors may refuse to include a particular branded drug on their formularies or otherwise restrict patient access to a branded drug when a less costly generic equivalent or other alternative is available. In addition, because each third-party payor individually approves coverage and reimbursement levels, obtaining coverage and adequate reimbursement is a time-consuming and costly process. Further, one payor’s determination to provide coverage for a drug product does not assure that other payors will also provide coverage for the drug product. We may be required to provide scientific and clinical support for the use of any product to each third-party payor separately with no assurance that approval would be obtained, and we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. We cannot be certain that our product candidates will be considered cost-effective. This process could delay the market acceptance of any product candidates for which we may receive approval and could have a negative effect on our future revenues and operating results.

Federal and State Fraud and Abuse and Data Privacy and Security Laws and Regulations

In addition to FDA restrictions on marketing of pharmaceutical products, federal and state laws restrict business practices in the pharmaceutical industry. These laws include anti-kickback and false claims laws and regulations as well as data privacy and security laws and regulations. The laws that will affect our operations include, but are not limited to:

We may also be subject to federal and state laws that govern the privacy and security of other personal information, including federal and state consumer protection laws, state data security laws, and data breach notification laws. A data breach affecting sensitive personal information, including health information, could result in significant legal and financial exposure and reputational damages.

Because of the breadth of these laws and the narrowness of available statutory and regulatory exemptions, it is possible that some of our business activities could be subject to challenge, investigation or legal action under one or more of such laws. If our operations are found to be in violation of any of the federal and state laws described above or any other governmental regulations that apply to us, we may be subject to significant civil, criminal, and administrative penalties, including, without limitation, damages, fines, imprisonment, disgorgement, exclusion from participation in government healthcare programs, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations.

To the extent that any of our product candidates receive approval and are sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws, international data protection laws (including the General Data Protection Directive ((EU) 2016/679) on the protection of individuals with regard to the processing of personal data and on the free movement of such data as well as EU member state implementing legislation), and implementation of corporate compliance programs and reporting of payments or transfers of value to healthcare professionals.

In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any product candidates for which we obtain marketing approval. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. In March 2010, then President Obama signed into law the Affordable Care Act, which substantially changed the way healthcare will be financed by both governmental and private insurers, and significantly impacts the pharmaceutical industry. Among the provisions of the Affordable Care Act of importance to our business, including, without limitation, our ability to commercialize, and the prices we may obtain for, any of our product candidates that are approved for sale, are the following:

There ~~remain~~have been executive, judicial and Congressional challenges to certain aspects of the Affordable Care ~~Act, and we expect such challenges to continue.~~Act. For example, the Tax Cuts and Jobs Act of 2017, or Tax Act, included a provision which repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the Affordable Care Act on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”. In addition, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the Affordable Care Act’s mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also ~~eliminates~~eliminated the health insurer tax. On ~~December 14, 2018,~~June 17, 2021, the U.S. Supreme Court dismissed a ~~Texas U.S. District Court Judge ruled~~challenge on procedural grounds that argued the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by the U.S. Congress as part of the Tax Cuts and Jobs Act of 2017 Act. Additionally, on December 18, 2019, the U.S. Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the Affordable Care Act are invalid as well. It is unclear how this decision, future decisions, subsequent appeals, and other efforts to repeal and replaceCongress. Thus, the Affordable Care Act will remain in effect in its current form. Prior to the U.S. Supreme Court ruling, on January 28, 2021, President Biden issued an executive order that initiated a special enrollment period for purposes of obtaining health insurance coverage through the Affordable Care Act marketplace. The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Affordable Care Act. It is possible that the PPACA will be subject to judicial or Congressional challenges in the future. It is unclear how any such challenges and the healthcare reform measures of the Biden administration will impact the Affordable Care Act.

Further, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries, Presidential executive orders, and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs. At the federal level, the Trump ~~administration’s~~administration used several means to propose or implement drug pricing reform, including through federal budget ~~proposal for fiscal year 2021 includes a $135 billion allowance to support legislative~~ proposals, ~~seeking to reduce drug prices, increase competition, lower out-of-pocket drug costs for patients,~~executive orders and ~~increase patient access to lower-cost generic~~policy initiatives. For example, on July 24, 2020 and ~~biosimilar drugs. The~~September 13, 2020, the Trump administration ~~also~~announced several executive orders related to prescription drug pricing that seek to implement several of the administration’s proposals. As a result, the FDA released a ~~“Blueprint”~~final rule and guidance in September 2020, providing pathways for states to ~~lower drug prices~~build and ~~reduce out~~submit importation plans for drugs from Canada. Further, on November 20, 2020, the U.S. Department of ~~pocket costs of drugs that contains additional proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize~~Health & Human Services, or HHS, finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to ~~lower~~plan sponsors under Medicare Part D, either directly or through pharmacy benefit managers, unless the ~~list~~ price reduction is required by law. The implementation of ~~their products~~the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and ~~reduce~~manufacturers, the ~~out~~implementation of ~~pocket costs of drug products paid by consumers. For example, in May 2019,~~which have also been delayed until January 1, 2023. On December 27, 2021, CMS issued a final rule ~~to allow~~that rescinded an interim final rule implementing the Trump administration’s Most Favored Nation executive order, which would tie Medicare ~~Advantage plans the option to use step therapy for~~ Part B payments for certain physician-administered drugs ~~beginning January 1, 2020. This final rule codified CMS’s policy change~~to the lowest price paid in other economically advanced countries. In July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to Biden’s executive order, on September 9, 2021, the U.S. Department of Health and Human Services, or HHS, released a Comprehensive Plan for Addressing High Drug Prices that ~~was effective January 1, 2019. While some~~outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these ~~and other measures may require additional authorization to become effective, Congress and the Trump administration have each indicated that it will continue to seek new legislative and/~~principles. No legislation or administrative ~~measures~~actions have been finalized to ~~control drug costs.~~implement these principles. Congress is also considering additional health reform measures. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk

purchasing. It is also possible that additional governmental action will be taken in response to the COVID-19 pandemic.

The full impact on our business of the Affordable Care Act and other new laws is uncertain but may result in additional reductions in Medicare and other healthcare funding. Nor is it clear whether other legislative changes will be adopted, if any, or how such changes would affect the demand for our products once commercialized.

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our product candidates to the extent we choose to sell any products outside of the United States. Whether or not we obtain FDA approval for a product, we must obtain approval of a product by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country and the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. As in the United States, post-approval regulatory requirements, such as those regarding product manufacture, marketing, or distribution would apply to any product that is approved outside the United States.

We are also subject to numerous federal, state and local laws relating to such matters as safe working conditions, manufacturing practices, environmental protection, fire hazard control, and disposal of hazardous or

potentially hazardous substances. We may incur significant costs to comply with such laws and regulations now or in the future.

As of ~~March 4, 2020,~~February 25, 2022, we had 3559 full-time employees. Of the full-time employees, 2041 were primarily engaged in research and development activities and 1215 have an M.D. or Ph.D. degree. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees. The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of equity-based compensation awards and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

We consider a number of measures and objectives in managing our human capital assets, including, among others, employee engagement, development, and training, talent acquisition and retention, employee safety and wellness, diversity and inclusion, and compensation and pay equity. We provide our employees with salaries and bonuses intended to be competitive for our industry, opportunities for equity ownership, development programs that enable continued learning and growth and a robust benefits package to promote well-being across all aspects of their lives, including health care, retirement planning and paid time off. In addition, we have conducted employee surveys to gauge employee engagement and identify areas of future focus for our human capital practices and benefits offerings.

We believe that a diverse workforce is critical to our success and we are fundamentally committed to creating and maintaining a work environment in which employees are treated fairly, with dignity, decency, respect and in accordance with all applicable laws. We understand that varied perspectives lead to the best ideas and outcomes. We believe that by creating a workplace where every individual can feel welcome and valued, we will be better able

to achieve our corporate objectives. All employees must adhere to a code of business conduct and ethics and our employee handbook, which combined, define standards for appropriate behavior and are annually trained to help prevent, identify, report, and stop any type of discrimination and harassment. Our recruitment, hiring, development, training, compensation, and advancement is based on qualifications, performance, skills, and experience without regard to gender, race, or ethnicity.

We were incorporated in Delaware in 2005. In 2011, we established a wholly owned subsidiary in the United Kingdom, ~~and~~ in 2014 we established a wholly owned U.S. ~~subsidiary.~~subsidiary, and in 2021, we established a wholly owned subsidiary in the Netherlands. There have been no material activities for these entities to date. We currently operate in one segment.

Our principal executive offices are located at 35 Gatehouse Drive, Building D, Floor 3, Waltham, Massachusetts 02451 and our telephone number is (781) 419-1400. Our corporate website address is www.syndax.com. Information contained on or accessible through our website is not a part of this Annual Report on Form 10-K, and the inclusion of our website address in this Annual Report on Form 10-K is an inactive textual reference only.

We file electronically with the SEC, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act. We make available on our website at www.syndax.com, under “Investors,” free of charge, copies of these reports as soon as reasonably practicable after filing or furnishing these reports with the SEC.

This Annual Report on Form 10-K contains forward-looking information based on our current expectations. Because our business is subject to many risks and our actual results may differ materially from any forward-looking statements made by or on behalf of us, this section includes a discussion of important factors that could affect our business, operating results, financial condition and the trading price of our common stock. You should carefully consider these risk factors, together with all of the other information included in this Annual Report on Form 10-K as well as our other publicly available filings with the Securities and Exchange Commission.

Our business is subject to numerous risks and uncertainties, of which you should be aware before making a decision to invest in our securities. These risks and uncertainties include, among others, the following:

The ongoing COVID-19 pandemic could adversely impact our business, including our clinical trials.

The ongoing COVID-19 pandemic has resulted in travel and other restrictions in order to reduce the spread of the disease, including state and local orders across the United States and other countries worldwide, which, among other things, direct individuals to shelter at their places of residence, direct businesses and governmental agencies to cease non-essential operations at physical locations, prohibit certain non-essential gatherings, and order cessation of non-essential travel. In response to these public health directives and orders, we have implemented work-from-home policies for our employees. The effects of executive orders may disrupt our business and delay our clinical programs and timelines, the magnitude of which will depend, in part, on the length and severity of the restrictions and other limitations on our ability to conduct our business in the ordinary course. These and similar, and perhaps more severe, disruptions in our operations could negatively impact our business, operating results and financial condition.

While the COVID-19 pandemic has not yet had a material impact on our business operations, quarantines and various government orders related to the pandemic, including its variants, may adversely impact our business operations and the business operations of our contract research organizations conducting our clinical trials and our third-party manufacturing facilities in the United States and other countries. In particular, if the pandemic continues to persist for an extended period of time and continues to impact essential distribution systems such as FedEx and postal delivery or if it results in facility closures facility closures for cleaning and/or insufficient staff, these ongoing constraints associated with the pandemic could cause disruptions to our supply chain and operations, including associated delays in the manufacturing and supply of our products, which would adversely impact our ability to continue our clinical trial operations.

In addition, our clinical trials may be affected by the COVID-19 pandemic. For example, we have experienced delays in clinical site initiation and patient enrollment due to prioritization of hospital resources toward the COVID-19 pandemic. Patients may not be able to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services. Similarly, our ability to recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19, could be limited, which in turn could adversely impact our clinical trial operations. As a result, we may face delays in meeting our anticipated timelines for our ongoing and planned clinical trials.

The spread of COVID-19, including its variants, has caused a broad impact globally and may materially affect us economically. While the full extent of the economic impact brought by, and the duration of, the pandemic may be difficult to assess or predict, it has resulted in uncertainty in macroeconomic conditions and result in significant disruption of global financial markets, reducing our ability to access capital, which could in the future negatively affect our liquidity. In addition, a recession or market correction resulting from the pandemic could materially affect our business and the value of our common stock.

COVID-19 continues to evolve rapidly, and multiple variants of the virus that cause COVID-19 are circulating globally. The extent to which the COVID-19 pandemic impacts our business, our clinical development and regulatory efforts will depend on future developments that are highly uncertain and cannot be predicted with confidence, such as the duration of the outbreak, travel restrictions, quarantines, social distancing requirements, business closures in the United States and other countries, the rollout of mass vaccinations for COVID-19 and the effectiveness of other actions taken in the United States and other countries to contain and treat the disease. While vaccines have been approved and are being deployed, the timing of achieving widespread vaccination remains uncertain, and the vaccines may be less effective against new variants, potentially leading to the reimpositions of restrictions in an effort to mitigate risks to public health, especially as more infectious variants of the virus emerge for a prolonged period of time, further delaying the return of the global economy to pre-pandemic levels.

Accordingly, we do not yet know the full extent of potential delays or impacts on our business, our clinical and regulatory activities, healthcare systems or the global economy as a whole. However, these impacts could adversely affect our business, financial condition, results of operations and growth prospects.

In addition, to the extent the ongoing COVID-19 pandemic adversely affects our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties described in this “Risk Factors” section.

We are currently developing several product candidates. If we are unable to successfully complete clinical development of, obtain regulatory approval for and commercialize our product candidates, our business prospects will be significantly harmed.

Our financial success will depend substantially on our ability to effectively and profitably commercialize our product candidates. In order to commercialize our product candidates, we will be required to obtain regulatory approvals by establishing that each of them is sufficiently safe and effective. The clinical and commercial success of our product candidates will depend on a number of factors, including the following:

If we fail to obtain regulatory approval for our product candidates, we will not be able to generate product sales, which will have a material adverse effect on our business and our prospects.

SNDX-5613 has undergone limited clinical testing and we may fail to show that the drug is well tolerated and provides sufficient clinical benefit for patients.

Research suggests that certain acute leukemias, such as mixed lineage leukemia-rearranged, or MLLr, leukemias and nucleophosmin 1, or NPM1, mutant acute myeloid leukemia, or AML, are driven by the interaction of menin, a nuclear protein involved in transcription, with the N-terminus of MLL1 protein, a histone methyl transferase. In NPM1 mutant AML the interaction with menin occurs via the wild type MLL1 protein, and in MLLr acute leukemias, the interaction occurs via a mutant form of MLL1, a fusion protein known as MLLr. MLLr results from a rare, spontaneous fusion between the N-terminus of the mixed lineage leukemia protein-1, or MLL1, and a host of signaling molecules and nuclear transcription factors. This fusion produces an aberrant transcription program that drives leukemic transformation. In pre-clinical animal models, small molecule inhibitors of the menin-MLLr interaction, such as SNDX-5613, which bind to, and block the interaction of menin with either MLLr or MLL1, have demonstrated deep and durable single agent treatment effects in multiple leukemic xenograft models harboring MLL fusions or NPM1 mutations. Our strategy for developing SNDX-5613 is to conduct a Phase 31/2 clinical trial in relapsed/refractory patients with MLLr and NPM1 mutant acute leukemias and determine if the observed clinical efficacy supports further development. The Phase 1 portion of the trial is assessing the safety, tolerability and pharmacokinetics of SNDX-5613, and seeks to establish a recommended Phase 2 dose. It is open label, and we have released and may in the future release results from time to time that reflect small numbers of patients which may not be accurately predictive of safety or efficacy results later in the trial or in subsequent trials. The Phase 2 portion is evaluating the efficacy of SNDX-5613 across three expansion cohorts enrolling pediatric and adult patients with MLLr acute lymphoblastic leukemia, or ALL, MLLr acute myeloid leukemia, or AML, and NPM1 mutant AML. While we believe that we have established sufficient efficacy to warrant continued development in these indications, we have not yet sufficiently demonstrated a favorable risk-benefit of SNDX-5613 in patients.

Axatilimab has undergone limited clinical testing and we may fail to show that this drug is well tolerated and provides a clinical benefit for patients.

Preclinical studies suggest that CSF-1/CSF-1R signaling may be the key regulatory pathway involved in the expansion and infiltration of donor derived macrophages that mediate the disease processes involved in cGVHD and other fibrotic or inflammatory diseases. Nonclinical studies and analysis of patient samples indicates that the cGVHD inflammatory disease process is a result of a complex interaction between host and donor immune cells including B cells, and regulatory T cells with M2 differentiated macrophages in target tissue appearing to represent the common distal mediator of fibrosis. Therefore, we hypothesize that a CSF-1R signal inhibitor such as axatilimab may play a meaningful role as a monotherapy agent in the treatment of cGVHD. Our approach is to conduct a Phase 1/2 clinical trial with axatilimab in subjects with active cGVHD who have failed at least two prior lines of therapy. Following our end of Phase 1 meeting with the FDA, we have aligned on a regulatory path for axatilimab for the treatment of cGVHD and commenced a pivotal Phase 2 trial, AGAVE-201, to assess the safety and efficacy of different doses and schedules of axatilimab for the treatment of patients with cGVHD. While we believe that we have established sufficient efficacy to warrant continued development in this indication, we have not yet sufficiently demonstrated a favorable risk-benefit of axatilimab in patients.

Interim top-line and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publish interim top-line or preliminary data from our clinical trials. For example, in April and December 2021, we announced interim data from our Phase 1/2 clinical trial of ~~entinostat in combination with exemestane in advanced HR+, HER2- breast cancer patients fails to demonstrate safety and efficacy~~SNDX-5613. Interim data from clinical trials that we may complete are subject to the ~~satisfaction~~risk that one or more of ~~regulatory authorities~~the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Preliminary or ~~does~~top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. Preliminary or top-line data may include, for example, data regarding a small percentage of the patients enrolled in a clinical trial, and such preliminary data should not ~~otherwise produce positive~~ be viewed as an indication, belief or guarantee that other patients enrolled in such clinical trial will achieve similar

results weor that the preliminary results from such patients will be maintained. As a result, interim and preliminary data should be viewed with caution until the final data are available. Differences between preliminary or interim data and final data could significantly harm our business prospects and may cause the trading price of our common stock to fluctuate significantly.

We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of ~~entinostat.~~any of our product candidates.

Before obtaining marketing approval from regulatory authorities for the sale of ~~entinostat,~~any of our product candidates, we or our collaborators must conduct extensive trials to demonstrate the safety and efficacy of ~~entinostat~~the product candidates in humans. We have entered into an arrangement with ECOG-ACRIN Cancer Research Group, or ECOG-ACRIN, to conduct the Phase 3 clinical trial of entinostat in combination with exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative, or (HR+, HER2-, breast cancer patients. The National Cancer Institute, or NCI, designed the trial to measure two primary endpoints, progression-free survival, or PFS, and overall survival, or OS. We received the final PFS analysis from ECOG-ACRIN in October 2018 and we expect to receive the final OS analysis no later than the second quarter of 2020. In October 2018, ECOG-ACRIN informed us that the trial did not achieve the first primary endpoint of improving PFS, which would have provided the earliest regulatory filing opportunity. In accordance with the trial protocol, ECOG-ACRIN is confidentially holding the findings from the PFS analysis until reporting final OS results. We will not be able to submit an NDA unless and until we receive data demonstrating that the trial has achieved the primary endpoint for OS. In addition, based on scientific advice that we received from the European Medicines Agency, the current Phase 3 clinical trial may not be sufficient to receive

~~regulatory approval in Europe for entinostat to treat advanced HR+, HER2- breast cancer, and it is unclear whether we would be able to complete an alternate clinical trial that would be sufficient.~~

Despite the results reported in our Phase 2b clinical trial for entinostat in advanced estrogen receptor positive, or ER+, breast cancer, we do not know whether the Phase 3 clinical trial in advanced HR+, HER2- breast cancer will demonstrate adequate efficacy and safety to result in regulatory approval to market entinostat in any particular cancer indications or jurisdiction. Additionally, while we do not expect that there will be overlapping toxicities between entinostat and exemestane, we cannot be certain that we will not observe these toxicities or unexpected adverse drug reactions in the Phase 3 clinical trial.

Clinical testing is expensive and difficult to design and implement, can take many years to complete and is inherently uncertain as to the outcome. A failure of one or more trials can occur at any stage of testing. The outcome of preclinical studies and early clinical trials may not accurately predict the success of later trials, and interim results of a trial do not necessarily predict final results. For example, ~~with~~in May 2020, we announced that ECOG-ACRIN advised us that the ~~emergence~~E2112 trial did not achieve the primary endpoint of ~~the new therapies such as~~ ~~Verzenio~~, ~~Kisqali~~, ~~Ibrance~~ ~~and~~ ~~Piqray~~ ~~patients enrolled~~demonstrating a statistically significant overall survival benefit over hormone therapy alone in the Phase 3 clinical trial ~~may be different than those enrolled in~~and we decided to deprioritize the entinostat program to focus resources on advancing the remainder of our ~~previous Phase 2b clinical trial in that they may have received a CDK 4/6 inhibitor prior to our trial and therefore may respond differently to treatment with entinostat.~~pipeline. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials.

~~The failure~~We are dependent upon our collaboration with Incyte to further develop and commercialize axatilimab. If we or Incyte fail to perform as expected or if the collaboration is terminated as a result of ~~ECOG-ACRIN~~actions by the Federal Trade Commission or the ~~NCI~~Department of Justice, the potential for us to ~~adequately~~generate future revenues under the collaboration could be significantly reduced, the development and/or commercialization of axatilmab may be terminated or substantially delayed, and our business could be adversely affected.

We are subject to numerous risks related to the Incyte Agreement to collaborate on the development and commercialization of axatilimab.

For example, there is no assurance that the parties will achieve any of the regulatory development or sales milestones, that we will receive any future milestone or royalty payments under the collaboration agreement or that the collaboration will not be unwound as a result of actions by the Federal Trade Commission or the Department of Justice. Incyte’s activities may be influenced by, among other things, the efforts and allocation of resources by Incyte, which we cannot control. If Incyte does not perform ~~its obligations and responsibilities~~ in the ~~conduct of the Phase 3 clinical trial~~manner we expect or ~~to meet expected deadlines could substantially harm our business because we may not obtain regulatory approval for entinostat~~fulfill its responsibilities in a timely manner, or at ~~all.~~

We have entered into an arrangement with ECOG-ACRIN, pursuant to which it, with sponsorship and funding support by the NCI, is conducting the Phase 3 clinical trial of entinostat in combination with exemestane in advanced HR+, HER2- breast cancer patients. While we provide operational and logistical support for the trial, we have limited control of their activities. We cannot control whether ECOG-ACRIN will devote sufficient time and resources to the trial, including as a result of any reduction or delay in government funding or sponsorship of the activities of ECOG-ACRIN or the NCI. If ECOG-ACRIN or the NCI does not successfully carry out its obligations and responsibilities or meet expected deadlines or if the quality or accuracy ofall, the clinical ~~data that ECOG-ACRIN obtains is compromised~~development, manufacturing, regulatory approval, and commercialization efforts related to axatilimab could be delayed or terminated. In addition, our license with Incyte may be unsuccessful due to ~~the failure to adhere to Good Clinical Practices, or GCPs, clinical protocols, regulatory requirements or for~~ other reasons, the Phase 3 clinical trial may be extended, delayed or terminated, and we may not be able to obtain regulatory approval for, or successfully commercialize, entinostat. As a result, our results of operations and the commercial prospects for entinostat would be harmed, our costs could increase and our ability to generate revenues could be delayed.

Although the Phase 3 clinical trial is being conducted by ECOG-ACRIN, we are responsible for ensuring that each of our trials is conducted in accordance with the applicable protocol and legal, regulatory and scientific standards, and our reliance on ECOG-ACRIN does not relieve us of our regulatory responsibilities. We are required to comply with GCP, which are regulations and guidelines enforced by the U.S. Food and Drug Administration, or FDA, the Competent Authorities of the Member States of the European Economic Area and foreign regulatory authorities for any product in clinical development. Regulatory authorities enforce GCP through periodic inspections of trial sponsors, principal investigators and clinical trial sites. If we fail to comply with applicable GCP, the clinical data generated in our trials may be deemed unreliable and the FDA or foreign regulatory authorities may require us to perform additional trials before approving our marketing applications. We cannot assure that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our trials comply with GCP requirements. In addition, we must conduct our trials with products produced under current Good Manufacturing Practices regulations, or cGMP requirements. Failure to comply with any of these regulations may require us to repeat preclinical and clinical trials, which would delay the regulatory development process.

If there are delays in completing the Phase 3 clinical trial for entinostat in advanced HR+, HER2- breast cancer, we will be delayed in commercializing entinostat, our development costs may increase and our business may be harmed.

The Phase 3 clinical trial of entinostat in combination with exemestane in advanced HR+, HER2- breast cancer commenced in the second quarter of 2014, and we expect to receive the final OS analysis no later than the second quarter of 2020. Our product development costs could increase if we experience delays in the overall number of survival events. Significant trial delays also could shorten any periods during which we may have the exclusive right to commercialize entinostat or allow our competitors to bring products to market before we do, which would impair our ability to successfully capitalize on entinostat and may harm our business, results of operations and prospects. Events that may result in a delay or unsuccessful completion of clinical development of entinostat include, among other things:

An inability by us to timely complete clinical development could result in additional costs to us or impair our ability to generate product revenues or development, regulatory, commercialization and sales milestone payments and royalties on product sales.

Although the NCI has entered into a Special Protocol Assessment, or SPA, agreement with the FDA relating to the pivotal Phase 3 clinical trial of entinostat for advanced HR+, HER2- breast cancer, this agreement does not guarantee any particular outcome with respect to regulatory review of the trial or any associated NDA for entinostat.

The protocol for the pivotal Phase 3 trial of entinostat in combination with exemestane in advanced HR+, HER2- breast cancer was reviewed and agreed upon by the FDA under a SPA agreement with the NCI. The SPA agreement allows for FDA evaluation of whether a clinical trial protocol could form the primary basis of an efficacy

claim in support of an NDA. The SPA is an agreement that a Phase 3 clinical trial’s design, clinical endpoints, patient population and statistical analyses are sufficient to support the efficacy claim. Agreement on the SPA is not a guarantee of approval; and there is no assurance that the design of, or data collected from, the trial will be adequate to obtain the requisite regulatory approval. In October 2018, ECOG-ACRIN informed us that the trial did not achieve the statistical hurdle for the first primary endpoint of improving PFS, which would have provided the earliest regulatory filing opportunity. Further, obtaining clinical trial data meeting the OS endpoint in satisfaction of the SPA does not guarantee approval. The SPA is not binding on the FDA if public health concerns unrecognized at the time the SPA was entered into become evident or other new scientific concerns regarding product safety or efficacy arise. In addition, upon written agreement of both the FDA and the NCI, the SPA may be changed, and the FDA retains significant latitude and discretion in interpreting the terms of the SPA and any resulting trial data. As a result, we do not know how the FDA will interpret the parties’ respective commitments under the SPA, how it will interpret the data and OS results from the pivotal Phase 3 clinical trial, whether the FDA will require that we conduct or complete one or more additional clinical trials to support potential approval or whether entinostat will receive any regulatory approvals. ECOG-ACRIN, with sponsorship and funding support from the NCI, is conducting the pivotal Phase 3 clinical trial, which began enrollment in the second quarter of 2014.

A breakthrough therapy designation by the FDA for entinostat may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that entinostat will receive marketing approval.

We received breakthrough therapy designation from the FDA for entinostat when used in combination with exemestane based on the OS results from our completed Phase 2b clinical trial in advanced HR+, HER2- breast cancer. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The Phase 2b trial showed statistically significant improvements in PFS, the primary endpoint, and OS, an exploratory endpoint. Receipt of a breakthrough therapy designation for a drug candidate may not result in a faster development process or review compared to drugs considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, the FDA may later decide that entinostat no longer meets the conditions for qualification or decide that the time period for FDA review will not be shortened. For instance, our Phase 3 trial in HR+, HER2- breast cancer patients failed to achieve one of its primary endpoints of improving PFS. We expect to receive final analysis on the second primary endpoint, OS, no later than the second quarter of 2020. If the results do not confirm the improvement in OS observed in our Phase 2b clinical trial, the FDA may rescind our breakthrough therapy designation.

~~We do not currently have any sales, marketing or distribution experience or infrastructure.~~

In order to market any approved product candidate in the future, we must build our sales, marketing, managerial and other non-technical capabilities or make arrangements with third parties to perform these services, as we do not presently have all of these capabilities. To develop our internal sales, distribution and marketing capabilities, we would have to invest significant amounts of financial and management resources in the future. For drugs where we decide to perform sales, marketing and distribution functions ourselves, we could face a number of challenges, including that:

Alternatively, we may rely on third parties to launch and market our product candidates, if approved. We may have limited or no control over the sales, marketing and distribution activities of these third parties and our future revenue may depend on the success of these third parties. Additionally, if these third parties fail to comply with all applicable legal or regulatory requirements, the FDA or another governmental agency could take enforcement action that could jeopardize their ability and our ability to market our product candidates.

Entinostat, SNDX-5613 and SNDX-6352 are currently our only product candidates. Our financial success will depend substantially on our ability to effectively and profitably commercialize our product candidates. In order to commercialize our product candidates, we will be required to obtain regulatory approvals by establishing that each of them is sufficiently safe and effective. The clinical and commercial success of our product candidates will depend on a number of factors, including, without limitation, the following:

~~If we fail to obtain regulatory approval for our product candidates, we will not~~ be ~~able to generate product sales, which will have a material adverse effect~~realized on our ~~business and our prospects.~~

Our strategy of combining entinostat with immune checkpoint inhibitors has undergone limited clinical testing and we may fail to show that the combination is well tolerated and demonstrates additional clinical benefit from the combination.

Preclinical studies conducted by us and others suggest a strong rationale for combining entinostat with immune checkpoint inhibitors, including PD-1 pathway antagonists, to enhance the immune system’s ability to detect and eliminate tumor cells. Our approach was to conduct Phase 1 and 2 clinical trials in patients with tumors that are known to be responsive to PD-1 pathway antagonists and assess both the safety and efficacy of the combination of entinostat plus a PD-1 pathway antagonist. Our initial clinical data is supportive of our hypothesis as we have seen clinical benefit from the combination of entinostat plus pembrolizumab in patients with metastatic melanoma and non-small cell lung cancer. However, we have not yet sufficiently demonstrated a favorable risk-benefit of this combination in patients, and we may be unable to establish efficacy to warrant regulatory submissionanticipated timeline or approval. In the first quarter of 2019, we completed a full portfolio prioritization assessment and have determined to place the initiation of potential registration trials in non-small cell lung cancer and melanoma on hold until we receive final OS results from E2112.

~~Our strategy for developing SNDX-6352 has undergone limited clinical testing and we may fail to show that this drug is well tolerated and provides a clinical benefit for patients.~~

Preclinical studies suggest that CSF-1/CSF-1R signaling may be the key regulatory pathway involved in the expansion and infiltration of donor derived macrophages that mediate the disease processes involved in Graft Versus Host Disease, or cGVHD. Nonclinical studies and analysis of patient samples indicates that the cGVHD inflammatory disease process is a result of a complex interaction between host and donor immune cells including B cells, and regulatory T cells with M2 differentiated macrophages in target tissue appearing to represent the common distal mediator of fibrosis. Therefore, we hypothesize that a CSF-1R signal inhibitor such as SNDX-6352 may play a meaningful role as a monotherapy agent in the treatment of cGVHD. Our approach is to conduct Phase 1 clinical trial with SNDX-6352 in subjects with active cGVHD who have failed at least two prior lines of therapy. If our initial clinical data lend support for our hypothesis, we plan to continue developing SNDX-6352 in this indication. At this time however, we have not yet sufficiently demonstrated a favorable risk-benefit of SNDX-6352 in patients and we may be unable to establish sufficient efficacy to warrant continued development in this indication.

~~Our strategy for developing SNDX-5613 has undergone limited clinical testing and we may fail to show that the drug is well tolerated and provides clinical benefit for patients.~~

Research suggests that certain acute leukemias, such as mixed lineage leukemia-rearranged, or MLLr, leukemias and nucleophosmin 1, or NPM1, mutant acute myeloid leukemia, or AML, are driven by the interaction of menin, a nuclear protein involved in transcription, with MLL-r, a rare, spontaneous fusion between the N-terminus of the mixed lineage leukemia protein-1, or MLL1, and a host of signaling molecules and nuclear transcription factors. This fusion produces an aberrant transcription program that drives leukemic transformation., also known as KMT2A. In pre-clinical animal models, small molecule inhibitors of the menin-MLL-r interactionmolecules, such as SNDX-5613, which bind to, and block the interaction of menin with MLL1, have demonstrated deep and durable single agent treatment effects in multiple leukemic xenograftsxenograft models harboring MLL fusions or NPM1 mutations. Our approachstrategy for developing SNDX-5613 is to conduct a Phase 1/2 clinical trial in patients with MLL-r leukemia and assess bothrelapsed/refractory acute leukemias. The Phase 1 portion of the trial is assessing the safety, tolerability and pharmacokinetics of SNDX-5613, and seeks to establish a recommended Phase 2 dose. The Phase 2 portion will evaluate efficacy of SNDX-5613, as defined by Complete Remission rate, across three expansion cohorts enrolling adult patients with MLL-r acute lymphoblastic leukemia, or ALL, MLL-r acute myeloid leukemia, or AML, and NPM1 mutant AML. If our initial clinical data lend support for our hypothesis, we plan to continue developing SNDX-5613 in one or more of these indications. At this time however, we have not yet sufficiently demonstrated a favorable risk-benefit of SNDX-5613 in patients, and we may be unable to establish sufficient efficacy to warrant continued development in one or more of these indications.

We may be unable to transfer, qualify and validate an assay for determining peripheral monocyte levels to be used in conjunction with a future registration enabling non-small cell lung cancer, or NSCLC, trial.

In October 2018, we announced that we are proceeding with a registration trial in NSCLC patients whose disease has progressed after both platinum-based combination chemotherapy and a PD-1 antagonist therapy. We designed the trial to both validate a classical monocyte biomarker and demonstrate that the combination therapy of entinostat plus ~~Keytruda~~ is superior to standard of care chemotherapy in a high monocyte population. This trial will require testing patients for levels of circulating classical monocytes prior to treatment before assigning them to the appropriate arm of the trial. The assay that our academic collaborators have used to determine circulating levels of classical monocytes has not been developed or validated to the qualifications that the FDA may require for patient selection. We are working to measure circulating levels of cells, including monocytes, but we may not be able to successfully transfer, qualify and validate an assay for determining peripheral monocyte levels that will be acceptable to the FDA. In the first quarter of 2019, we completed a full portfolio prioritization assessment and have determined to place the initiation of this trial on hold until we receive final OS results from E2112.all.

If we ~~are~~ or our collaborators are unable to enroll patients in clinical trials, these clinical trials may not be completed on a timely basis or at all.

The timely completion of clinical trials largely depends on patient enrollment. Many factors affect patient enrollment, including:

As a result of the above factors, there is a risk that our or our collaborators’ clinical trials may not be completed on a timely basis or at all.

~~The actions of Kyowa Kirin Co., Ltd., or KKC, Eddingpharm Investment Company Limited, or Eddingpharm, and any other current or future sublicensees could adversely affect our business.~~

We currently sublicense entinostat to third parties for development and commercialization in certain foreign jurisdictions. Specifically, we have a sublicense agreement with KKC under which we granted KKC an exclusive sublicense to develop and commercialize entinostat in Japan and Korea as well as a sublicense agreement with Eddingpharm under which we granted Eddingpharm an exclusive sublicense to develop and commercialize entinostat in China and select Asian countries. It is possible that any clinical trials conducted by KKC, Eddingpharm and other current or future sublicensees in their respective jurisdictions could have negative results, which in turn could have a material adverse effect on the development of entinostat for development and commercialization in the United States and the rest of the world.

~~We are dependent on UCB Biopharma Sprl, or UCB, to comply with the terms of our license agreement for SNDX-6352.~~

Our commercial success also depends upon our ability to develop, manufacture, market and sell SNDX-6352. In July 2016, we entered into the UCB license agreement pursuant to which we obtained a worldwide, sublicenseable, exclusive license to SNDX-6352, an IND-ready anti-CSF-1R monoclonal antibody. Under the UCB license agreement, we are dependent on UCB’s performance of its responsibilities and its cooperation with us. UCB may not perform its obligations under the UCB license agreement or otherwise cooperate with us. We cannot control whether UCB will devote the necessary resources to its obligations under the UCB license agreement, nor can we control the timing of its performance. Additionally, certain of the rights licensed to us under the UCB license agreement are in-licensed by UCB from third parties. We are dependent on UCB maintaining the applicable third-party license agreements in full force and effect, which may include activities and performance obligations that are not within our control. If any of these third-party license agreements terminate, certain of our rights to develop, manufacture, commercialize or sell SNDX-6352 may be terminated as well. The occurrence of any of these events could adversely affect the development and commercialization of SNDX-6352, and materially harm our business.

We may be required to relinquish important rights to and control over the development and commercialization of our product candidates to our current or future collaborators.

Our collaborations, including any future strategic collaborations we enter into, could subject us to a number of risks, including:

We ~~may~~ periodically explore a variety of possible strategic collaborations in an effort to gain access to additional product candidates or resources. At the current time, we cannot predict what form such a strategic collaboration might take. We are likely to face significant competition in seeking appropriate strategic collaborators, and strategic collaborations can be complicated and time consuming to negotiate and document. We may enter into strategic collaborations that we subsequently no longer wish to pursue, and we may not be able to negotiate strategic collaborations on acceptable terms, or at all. We are unable to predict when, if ever, we will enter into any additional strategic collaborations because of the numerous risks and uncertainties associated with establishing them.

The regulatory approval processes of the FDA and foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable. Our inability to obtain regulatory approval for our product candidates could harm our business.

The time required to obtain approval by the FDA and foreign regulatory authorities is unpredictable, but typically takes many years following the commencement of preclinical studies and clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions. We have not obtained regulatory approval for any of our product candidates, and it is possible that we will never obtain regulatory approval for our existing product candidates or any future product candidates.

~~Our~~Due to the ongoing COVID-19 pandemic, it is possible that we could experience delays in the timing of our interactions with regulatory authorities due to absenteeism by governmental employees, inability to conduct planned physical inspections related to regulatory approval, or the diversion of regulatory authority efforts and attention to approval of other therapeutics or other activities related to COVID-19, which could delay anticipated approval decisions and otherwise delay or limit our ability to make planned regulatory submissions or obtain new product approvals. In addition, our product candidates could fail to receive regulatory approval from the FDA or foreign regulatory authorities for ~~many~~other reasons, including but not limited to:

The FDA or foreign regulatory authorities may require more information, including additional preclinical or clinical data, to support approval, which may delay or prevent approval and our commercialization plans, or may cause us to decide to abandon our development program. Even if we were to obtain approval, regulatory authorities may approve one or more of our product candidates for a more limited patient population than we request, may grant approval contingent on the performance of costly post-marketing trials, may impose a risk evaluation and mitigation

strategy, or REMS, or foreign regulatory authorities may require the establishment or modification of a similar strategy that may, for instance, restrict distribution of ~~entinostat~~one or more of our product candidates and impose burdensome implementation requirements on us, or may approve it with a label that does not include the labeling claims necessary or desirable for the successful commercialization of ~~entinostat,~~one or more of our product candidates, all of which could limit our ability to successfully commercialize our product candidates.

We are not developing entinostat as a monotherapy. A shortage in the supply of exemestane or other drugs used in combination with entinostat or cessation of development efforts for investigational agents being studied with entinostat could increase our development costs and adversely affect our ability to commercialize entinostat, and any unexpected adverse events with any of the drugs used in combination with entinostat could halt or delay development of entinostat.

Cancer drugs have from time to time been in short supply and, because many or all of these cancer drugs are also widely used in cancer treatment currently, we will compete with a broad range of healthcare providers and other companies for availability of those drugs. Any shortage of exemestane or other drugs that we are testing in combination with entinostat could adversely affect our ability to timely conduct the Phase 3 clinical trial in advanced HR+, HER2- breast cancer, our future potential Phase 3 clinical trial in NSCLC, any future clinical trials in melanoma, and if entinostat receives regulatory approval, to commercialize entinostat for treatment of advanced HR+, HER2- breast cancer, NSCLC, or melanoma. A shortage of supply may also result in an increase, which could be significant, in our costs of procuring exemestane.

Additionally, because entinostat is being developed for use in combination with other cancer treatments, the development of entinostat may be delayed or halted if unexpected adverse events occurring in patients are attributed to entinostat. Likewise, new adverse events emerging from commercialized or development stage drugs being administered with entinostat may limit or halt the potential of such combinations.

Our product candidates may not achieve adequate market acceptance among physicians, patients, healthcare payors and others in the medical community to be commercially ~~successful.~~successful.

Even if our product candidates receive regulatory approval, they may not gain sufficient market acceptance among physicians, patients, healthcare payors and others in the medical community. Our commercial success also depends on coverage and adequate reimbursement by third-party payors, including government payors, which may be difficult or time-consuming to obtain, may be limited in scope and may not be obtained in all jurisdictions in which we may seek to market our product candidates. The degree of market acceptance will depend on a number of factors, including:

If our product candidates are approved but do not achieve an adequate level of acceptance by physicians, hospitals, healthcare payors and patients, we may not generate sufficient revenue to become or remain profitable.

We rely on third-party suppliers to manufacture and distribute our clinical drug supplies for our product candidates, we intend to rely on third parties for commercial manufacturing and distribution of our product candidates and we expect to rely on third parties for manufacturing and distribution of preclinical, clinical and commercial supplies of any future product candidates.

We do not currently have, nor do we plan to acquire, the infrastructure or capability to manufacture or distribute preclinical, clinical or commercial quantities of drug substance or drug product, including our existing product candidates. While we expect to continue to depend on third-party manufacturers for the foreseeable future, we do not have direct control over the ability of these manufacturers to maintain adequate manufacturing capacity and capabilities to serve our needs, including quality control, quality assurance and qualified personnel. In additional, public health epidemics, such as the ~~coronavirus currently impacting China and elsewhere,~~COVID-19 pandemic, may impact the ability of our existing or future manufacturers to perform their obligations to us.

We are dependent on our third-party manufacturers for compliance with cGMPs and for manufacture of both active drug substances and finished drug products. Facilities used by our third-party manufacturers to manufacture drug substance and drug product for commercial sale must be approved by the FDA or other relevant foreign regulatory agencies pursuant to inspections that will be conducted after we submit our NDA or relevant foreign regulatory submission to the applicable regulatory agency. If our third-party manufacturers cannot successfully manufacture materials that conform to our specifications and/or the strict regulatory requirements of the FDA or foreign regulatory agencies, they will not be able to secure and/or maintain regulatory approval for their manufacturing facilities. Furthermore, these third-party manufacturers are engaged with other companies to supply and/or manufacture materials or products for such companies, which also exposes our third-party manufacturers to regulatory risks for the production of such materials and products. As a result, failure to meet the regulatory requirements for the production of those materials and products may also affect the regulatory clearance of a third-party manufacturers’ facility. If the FDA or a foreign regulatory agency does not approve these facilities for the manufacture of our product candidates, or if it withdraws its approval in the future, we may need to find alternative manufacturing facilities, which would impede or delay our ability to develop, obtain regulatory approval for or market our product candidates, if approved.

Even if our product candidates receive regulatory approval, they may still face future development and regulatory difficulties.

Even if we obtain regulatory approval for our product candidates, they would be subject to ongoing requirements by the FDA and foreign regulatory authorities governing the manufacture, quality control, further development, labeling, packaging, storage, distribution, safety surveillance, import, export, advertising, promotion, recordkeeping and reporting of safety and other post-market information. The FDA and foreign regulatory authorities will continue to monitor closely ~~monitor~~ the safety profile of any product even after approval. If the FDA or foreign regulatory authorities become aware of new safety information after approval of a product candidate, they may require labeling changes or establishment of a REMS or similar strategy, impose significant restrictions on its indicated uses or marketing, or impose ongoing requirements for potentially costly post-approval studies or post-market surveillance.

In addition, manufacturers of drug products and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance with cGMP regulations and standards. If we or a regulatory agency discover previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including withdrawal of the product from the market or suspension of manufacturing, or we may recall the product from distribution. If we, or our third-party manufacturers, fail to comply with applicable regulatory requirements, a regulatory agency may:

The occurrence of any event or penalty described above may inhibit our ability to commercialize and generate revenue from the sale of our product candidates.

Advertising and promotion of any product candidate that obtains approval in the United States will be heavily scrutinized by the FDA, the Department of Justice, the Department of Health and Human Services’ Office of Inspector General, state attorneys general, members of Congress, other government agencies and the public. While physicians may prescribe products for off-label uses as the FDA and other regulatory agencies do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional communications from companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued. Companies may only share truthful and not misleading information that is otherwise consistent with a product’s FDA approved labeling. Violations, including promotion of our products for unapproved (or off-label) uses, may be subject to enforcement letters, inquiries and investigations, and civil and criminal sanctions by the government. Additionally, foreign regulatory authorities will heavily scrutinize advertising and promotion of any product candidate that obtains approval in their respective jurisdictions.

In the United States, engaging in the impermissible promotion of our products for off-label uses can also subject us to false claims litigation under federal and state statutes, which can lead to administrative, civil and criminal penalties, damages, monetary fines, disgorgement, individual imprisonment, exclusion from participation in Medicare, Medicaid and other federal healthcare programs, curtailment or restructuring of our operations and agreements that materially restrict the manner in which a company promotes or distributes drug products. These false claims statutes include, but are not limited to, the federal civil False Claims Act, which allows any individual to bring a lawsuit against an individual or entity, including a pharmaceutical or biopharmaceutical company on behalf of the federal government alleging the knowing submission of false or fraudulent claims, or causing to present such false or fraudulent claims, for payment or approval by a federal program such as Medicare or Medicaid. These False Claims Act lawsuits against pharmaceutical and biopharmaceutical companies have increased significantly in number and breadth, leading to several substantial civil and criminal settlements regarding certain sales practices, including promoting off-label drug uses involving fines in excess of $1.0 billion. This growth in litigation has increased the risk that a pharmaceutical company will have to defend a false claim action, pay settlement fines or restitution, agree to comply with burdensome reporting and compliance obligations, and be excluded from participation in Medicare, Medicaid and other federal and state healthcare programs. If we, or any partner that we may engage, do not lawfully promote our approved products, we may become subject to such litigation, which may have a material adverse effect on our business, financial condition and results of operations.

Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial scope of their approved use, or result in significant negative consequences following any marketing approval.

Undesirable side effects caused by our product candidates could cause the interruption, delay or halting of the trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other foreign regulatory authorities. In our Phase 2b clinical trial of entinostat in advanced HR+, HER2- breast cancer, the most significant adverse events were fatigue, gastrointestinal disturbances and hematologic toxicities, all of which occurred in higher numbers than in the placebo group. Results of the clinical trials may reveal a high and unacceptable severity and prevalence of side effects or other unexpected characteristics. In such event, the trials could be suspended or terminated, or the FDA or foreign regulatory authorities could deny approval of our product candidates for any or all targeted indications. Drug-related side effects could affect patient recruitment or the ability of enrolled subjects to complete the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects.

Additionally, if our product candidates receive marketing approval, and we or others later identify undesirable side effects, a number of potentially significant negative consequences could result, including:

Any of these events could prevent us from achieving or maintaining market acceptance of our product candidates for use in targeted indications or otherwise materially harm its commercial prospects, if approved, and could harm our business, results of operations and prospects.

Our failure to obtain regulatory approval in international jurisdictions would prevent us from marketing our product candidates outside the United States.

In order to market and sell our product candidates in other jurisdictions, we must obtain separate marketing approvals for those jurisdictions and comply with their numerous and varying regulatory requirements. We may not obtain foreign regulatory approvals on a timely basis, or at all. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, product reimbursement approvals must be secured before regulatory authorities will approve the product for sale in that country. Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our product candidates in certain countries. Further, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries and regulatory approval in one country does not ensure approval in any other country, while a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory approval process in others. For example, based on scientific advice that we received from the European Medicines Agency in March 2014, the current Phase 3 clinical trial is likely to be insufficient to receive regulatory approval in Europe for entinostat to treat advanced HR+, HER2- breast cancer. Our failure to obtain approval of our product candidates by foreign regulatory authorities may negatively impact the commercial prospects of such product candidates and our business prospects could decline. Also, if regulatory approval for our product candidates is granted, it may be later withdrawn. If we fail to comply with the regulatory requirements in international jurisdictions and receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential for our product candidates will be harmed and our business may be adversely affected.

We face significant competition from other biotechnology and pharmaceutical companies, and our operating results will suffer if we fail to compete effectively.

Even if ~~entinostat in combination with exemestane were approved for treatment~~any of ~~advanced HR+, HER2- breast cancer, it~~our product candidates received regulatory approval, such product candidates would face competition from other therapies ~~recently approved for use~~ in ~~combination with hormone therapy in this population, including~~ ~~Ibrance~~, ~~Kisqali~~, ~~Afinitor~~, ~~Verzenio~~, ~~Piqray~~ ~~and other therapies under FDA review or currently in Phase 3 clinical development.~~

~~The pharmacologic treatment of NSCLC and melanoma patients has included chemotherapies and therapies targeting specific gene mutations. Over~~ the past few years, immune checkpoint inhibitors have been approved for NSCLC and melanoma. Currently there are few approved combination immuno-oncology therapies although numerous drugs are undergoing active clinical investigation. We believe that if entinostat in combination with ~~Keytruda~~ were approved for the treatment of NSCLC or melanoma it would face competition from standard-of-care approaches and other investigational drugs being tested in combination with any of these approaches.

~~Chronic~~relevant indication. For example, chronic graft versus host disease has historically been managed by off-label treatments. However, in ~~2017~~the past five years, the FDA has approved three drugs, ibrutinib (Imbruvica®), belomosidil (Rezurock®) ~~became the first drug approved~~and ruxolitinib (Jakafi®), for use in patients with cGVHD after failure of one or more lines of systemic therapy. ~~KD-025 and Ruxolitinib (Jakafi®), are currently in registration-directed studies to treat steroid refractory cGVHD patients and, if approved,~~All three of these drugs may ~~also~~ compete with ~~SNDX-6352.~~axatilimab in patients diagnosed with cGVHD.

SNDX-5613 is being developed for the treatment of adult and pediatric patients with ~~MLL-r~~MLLr ALL, MLLr AML and NPM1 mutant AML. At this time, there are no drugs approved for these defined populations and patients are managed using the standard of care treatment regimens developed for general AML and ALL populations. While there are other agents in early development for similar populations, SNDX-5613 has the potential to be the first defined therapy for patients with MLLr ALL, MLLr AML and/or NPM1 mutant AML.

Many of our existing or potential competitors have substantially greater financial, technical and human resources than we do and significantly greater experience in the discovery and development of product candidates, obtaining FDA and other regulatory approvals of products and the commercialization of those products. Our competitors may be more successful than us in obtaining FDA approval for drugs and achieving widespread market acceptance. Our competitors’ drugs may be more effective or more effectively marketed and sold than any drug we may commercialize and may render our product candidates obsolete or non-competitive before we can recover the expenses of developing and commercializing any of our product candidates. Our competitors may also obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours. We anticipate that we will face intense and increasing competition as new drugs enter the market and advanced technologies become available.

We believe that our ability to successfully compete will depend on, among other things:

Even if we obtain regulatory approval of our product candidates, the availability and price of our competitors’ products could limit the demand and the price we are able to charge. We may not be able to implement our business plan if the acceptance of our product candidates is inhibited by price competition or the reluctance of physicians to switch from existing methods of treatment, or if physicians switch to other new drug or biologic products or choose to reserve our drugs for use in limited circumstances.

~~Adverse events~~The actions of Eddingpharm Investment Company Limited, or Eddingpharm, and any other current or future sublicensees could adversely affect our business.

We currently exclusively sublicense entinostat to Eddingpharm for development and commercialization of entinostat in China and select Asian countries. In December 2021, Eddingpharm announced that the results of its multi-center, randomized, double-blinded, placebo-controlled Phase III registration trial, which was designed to evaluate entinostat plus exemestane compared to placebo plus exemestane in patients with locally advanced or metastatic HR positive, HER2 negative breast cancer who have previously progressed on hormone therapy, showed that entinostat plus exemestane improved progression free survival, overall response rate and disease control rate, compared with placebo plus exemestane in patients with advanced HR positive, HER2 negative breast cancer who had progressed after previous endocrine therapy. Nonetheless, it is possible that any future clinical trials conducted by Eddingpharm, including the forthcoming overall survival data in its ongoing Phase III registration trial, and trials by other current or future sublicensees in their respective jurisdictions could have negative results, which in turn could have a material adverse effect on the development of entinostat for development and commercialization in the ~~field~~United States and the rest of ~~immuno-oncology could damage public perception~~the world.

We are dependent on UCB Biopharma Sprl, or UCB, to comply with the terms of our ~~product candidates and negatively affect our business.~~license agreement for axatilimab.

~~The~~Our commercial success also depends upon our ability to develop, manufacture, market and sell axatilimab. In July 2016, we entered into the UCB license agreement pursuant to which we obtained a worldwide, sublicenseable, exclusive license to axatilimab, an IND-ready anti-CSF-1R monoclonal antibody. Certain of the rights licensed to us under the UCB license agreement are in-licensed by UCB from third parties. We are dependent on UCB maintaining the applicable third-party license agreements in full force and effect, which may include activities and performance obligations that are not within our control. If any of these third-party license agreements terminate, certain of our ~~product candidates will depend in part on public acceptance~~rights to develop, manufacture, commercialize or sell axatilimab may be terminated as well. The occurrence of any of these events could adversely affect the ~~use~~development and commercialization of ~~cancer immunotherapies. Adverse events in clinical trials of~~axatilimab, and materially harm our product candidates or in clinical trials of others developing similar products and the resulting publicity, as well as any other adverse events in the field of immuno-oncology that may occur in the future, could result in a decrease in demand for any products that we may develop. If public perception is influenced by claims that the use of cancer immunotherapies is unsafe, our product candidates may not be accepted by the general public or the medical community.

Future adverse events in immuno-oncology or the biopharmaceutical industry could also result in greater governmental regulation, stricter labeling requirements and potential regulatory delays in the testing or approvals of our products. Any increased scrutiny could delay or increase the costs of obtaining regulatory approval for our product candidates.business.

Our employees, consultants and collaborators may engage in misconduct or other improper activities, including insider trading and non-compliance with regulatory standards and requirements.

We are exposed to the risk that our employees, consultants, distributors, and collaborators may engage in fraudulent or illegal activity. Misconduct by these parties could include intentional, reckless or negligent conduct or disclosure of unauthorized activities to us that violates the regulations of the FDA and non-U.S. regulators, including those laws requiring the reporting of true, complete and accurate information to such regulators, manufacturing

standards, healthcare fraud and abuse laws and regulations in the United States and abroad or laws that require the true, complete and accurate reporting of financial information or data. In particular, sales, marketing and business arrangements in the healthcare industry, including the sale of pharmaceuticals, are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. It is not always possible to identify and deter misconduct by our employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations. If any such actions are instituted against us and we are not successful in defending ourselves or asserting our rights, those actions could result in the imposition of significant fines or other sanctions, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, disgorgement, individual imprisonment, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws, contractual damages, reputational harm, diminished profits and future earnings and curtailment of operations, any of which could adversely affect our ability to operate our business and our results of operations. Whether or not we are successful in defending against such actions or investigations, we could incur substantial costs, including legal fees, and divert the attention of management in defending ourselves against any of these claims or investigations.

We must attract and retain additional highly skilled employees in order to succeed.

To succeed, we must recruit, retain, manage and motivate qualified clinical, scientific, technical and management personnel and we face significant competition for experienced personnel. If we do not succeed in attracting and retaining qualified personnel, particularly at the management level, it could adversely affect our ability to execute our business plan and harm our operating results. In particular, the loss of one or more of our executive officers could be detrimental to us if we cannot recruit suitable replacements in a timely manner. The competition for qualified personnel in the pharmaceutical industry is intense and as a result, we may be unable to continue to attract and retain qualified personnel necessary for the development of our business or to recruit suitable replacement personnel.

Many of the other pharmaceutical companies that we compete against for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than we do. They also may provide more diverse opportunities and better chances for career advancement. Some of these characteristics may be

more appealing to high-quality candidates than what we have to offer. If we are unable to continue to attract and retain high-quality personnel, the rate and success at which we can discover and develop product candidates and our business will be limited.

Even if we commercialize our product candidates, they or any other product candidates that we develop, may become subject to unfavorable pricing regulations or third-party coverage or reimbursement practices, which could harm our business.

Our ability to successfully commercialize our existing product candidates, or any other product candidates that we develop, will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from third-party payors, including government healthcare programs, private health insurers, managed care plans and other organizations. Third-party payors determine which medications they will cover and establish reimbursement levels. Third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products.

We cannot be sure that coverage and reimbursement will be available for any product that we commercialize and, if reimbursement is available, what the level of reimbursement will be. Limitation on coverage and reimbursement may impact the demand for, or the price of, and our ability to successfully commercialize ~~entinostat or~~ any ~~other~~ product candidates that we develop.

There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the indications for which the drug is approved by the FDA or foreign regulatory

authorities. Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may only be temporary. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States.

Private payors often follow decisions by the Centers for Medicare & Medicaid Services, or CMS, regarding coverage and reimbursement to a substantial degree. However, one payor’s determination to provide coverage for a drug product does not assure that other payors will also provide coverage for the drug product. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could have an adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.

The regulations that govern marketing approvals, coverage and reimbursement for new drug products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we may obtain marketing approval for our product candidates in a particular country, but be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, which could negatively impact the revenues we generate from the sale of the product in that particular country. Adverse pricing limitations may hinder our ability to recoup our investment even if our product candidates obtain marketing approval.

There can be no assurance that our product candidates, if they are approved for sale in the United States or in other countries, will be considered medically reasonable and necessary for a specific indication, that it will be considered cost effective by third-party payors, that coverage and an adequate level of reimbursement will be available, or that third-party payors’ reimbursement policies will not adversely affect our ability to sell our product candidates profitably.

Current and future legislation may increase the difficulty and cost for us to commercialize our product candidates and affect the prices we may obtain.

The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any product candidate for which we obtain marketing approval. For example, then President Obama signed into law the Affordable Care Act. Among other cost containment measures, the Affordable Care Act established an annual, nondeductible fee on any entity that manufactures or imports branded prescription drugs and biologic agents, a Medicare Part D coverage gap discount program, and a formula that increased the rebates a manufacturer must pay under the Medicaid Drug Rebate Program. There ~~remain~~have been executive, judicial and Congressional challenges ~~as well as recent efforts by the Trump administration~~ to ~~repeal or replace~~ certain aspects of the Affordable Care Act. Since January 2017, President Trump has signed two Executive Orders designed to delay the implementation of certain provisions of the Affordable Care Act or otherwise circumvent some of the requirements for health insurance mandated by the Affordable Care Act. Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the Affordable Care Act. While Congress has not passed comprehensive repeal legislation, several bills affecting the implementation of certain taxes under the Affordable Care Act have been signed into law. The Tax Cuts and Jobs Act of 2017 includes a provision ~~repealing,~~that repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the Affordable Care Act on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” ~~Additionally,~~On June 17, 2021, the ~~2020 federal spending package permanently eliminated, effective January 1, 2020, the Affordable Care Act’s mandated “Cadillac” tax~~U.S. Supreme Court dismissed a challenge on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminates the health insurer tax. Further, the Bipartisan Budget Act of 2018, or the BBA, among other things, amendedprocedural grounds that argued the Affordable Care Act ~~effective January 1, 2019, to increase from 50% to 70% the point-of-sale discount that~~ is ~~owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.”~~ ~~In December 2018, CMS published a final rule permitting further collections and payments to and from certain~~ ~~Affordable Care Act~~ qualified health plans and health insurance issuers under its risk adjustment program in response to the outcome of federal district court litigation regarding the method CMS uses to determine this risk adjustment. On December 14, 2018, a Texas U.S. District Court Judge ruled that the ~~Affordable Care Act is~~ unconstitutional in its entirety because the “individual mandate” was repealed by ~~the U.S. Congress as part of the Tax~~ ~~Cuts and Jobs Act of 2017~~ Act. Additionally, on December 18, 2019, the U.S. Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions ofCongress. Thus, the Affordable Care Act ~~are invalid as well.~~will remain in effect in its current form. Moreover, prior to the U.S. Supreme Court ruling, January 28, 2021, President Biden issued an executive order that initiated a special enrollment period for purposes of obtaining health insurance coverage through the Affordable Care Act marketplace. The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining

Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Affordable Care Act. It is possible that the Affordable Care Act will be subject to judicial or Congressional challenges in the future. It is unclear how ~~this decision, future decisions, subsequent appeals,~~any such challenges and ~~other efforts to repeal and replace~~ the ~~Affordable Care Act~~healthcare reform measures of the Biden administration will impact the Affordable Care Act and our business. ~~In addition, Congress may consider other legislation to repeal and replace elements of the Affordable Care Act.~~

Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. For example, in August 2011, then President Obama signed into law the Budget Control Act of 2011, which, among other things, created the Joint Select Committee on Deficit Reduction to recommend to Congress proposals in spending reductions. The Joint Select Committee on Deficit Reduction did not agree upon a targeted deficit reduction of at least $1.2 trillion for fiscal years 2012 through 2021, triggering the ~~Affordable Care Act’s~~legislation’s automatic reduction to several government programs. This included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, effective as of 2013. Further legislation ~~including the BBA,~~ has extended the 2% reduction to ~~2029.~~2031 with the exception of a temporary suspension from May 1, 2020 through March 31, 2022 due to the COVID-19 pandemic, unless additional congressional action is taken. In January 2013, then President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Further, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries, Presidential executive orders, and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs. At the federal level, the Trump ~~administration’s~~administration used several means to propose or implement drug pricing reform, including through federal budget ~~proposal for fiscal years 2021 includes a $135 billion allowance to support legislative~~ proposals, ~~seeking to reduce drug prices, increase competition, lower out-of-pocket drug costs for patients,~~executive orders and ~~increase patient access to lower-cost generic~~policy initiatives. For example, on July 24, 2020 and ~~biosimilar drugs. The~~September 13, 2020, the Trump administration ~~also~~announced several executive orders related to prescription drug pricing that sought to implement several of the administration’s proposals. As a result, the FDA released a ~~“Blueprint”~~final rule and guidance in September 2020, providing pathways for states to ~~lower drug prices~~build and ~~reduce out~~submit importation plans for drugs from Canada. Further, on November 20, 2020, the U.S. Department of ~~pocket costs of drugs that contains additional proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize~~Health & Human Services, or HHS, finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to ~~lower~~plan sponsors under Medicare Part D, either directly or through pharmacy benefit managers, unless the ~~list~~ price reduction is required by law. The implementation of ~~their products~~the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and ~~reduce~~manufacturers, the ~~out~~implementation of ~~pocket costs of drug products~~which have also been delayed by the Biden administration until January 1, 2023. On November 20, 2020, the Centers for Medicare & Medicaid Services, or CMS, issued an interim final rule implementing the Trump administration’s Most Favored Nation, or MFN, executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid ~~by consumers. For example, May 2019,~~in other economically advanced countries. On December 27, 2021, CMS issued a final rule ~~to allow Medicare Advantage plans~~that rescinded the ~~option to use step therapy for part B drugs beginning January 1, 2020. This~~interim final rule codified CMS’s policy change that was effective January 1, 2019. While some of these and other measures may require additional authorization through additional legislation to become effective, Congress andimplementing the Trump administration’s Most Favored Nation executive order. In July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to Biden’s executive order, on September 9, 2021, the U.S. Department of Health and Human Services, or HHS, released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles. No legislation or administrative actions have ~~each indicated that it will continue~~been finalized to ~~seek new legislative administrative and executive measures, including the President’s issuance of future executive orders, to control drug costs.~~implement these principles. Congress is also considering additional health reform measures. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

It is also possible that additional governmental action is taken in response to the COVID-19 pandemic. We cannot predict the likelihood, nature or extent of government regulations that may arise from future legislation, administrative or executive action. We expect that the Affordable Care Act, as well as other current or future healthcare reform measures may result in more rigorous coverage criteria and in additional downward pressure on

the price that we receive for any approved product. This could seriously harm our future revenues. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our products.

We do not currently have any sales, marketing or distribution experience or infrastructure.

In order to market any approved product candidate in the future, we must build our sales, marketing, managerial and other non-technical capabilities or make arrangements with third parties to perform these services, as we do not presently have all of these capabilities. To develop our internal sales, distribution and marketing capabilities, we must invest significant amounts of financial and management resources in the future. For drugs where we decide to perform sales, marketing and distribution functions ourselves, we could face a number of challenges, including that:

Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of our product candidates.

We face an inherent risk of product liability exposure related to the testing of our product candidates in human trials and will face an even greater risk if we commercially sell any products that we may develop. Product liability claims may be brought against us by subjects enrolled in our trials, patients, healthcare providers or others using, administering or selling our products. If we cannot successfully defend ourselves against claims that our product candidates or other products that we may develop caused injuries, we could incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

While we currently hold trial liability insurance coverage consistent with industry standards, this may not adequately cover all liabilities that we may incur. We also may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise in the future. We intend to expand

our insurance coverage for products to include the sale of commercial products if we obtain marketing approval for our product candidates, but we may be unable to obtain commercially reasonable product liability insurance. A

successful product liability claim or series of claims brought against us, particularly if judgments exceed our insurance coverage, could decrease our cash and adversely affect our business and financial condition.

Our relationships with healthcare providers, customers and third-party payors will be subject to applicable anti-kickback, fraud and abuse, transparency and other healthcare laws and regulations as well as privacy and data security laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, fines, exclusion from participation in government healthcare programs, curtailments or restrictions of our operations, administrative burdens and diminished profits and future ~~earnings.~~earnings

Healthcare providers, including physicians and third-party payors play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our current and future arrangements with ~~physicians,~~healthcare providers, third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we conduct clinical research and market, sell and distribute our products for which we obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations, include, but are not limited to, the following:

Efforts to ensure that our business arrangements with third parties and our business generally, will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, contractual damages, reputational harm, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations. Defending against any such actions can be costly, time-consuming and may require significant financial and personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired. Further, if any physician or other healthcare provider or entity with whom we expect to do business is found not to be in compliance with applicable laws, that person or entity may be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs.

~~The novel coronavirus outbreak could impact~~Significant disruptions of our ~~business.~~

~~In December 2019, a novel strain of coronavirus was reported in China and other countries, including the United States. Global health concerns, such as coronavirus,~~information technology systems or data security incidents could result in ~~social, economic~~significant financial, legal, regulatory, business and ~~labor instability~~reputational harm to us.

We are increasingly dependent on information technology systems and infrastructure, including mobile technologies, to operate our business. In the ordinary course of our business, we collect, store, process and transmit large amounts of sensitive information, including intellectual property, proprietary business information, personal information and other confidential information. It is critical that we do so in a secure manner to maintain the ~~countries in which~~confidentiality, integrity and availability of such sensitive information. We have also outsourced elements of our operations (including elements of our information technology infrastructure) to third parties, and as a result, we manage a number of third-party vendors who may or could have access to our computer networks, our confidential information or the confidential information of third parties ~~with whom we engage operate. We cannot presently predict~~that is in our possession. In addition, those third-party vendors may in turn subcontract or outsource some of their responsibilities to other parties. While all information technology operations are inherently vulnerable to inadvertent or intentional security breaches, incidents, attacks and exposures, the ~~scope~~accessibility and ~~severity~~distributed nature of ~~any potential business shutdowns~~our information technology systems, and the sensitive information stored on those systems, make such systems potentially vulnerable to unintentional or ~~disruptions, but if we or any of the third parties with whom we engage, including the suppliers, clinical trial sites, regulators~~malicious, internal and ~~other third parties with whom we conduct business, were to experience shutdowns or other business disruptions,~~external attacks on our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively impacted. It is also possible that global health concerns such as this one could disproportionately impact the hospitals and clinical sites, as well as recruitment and retention, in a region or city whose health care system becomes overwhelmedtechnology environment. In addition, due to the ~~illness.~~COVID-19 pandemic, we have enabled substantially all of our employees to work remotely, which may make us more vulnerable to cyberattacks. Potential vulnerabilities can be exploited from inadvertent or intentional actions of our employees, third-party vendors, business partners, or by malicious third parties. Attacks of this nature are increasing in their frequency, levels of persistence, sophistication and intensity, and are being conducted by sophisticated and organized groups and individuals with a wide range of motives (including, but not limited to, industrial espionage) and expertise, including organized criminal groups, “hacktivists,” nation states and others. In addition to the extraction of sensitive information, such attacks could include the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other means to affect service reliability and threaten the confidentiality, integrity and availability of information. The ~~extent to which~~prevalent use of mobile devices further increases the ~~coronavirus impacts~~risk of data security incidents.

Significant disruptions of our, our third-party vendors’ and/or business partners’ information technology systems or other similar data security incidents could adversely affect our business ~~will depend on future developments, which are highly uncertain and cannot be predicted, including new~~operations and/or result in the loss, misappropriation and/or unauthorized access, use or disclosure of, or the prevention of access to, sensitive information, which ~~may emerge concerning the severity of the coronavirus~~could result in financial, legal, regulatory, business and ~~the actions~~reputational harm to ~~contain the coronavirus~~us. In addition, information technology system disruptions, whether from attacks on our technology environment or from computer viruses, natural disasters, terrorism, war and ~~to address its impact, including on financial markets or otherwise. The occurrence of any of these disruptions~~telecommunication and electrical failures, could ~~have~~result in a material ~~adverse effect on~~disruption of our development programs and our business operations. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.

There is no way of knowing with certainty whether we have experienced any data security incidents that have not been discovered. While we have no reason to believe this to be the case, attackers have become very sophisticated in the ways that they conceal access to systems. Many companies that have been attacked are not aware that they have been attacked. Any event that leads to unauthorized access, use or disclosure of personal information, including but not limited to personal information regarding employees or clinical trial patients, could disrupt our business, harm our reputation, compel us to comply with applicable federal and/or state breach notification laws and foreign law equivalents, subject us to time consuming, distracting and expensive litigation, regulatory investigation and oversight, mandatory corrective action, require us to verify the correctness of database contents, or otherwise subject us to liability under laws, regulations and contractual obligations, including those that protect the privacy and security of personal information. This could result in increased costs to us, and result in significant legal and financial exposure and/or reputational harm. Any failure or perceived failure by us or our vendors or business partners to comply with our privacy, confidentiality or data security-related legal or other obligations to third parties, or any further security incidents or other inappropriate access events resulting in the unauthorized access, release or transfer of sensitive information, which could include personally identifiable information, may result in governmental investigations, enforcement actions, regulatory fines, litigation, or public statements against us by advocacy groups or others, and could cause third parties, including clinical sites, regulators or current and potential partners, to lose trust in us or we could be subject to claims by third parties that we have breached our privacy- or confidentiality-related obligations, which could materially and adversely affect our business and prospects. Moreover, data security incidents and other inappropriate access can be difficult to detect. Any delay in identifying them may lead to increased harm of the type described above. While we have implemented security measures to protect our ~~results~~information technology systems and infrastructure, there can be no assurance that such measures will successfully prevent service interruptions or security incidents. Further, because of ~~operation and financial condition.~~the work-from-home policies we implemented due to COVID-19, information that is normally protected, including company confidential information, may be less secure.

We have incurred net losses since our inception, except 2021, and anticipate that we will continue to incur net losses for the foreseeable future.

Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate efficacy or an acceptable safety profile, gain regulatory approval or be commercially viable. We are a clinical stage biopharmaceutical company with limited operating history. We have no products approved for commercial sale and have not generated any product revenues to date, and we continue to incur significant research and development and other expenses related to our ongoing operations and clinical development of ~~entinostat.~~our product candidates. As a result, we are not and have never been profitable and have incurred losses in each period since our inception in 2005.

For the year ended December 31, ~~2019,~~2021, we reported a net ~~loss~~income of ~~$56.0 million; and as~~$24.9 million. We reported a net income attributable to stockholders of $24.9 million for the year ended December 31, 2021. As of December 31, ~~2019,~~2021, we had an accumulated deficit of ~~$495.5~~$543.7 million, which included non-cash charges for stock-based compensation, preferred stock accretion and historical extinguishment charges. We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our pre-commercialization activities for, and our research and development of, and seek regulatory approvals for, our product candidates. We may also encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our

expenses and our ability to generate revenues, if any. Our prior losses and expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital.

We currently have no source of product revenue and may never achieve or maintain profitability.

Our ability to generate product revenue and become profitable depends upon our ability to successfully commercialize our product candidates. We do not anticipate generating revenue from the sale of our product candidates for the foreseeable future. Our ability to generate future product revenue also depends on a number of additional factors, including, but not limited to, our ability to:

In addition, because of the numerous risks and uncertainties associated with drug development, we are unable to predict the timing or amount of increased expenses, and if or when we will achieve or maintain profitability. In addition, our expenses could increase beyond expectations if we decide to or are required by the FDA or foreign regulatory authorities to perform studies or trials in addition to those that we currently anticipate. Even if we complete the development and regulatory processes described above, we anticipate incurring significant costs associated with launching and commercializing our current product candidates and any other product candidates we may develop.

Even if we generate revenues from the sale of our product candidates, we may not become profitable and may need to obtain additional funding to continue operations or acquire additional products that will require additional funding to develop them. If we fail to become profitable or do not sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce our operations or even shut down.

We will require additional capital to finance our planned operations, which may not be available to us on acceptable terms, or at all. As a result, we may not complete the development and commercialization of, or obtain regulatory approval for our existing product candidates or develop new product candidates.

Our operations have consumed substantial amounts of cash since our inception, primarily due to our research and development efforts. We expect our research and development expenses to increase substantially in connection

with our ongoing and planned activities. We believe that our existing cash, cash equivalents and short-term investments will fund our projected operating expenses and capital expenditure requirements for at least the next 12 months. Unexpected circumstances may cause us to consume capital more rapidly than we currently ~~anticipate.~~anticipate, including as a result of the COVID-19 pandemic. For example, we may discover that we need to conduct additional activities that exceed our current budget to achieve appropriate rates of patient enrollment, which would increase our development costs.

In any event, we will require additional capital to continue the development of, obtain regulatory approval for, and to commercialize our existing product candidates and any future product candidates. Any efforts to secure

additional financing may divert our management from our day-to-day activities, which may adversely affect our ability to develop and commercialize our product candidates. ~~In addition,~~The COVID-19 pandemic has resulted in periods of significant disruption of global financial markets. If future disruption or volatility occur, we could experience an inability to access additional capital. We cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all. If we do not raise additional capital when required or on acceptable terms, we may need to:

If we need to conduct additional fundraising activities and we do not raise additional capital in sufficient amounts or on terms acceptable to us, we may be unable to pursue development and commercialization efforts, which will harm our business, operating results and prospects.

Our future funding requirements, both short- and long-term, will depend on many factors, including:

If we cannot expand our operations or otherwise capitalize on our business opportunities because we cannot secure sufficient capital, our business, financial condition and results of operations could be materially adversely affected.

The terms of our loan and security agreements place restrictions on our operating and financial flexibility. If we raise additional capital through debt financing, the terms of any new debt could further restrict our ability to operate our business.

Our amended loan and security agreement, or the Loan Agreement, with Hercules Capital, Inc., or Hercules, for aggregate maximum borrowings of up to ~~$30.0~~$80.0 million, or the Credit Facility, is collateralized by substantially all of our and our subsidiaries personal property and other assets, other than our intellectual property. As of ~~March 1, 2020,~~December 31, 2021, the outstanding principal balance under the Credit Facility was $20.0 ~~million, resulting from the closing of the first tranche of funding which occurred on February 7, 2020.~~million. The Credit Facility contains customary representations, warranties, affirmative and negative covenants and events of default applicable to us and our subsidiaries.

If we default under the Credit Facility, Hercules may accelerate all of our repayment obligations and exercise all of their rights and remedies under the Credit Facility and applicable law, potentially requiring us to renegotiate our agreement on terms less favorable to us. Further, if we are liquidated, the lenders’ right to repayment would be senior to the rights of the holders of our common stock to receive any proceeds from the liquidation. Hercules could declare a default upon the occurrence of any event, among others, that they interpret as a material adverse effect or a change of control as delineated under the Credit Facility, payment defaults, or breaches of covenants thereby requiring us to repay the loan immediately or to attempt to reverse the declaration of default through negotiation or litigation. Any declaration by the lender of an event of default could significantly harm our business and prospects and could cause the price of our common stock to decline. If we raise any additional debt financing, the terms of such additional debt could further restrict our operating and financial flexibility.

~~The Tax Cuts and Jobs Act of 2017, or the Tax Act, and possible future changes~~Changes in tax laws or regulations could materially adversely affect our company.

New tax laws or regulations could be enacted at any time, and existing tax laws or regulations could be interpreted, modified or applied in a manner that is adverse to us, which could adversely affect our business and financial condition.

~~On December 22,~~ These changes could require us to pay additional taxes on a prospective or retroactive basis, as well as penalties, interest and other costs for past amounts deemed to be due, and also could increase our compliance, operating and other costs, as well as the costs of any future products. For example, tax legislation enacted in 2017 ~~President Trump signed into law~~made many significant changes to the ~~Tax Act,~~U.S. tax laws, some of which ~~significantly revised~~were further modified in 2020, and may be modified or repealed in the ~~Internal Revenue Code of 1986, as amended,~~future by the current or ~~the Code. Future~~a future U.S. administration. Regulatory or other guidance from the ~~U.S.~~ Internal Revenue Service and other tax authorities with respect to ~~the Tax Act~~any tax legislation also may affect us, and certain aspects of the Tax Act could be repealed or modified in future legislation. Changes in corporate tax rates, the realization of net deferred tax assets relating to our U.S. operations, the taxation of foreign earnings, the deductibility of expenses, and the reduction of the Orphan Drug Credit from 50% to 25% of clinical costs under the Tax Act or future tax reform legislation could have a material impact on the value of our deferred tax assets, could result in significant one-time charges in the current or future taxable years, and could increase our future U.S. tax expense. The foregoing items, as well as any other future changes in tax laws, could have a material adverse effect on our business, cash flow, financial condition, or results of operations.us. In addition, it is uncertain if and to what extent various states will conform to ~~the Tax Act~~current federal law, or any newly enacted federal tax legislation. Changes in corporate tax rates, the utilization of net operating losses and other deferred tax assets, the deductibility of expenses, and the taxation of foreign earnings, as applicable, could increase our future tax expense and could have a material adverse impact on our business and financial condition.

Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.

We have incurred substantial losses during our history. We do not expect to become profitable in the near future, and we may never achieve profitability. Unused losses generally are available to be carried forward to offset future taxable income, if any. Under Sections 382 and 383 of the Code if a corporation undergoes an “ownership change,” generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards, or NOLs, and other pre-change tax attributes (such as research tax credits) to offset its post-change taxable income or taxes may be limited. We completed an analysis through ~~March~~December 31, ~~2019~~2020 and determined that on March 30, 2007, ~~and~~ August 21, 2015, and May 4, 2020, ownership changes had occurred. We ~~may have experienced an ownership change since March 31, 2019, and we~~ may also experience ownership changes in the future as a result of shifts in our stock ownership, some of which may be outside of our control. As a result, our ability to use our pre-change NOLs to offset U.S. federal taxable income may be subject to limitations, which could potentially result in increased future tax liability to us. In addition, at the state level, there may be periods during which the use of NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.

If we are unable to obtain or protect intellectual property rights, we may not be able to compete effectively in our market.

Our success depends in significant part on our and our licensors’ and licensees’ ability to establish, maintain and protect patents and other intellectual property rights and operate without infringing the intellectual property rights of others. We have filed patent applications both in the United States and in foreign jurisdictions to obtain patent rights to inventions we have discovered. We have also licensed from third parties rights to patent portfolios. Some of these licenses give us the right to prepare, file and prosecute patent applications and maintain and enforce patents we have licensed, and other licenses may not give us such rights.

The patent prosecution process is expensive and time-consuming, and we and our current or future licensors and licensees may not be able to prepare, file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we or our licensors or licensees will fail to identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late to obtain patent protection on them. Moreover, in some circumstances, we may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the patents, covering technology that we license from or license to third parties and are reliant on our licensors or licensees. Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business. If our current or future licensors or licensees fail to establish, maintain or protect such patents and other intellectual property rights, such rights may be reduced or eliminated. If our licensors or licensees are not fully cooperative or disagree with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised.

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. As a result, the issuance, scope, validity, enforceability and commercial value of our and our current or future licensors’ or licensees’ patent rights are highly uncertain. Our and our licensors’ or licensees’ pending and future patent applications may not result in patents being issued which protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. The patent examination process may require us or our licensors or licensees to narrow the scope of the claims of our or our licensors’ or licensees’ pending and future patent applications, which may limit the scope of patent protection that may be obtained. It is possible that third parties with products that are very similar to ours will circumvent our or our licensors’ or licensees’ patents by means of alternate designs or processes. We cannot be certain that we are the first to invent the inventions covered by pending patent applications and, if we are not, we may be subject to priority disputes. We may be required to disclaim part or all of the term of certain patents or all of the term of certain patent applications. There may be prior art of which we are not aware that may affect the validity or enforceability of a patent claim. There also may be prior art of which we are aware, but which we do not believe affects the validity or enforceability of a claim, which may, nonetheless, ultimately be found to affect the validity or enforceability of a claim. No assurance can be given that if challenged, our patents would be declared by a court to be valid or enforceable or that even if found valid and enforceable, a competitor’s technology or product would be found by a court to infringe our patents. We may analyze patents or patent applications of our competitors that we believe are relevant to our activities, and consider that we are free to operate in relation to our product candidate, but our competitors may achieve issued claims, including in patents we consider to be unrelated, which block our efforts or may potentially result in our product candidate or our activities infringing such claims. The possibility exists that others will develop products which have the same effect as our products on an independent basis which do not infringe our patents or other intellectual property rights, or will design around the claims of patents that we have had issued that cover our products. Our and our licensors’ or licensees’ patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications, and then only to the extent the issued claims cover the technology.

Furthermore, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours. Entinostat composition of matter U.S.

Patent RE39,754, which we licensed from Bayer, covers the chemical entity of entinostat and any crystalline or non-crystalline form of entinostat and expired in September 2017.

The portfolio we licensed from Bayer also includes U.S. Patent 7,973,166, or the ‘166 patent, which covers a crystalline polymorph of entinostat which is referred to as crystalline polymorph B, the crystalline polymorph used in the clinical development of entinostat. Many compounds can exist in different crystalline forms. A compound which in the solid state may exhibit multiple different crystalline forms is called polymorphic, and each crystalline form of the same chemical compound is termed a polymorph. A new crystalline form of a compound may arise, for example, due to a change in the chemical process or the introduction of an impurity. Such new crystalline forms may be patented. The ‘166 patent expires in 2029. On March 7, 2014, our licensor Bayer applied for reissue of the ‘166 patent. The reissue application seeks to add three inventors not originally listed on the ‘166 patent. The reissue application does not seek to amend the claims issued in the ‘166 patent. On April 28, 2015, the USPTO re-issued the ‘166 patent as U.S. patent RE45,499. RE45,499 reissued with the same claims originally issued in the ‘166 patent and the list of inventors on RE45,499 now lists the additional three inventors that were not included on the ‘166 patent. The ‘166 patent has now been surrendered in favor of RE45,499. RE45,499 has the same term as the initial term of the ‘166 patent, which expires in August 2029. After expiry of RE39,754, which occurred in September 2017, a competitor may develop a competing polymorphic form other than based on polymorph B, which could compete with polymorph B.

In spite of our efforts and efforts of our licensor, we may not be successful in defending the validity of the claims of the RE45,499 reissue patent or any of its foreign counterparts. If the claims of the ‘166 patent or any of its counterparts are found to be invalid by a competent court, we may not be able to effectively block entry of generic versions of our entinostat crystalline polymorph B candidate products into markets where the crystalline polymorph B patent claims are found to be invalid. Additionally, even if we submit an NDA before the expiration of U.S. Patent RE45,499 and are successful in obtaining an extension of the term of U.S. Patent RE45,499 based on FDA regulatory delays, such extension will only extend the term of RE45,499 for a few additional years (up to a maximum of five additional years for patent claims covering a new chemical entity).

The portfolio that we licensed from UCB includes ~~patent~~granted patents and applications with pending claims directed to the composition of matter of ~~SNDX-6352~~axatilimab (a humanized, full-length IgG4 (kappa light chain) antibody with high affinity for the CSF-1R) as well as claims directed to methods of use of ~~SNDX-6352.~~axatilimab. There is no guarantee that any further patents will be granted based on the pending applications we licensed from UCB or even if one or more patents are granted that the claims issued in those patents would cover ~~SNDX-6352~~axatilimab or methods of using ~~SNDX-6352.~~axatilimab. Based on the priority date and filing date of the applications in the portfolio we licensed from UCB, we expect that ~~a patent,~~additional patents, if any, granted based on the currently pending applications would expire in 2034. The actual term of any patents granted based on the pending applications we licensed from UCB can only be determined after such patents are actually granted.

The portfolio that we licensed from Vitae Pharmaceuticals, which is now a subsidiary of ~~Allergan,~~AbbVie Inc. (“AbbVie”), includes ~~patent~~granted patents and applications with pending claims directed to inhibitors of the interaction of menin with MLL and MLL fusion proteins, pharmaceutical compositions containing the same, and their use in the treatment of cancer and other diseases mediated by the menin-MLL interaction. There is no guarantee that any additional patents will be granted based on the pending applications that we licensed from ~~Allergan~~AbbVie or even if one or more patents are granted that the claims issued in those patents would cover the desired lead compounds, compositions, and methods of use thereof. Based on the priority date and filing date of the applications in the portfolio that we licensed from ~~Allergan,~~AbbVie, we expect that a patent, if any, granted based on the currently pending applications would expire in ~~2036.~~2037. The actual term of any patents granted based on the pending applications that we licensed from ~~Allergan~~AbbVie can only be determined after such patents are actually granted.

We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting, enforcing and defending patents on product candidates in all countries throughout the world is prohibitively expensive, and our or our licensors’ intellectual property rights in some countries outside the United States can be less extensive than those in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we and our licensors may not be able to prevent third parties from practicing our and our licensors’ inventions in countries outside the United States, or from selling or importing products made using our and our licensors’ inventions in and into the United States or other jurisdictions. Competitors may use our and our licensors’

technologies in jurisdictions where we have not obtained patent protection to develop their own products and may export otherwise infringing products to territories where we and our licensors have patent protection, but enforcement is not as strong as that in the United States. These products may compete with our product candidates and our and our licensors’ patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals, which could make it difficult for us and our licensors to stop the infringement of our and our licensors’ patents or marketing of competing products in violation of our and our licensors’ proprietary rights generally. Proceedings to enforce our and our licensors’ patent rights in foreign jurisdictions could result in substantial costs and divert our attention from other aspects of our business, could put our and our licensors’ patents at risk of being invalidated or interpreted narrowly and our and our licensors’ patent applications at risk of not issuing and could provoke third parties to assert claims against us or our licensors. We or our licensors may not prevail in any lawsuits that we or our licensors initiate and the damages or other remedies awarded, if any, may not be commercially meaningful.

The requirements for patentability may differ in certain countries, particularly developing countries. For example, unlike other countries, China has a heightened requirement for patentability, and specifically requires a detailed description of medical uses of a claimed drug. In India, unlike the United States, there is no link between regulatory approval of a drug and its patent status. Furthermore, generic drug manufacturers or other competitors may challenge the scope, validity or enforceability of our or our licensors’ patents, requiring us or our licensors to engage in complex, lengthy and costly litigation or other proceedings. Generic drug manufacturers may develop, seek approval for, and launch generic versions of our products. In addition to India, certain countries in Europe and developing countries, including China, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those countries, we and our licensors may have limited remedies if patents are infringed or if we or our licensors are compelled to grant a license to a third party, which could materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our and our licensors’ efforts to enforce intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we own or license.

If we breach ~~our license agreement with Bayer related to entinostat or if the license agreement is otherwise terminated, we could lose the ability to continue the development and commercialization of entinostat.~~

Our commercial success depends upon our ability to develop, manufacture, market and sell entinostat. In March 2007, we entered into a license, development and commercialization agreement, or the Bayer license agreement, with Bayer pursuant to which we obtained a worldwide, exclusive license to develop and commercialize entinostat and any other products containing the same active ingredient. The Bayer license agreement, as amended, permits us to use entinostat or other licensed products under the Bayer license agreement for the treatment of any human disease, and we are obligated to use commercially reasonable efforts to develop, manufacture and commercialize licensed products for all commercially reasonable indications.

We are obligated to pay Bayer up to approximately $50 million in the aggregate upon obtaining certain milestones in the development and marketing approval of entinostat, assuming that we pursue at least two different indications for entinostat or any other licensed product under the Bayer license agreement. We are also obligated to pay Bayer up to $100 million in aggregate sales milestones, and a tiered, single-digit royalty on net sales by us, our affiliates and sublicensees of entinostat and any other licensed products under the Bayer license agreement. We are obligated to pay Bayer these royalties on a country-by-country basis for the life of the relevant licensed patents covering such product or 15 years after the first commercial sale of such product in such country, whichever is longer. We cannot determine the date on which our royalty payment obligations to Bayer would expire because no commercial sales of entinostat have occurred and the last-to-expire relevant patent covering entinostat in a given country may change in the future.

The Bayer license agreement will remain in effect until the expiration of our royalty obligations under the agreement in all countries. Either party may terminate the Bayer license agreement in its entirety or with respect to certain countries in the event of an uncured material breach by the other party. Either party may terminate the Bayer license agreement if voluntary or involuntary bankruptcy proceedings are instituted against the other party, if the other party makes an assignment for the benefit of creditors, or upon the occurrence of other specific events relating to the insolvency or dissolution of the other party. Bayer may terminate the Bayer license agreement if we seek to revoke or challenge the validity of any patent licensed to us by Bayer under the Bayer license agreement or if we procure or assist a third party to take any such action.

If the Bayer license agreement is terminated, we would not be able to develop, manufacture, market or sell entinostat and would need to negotiate a new or reinstated agreement, which may not be available to us on equally favorable terms, or at all.

~~If we breach~~ the UCB license agreement related to ~~SNDX-6352~~axatilimab or if the UCB license agreement is otherwise terminated, we could lose the ability to continue the development and commercialization of ~~SNDX-6352.~~axatilimab.

Our commercial success depends upon our ability to develop, manufacture, market and sell ~~SNDX-6352.~~axatilimab. Subject to the achievement of certain milestone events, we may be required to pay UCB up to $119.5 million in one-time development and regulatory milestone payments over the term of the UCB license agreement. If we or any of our affiliates or sublicensees commercializes ~~SNDX-6352,~~axatilimab, we will also be obligated to pay UCB low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $250 million in potential one-time sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, we may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with UCB.

Either party may terminate the UCB license agreement in its entirety or with respect to certain countries in the event of an uncured material breach by the other party. Either party may terminate the UCB license agreement if voluntary or involuntary bankruptcy proceedings are instituted against the other party, if the other party makes an assignment for the benefit of creditors, or upon the occurrence of other specific events relating to the insolvency or dissolution of the other party. UCB may terminate the UCB license agreement if we seek to revoke or challenge the validity of any patent licensed to us by UCB under the UCB license agreement or if we procure or assist a third party to take any such action.

Unless terminated earlier in accordance with its terms, the UCB license agreement will continue on a country-by-country and product-by-product basis until the later of: (i) the expiration of all of the licensed patent rights in such country; (ii) the expiration of all regulatory exclusivity applicable to the product in such country; and (iii) 10 years from the date of the first commercial sale of the product in such country. We cannot determine the date on which our royalty payment obligations to UCB would expire because no commercial sales of ~~SNDX-6352~~axatilimab have occurred and the last-to-expire relevant patent covering ~~SNDX-6352~~axatilimab in a given country may change in the future.

If the UCB license agreement is terminated, we would not be able to develop, manufacture, market or sell ~~SNDX-6352~~axatilimab and would need to negotiate a new or reinstated agreement, which may not be available to us on equally favorable terms, or at all.

If we breach the license agreement related to SNDX-5613 or if the license agreement is otherwise terminated, we could lose the ability to continue the development and commercialization of SNDX-5613.

Our commercial success depends upon our ability to develop, manufacture, market and sell SNDX-5613. Subject to the achievement of certain milestone events, we may be required to pay Vitae, which is now a subsidiary of ~~Allergan,~~AbbVie, up to $99 million in one-time development and regulatory milestone payments over the term of the ~~Allergan~~AbbVie license agreement. In the event that we or any of our affiliates or sublicensees commercializes SNDX-5613, we will also be obligated to pay ~~Allergan~~AbbVie low single to low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $70 million in potential one-time sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, we may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with ~~Allergan.~~AbbVie. In June 2019, we achieved certain development and regulatory milestones. As a result, in June 2019, we recorded $4.0 million as research and development expense. The amount was paid in 2020.

Either party may terminate the license agreement in its entirety or with respect to certain countries in the event of an uncured material breach by the other party. Either party may terminate the license agreement if voluntary or involuntary bankruptcy proceedings are instituted against the other party, if the other party makes an assignment for the benefit of creditors, or upon the occurrence of other specific events relating to the insolvency or dissolution of the other party. ~~Allergan~~AbbVie may terminate the license agreement if we seek to revoke or challenge the validity of any patent licensed to us by ~~Allergan~~AbbVie under the license agreement or if we procure or assist a third party to take any such action.

Unless terminated earlier in accordance with its terms, the license agreement will continue on a country-by-country and product-by-product basis until the later of: (i) the expiration of all of the licensed patent rights in such country; (ii) the expiration of all regulatory exclusivity applicable to the product in such country; and (iii) 10 years from the date of the first commercial sale of the product in such country. We cannot determine the date on which our royalty payment obligations to ~~Allergan~~AbbVie would expire because no commercial sales of SNDX-5613 have occurred and the last-to-expire relevant patent covering SNDX-5613 in a given country may change in the future.

If the license agreement is terminated, we would not be able to develop, manufacture, market or sell SNDX-5613 and would need to negotiate a new or reinstated agreement, which may not be available to us on equally favorable terms, or at all.

If we breach our license agreement with Bayer related to entinostat or if the license agreement is otherwise terminated, we could lose the ability to continue the development and commercialization of entinostat.

We have a license, development and commercialization agreement, or the Bayer license agreement, with Bayer pursuant to which we obtained a worldwide, exclusive license to develop and commercialize entinostat and any other products containing the same active ingredient. The Bayer license agreement, as amended, permits us to use entinostat or other licensed products under the Bayer license agreement for the treatment of any human disease, and we are obligated to use commercially reasonable efforts to develop, manufacture and commercialize licensed products for all commercially reasonable indications.

Changes in patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.

As is the case with other biotechnology and pharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involve technological and legal complexity, and obtaining and enforcing biopharmaceutical patents is costly, time-consuming, and inherently uncertain. The Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our and our licensors’ ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on decisions by Congress, the federal courts, and the U.S. Patent and Trademark Office, or USPTO, the laws and regulations governing patents could change in unpredictable ways that may weaken our and our licensors’ ability to obtain new patents or to enforce existing patents and patents we and our licensors or collaborators may obtain in the future. In view of recent developments in U.S. patent laws, in spite of our efforts and the efforts of our licensors, we may face difficulties in obtaining allowance of our biomarker based patient selection patent claims or if we are successful in obtaining allowance of our biomarker based patient selection claims, we or our licensor may be unsuccessful in defending the validity of such claims if challenged before a competent court.

Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our and our licensors’ patent applications and the enforcement or defense of our or our licensors’ issued patents. On September 16, 2011, the Leahy-Smith America Invents Act, or the America Invents Act, was signed into law. The America Invents Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications are prosecuted and may also affect patent litigation. The USPTO recently developed new regulations and procedures to govern administration of the American Invents Act, and many of the substantive changes to patent law associated with the America Invents Act and in particular, the first to file provisions, only became effective on March 16, 2013. Accordingly, it is not clear what, if any, impact the America Invents Act will have on the operation of our business. However, the America Invents Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our or our licensors’ patent applications and the enforcement or defense of our or our licensors’ issued patents, all of which could harm our business and financial condition.

Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.

Periodic maintenance and annuity fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent or patent application include failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. If we or our licensors fail to maintain the patents and

patent applications covering our product candidates, our competitors might be able to enter the market, which would harm our business.

We may become involved in lawsuits to protect or enforce our intellectual property, which could be expensive, time-consuming and unsuccessful and have an adverse effect on the success of our business and on our stock price.

Third parties may infringe our or our licensors’ patents or misappropriate or otherwise violate our or our licensors’ intellectual property rights. In the future, we or our licensors may initiate legal proceedings to enforce or defend our or our licensors’ intellectual property rights, to protect our or our licensors’ trade secrets or to determine the validity or scope of intellectual property rights we own or control. Also, third parties may initiate legal proceedings against us or our licensors to challenge the validity or scope of intellectual property rights we own or control. The proceedings can be expensive and time-consuming and many of our or our licensors’ adversaries in these proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than we or our licensors can. Accordingly, despite our or our licensors’ efforts, we or our licensors may not be able to prevent third parties from infringing upon or misappropriating intellectual property rights we own or control, particularly in countries where the laws may not protect our rights as fully as in the United States. Litigation could result in substantial costs and diversion of management resources, which could harm our business and financial results. In addition, in an infringement proceeding, a court may decide that a patent owned by or licensed to us is invalid or unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our or our licensors’ patents do not cover the technology in question. An adverse result in any litigation proceeding could put one or more of our or our licensors’ patents at risk of being invalidated, held unenforceable or interpreted narrowly.

Third-party preissuance submission of prior art to the USPTO, or opposition, derivation, reexamination, inter partes review or interference proceedings, or other preissuance or post-grant proceedings in the United States or other jurisdictions provoked by third parties or brought by us or our licensors or collaborators may be necessary to determine the priority of inventions with respect to our or our licensors’ patents or patent applications. An unfavorable outcome could require us or our licensors to cease using the related technology and commercializing our product candidates, or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us or our licensors a license on commercially reasonable terms or at all. Even if we or our licensors obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us or our licensors. In addition, if the breadth or strength of protection provided by our or our licensors’ patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates. Even if we successfully defend such litigation or proceeding, we may incur substantial costs and it may distract our management and other employees. We could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this process. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a downward effect on the price of shares of our common stock.

Third parties may initiate legal proceedings against us alleging that we infringe their intellectual property rights or we may initiate legal proceedings against third parties to challenge the validity or scope of intellectual property rights controlled by third parties, the outcome of which would be uncertain and could have an adverse effect on the success of our business.

Third parties may initiate legal proceedings against us or our licensors or collaborators alleging that we or our licensors or collaborators infringe their intellectual property rights or we or our licensors or collaborators may initiate legal proceedings against third parties to challenge the validity or scope of intellectual property rights controlled by third parties, including in oppositions, interferences, reexaminations, inter partes reviews or derivation proceedings before the United States or other jurisdictions. These proceedings can be expensive and time-consuming and many of our or our licensors’ adversaries in these proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than we or our licensors or collaborators can.

An unfavorable outcome could require us or our licensors or collaborators to cease using the related technology or developing or commercializing our product candidates, or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us or our licensors or collaborators a license on commercially reasonable terms or at all. Even if we or our licensors or collaborators obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us or our licensors or collaborators. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business.

We may be subject to claims by third parties asserting that we or our employees have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.

Many of our employees, including our senior management, were previously employed at universities or at other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Some of these employees executed proprietary rights, non-disclosure and non-competition agreements in connection with such previous employment. Although we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these employees have used or disclosed confidential information or intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer. Litigation may be necessary to defend against these claims.

In addition, for some of our in-licensed patents and patent applications, we do not have access to every patent assignments or employee agreements demonstrating that all inventors have assigned their rights to the inventions or related patents. As a result, we may be subject to claims of ownership by such inventors.

If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel or sustain damages. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license from such third party to commercialize our technology or products. Such a license may not be available on commercially reasonable terms or at all. Even if we successfully prosecute or defend against such claims, litigation could result in substantial costs and distract management.

Our inability to protect our confidential information and trade secrets would harm our business and competitive position.

In addition to seeking patents for some of our technology and products, we also rely on trade secrets, including unpatented know-how, technology and other proprietary information, to maintain our competitive position. We seek to protect these trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, third-party manufacturers, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and consultants. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable. In addition, some courts both within and outside the United States may be less willing or unwilling to protect trade secrets. If a competitor lawfully obtained or independently developed any of our trade secrets, we would have no right to prevent such competitor from using that technology or information to compete with us, which could harm our competitive position.

~~Significant disruptions of our information technology systems or data security incidents could result in significant financial, legal, regulatory, business and reputational harm to us.~~

We are increasingly dependent on information technology systems and infrastructure, including mobile technologies, to operate our business. In the ordinary course of our business, we collect, store, process and transmit large amounts of sensitive information, including intellectual property, proprietary business information, personal information and other confidential information. It is critical that we do so in a secure manner to maintain the confidentiality, integrity and availability of such sensitive information. We have also outsourced elements of our operations (including elements of our information technology infrastructure) to third parties, and as a result, we manage a number of third-party vendors who may or could have access to our computer networks, our confidential information or the confidential information of third parties that is in our possession. In addition, those third party vendors may in turn subcontract or outsource some of their responsibilities to other parties. While all information technology operations are inherently vulnerable to inadvertent or intentional security breaches, incidents, attacks and exposures, the accessibility and distributed nature of our information technology systems, and the sensitive information stored on those systems, make such systems potentially vulnerable to unintentional or malicious, internal and external attacks on our technology environment. Potential vulnerabilities can be exploited from inadvertent or intentional actions of our employees, third-party vendors, business partners, or by malicious third parties. Attacks of this nature are increasing in their frequency, levels of persistence, sophistication and intensity, and are being conducted by sophisticated and organized groups and individuals with a wide range of motives (including, but not limited to, industrial espionage) and expertise, including organized criminal groups, “hacktivists,” nation states and others. In addition to the extraction of sensitive information, such attacks could include the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other means to affect service reliability and threaten the confidentiality, integrity and availability of information. The prevalent use of mobile devices further increases the risk of data security incidents.

Significant disruptions of our, our third-party vendors’ and/or business partners’ information technology systems or other similar data security incidents could adversely affect our business operations and/or result in the loss, misappropriation and/or unauthorized access, use or disclosure of, or the prevention of access to, sensitive information, which could result in financial, legal, regulatory, business and reputational harm to us. In addition, information technology system disruptions, whether from attacks on our technology environment or from computer viruses, natural disasters, terrorism, war and telecommunication and electrical failures, could result in a material disruption of our development programs and our business operations. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.

There is no way of knowing with certainty whether we have experienced any data security incidents that have not been discovered. While we have no reason to believe this to be the case, attackers have become very sophisticated in the ways that they conceal access to systems. Many companies that have been attacked are not aware that they have been attacked. Any event that leads to unauthorized access, use or disclosure of personal information, including but not limited to personal information regarding employees or clinical trial patients, could disrupt our business, harm our reputation, compel us to comply with applicable federal and/or state breach notification laws and foreign law equivalents, subject us to time consuming, distracting and expensive litigation, regulatory investigation and oversight, mandatory corrective action, require us to verify the correctness of database contents, or otherwise subject us to liability under laws, regulations and contractual obligations, including those that protect the privacy and security of personal information. This could result in increased costs to us, and result in significant legal and financial exposure and/or reputational harm. Any failure or perceived failure by us or our vendors or business partners to comply with our privacy, confidentiality or data security-related legal or other obligations to third parties, or any further security incidents or other inappropriate access events resulting in the unauthorized access, release or transfer of sensitive information, which could include personally identifiable information, may result in governmental investigations, enforcement actions, regulatory fines, litigation, or public statements against us by advocacy groups or others, and could cause third parties, including clinical sites, regulators or current and potential partners, to lose trust in us or we could be subject to claims by third parties that we have breached our privacy- or confidentiality-related obligations, which could materially and adversely affect our business and prospects. Moreover, data security incidents and other inappropriate access can be difficult to detect. Any delay in identifying them may lead to increased harm of the type described above. While we have implemented security measures to protect our information technology systems and infrastructure, there can be no assurance that such measures will successfully prevent service interruptions or security incidents.

The market price of our stock may be volatile and you could lose all or part of your investment.

The trading price of our common stock is highly volatile and subject to wide fluctuations in response to various factors, some of which we cannot control. In addition to the factors discussed in this “Risk Factors” section and elsewhere in this report, these factors include:

In addition, the stock market in general, and the Nasdaq Global Select Market and biopharmaceutical companies in particular, frequently experiences extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of such ~~companies.~~companies,including very recently in connection with the ongoing COVID-19 pandemic, which has resulted in decreased stock prices for many companies notwithstanding the lack of a fundamental change in their underlying business models or prospects. Broad market and industry factors, including potentially worsening economic conditions and other adverse effects or developments relating to the ongoing COVID-19 pandemic, may negatively affect the market price of our common stock, regardless of our actual operating performance. The realization of any of the above risks or any of a broad range of other risks, including those described in this “Risk Factors” section, could have a dramatic and negative impact on the market price of our common stock.

We may sell additional equity or debt securities or enter into other arrangements to fund our operations, which may result in dilution to our stockholders and impose restrictions or limitations on our business.

Until we can generate a sufficient amount of revenue from our products, if ever, we expect to finance future cash needs through public or private equity or debt offerings. If we raise additional funds through the issuance of additional equity or debt securities, it may result in dilution to our existing stockholders and/or increased fixed payment obligations. In August 2019, we filed a shelf registration statement on Form S-3 (Registration No. 333-233564) that allows us to sell up to an aggregate of $300 million of our common stock, which includes up to $50.0 million designated for an at-the-market offering program. As of December 31, 2019, $50.0 million of common stock remained available for sale under the at-the-market offering program. We have sold no shares of common stock pursuant to the ATM program from December 31, 2019 through the date of this filing. Further, in January 2020,For example, during 2021, we sold ~~3,036,719~~a total of 3,802,144 shares of our common stock ~~at a price per share of $8.00~~ and pre-funded warrants to purchase ~~1,338,287~~1,142,856 shares of our common ~~stock for gross proceeds of approximately $35.0 million. Upon the completion of the 2020 offering, we had 5,838,287 pre-funded warrant shares outstanding.~~stock. The pre-funded warrants are exercisable into shares of common stock for $0.0001 per share. The shares of common stock into which the warrants may be exercised are considered outstanding for the purposes of computing earnings per share.

~~We also have two outstanding series of warrants, Series 1 warrants and Series 2 warrants.~~ As of December 31, ~~2019, there were 2,297,517~~2021, we had 3,975,024 pre-funded warrants outstanding. The issuance of these shares of our common stock ~~issuable upon~~resulted, and any future issuance pursuant to the exercise of ~~Series 1~~the outstanding pre-funded warrants outstanding, at an exercise price of $12.00 per share, and there were 2,297,522 shares of our common stock issuable upon the exercise of Series 2 warrants outstanding, at an exercise price of $18.00 per share. The Series 1 warrants and Series 2 warrants contain a one-time exercise price adjustment. If we sell shares or share equivalents at less than $12.00 per share at a time when our Series 1 warrants and Series 2 warrants are outstanding, then an exercise price for those warrants would be adjusted downward, which will result, in ~~us receiving less proceeds than we otherwise would and could result in further~~ dilution to our stockholders if such warrants were then exercised. As a result of the 2020 offering, the initial exercise price of the Series 1 warrants was reduced to $10.00 per share and the initial exercise price of the Series 2 warrants was reduced to $13.00 per share. To the extent that these have been or may be exercised, our stockholders may experience further dilution.stockholders.

We may also seek additional funding through government or other third-party funding and other collaborations, strategic alliances and licensing arrangements. These financing activities may have an adverse

impact on our stockholders’ rights as well as on our operations, and such additional funding may not be available on reasonable terms, if at all. Furthermore, these securities may have rights senior to those of our common stock and

could contain covenants that would restrict our operations and potentially impair our competitiveness, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business. For example, on ~~February 7, 2020,~~December 22, 2021, we entered into ~~the Credit Facility~~Amendment No. 1 to our Loan Agreement with Hercules, which provided for increased aggregate maximum borrowings of up to ~~$30.0~~$80.0 million ~~consisting~~in multiple tranches. Our only borrowings to date under the Loan Agreement are the first tranche of ~~(i) a term loan of up to~~ $20.0 million, which ~~was funded~~we drew upon on February 7, ~~2020, and (ii) subject to Hercules’ investment committee approval, an additional term loan of up to $10.0 million, available for borrowing from February 7, 2020 to December 15,~~ 2020. Borrowings under the ~~loan agreement~~Loan Agreement are collateralized by substantially all of our and our subsidiaries personal property and other assets, other than our intellectual property. In addition, the ~~loan agreement~~Loan Agreement includes customary affirmative and restrictive covenants and representations and warranties, including a covenant against the occurrence of a “change in control,” financial reporting obligations, and certain limitations on indebtedness, liens (including a negative pledge on intellectual property and other assets), investments, distributions (including dividends), collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, and deposit accounts.

Additionally, if we seek funds through arrangements with collaborative partners, these arrangements may require us to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us. Any of these events could significantly harm our business, financial condition and prospects.

If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our stock, our stock price and trading volume could decline.

The trading market for our common stock is influenced by the research and reports that industry or securities analysts publish about us or our business. If no or few securities or industry analysts continue coverage of us, the trading price for our stock could be negatively impacted. If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if our trials or operating results fail to meet the expectations of analysts, our stock price could decline. If one or more of these analysts cease coverage of us or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.

Our principal stockholders and management own a significant percentage of our stock and will be able to exert significant influence control over matters subject to stockholder approval.

As of December 31, ~~2019,~~2021, our executive officers, directors, holders of 5% or more of our capital stock and their respective affiliates beneficially ~~own~~owned approximately ~~64.0%~~39.7% of our outstanding voting stock and options. ~~These~~As a result, these stockholders ~~may be able~~will continue to ~~determine~~have a significant influence over all matters requiring stockholder approval. For example, these stockholders may be able to ~~control~~influence elections of directors, amendments of our organizational documents, or approval of any merger, sale of assets or other major corporate transaction. This may prevent or discourage unsolicited acquisition proposals or offers for our common stock that you may feel are in your best interest as one of our stockholders. The interests of this group of stockholders may not always coincide with your interests or the interests of other stockholders and they may act in a manner that advances their best interests and not necessarily those of other stockholders, including seeking a premium value for their common stock, and might affect the prevailing market price for our common stock.

~~We are an “emerging growth company”~~Effective as ~~defined in the JOBS Act and a “smaller reporting company” and may avail ourselves~~ of ~~reduced disclosure requirements applicable to such companies, which could make our common stock less attractive to investors and adversely affect the market price of our common stock.~~

For so long as we remain an “emerging growth company” as defined in the JOBS Act, we may take advantage of certain exemptions from various requirements applicable to public companies that are not “emerging growth companies” including:

~~We may take advantage of these exemptions until~~December 31, 2021, we are ~~no longer an “emerging growth company.” We would cease to be an “emerging growth company” upon the earliest of: (i) December 31, 2021; (ii) the first fiscal year after~~a large accelerated filer, which will increase our ~~annual gross revenues are $1.07 billion or more; (iii) the date~~costs and demands on ~~which we have, during the previous three-year period, issued more than $1.0 billion in non-convertible debt securities; or (iv) as~~management.

As a result of ~~the end of any fiscal year in which~~ the market value of our common stock held by non-affiliates ~~exceeded $700 million~~ as of ~~the end~~June 30, 2021, we are a large accelerated filer as of ~~the second quarter of that fiscal year.~~

~~We currently take advantage of some, but not all, of the reduced regulatory~~December 31, 2021, and ~~reporting requirements that are available to us so long as we~~no longer qualify as an ~~“emerging~~EGC. Additionally, due to our public float as of June 30, 2021, we will no longer qualify as a smaller reporting company as defined in the Exchange Act. However, we are not required to reflect the change in our smaller reporting company status, and comply with the associated increased disclosure obligations, until our quarterly report on Form 10-Q for the three-month period ending March 31, 2022.

As a large accelerated filer, we are subject to certain disclosure and compliance requirements that apply to other public companies that did not previously apply to us due to our status as an emerging growth company.~~” For example,~~ These requirements include, but are not limited to:

We expect that compliance with the additional requirements of being a large accelerated filer will increase our legal and financial compliance costs and may cause management and other personnel to divert attention from operational and other business matters to devote increased time to public company reporting requirements. In addition, if we ~~have irrevocably elected~~are not ~~to take advantage of the extension of time~~able to comply with ~~new or revised financial accounting standards available under Section 102(b)~~changing requirements in a timely manner, the market price of the JOBS Act. Our independent registered public accounting firm is not be required to provide an attestation report on the effectiveness of our internal control over financial reporting so long as we qualify as an “emerging growth company,” which may increase the risk that material weaknesses or significant deficiencies in our internal control over financial reporting go undetected. Likewise, so long as we qualify as an “emerging growth company,” we may elect not to provide you with certain information, including certain financial information and certain information regarding compensation of our executive officers, that we would otherwise have been required to provide in filings we make with the Securities and Exchange Commission, or SEC, which may make it more difficult for investors and securities analysts to evaluate our company. We cannot predict if investors will find our common stock ~~less attractive because~~could decline, and we ~~may rely on these exemptions. If some investors find our common stock less attractive as a result, there may~~could be ~~a less active trading market for our common stock,~~subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities, which would require additional financial and ~~our stock price may be more volatile and may decline.~~

Wemanagement resources are also a smaller reporting company as defined in the Securities Exchange Act of 1934, as amended, or the Exchange Act. We may continue to be a smaller reporting company even after we are no longer an emerging growth company. We may take advantage of certain of the scaled disclosures available to smaller reporting companies and will be able to take advantage of these scaled disclosures for so long as (i) our voting and non-voting common stock held by nonaffiliates is less than $250.0 million measured on the last business day of our second fiscal quarter or (ii) our annual revenue is less than $100.0 million during the most recently completed fiscal year and our voting and non-voting common stock held by non-affiliates is less than $700.0 million measured on the last business day of our second fiscal quarter.

~~We will continue to incur significant costs as a result of operating as a public company, and our management will devote substantial time to compliance initiatives.~~

As a public company, we will incur significant legal, accounting and other expenses that we did not incur as a private company, and these expenses may increase even more after we are no longer an “emerging growth company.” We are subject to the reporting requirements of the Exchange Act, the Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Protection Act, as well as rules adopted, and to be adopted, by the SEC and the Nasdaq Global Select Market.

~~Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall.~~

Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. In August 2019, we entered into a sales agreement with Cowen and Company, LLC, or Cowen, under which we may issue and sell shares of our common stock having aggregate sales proceeds of up to $50.0 million from time to time through Cowen, acting as agent, in a series of one or more ATM equity offerings, or the 2019 ATM Program. Cowen is not required to sell any specific amount but acts as our sales agent using commercially reasonable efforts consistent with its normal trading and sales practices. To date no shares of common stock were sold under the 2019 ATM program.

We may be subject to securities litigation, which is expensive and could divert management attention.

The market price of our common stock may be volatile, and in the past, companies that have experienced volatility in the market price of their stock have been subject to securities class action litigation. We may be the target of this type of litigation in the future. Securities litigation against us could result in substantial costs and divert our management’s attention from other business concerns, which could seriously harm our business.

If we fail to maintain an effective system of internal control over financial reporting in the future, we may not be able to accurately report our financial condition, results of operations or cash flows, which may adversely affect investor confidence in us and, as a result, the value of our common stock.

The Sarbanes-Oxley Act requires, among other things, that we maintain effective internal controls for financial reporting and disclosure controls and procedures. Commencing after the filing of our initial annual report on Form 10-K, we ~~will be~~have been required, under Section 404 of the Sarbanes-Oxley Act, to furnish a report by management on, among other things, the effectiveness of our internal control over financial reporting. This assessment ~~will need~~needs to include disclosure of any material weaknesses identified by our management in our internal control over financial reporting. A material weakness is a deficiency, or combination of deficiencies, in internal control over financial reporting that results in more than a reasonable possibility that a material misstatement of annual or interim financial statements will not be prevented or detected on a timely basis. Section 404 of the Sarbanes-Oxley Act also generally requires an attestation from our independent registered public accounting firm on the effectiveness of our internal control over financial reporting. ~~However, for as long as~~

While we ~~remain~~were an ~~emerging growth company as defined in the JOBS Act, we intend to take advantage of the exemption permitting us not to comply with the~~EGC, our independent registered public accounting firm was not required to attest to the effectiveness of our internal controls over financial reporting pursuant to Section 404. This exemption no longer applies to us as of December 31, 2021. Accordingly, beginning with this annual report on Form 10-K for the year ending December 31, 2021, we are required to include an attestation ~~requirement.~~from our independent registered public accounting firm on the effectiveness of our internal control over financial reporting. Our compliance with Section 404 ~~will require~~requires that we incur substantial expense and expend significant management efforts. We currently do not have an internal audit group, and we will need to hire additional accounting and financial staff with appropriate public company experience and technical accounting knowledge, and compile the system and process documentation necessary to perform the evaluation needed to comply with Section 404. We may not be able to complete our evaluation, testing and any required remediation in a timely fashion. During the evaluation and testing process, if we identify one or more material weaknesses in our internal control over financial reporting, we will be unable to assert that our internal control over financial reporting is effective. We cannot assure you that there will not be material weaknesses or significant deficiencies in our internal control over financial reporting in the future. Any failure to maintain internal control over financial reporting could severely inhibit our ability to accurately report our financial condition, results of operations or cash flows. If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a

material weakness or significant deficiency in our internal control over financial reporting once that firm begin its Section 404 reviews, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by the Nasdaq Global Select Market, the SEC or other regulatory authorities. Failure to remedy any material weakness in our internal control over financial reporting, or to implement or maintain other effective control systems required of public companies, could also restrict our future access to the capital markets.

Some provisions of our charter documents and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would benefit our stockholders and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our amended and restated certificate of incorporation and amended and restated bylaws, as well as provisions of Delaware law, could make it more difficult for a third party to acquire us or increase the cost of acquiring us, even if doing so would benefit our stockholders, or remove our current management. These provisions include a classified board of directors, a prohibition on actions by written consent of our stockholders and the ability of our board of directors to issue preferred stock without stockholder approval. These provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors, who are responsible for appointing the members of our management. Because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, or the DGCL, which may discourage, delay or prevent someone from acquiring us or merging with us whether or not it is desired by or beneficial to our stockholders. Under the DGCL, a corporation may not, in general, engage in a business combination with any holder of 15% or more of its capital stock unless the holder has held the stock for three years or, among other things, the board of directors has approved the transaction. Any provision of our amended and restated certificate of incorporation or amended and restated bylaws or Delaware law that has the effect of delaying or deterring a change of control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock and could also affect the price that some investors are willing to pay for our common stock.

Our headquarters is currently located in Waltham, Massachusetts, and consists of 12,207 square feet of leased office space under a lease that expires on ~~March 1, 2022.~~February 28, 2025. We also have 4,039 square feet of leased office space in New York, New York, under a lease that expires on ~~February 28, 2021.~~August 31, 2022. We believe that our existing facilities are sufficient for our needs for the foreseeable future. If we determine that additional or new facilities are needed in the future, we believe that sufficient options would be available to us on commercially reasonable terms.

Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

Our common stock began trading on the Nasdaq Global Select Market on March 2, 2016, under the symbol “SNDX.” Prior to that time, there was no public market for our common stock.

As of ~~March 4, 2020,~~February 24, 2022, we had approximately 5117 holders of record of our common stock. Certain shares are held in “street” name and accordingly, the number of beneficial owners of such shares is not known or included in the foregoing number. This number of holders of record also does not include stockholders whose shares may be held in trust by other entities.

We have never declared or paid any cash dividends on our common stock. We currently intend to retain future earnings to fund the development and growth of our business. We do not expect to pay any cash dividends in the foreseeable future. Any future determination to pay dividends will be made at the discretion of our board of directors and will depend on then-existing conditions, including our financial conditions, operating results, contractual restrictions, capital requirements, business prospects and other factors our board of directors may deem relevant.

The ~~following table sets forth~~performance graph shown below compares the annual change in cumulative total shareholder return on our ~~selected consolidated financial data. We derived~~common shares with the ~~consolidated statement of operations data for~~Nasdaq Composite Index and the ~~years~~Nasdaq Biotechnology Index from December 31, 2016, through the year ended December 31, ~~2019, 2018, and 2017 and the consolidated balance sheet data as~~2021. The graph assumes an investment of ~~December 31, 2019 and 2018, from our audited consolidated financial statements, included elsewhere in this Annual Report~~$100 on ~~Form 10-K. The following selected consolidated statements of operations data for the years ended~~ December 31, 2016 ~~and 2015~~in our common shares, the Nasdaq Composite Index and the ~~selected consolidated balance sheet data as~~Nasdaq Biotechnology Index and assumes that any dividends are reinvested. All index values are weighted by the capitalization of ~~December 31, 2017, 2016 and 2015~~the companies included in the index. The comparisons shown in the graph below are ~~derived from our audited consolidated financial statements not~~based upon historical data. The stock price performance included in this ~~Annual Report on Form 10-K. Our historical results are~~graph is not necessarily indicative of ~~results~~future stock price performance. The following performance graph and related information shall not be deemed to be ~~expected~~“soliciting material” or to be “filed” with the Securities and Exchange Commission, or SEC, for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, nor shall such information be incorporated by reference into any ~~period in~~future filing under the ~~future. The selected consolidated financial data presented below should be read in conjunction with “Management’s~~Exchange Act or Securities Act, except to the extent that we specifically incorporate it by reference into such filing.

Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our consolidated financial statements and the related notes thereto, included elsewhere in this Annual Report on Form 10-K. The selected consolidated financial data in this section is not intended to replace our consolidated financial statements and the related notes thereto.

~~Item 7. Management’s Discussion and Analysis of~~ ~~Financial Condition and Results of Operations~~

The following discussion and analysis should be read in conjunction with “Selected Financial Data” and our consolidated financial statements and related notes included elsewhere in this Annual Report on Form 10-K. This discussion and analysis and other parts of this Annual Report on Form 10-K contain forward-looking statements based upon current beliefs, plans and expectations that involve risks, uncertainties and assumptions, such as statements regarding our plans, objectives, expectations, intentions and projections. Our actual results and the timing of selected events could differ materially from those anticipated in these forward-looking statements as a result of several factors, including those set forth under “Risk Factors” and elsewhere in this Annual Report on Form 10-K. You should carefully read the “Risk Factors” section of this Annual Report on Form 10-K to gain an understanding of the important factors that could cause actual results to differ materially from our forward-looking statements. Please also see the section entitled “Special Note Regarding Forward-Looking Statements.”

For the discussion of the financial condition and results of operations for the year ended December 31, ~~2018~~2020 compared to the year ended December 31, ~~2017,~~2019, refer to "Management's Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations" and "—Liquidity and Capital Resources" included in the Annual Report on Form 10-K filed with the SEC on March ~~7, 2019, and as amended on March 18, 2019, and is incorporated by reference herein.~~12, 2021.

We are a ~~clinical stage~~clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Our two lead product candidates are SNDX-5613 and SNDX-6352, or axatilimab. We are developing ~~our lead product candidate, entinostat, a once-weekly, oral, small molecule, Class I HDAC inhibitor, in combination~~SNDX-5613, targeting the binding interaction of menin with ~~exemestane~~the mixed lineage leukemia 1 (MLL1) protein for the treatment of MLL-rearranged, or MLLr, acute leukemias and ~~several approved PD-1/PD-L1 antagonists. Our pipeline also includes SNDX-6352,~~nucleophosmin 1, or NPM1, mutant acute myeloid leukemia (AML), as well as axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1, or CSF-1 ~~receptor, as well as a portfolio~~receptor. We have deprioritized the development of ~~potent and selective inhibitors, including~~entinostat, our ~~lead candidate SNDX-5613, targeting~~once-weekly, oral, small molecule, Class I HDAC inhibitor, to focus resources on advancing the ~~binding interaction~~remainder of ~~menin with mixed lineage leukemia-rearranged, or MLLr, and acute myeloid leukemia, or AML, with a mutated nucleophosmin 1, or NPM1.~~our pipeline. We plan to continue to leverage the technical and business expertise of our management team and scientific collaborators to license, acquire and develop additional ~~cancer therapies~~therapeutics to expand our pipeline.

We have no products approved for commercial sale and have not generated any product revenues from product sales to date. We continue to incur significant research and development and other expenses related to our ongoing operations. ~~As a result,~~We have generated minimal license revenue, except for in 2021. Other than in 2021, we ~~are not and~~ have never been profitable and have incurred losses in each period since our inception in 2005. For the year ended December 31, 2021, we reported a net profit of $24.9 million, and for the years ended December 31, ~~2019, 2018,~~2020, and ~~2017,~~2019, we reported a net loss of $73.2 million and $56.0 million, ~~$74.0~~respectively. For the year ended December 31, 2021, we reported a net profit attributable to common stockholders of $24.9 million, and ~~$60.8~~for the years ended December 31, 2020, and 2019, we reported a net loss attributable to common stockholders of $77.1 million and $56.0 million, respectively. As of December 31, ~~2019,~~2021, we had an accumulated deficit of ~~$495.5~~$543.7 million, which included non-cash charges for stock-based compensation, preferred stock accretion and extinguishment charges. As of December 31, ~~2019,~~2021, we had cash, cash equivalents and short-term investments of ~~$59.8~~$439.9 million.

We continue to ~~anticipate that~~monitor our daily operations and program timelines during the ~~E2112 trial will reach 410 death events~~ongoing COVID-19 pandemic. The health and safety of our employees as well as the patients and people participating in and operating our clinical trials are of paramount importance. COVID-19, including its variants did not impact our financial guidance or changed our timelines for clinical data in 2021.

We continue to address and mitigate the impact of the ongoing COVID-19 pandemic on our employees and our business. While we are not experiencing financial impacts at this time, given the changes in global macroeconomic conditions, the overall disruption of global healthcare systems, potential limitations to the efficacy of vaccines for COVID-19, the evolution of multiple variants of the virus and the other risks and uncertainties associated with the pandemic, our business, financial condition, results of operations and growth prospects could be materially adversely affected. We continue to closely monitor the COVID-19 situation as we evolve our business continuity plans and response strategy. In March 2020, our workforce transitioned to working remotely. We have gradually reopened our offices to allow employees to return to the office, while also supporting remote working options.

We are working closely our third-party manufacturers, distributors and other partners to manage our supply chain activities and mitigate potential disruptions to our product supplies as a result of the COVID-19 pandemic. We currently expect to have adequate supplies of SNDX-5613 and axatilimab. If the COVID-19 pandemic continues to persist and if it impacts essential distribution systems such as FedEx and postal delivery or if it results in facility closures for cleaning and/or insufficient staff, we could experience disruptions to our supply chain and operations, and associated delays in the ~~second quarter~~manufacturing and supply of ~~2020, which will trigger~~our products, and to our clinical trial operations.

With respect to clinical development, we continue to take measures to implement remote and virtual approaches, including remote patient monitoring where possible, to maintain patient safety and trial continuity and to preserve study integrity. We have, and may continue to experience, disruptions and/or delays in our ability to initiate trial sites and enroll and assess patients. As the ~~final overall survival (OS) analysis. E2112 is~~COVID-19 pandemic continues, we anticipate an ongoing, though minimal, impact on our NCI-sponsored, ECOG-ACRIN-led Phase 3 registration trial of entinostat, a Class I selective HDAC inhibitor, plus exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer. A positive OS assessment would allow usability to ~~file for full regulatory approval~~maintain patient enrollment in the ~~U.S.~~

~~The E2112~~AUGMENT-101 and AGAVE trials. We could also see an impact on the ability to supply study drug, report trial ~~design was informed by~~results, or interact with regulators, ethics committees or other important agencies due to limitations in regulatory authority employee resources or otherwise. In addition, we rely on contract research organizations or other third parties to assist us with clinical trials, and we cannot guarantee that they will continue to perform their contractual duties in a timely and satisfactory manner as a result of the ~~Phase 2b ENCORE 301 trial,~~COVID-19 pandemic. If the COVID-19 pandemic continues, we could experience significant disruptions to our clinical development timelines, which would adversely affect our business, financial condition, results of which led to entinostat's Breakthrough Therapy designation in HR+ breast cancer, in which patients receiving the entinostat/exemestane combination demonstrated a clinically meaningful OS benefit over treatment with exemestane alone. In preparation for the potential launch of entinostat in the U.S. in 2021, we are actively engaged in the expansion of our commercialoperations and ~~medical affairs functions.~~

~~We recently announced two preclinical publications in~~ ~~Cancer Cell~~ ~~and~~ ~~Science~~ magazine supporting the potential for inhibitors of the MLL1-Menin interaction to serve as a treatment of acute leukemia patients with mixed lineage leukemia rearranged (MLL-r) or nucleophosmin (NPM1) mutations. These findings provide additional support for our ongoing AUGMENT-101 trial, a Phase 1/2 open-label trial of SNDX-5613, our potent, highly selective oral Menin inhibitor, in adults with relapsed/refractory acute leukemias, including MLL-r acute lymphoblastic leukemia (ALL), MLL-r acute myeloid leukemia (AML) and NPM1 mutant AML.

Enrollment is ongoing in the Phase 1 dose escalation portion of AUGMENT-101. Following completion of the Phase 1 portion of the trial, which will establish a recommended Phase 2 dose, the Phase 2 portion will evaluate efficacy, as defined by Complete Response rate (per International Working Group response criteria), across three expansion cohorts: MLL-r ALL, MLL-r AML, and NPM1 mutant AML.

As previously communicated, we anticipate presenting initial clinical data from AUGMENT-101 at a medical conference in the fourth quarter of 2020. Due to the open-label nature of the trial, meaningful interim data, including pharmacokinetic, pharmacodynamic and efficacy data, may be available earlier in the year.

Enrollment of patients to the Phase 2 expansion cohort of axatilamab, the Company’s anti-CSF-1R monoclonal antibody, for the treatment of chronic graft versus host disease (cGVHD) is underway. The decision to move to the Phase 2 expansion was driven by ~~recently reported~~ encouraging proof of concept results from the Phase 1 portion of the trial, in which responses were observed in all evaluable patients as of the data cutoff date, with no dose limiting toxicities reported.

The Phase 2 expansion cohort is expected to enroll up to 22 patients to further characterize the safety and efficacy of 1.0 mg/kg of axatilamab administered every two weeks. We expect to present additional results from the Phase 1/2 trial in the fourth quarter of 2020.growth prospects.

To date, we have not generated any product revenues. Our ability to generate revenue and become profitable depends upon our ability to obtain marketing approval of and successfully commercialize our product candidates. Our revenues for the ~~years~~year ended December 31, ~~2019~~2021 and ~~2018~~2020 have been solely derived from our license, ~~agreement~~development and commercialization agreements with Kyowa Kirin Co., Ltd., or KKC, ~~under which~~and with Incyte Pharmaceuticals, Inc, or Incyte.

We granted Incyte an exclusive license to develop and commercialize axatilimab in the United States and the rest of the world. In 2021, we received $152.0 million total consideration from the Incyte Agreements. We allocated $126.6 million of the total consideration received to the license, and such amount was recognized as license revenue upon transfer of license to Incyte in December 2021 .

We granted KKC an exclusive license to develop and commercialize entinostat in Japan and Korea, or the KKC license agreement. In 2015, we received a $25.0 million upfront payment from KKC, inclusive of an equity investment. We allocated $17.3 million of the upfront payment to the license fee, and such fee is being recognized as revenue ratably over our expected performance period (currently expected to be through 2029). The balance of the upfront payment of $7.7 million was allocated to ~~KKC~~KKC’s purchase of shares of our convertible preferred stock.

In ~~October 2017,~~September 2021, KKC ~~enrolled~~informed us that they discontinued the ~~first Japanese patient into~~entinostat program and cancelled the license to develop and commercialize entinostat. As a local pivotal study of entinostat for the treatment of hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. In accordance with the terms of the KKC License Agreement,result, we recognized $12.4 million in ~~December 2017 we received a $5.0 million milestone payment from KKC for achievement of the development milestone.~~revenue which was previously deferred.

Since our inception, we have primarily focused on our clinical development programs. Research and development expenses consist primarily of costs incurred for the development of our product candidates and include:

Internal and external research and development costs are expensed as they are incurred. Cost-sharing amounts received by us are recorded as reductions to research and development expense. Costs for certain development activities, such as clinical trials, are recognized based on an evaluation of the progress to completion of specific tasks using data such as patient enrollment, clinical site activations or other information provided to us by our vendors.

Research and development activities are central to our business model. Drug candidates in late stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of late-stage clinical trials. We plan to ~~increase~~continue to spend a significant amount of our resources on research and development ~~expenses~~activities for the foreseeable future as we continue to advance the development of our product candidates. The amount of research and development expenses allocated to external spending will continue to grow, while we expect our internal spending to grow at a slower and more controlled pace. ~~From inception through December 31, 2019, we have incurred $254.7 million in research and development expenses.~~

It is difficult to determine, with certainty, the duration and completion costs of our current or future preclinical programs, clinical studies and clinical trials of our product candidates. The duration, costs and timing of clinical studies and clinical trials of our product candidates will depend on a variety of factors that include, but are not limited to, the following:

In addition, the probability of success for each drug product candidate will depend on numerous factors, including competition, manufacturing capability and commercial viability. The successful development of our product candidates is highly uncertain. At this time, we cannot reasonably estimate the nature, timing or costs of the efforts that will be necessary to complete the remainder of the development of our product candidates for the period, if any, in which material net cash inflows from these potential product candidates may commence. Clinical development timelines, the probability of success and development costs can differ materially from expectations.

General and administrative expenses consist primarily of employee-related expenses, including salaries, benefits, non-cash stock-based compensation and travel expenses, for our employees in executive, finance, business

development and support functions. Other general and administrative expenses include facility-related costs not otherwise allocated to research and development expenses and accounting, tax, legal and consulting services. We anticipate that our general and administrative expenses will increase in the future as we increase our headcount to support our continued research and development and potential commercialization of our product candidates. Additionally, if and when we believe a regulatory approval of the first product candidate appears likely, we anticipate an increase in payroll and related expenses as a result of our preparation for commercial operations, especially as it relates to the sales and marketing of our product candidates.

Interest expense consists primarily of interest expense on our term loan, operational and capital leases.

Interest income consists of ~~interest~~ income earned on our cash, cash equivalents and short-term investment balances. ~~Interest expense consists primarily~~

Other (expense) income includes income recorded for the change in fair value of ~~interest expense~~derivative liability established based on ~~operating and capital leases.~~the terms under of the Letter Agreement with connection with the share purchase agreement.

From time to time, new accounting pronouncements are issued by the Financial Accounting Standards Board, or FASB, or other standard setting bodies and adopted by us as of the specified effective date. Unless otherwise discussed in Note 3 to our audited consolidated financial statements included in this Annual Report on Form 10-K, we believe that the impact of recently issued standards that are not yet effective will not have a material impact on our financial position or results of operations upon adoption.

Our management’s discussion and analysis of financial condition and results of operations are based on our financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States of America. The preparation of these financial statements requires us to make estimates and judgments that affect the reported amounts of assets, ~~and~~ liabilities ~~revenues~~ and expenses and ~~other~~the disclosure of contingent assets and liabilities in our financial ~~information.~~statements. We base our estimates on historical experience, known trends and events and various other factors that are believed to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. In making estimates and judgments, management employs critical accounting policies.

~~While our significant~~ Our critical accounting policies are ~~more fully~~ described in greater detail in Note 3 to our audited consolidated financial statements included ~~elsewhere~~ in this Annual Report on Form ~~10-K,~~10-K.

We have listed below our critical accounting estimates that we believe ~~that~~to have the ~~following accounting policies are critical to the process of making significant~~greatest potential impact on our consolidated financial statements. Historically, our assumptions, judgments and estimates ~~in the preparation of~~relative to our ~~consolidated financial statements and understanding and evaluating our reported financial~~critical accounting estimates have not differed materially from actual results.

~~On January 1, 2018, we adopted Financial Accounting Standards Board Accounting Standards Codification Topic 606,~~ We enter into license agreements for the development and commercialization of our product candidates. License agreements may include non-refundable upfront payments, contingent payments based on the occurrence of specified events under our license arrangements, partial or complete reimbursement of research and development expenses, license fees and royalties on sales of entinostat if they are successfully approved and commercialized. Our performance obligations under the license agreements may include the transfer of intellectual property rights in the form of licenses, obligations to provide research and development services and related materials and participation on certain development and/or commercialization committees.

Revenue ~~from Contracts with Customers,~~is recognized when, or ~~ASC 606 using the modified retrospective method applied to those contracts~~as, performance obligations are satisfied, which ~~were not completed as of January 1, 2018. The provisions of ASC 606 supersedes the revenue recognition requirements in Topic 605 “Revenue Recognition,” and requires entities to recognize revenue~~occurs when control of the promised ~~goods~~products or services is transferred to ~~customers~~customers. Revenue is measured as the amount of consideration the Company expects to receive in exchange for transferring products or services to a customer (“transaction price”). To the extent that the transaction price includes variable consideration, we estimate the amount of variable consideration that should be included in the transaction price utilizing the most likely amount method. Variable consideration is included in the transaction price if, in our judgment, it is probable that a significant future reversal of cumulative revenue under the contract will not occur. Estimates of variable consideration and determination of whether to include estimated amounts in the transaction price are based largely on an assessment of our anticipated performance and all information (historical, current and forecasted) that is reasonably available.

We assessed the promises to determine if they are distinct performance obligations. Once the performance obligations are determined, the transaction price is allocated based on a relative standalone selling price basis. Milestone payments and royalties are typically considered variable consideration at anthe outset of the contract and are recognized in the transaction price either upon occurrence or when the constraint of a probable reversal is no longer applicable.

Licenses of intellectual property: If the license to our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize revenues from non-refundable, up-front fees allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, we utilize judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from non-refundable, up-front fees. Arrangements containing licenses to our intellectual property typically provide for a know-how transfer period. These arrangements may or may not also include rights to future updates of that intellectual property and related know-how. Revenues from non-refundable, up-front fees allocated to the licenses are recognized as the license is transferred to the customer and the customer is able to use and benefit from the license. This generally takes place over the related know-how transfer period, or if applicable, over the term of transfer of future updates to the intellectual property.

Development Milestone Payments: At the inception of each arrangement that includes development milestone payments, the Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that ~~reflects~~a significant revenue reversal would not occur, the ~~consideration~~associated milestone value is included in the transaction price. Milestone payments that are not within our control or the licensee, such as regulatory approvals, are generally not considered probable of being achieved until those approvals are received. The transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis, for which we recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, we re-evaluate the probability of achievement of such development milestones and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect license fees and earnings in the period of adjustment. For development milestones related to the KKC Agreement, we do not take a substantive role or control the research, development or commercialization of any products generated by KKC. Therefore, we are not able to reasonably estimate when, if at all, any development milestone payments may be payable to us. As such, the development milestone payments associated with the KKC Agreement involve a substantial degree of uncertainty and risk that they may never be received.

Commercial Milestone Payments and Royalties: For arrangements that include sales-based royalties, including milestone payments based on the level of commercial sales, and the license is deemed to be the predominant item to which the ~~entity expects~~royalties or commercial milestones relate, we will recognize revenue at the later of when the related sales occur or when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date no commercial milestone payments or royalties have been achieved.

When no performance obligations are required of us, or following the completion of the performance obligation period, such amounts are recognized as revenue upon transfer of control of the goods or services to the customer. Generally, all amounts received or due other than sales-based milestones and royalties are classified as license fees. Sales-based milestones and royalties will be recognized as royalty revenue at the later of when the related sales occur or when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).

Deferred revenue arises from amounts received in advance of the culmination of the earnings process and is recognized as revenue in future periods as performance obligations are satisfied. Deferred revenue expected to be ~~entitled to in exchange for those~~recognized within the next twelve months is classified as a current liability. Upfront payment contract liabilities resulting from our license agreements do not represent a financing component as the payment is not financing the transfer of goods or ~~services. The reported results for 2019~~services, and ~~2018 reflect~~ the ~~application of ASC 606 guidance, while~~technology underlying the reported results for 2017 were prepared under the guidance of ASC 605, Revenue Recognition (ASC 605). The adoption of ASC 606 requires us to provide expanded disclosures related to our contracts with customers but did not have a material impact on the Company’s consolidated financial position, results of operations, equity or cash flows as of the adoption date. See note 4 to our consolidated financial statements included elsewhere herein for additional information on the impact of ASC 606 on our consolidated financial statements.licenses granted reflects research and development expenses already incurred by us.

For license fee revenues, we recorded revenues of $126.6 million relating to the Incyte Agreement and $13.3 million relating to the KKC Agreement.

We applied ~~and may continue~~significant judgment to ~~apply~~our Incyte Agreement. We evaluated whether our contractual obligations represented distinct performance obligations. Such evaluation required judgment since it was made from the customer’s perspective. We determined that the transfer of the license to Incyte was a distinct performance obligation, separate from the ongoing collaboration activities. As such, we estimated the standalone selling price to be $126.6 million which we recognized as $126.6 million of license revenue for the year ended December 31, 2021.

We applied significant judgment to our KKC Agreement. We evaluated whether our contractual obligations represented distinct performance obligations. Such evaluation

required judgment since it was made from the customer’s perspective. We determined that our performance obligations under the collaboration at contract inception were not distinct and represented a single performance obligation. ~~The~~In September 2021, KKC agreement also includes variable consideration. We assess variable consideration at each reporting period as to whether it is not subject to significant future reversal and, therefore, should be included in the transaction price. For development milestones related to the KKC Agreement, the Company does not take a substantive role or control the research, development or commercialization of any products generated by KKC. Therefore, the Company is not able to reasonably estimate when, if at all, any development milestone payments may be payable to the Company. As such, the development milestone payments associated with the KKC Agreement involve a substantial degree of uncertainty and riskinformed us, that they ~~may never be received. Sales-based milestones~~have discontinued the entinostat program and ~~royalties will be~~have cancelled the license to develop and commercialize entinostat. As a result, we recognized ~~as royalty~~$12.4 million in revenue ~~in the period the related sale occurred.~~which was previously deferred.

As part of the process of preparing our consolidated financial statements, we are required to estimate our accrued research and development expenses. This process involves reviewing contracts and vendor agreements, communicating with our applicable personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual cost. We make estimates of our accrued expenses as of each balance sheet date in our consolidated financial statements based on facts and circumstances known to us at that time. Examples of estimated accrued research and development expenses include fees paid to contract research organizations, or CROs, and investigative sites in connection with clinical studies and to vendors related to product manufacturing and development of clinical supplies.

We base our expenses related to clinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple research institutions and CROs that conduct and manage clinical studies on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows and expense recognition. Payments under some of these contracts depend on factors out of our control, such as the successful enrollment of patients and the completion of clinical trial milestones. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual accordingly. Although we do not expect our estimates to be materially different from amounts actually incurred, if our estimates of the status and timing of services performed differ from the actual status and timing of services performed, we may report amounts that are too high or too low in any particular period. To date, we have not experienced any significant adjustments to our estimates.

The following table summarizes our results of operations for the years ended December 31, ~~2019, 2018~~2021, 2020 and ~~2017:~~

Years Ended
December 31,

2019 - 2018 Increase
(Decrease)

2018 - 2017 Increase
(Decrease)

(in thousands)

2019

2018

2017

$

%

$

%

Revenues:

License fees

$
1,517

$
1,517

$
2,108

$
-

0
%

$
(591
)

(28
)%
Total revenues

1,517

1,517

2,108

-

0
%

(591
)

(28
)%
Operating expenses:

Research and development

42,994

60,106

48,201

(17,112
)

(28
)%

11,905

25
%
General and administrative

16,062

17,287

15,861

(1,225
)

(7
)%

1,426

9
%
Total operating expenses

59,056

77,393

64,062

(18,337
)

(24
)%

13,331

21
%
Loss from operations

(57,539
)

(75,876
)

(61,954
)

(18,337
)

(24
)%

13,922

22
%
Other (expense) income:

Interest (expense) income, net

1,571

1,942

1,421

(371
)

(19
)%

521

37
%
Other (expense) income, net

(79
)

(27
)

(269
)

(52
)

(193
)%

242

90
%
Total other income

1,492

1,915

1,152

(423
)

(22
)%

763

66
%
Net loss

$
(56,047
)

$
(73,961
)

$
(60,802
)

$
(17,914
)

(24
)%

$
13,159

22
%

For a comparison of our results of operations for the fiscal years ended December 31, ~~2018~~2021 and December 31, ~~2017,~~2020, see “Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations” of our Annual Report on Form 10-K for the fiscal year ended December 31, ~~2018,~~2020, filed with the SEC on March ~~7, 2019.~~12, 2021.

	Years Ended December 31,									2021 - 2020 Increase (Decrease)						2020 - 2019 Increase (Decrease)
(in thousands)	2021			2020			2019			$			%			$			%
Revenues:
License fees	$	139,709		$	1,517		$	1,517		$	138,192			9110	%	$	—			0	%
Total revenues		139,709			1,517			1,517			138,192			9110	%		—			0	%
Operating expenses:
Research and development		88,248			50,435			42,994			37,813			75	%		7,441			17	%
General and administrative		25,241			22,505			16,062			2,736			12	%		6,443			40	%
Total operating expenses		113,489			72,940			59,056			40,549			56	%		13,884			24	%
Income (Loss) from operations		26,220			(71,423	)		(57,539	)		(97,643	)		(137	)%		13,884			24	%
Other (expense) income:
Interest income		403			841			1,571			(438	)		(52	)%		(730	)		(46	)%
Interest expense		(1,899	)		(2,357	)		—			458			(19	)%		(2,357	)		100	%
Other (expense) income		202			(219	)		(79	)		421			192	%		(140	)		(177	)%
Total other (expense) income		(1,294	)		(1,735	)		1,492			441			(25	)%		(3,227	)		(216	)%
Net income (loss)	$	24,926		$	(73,158	)	$	(56,047	)	$	(98,084	)		(134	)%	$	17,111			31	%

For the years ended December 31, ~~2019~~2021 and ~~2018,~~2020, we recognized license fees of $139.7 million and $1.5 million, derived from the Incyte and KKC license ~~agreement.~~agreements, respectively. For additional information on our agreement with Incyte and KKC, please refer to Note 4 Revenue, to these consolidated financial statements.

For the year ended December 31, ~~2019,~~2021, our total research and development expenses ~~decreased $17.1~~increased by $37.8 million, or ~~28%~~75%, to ~~$43.0~~$88.2 million from ~~$60.1~~$50.4 million for the prior year due to ~~decreases~~increases in clinical trial activities expenses of ~~$11.1~~$31.3 million, professional expenses of $1.2 million, and employee related expenses of ~~$1.3~~$5.3 million. The increase in clinical activities expenses was due to increased study activities related to SNDX-5613 of $7.7 million, ~~professional expenses~~increased CMC batch production costs for the Menin program of ~~$4.4~~$9.5 million, increased study activity related to axatilimab of $9.3 million, increased development activities for the Menin program of $4.1 million and ~~facility costs~~for axatilimab of ~~$0.3~~$1.1 million, and an increase in license fees of $2.3 million, which were offset by reduction in the entinostat program of $2.7 million. The ~~decrease~~increase in ~~clinical trial activities was~~employee related expense is primarily due to ~~decreases in spending related to our ENCORE programs~~salary and benefits of ~~$5.0 million, costs related to SNDX-6352 trials of $1.6 million, reduced clinical pharmacology programs of $0.4 million, reduced pharmacovigilance of $0.6~~$3.3 million and ~~research studies~~increase in stock-based compensation of ~~$1.3~~$2.0 million and chemical, manufacturing and control (CMC) activities related to SNDX-6352 of $9.4 million. This was partially offset by a $4.0 million expense recognized in 2019 upon achievement of certain milestones in connection with the menin program, increased clinical spending on menin of $2.9 million and increased spending on our E2112 program of $0.4 million. The decrease in employee compensation costs was primarily due to decreased headcount and travel, offset by increased stock option expenses. Professional fees decreased due to reduced NDA preparation expenses of $3.8 million and decreased contracted research of $0.6 million.increase in headcount.

We expect research and development expenses to fluctuate from quarter to quarter depending on the timing of clinical trial activities, clinical manufacturing and other development activities.

	Years Ended December 31,				Increase (Decrease)						Years Ended December 31,				Increase (Decrease)
(in thousands)	2019		2018		$			%			2021		2020		$		%
External research and development expenses	$	28,990	$	44,545	$	(15,555	)		(35	)%	$	68,468	$	36,303	$	32,165		89	%
Internal research and development expenses		14,004		15,561		(1,557	)		(10	)%		19,780		14,132		5,648		40	%
Total research and development expenses	$	42,994	$	60,106	$	(17,112	)		(28	)%	$	88,248	$	50,435	$	37,813		75	%

For the year ended December 31, ~~2019,~~2021, our total general and administrative expenses ~~decreased $1.2~~increased by $2.7 million, or 7%12%, to ~~$16.1~~$25.2 million, from ~~$17.3~~$22.5 million for the prior year. The ~~decrease~~increase in general and administrative expenses was primarily due to ~~decreased professional fees~~increased employee related expenses of $2.7 million. The increase in employee related expenses is due to an increase in stock compensation expense of $2.3 million and $0.4 million for salary and benefits due to increased headcount. The increased stock compensation expense includes $0.7 million ~~reduced legal spending of $0.4 million and decreased employee compensation of $0.1 million. The decrease in employee compensation was due to decreased non-cash charges~~ related to ~~stock-based compensation~~the modification of ~~$0.3 million, partially offset by increased salaries and bonuses~~option agreements in connection with the retirement of ~~$0.2 million.~~ a certain employees.

For the year ended December 31, ~~2019,~~2021, interest income, ~~(expense), net,~~ decreased ~~$0.5~~by $0.4 million from the prior year. This decrease was primarily due to a lower average cash and investment ~~balance.~~balance and lower interest rates on our investments.

~~Change in Fair Value~~Interest expense consists primarily of ~~Common Stock Warrant Liability~~interest expense on our term loan, operational and capital leases. The decrease is primarily due to our amended term loan. For additional information on the loan amendment agreement, please refer to Note 14, Loan Payable, to these financial statements.

Other (expense) income increased by $0.4 million from the prior year. This increase was primarily due to the change in fair value of ~~common stock warrant~~the derivative liability for the year ended December 31, 2017 decreased $1.7 million. There was no common stock warrant liability outstanding during the year ended December 31, 2017. At each period end until the closing of our IPO, the fair valuerecorded as of the outstanding common stock warrant liability was re-measured; and the change in the fair value was recorded in other expense in the consolidated statement of comprehensive loss. Upon the closing of our IPO, the antidilution provision of the warrant expired and the warrant liability was reclassified to additional paid-in capital. Just prior to the reclassification, the warrant was re-measured using current assumptions on that date, and the change in fair value was recorded in other expense.Incyte Agreement.

As of December 31, ~~2019,~~2021, we had cash, cash equivalents and short-term investments totaling ~~$59.8~~$439.9 million. Since our inception, our operations have been primarily financed by net proceeds from our IPO, our follow-on stock ~~offering,~~offerings, our term loan, sale of convertible preferred stock and convertible debt securities and proceeds from our license agreements. We believe that our cash, cash equivalents and short-term investments as of December 31, ~~2019, in combination with the net proceeds of our January 2020 equity financing and February 2020 debt financing, described below,~~2021, will fund our projected operating expenses and capital expenditure requirements for at least the next 12 months. In addition to our existing cash, cash equivalents and short-term investments, we are eligible to receive research and development funding and to earn milestone and other contingent payments for the achievement of defined collaboration objectives and certain development, regulatory and commercial milestones and royalty payments under our collaboration agreements. Our ability to earn these milestone and contingent payments and the timing of achieving these milestones is primarily dependent upon the outcome of our collaborators’ research and development activities and is uncertain at this time.

In January 2020, we sold 3,036,719 shares of our common stock at a price per share of $8.00 and pre-funded warrants to purchase 1,338,287 shares of our common stock for gross proceeds of approximately $35.0 million. Upon the completion of the 2020 offering, we had 5,838,287 pre-funded warrant shares outstanding. The pre-funded warrants are exercisable into shares of common stock for $0.0001 per share. The shares of common stock into which the warrants may be exercised are considered outstanding for the purposes of computing earnings per share.

In March 2019, we issued to certain investors an aggregate of 2,095,039 shares of our common stock and 2,500,000 pre-funded warrants to purchase shares of our common stock, at a price of $6.00 per share of common stock and $5.9999 for each pre-funded warrant. We sold the shares of common stock and prefunded warrants together with two series of warrants, Series 1 warrants and Series 2 warrants, to purchase an aggregate of 4,595,039 shares of our common stock. The pre-funded warrants enable the holder to make a cash investment in our common stock without increasing their beneficial ownership in our common stock because the shares of common stock underlying the pre-funded warrant are not issued or issuable until the warrant is actually exercised or becomes exercisable without exceeding the ownership limitations set forth in the pre-funded warrant. Each Series 1 warrant has an initial exercise price of $12.00 per share of common stock and each Series 2 warrant has an initial exercise price of $18.00 per share of common stock, in each case subject to certain adjustments. The Series 1 warrants and Series 2 warrants contain a one-time exercise price adjustment. If we sell shares or share equivalents at less than $12.00 per share at a time when our Series 1 warrants and Series 2 warrants are outstanding, then an exercise price for those warrants would be adjusted downward, which will result in us receiving less proceeds than we otherwise would and could result in further dilution to our stockholders if such warrants were then exercised. As a result of the 2020 offering, the initial exercise price of the Series 1 warrants was reduced to $10.00 per share and the initial exercise price of the Series 2 warrants was reduced to $13.00 per share.

On ~~February 7, 2020,~~December 22, 2021, we entered into aAmendment No. 1 to our existing loan and security agreement, or the ~~Loan Agreement,~~First Amendment with the several banks and financial institutions or entities from time-to-time party thereto, or the Lender, and Hercules Capital, Inc., in its capacity as administrative agent for itself and the Lender, or ~~Hercules, which provides for aggregate maximum borrowings~~the Agent. The First Amendment amended that certain loan and security Agreement dated as of February 7, 2020, (as amended by the First Amendment, the Loan Agreement), among the Borrower, the Lender and the Agent.

The First Amendment increases the amount that we may borrow by $50.0 million, from up to $30.0 million ~~consisting of (i) a term loan of~~to up to ~~$20.0~~$80.0 million, in multiple tranches. The First Amendment increases the second tranche, or Tranche 2, from $10.0 million to $30.0 million with $15.0 million being available at our option through April 30, 2022 and another $15.0 million being available at our option through November 30, 2022, which ~~was funded on February 7, 2020, and (ii)~~availability period will be extended to April 30, 2023 if the first $15.0 million is drawn prior to April 30, 2022. The First Amendment also provides for a third tranche of $30.0 million, or Tranche 3, which is available, subject to ~~Hercules’~~the Agent’s investment committee approval, through an ~~additional term loan of up~~interest-only period. Our only borrowings to ~~$10.0 million, available for borrowing from February 7, 2020 to December 15, 2020, which we refer to as the Tranche 2 Advance. Borrowings~~date under the Loan Agreement ~~bear~~are the first tranche of $20.0 million, which we drew upon the closing of the Loan Agreement on February 7, 2020.

~~Borrowings under~~rate to the ~~Loan Agreement are repayable in monthly interest-only payments through October 1, 2021,~~greater of (y) 9.25% or ~~April 1, 2022 if~~(z) 6.00% plus the ~~Phase 3 clinical trial~~Wall Street Journal prime rate, (iv) applies a facility charge equal to 0.50% of ~~entinostat (E2112) in patients with advanced HR+, HER2- breast cancer has achieved the primary efficacy endpoint sufficient~~any future draws, (v) applies a 4.99% end of term charge to file an NDA as the next step in clinical development, or the Performance Milestone. After the interest-only payment period, borrowings under the Loan Agreement are repayable in equal monthly payments of principal and accrued interest untilany future draws payable on the maturity date, (vi) permits the entry into our collaboration and license agreement as previously disclosed with Incyte Corporation, and (vii) adds a minimum cash covenant applicable on the occurrence of certain events. The First Amendment also resets the prepayment premium requirements as of the ~~loan, which is either (i) September 1, 2023, or (ii) March 1, 2024 upon achievement~~date of the ~~Performance Milestone, or the Maturity Date. At our option, we may prepay all, but not less than all, of the outstanding borrowings,~~First Amendment so that any prepayments are subject to a prepayment premium equal to (i) 2.0% of the principal amount outstanding if the prepayment occurs during the first year following the ~~applicable loan being funded,~~Loan Amendment, (ii) 1.5% of the principal amount outstanding if the prepayment occurs during the second year following the ~~applicable loan being funded,~~Loan Amendment, and (iii) 1.0% of the principal amount outstanding at any time thereafter but prior to the Maturity Date. In addition, we paid a $100,000 facility charge upon closing and will pay a $50,000 facility charge in connection with the Tranche 2 Advance. The Loan Agreement also provides for a final payment, payable upon maturity ~~or the repayment in full of all obligations under the agreement, of up to $998,000.~~date.

Borrowings under the Loan Agreement are collateralized by substantially all of our and our subsidiaries personal property and other assets, other than our intellectual property. The Loan Agreement includes a minimum cash covenant of $12.5 million that applies commencing on September 30, 2020, subject to reduction upon satisfaction of certain conditions as set forth in the Loan Agreement. In addition, the Loan Agreement includes customary affirmative and restrictive covenants and representations and warranties, including a covenant against the occurrence of a “change in control,” financial reporting obligations, and certain limitations on indebtedness, liens (including a negative pledge on intellectual property and other assets), investments, distributions (including dividends), collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, and deposit accounts. The Loan Agreement also includes customary events of default, including payment defaults, breaches of covenants following any applicable cure period, the occurrence of certain events that could reasonably be expected to have a “material adverse effect” as set forth in the Loan Agreement, cross acceleration to third-party indebtedness and certain events relating to bankruptcy or insolvency. Upon the occurrence of an event of default, a default interest rate of an additional 5.0% may be applied to the outstanding principal balance, and Hercules may

declare all outstanding obligations immediately due and payable and take such other actions as set forth in the Loan Agreement.

In April 2017, we entered into a sales agreement with Cowen, under which we may issue and sell shares of our common stock having aggregate sales proceeds of up to $50.0 million from time to time, or the 2017 ATM Program. Shares sold pursuant to the sales agreement were sold pursuant to a shelf registration statement on Form S-3 (Registration No. 333-217172), which was declared effective on April 20, 2017. The proceeds from the offerings, if any, were used for general corporate purposes, including expenditures for research and development of our drug products. In 2019, prior to the effectiveness of the 2019 ATM Program, we sold 140,819 shares of common stock, with net proceeds of $0.9 million.

In August 2019, we entered into a new sales agreement with Cowen under which we may issue and sell shares of our common stock having aggregate sales proceeds of up to $50.0 million from time to time pursuant to the ATM program, or the 2019 ATM Program. Cowen is not required to sell any specific amount but acts as our sales agent using commercially reasonable efforts consistent with their normal trading and sales practices. This agreement replaced the sales agreement signed in April 2017. Shares sold pursuant to the sales agreement will be sold pursuant to a shelf registration statement on Form S-3 (Registration No. 333-233564), which was declared effective on September 10, 2019. Our common stock will be sold at prevailing market prices at the time of the sale; and as a result, prices may vary. We will pay Cowen up to 3% of the gross proceeds from any common stock sold through the sales agreement. The proceeds from the offerings, if any, will be used to fund the research and development of our product candidates, acquire or invest in businesses, products or technologies that are complementary to our own, although we have no current plans, commitments or agreements with respect to any acquisitions as of the date of this prospectus, and for working capital and general corporate purposes. As of December 31, 2019, $50.0 million of common stock remained available for sale under the 2019 ATM Program. No shares of common stock have been sold under the 2019 ATM Program from December 31, 2019 through the date of this filing.

We believe that our available cash, cash equivalents and short-term investments and continued access to our term loan are sufficient to fund existing and planned cash requirements. Our primary uses of capital are, and we expect will continue to be, compensation and related expenses, third-party clinical research and development services, clinical costs, legal and other regulatory expenses and general overhead costs. We have based our estimates on assumptions that may prove to be incorrect, and we could use our capital resources sooner than we currently expect.

Additionally, the process of testing drug candidates in clinical trials is costly, and the timing of progress in these trials is uncertain. We cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidates or whether, or when, we may achieve profitability. Our future capital requirements will depend on many factors, including:

We have no products approved for commercial sale and have not generated any product revenues from product sales to date. Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings and additional funding from license and collaboration arrangements. Except for any obligations of our collaborators to reimburse us for research and development expenses or to make milestone or royalty payments under our agreements with them, we will not have any committed external source of liquidity.

Our material cash requirements include the following contractual obligations as of December 31, 2021 and the effects that such obligations are expected to have on our liquidity and cash flows in future periods. For additional information, see our consolidated financial statements.

We have incurred losses and cumulative negative cash flows from operations since our ~~inception.~~inception, excluding year ending December 31, 2021. As of December 31, ~~2019,~~2021, we had an accumulated deficit of ~~$495.5~~$543.7 million. We anticipate that we will continue to incur significant losses for at least the next several years. We expect that our research and development and general and administrative expenses will continue to increase. As a result, we will need additional capital to fund our operations, which we may raise through a combination of the sale of equity, debt financings, or other sources, including potential collaborations. To the extent that we raise additional capital through the future sale of equity or debt, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing common stockholders. If we raise additional funds through collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or drug candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market drug candidates that we would otherwise prefer to develop and market ourselves.

In March 2021, we entered into a sales agreement with Cowen and Company, LLC, or Cowen, under which we may issue and sell shares of our common stock having aggregate sales proceeds of up to $75.0 million from time to time through Cowen, acting as agent, in a series of one or more ATM equity offerings, or the 2021 ATM Program. Cowen is not required to sell any specific amount but acts as our sales agent using commercially reasonable efforts consistent with its normal trading and sales practices. Shares sold pursuant to the sales agreement will be sold pursuant to a shelf registration statement on Form S-3 ASR (Registration No. 333-254661), which became automatically effective upon filing on March 24, 2021. Our common stock will be sold at prevailing market prices at the time of the sale; and as a result, prices may vary. As of December 31, 2021, we sold 277,629 shares of common stock under the 2021 ATM Program for net proceeds of approximately $5.1 million.

Net cash provided by operating activities for the year ended December 31, 2021 was $29.1 million and primarily consisted of our net income of $24.9 million adjusted for non-cash items including stock-based compensation of $13.3 million, non-cash operating lease expense of $0.4 million, an investment amortization of $0.6 million, a decrease in ~~Operating Activities~~non-cash interest expense associated with the term loan of $0.2 million, a decrease of the

derivative liability associated with the Incyte Agreements of $0.4 million, and a net decrease in operating assets and liabilities of $9.6 million. The significant items in the decrease in operating assets and liabilities include a decrease in prepaid expenses and other assets of $1.4 million, an increase in accounts payable of $2.1 million, and a decrease in deferred revenue of $13.1 million partially offset by an increase in accrued expenses and other liabilities of $2.8 million.

Net cash used in operating activities for the year ended December 31, ~~2019~~2020 was ~~$50.6~~$71.3 million and primarily consisted of our net loss of ~~$56.0~~$73.2 million adjusted for non-cash items including stock-based compensation of ~~$6.0~~$9.1 million, non-cash interest expense associated with the term loan of $0.4 million, non-cash operating lease expense of $0.4 million, an investment amortization of $0.1 million and a net ~~increase~~decrease in operating assets and liabilities of ~~$0.1~~$7.9 million. The significant items in the ~~increase~~decrease in operating assets and liabilities include ~~an increase~~a decrease in prepaid expenses and other assets of ~~$0.3~~$4.3 million, a decrease in accounts payable of $2.7 million, and a decrease in deferred revenue of $1.5 million partially offset by increases in ~~accounts payable of $4.7 million and decease in~~ accrued expenses and other liabilities of ~~$3.4~~$0.6 million.

Net cash used in operating activities for the year ended December 31, 2018 was $68.5 million and primarily consisted of our net loss of $74.0 million adjusted for non-cash items including stock-based compensation of $6.2 million and a net decrease in operating assets and liabilities of $0.3 million. The significant items in the decrease in operating assets and liabilities include an increase in prepaid expenses and other assets of $1.0 million and a decrease in deferred revenue of $1.5 million partially offset by a decrease in accounts payable of $0.8 million and an increase in accrued expenses and other liabilities of $1.0 million.

Net cash ~~provided by~~used in investing activities for the year ended December 31, ~~2019~~2021 was ~~$12.8~~$40.9 million and was primarily due to the purchase of ~~$104.0~~$294.7 million of available-for-sale marketable securities partially offset by ~~$116.8~~$254.0 million in proceeds from the maturities of available-for-sale marketable securities.

Net cash provided by investing activities for the year ended December 31, ~~2018~~2020 was ~~$51.4~~$142.5 million and was primarily due to the ~~purchases~~purchase of $278.9 million of available-for-sale marketable securities ~~of $78.8~~partially offset by $136.4 million ~~and property and equipment of $0.2 million offset by~~in proceeds from the maturities of available-for-sale marketable ~~securities of $130.4 million.~~securities.

Net cash provided by financing activities for the year ended December 31, ~~2019~~2021 was ~~$28.6~~$118.5 million and was primarily due to the ~~$27.4~~$24.8 million of proceeds from ~~a direct placement~~issuances of common stock for Incyte Agreement, proceeds of $81.2 million from issuance of common stock, $5.1 million of proceeds from an at-the-market offering, ~~the $0.8~~$0.6 million of proceeds from the ~~2017 ATM Program,~~Incyte Agreement allocated to the derivate liability in connection with the side letter, and ~~the $0.4~~$6.7 million of proceeds from stock option exercises and ESPP purchases.

Net cash provided by financing activities for the year ended December 31, ~~2018~~2020 was ~~$15.7~~$304.4 million and was primarily due to the ~~net~~$242.8 million of proceeds from ~~“at-the-market” offerings~~issuances of ~~$15.5~~common stock, $34.9 million of proceeds from a direct placement offering, $19.7 million of proceeds from the term loan, and ~~$0.2~~$7.0 million of proceeds from stock ~~option~~options exercises and ESPP ~~employee stock~~ purchases.

~~The following table summarizes our significant contractual obligations as of December 31, 2019:~~

The contractual obligations table does not include any potential contingent payments upon the achievement by us of clinical, regulatory and commercial events, as applicable, or royalty payments we may be required to make under license or collaboration agreements we have entered into with various entities pursuant to which we have in-licensed certain intellectual property. See “Business—Collaborations,” “Business—License Agreements” and “Business—In-Licensed Intellectual Property” for additional information. The table also excludes potential payments we may be required to make under manufacturing agreements as the timing of when these payments will actually be made is uncertain and the payments are contingent upon the initiation and completion of future activities.

We also have employment agreements with executive officers and certain other key employees that would require us to make severance payments to them if we terminate their employment without cause or the they resign for good cause. The payments are contingent upon the occurrence of various future events, and the amounts payable under these provisions depend upon the level of compensation at the time of termination of employment, are therefore not calculable at this time, and, as a result, we have not included any such amounts in the above table.

At December 31, ~~2019,~~2021, we had federal and state tax net operating loss carryforwards of approximately ~~$68.0~~$73.5 million and ~~$33.1~~$34.6 million, respectively. The Company has generated federal NOLs of $48.5 million which have an indefinite carryforward period. The remaining $25.0 million of federal NOLs and the Company’s state ~~net operating loss carryforwards~~NOLs will begin to expire at various dates starting in 2025. Any federal net operating loss incurred in 2018 and in future years may now be carried forward indefinitely pursuant to the Tax Cuts and Jobs Act of 2017. It is uncertain if and to what extent various states will conform to the newly enacted federal tax law.2026. At December 31, ~~2019,~~2021, we had available income tax credits of approximately ~~$4.5~~$6.6 million, with ~~$2.9~~$4.1 million attributable to Federal R&D Credits and ~~$1.6~~$2.5 million attributable to state R&D Credits, which are available to reduce future income taxes, if any. These income tax credits begin to expire in ~~2021.~~2022.

Utilization of the net operating losses and credits may be subject to a substantial annual limitation due to ownership change limitations provided by the Internal Revenue Code of 1986, as amended. The annual limitation may result in the expiration of our net operating losses and credits before we can use them. We have recorded a valuation allowance on all of our deferred tax assets, including our deferred tax assets related to our net operating loss and research and development tax credit carryforwards.

~~We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and regulations of the SEC.~~

We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and may remain an emerging growth company for up to five years. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include:

We have taken advantage of reduced reporting burdens in this Annual Report on Form 10-K. In particular, in this Annual Report on Form 10-K, we have not included all of the executive compensation related information that would be required if we were not an emerging growth company. We may take advantage of these exemptions for up to five years or such earlier time that we are no longer an emerging growth company. We would cease to be an emerging growth company if we have more than $1.07 billion in annual revenues as of the end of any fiscal year, if we are deemed to be a large accelerated filer under the rules of the Securities and Exchange Commission, or SEC, or if we issue more than $1.0 billion of non-convertible debt over a three-year period. Section 107 of the JOBS Act provides that an emerging growth company can take advantage of the extended transition period for complying with new or revised accounting standards. Thus, an emerging growth company can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. We have irrevocably elected not to avail ourselves of this extended transition period and, as a result, we will adopt new or revised accounting standards on the relevant dates on which adoption of such standards is required for other public companies.

Item 7A. Quantitative and ~~Qualitative~~Qualitative Disclosures about Market Risk

The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates. As of December 31, ~~2019,~~2021, we had cash and cash equivalents of ~~$24.6~~$222.0 million, consisting of overnight investments, interest-bearing money market funds and highly rated corporate

bonds and short-term investments of ~~$35.2~~$217.9 million, consisting of commercial paper, highly rated corporate bonds and ~~credit card asset backed securities.~~treasuries. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates. The primary objectives of our investment activities are to ensure liquidity and to preserve principal while at the same time maximizing the income we receive from our marketable securities without significantly increasing risk. We have established guidelines regarding approved investments and maturities of investments, which are designed to maintain safety and liquidity. Due to the short-term maturities of our cash equivalents and the low risk profile of our short-term investments, an immediate 100 basis point change in interest rates would not have a material effect on the fair market value of our cash equivalents and short-term investments. We have the ability to hold our investments until maturity, and therefore, we would not expect our operating results or cash flows to be affected to any significant degree by the effect of a change in market interest rates on our investment portfolio.

We also have exposure to market risk on our Loan Agreement with Hercules. Our Loan Agreement accrues interest from its date of issue at a variable interest rate equal to the greater of (y) 9.25% or (z) 6.00% plus the Wall Street Journal prime rate. As of December 31, 2021, $20 million was outstanding under the Loan Agreement. The effect of a 100 basis points adverse change in market interest rates on our 2021 Loan Payable, in excess of applicable minimum floors, on our interest expense would be approximately $0.2 million per year.

We do not believe that inflation and changing prices had a significant impact on our results of operations for any periods presented herein.

Our consolidated financial statements, together with the report of our independent registered public accounting firm, appear in this Annual Report on Form 10-K beginning on page F-1.

Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure

Our management, with the participation of our principal executive officer and our principal financial officer, evaluated, ~~as of the end of the period covered by this Annual Report on Form 10-K,~~ the effectiveness ~~of our disclosure controls and procedures. Based on that evaluation~~ of our disclosure controls and procedures as of December 31, ~~2019, our principal executive officer and principal financial officer concluded that our disclosure controls and procedures as of such date are effective at the reasonable assurance level.~~2021. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, or the Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act are recorded, processed, summarized and reported within the time periods specified in the ~~SEC’s~~Securities and Exchange Commission’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by usa company in the reports ~~we file~~that it files or ~~submit~~submits under the Exchange Act is accumulated and communicated to our management, including our principal executive ~~officer~~ and principal financial ~~officer,~~officers, or persons performing similar functions, as appropriate to allow timely decisions regarding required disclosure. Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and our management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Based on evaluation of our disclosure controls and procedures as of December 31, 2021, our principle executive officer and principal financial officer concluded that, as of such date, our disclosure controls and procedures were effective at the reasonable assurance level.

Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as such term is defined in Rules 13a-15(f) and 15d-15(f) ofpromulgated under the Exchange ~~Act. Our management,~~Act as a process designed by, or under the supervision of, the company’s principal executive and principal financial officers to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. Because of its

inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Therefore, even those systems determined to be effective can provide only reasonable assurance with respect to financial statement preparation and presentation. Projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the ~~participation of our Chief Executive Officer and Chief Financial Officer, conducted an evaluation of~~policies or procedures may deteriorate.

Our management assessed the effectiveness of our internal control over financial reporting as of December 31, ~~2019 based on~~2021. In making this assessment, management used the ~~framework in Internal Control-Integrated Framework issued~~criteria set forth by the Committee of Sponsoring ~~Organizations~~organizations of the Treadway Commission ~~(2013 Framework)~~(COSO) in Internal Control – Integrated Framework (2013). Based on ~~the results of its evaluation,~~that assessment, our management concluded that, as of December 31, 2021, our internal control over financial reporting was ~~effective as of December 31, 2019.~~effective.

~~This~~Deloitte & Touche LLP, the independent registered public accounting firm that audited the consolidated financial statements included in this Annual Report on Form 10-K, ~~does not include~~has issued an attestation report on the effectiveness of ~~our registered public accounting firm due to an exemption established by the JOBS Act for “emerging growth companies.”~~internal control over financial reporting as of December 31, 2021, included herein.

~~There was no~~No change in our internal control over financial reporting ~~that~~(as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) occurred during ~~our most recent~~the fiscal quarter ended December 31, 2021 that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.

We have audited the internal control over financial reporting of Syndax Pharmaceuticals, Inc. and subsidiaries (the “Company”) as of December 31, 2021, based on criteria established in Internal Control — Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission (COSO). In our opinion, the Company maintained, in all material respects, effective internal control over financial reporting as of December 31, 2021, based on criteria established in Internal Control — Integrated Framework (2013) issued by COSO.

We have also audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the consolidated financial statements as of and for the year ended December 31, 2021, of the Company and our report dated March 1, 2022, expressed an unqualified opinion on those financial statements.

The Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the effectiveness of internal control over financial reporting, included in the accompanying Management's Annual Report on Internal Control over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal control over financial reporting based on our audit. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects. Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.

A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

The information required by this item is incorporated by reference to the information set forth in the sections titled “Information About Our Board of Directors,” “Executive Officers” and “The Board of Directors and Its Committees” and “Delinquent Section 16(a) Reports,” if applicable, in our ~~2020~~2022 Proxy Statement.

The information required by this item is incorporated by reference to the information set forth in the section titled “Executive Officer and Director Compensation” in our ~~2020~~2022 Proxy Statement.

Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

The information required by this item is incorporated by reference to the information set forth in the section titled “Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters” in our ~~2020~~2022 Proxy Statement.

Item 13. Certain Relationships and Related Transactions and Director Independence

The information required by this item is incorporated by reference to the information set forth in the section titled “The Board of Directors and Its Committees – Board Independence” and “Certain Relationships and Related Party Transactions” in our ~~2020~~2022 Proxy Statement.

The information required by this item is incorporated by reference to the information set forth in the section titled “Independent Registered Public Accounting Firm Fees” and “Pre-Approval Policies and Procedures” contained in Proposal 2 in our ~~2020~~2022 Proxy Statement.

All schedules have been omitted because they are not required or because the required information is given in the Consolidated Financial Statements or Notes thereto.

Pursuant to the requirements of Section 13 of 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

Each person whose individual signature appears below hereby authorizes and appoints ~~Briggs W. Morrison, M.D.~~Michael A. Metzger and Luke J. Albrecht, and each of them, with full power of substitution and resubstitution and full power to act without the other, as his or her true and lawful attorney-in-fact and agent to act in his or her name, place and stead and to execute in the name and on behalf of each person, individually and in each capacity stated below, and to file any and all amendments to this report on Form 10-K, and to file the same, with all exhibits thereto, and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing, ratifying and confirming all that said attorneys-in-fact and agents or any of them or their or his or her substitute or substitutes may lawfully do or cause to be done by virtue thereof.

Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the registrant and in the capacities and on the dates indicated.

We have audited the accompanying consolidated balance sheets of Syndax Pharmaceuticals, Inc. and ~~its~~ subsidiaries (the ~~“Company”~~"Company") as of December 31, ~~2019~~2021 and ~~2018, and~~2020, the related consolidated statements of operations, comprehensive ~~loss, stockholders’~~income (loss), stockholders' equity, and cash flows, for each of the three years in the period ended December 31, ~~2019,~~2021, and the related notes (collectively referred to as the "financial statements"). In our opinion, the financial statements present fairly, in all material respects, the financial position of the Company as of December 31, ~~2019~~2021 and ~~2018,~~2020, and the results of its operations and its cash flows for each of the three years in the period ended December 31, ~~2019,~~2021, in conformity with accounting principles generally accepted in the United States of America.

We have also audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company's internal control over financial reporting as of December 31, 2021, based on criteria established in Internal Control — Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission and our report dated March 1, 2022, expressed an unqualified opinion on the Company's internal control over financial reporting.

These financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the ~~Company’s~~Company's financial statements based on our audits. We are a public accounting firm registered with the ~~Public Company Accounting Oversight Board (United States) (PCAOB)~~PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits, we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting. Accordingly, we express no such opinion.

Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.

The critical audit matter communicated below is a matter arising from the current-period audit of the financial statements that was communicated or required to be communicated to the audit committee and that (1) relates to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective, or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates.

Revenue from Collaboration and License Agreement— Refer to Notes 3 and 4 to the financial statements

The Company recognizes revenue upon transfer of control of promised goods or services to customers in an amount that reflects the consideration the Company expects to receive in exchange for those goods or services. The Company’s collaborative research and license agreements contain multiple elements. In September 2021, the Company executed a collaboration and license agreement and a share purchase agreement (collectively, the “Incyte Agreement”) which became effective December 9, 2021. Upon the effectiveness of the Incyte Agreement the

Company received an upfront fee of $117 million and the Company issued 1,421,523 shares of common stock for an aggregate purchase price of $35 million, or $24.62 per share, for a total cash consideration $152 million.

Under the revenue portion of the Incyte Agreement the Company identified contract promises for the license. The Company determined that the license was capable of being distinct from the ongoing collaboration activities. Management estimated the standalone selling price of the license based on an application of the income approach by measuring the fair value of the discounted cash flows from commercialization. The valuation required management to make significant judgments and estimates relating to the probability of achieving both regulatory and commercial milestones, forecasted future cash flows and the selection of thediscount rates. Changes in these assumptions could have a significant impact on the standalone selling price and the revenue recorded.

Significant judgments and estimates were made by the management in determining revenue recognition for the Incyte Agreement, including the following:

Given the above factors, the related audit effort in evaluating management’s judgments and estimates made in the identification of the license as a distinct performance obligation and valuation of the license was extensive and required a high degree of auditor judgment.

Our audit procedures related to the Company’s revenue recognition for the Incyte Agreement included the following, among others:

	December 31,						December 31,
	2019			2018			2021			2020
ASSETS
Current assets:
Cash and cash equivalents	$	24,609		$	33,769		$	221,965		$	115,243
Restricted cash		-			101			115			115
Short-term investments		35,166			47,142			217,971			177,822
Prepaid expenses and other current assets		2,556			2,334			8,345			5,684
Total current assets		62,331			83,346			448,396			298,864
Property and equipment, net		281			373			278			192
Right-of-use asset		716			-			983			290
Other assets		197			219			—			1,267
Total assets	$	63,525		$	83,938		$	449,657		$	300,613
LIABILITIES AND STOCKHOLDERS' EQUITY
Current liabilities:
Accounts payable	$	6,178		$	1,439		$	5,669		$	3,508
Accrued expenses and other current liabilities		10,195			13,149			14,466			11,246
Current portion of deferred revenue		1,517			1,517			—			1,517
Current portion of right-of-use liability		478			-			361			316
Current portion of term loan								—			2,285
Derivative liability								187			—
Total current liabilities		18,368			16,105			20,683			18,872
Long-term liabilities:
Deferred revenue, less current portion		13,133			14,650			-			11,617
Right-of-use liability, less current portion		419			-			711			101
Term loan, less current portion								19,895			17,834
Other long-term liabilities		5			136			—			1
Total long-term liabilities		13,557			14,786			20,606			29,553
Total liabilities		31,925			30,891			41,289			48,425
Commitments (Note 14)
Commitments, contingencies and guarantees (Note 16)
Stockholders' equity:
Preferred stock, $0.001 par value, 10,000,000 shares authorized; 0 shares outstanding at December 31, 2019 and December 31, 2018, respectively		—			—
Common stock, $0.0001 par value, 100,000,000 shares authorized; 27,140,484 and 24,835,951 shares outstanding at December 31, 2019 and December 31, 2018, respectively		3			2
Preferred stock, $0.001 par value, 10,000,000 shares authorized; 0 shares outstanding at December 31, 2021 and December 31, 2020, respectively								—			—
Common stock, $0.0001 par value, 100,000,000 shares authorized; 54,983,105 and 47,881,223 shares outstanding at December 31, 2021 and December 31, 2020, respectively								6			5
Additional paid-in capital		527,067			492,493			952,019			820,815
Accumulated other comprehensive loss		—			(25	)		45			(4	)
Accumulated deficit		(495,470	)		(439,423	)		(543,702	)		(568,628	)
Total stockholders' equity		31,600			53,047			408,368			252,188
Total liabilities and stockholders' equity	$	63,525		$	83,938		$	449,657		$	300,613

The accompanying notes are an integral part of these consolidated financial statements.

Years Ended December 31,

2019

2018

2017

Revenues:

License fees

$
1,517

$
1,517

$
2,108

Total revenues

1,517

1,517

2,108

Operating expenses:

Research and development

42,994

60,106

48,201

General and administrative

16,062

17,287

15,861

Total operating expenses

59,056

77,393

64,062

Loss from operations

(57,539
)

(75,876
)

(61,954
)
Other income (expense):

Interest income (expense), net

1,571

1,942

1,421

Other (expense) income, net

(79
)

(27
)

(269
)
Total other income (expense)

1,492

1,915

1,152

Net loss

$
(56,047
)

$
(73,961
)

$
(60,802
)
Net loss attributable to common stockholders

$
(56,047
)

$
(73,961
)

$
(60,802
)
Net loss per share attributable to common stockholders—basic
and diluted

$
(1.84
)

$
(2.92
)

$
(2.90
)
Weighted-average common shares outstanding—basic
and diluted

30,490,783

25,371,511

20,997,211

	Years Ended December 31,
	2021			2020			2019
Revenues:
License fees	$	139,709		$	1,517		$	1,517
Total revenues		139,709			1,517			1,517
Operating expenses:
Research and development		88,248			50,435			42,994
General and administrative		25,241			22,505			16,062
Total operating expenses		113,489			72,940			59,056
Income (loss) from operations		26,220			(71,423	)		(57,539	)
Other (expense) income:
Interest expense		(1,899	)		(2,357	)		—
Interest income		403			841			1,571
Other (expense) income:		202			(219	)		(79	)
Total other (expense) income		(1,294	)		(1,735	)		1,492
Net income (loss)	$	24,926		$	(73,158	)	$	(56,047	)
Net income (loss) attributable to common stockholders	$	24,926		$	(77,064	)	$	(56,047	)

Net income (loss) Per Share:
Basic earnings (loss) per share attributable to common stockholders	$	0.48		$	(1.87	)	$	(1.84	)
Diluted earnings (loss) per share attributable to common stockholders	$	0.46		$	(1.87	)	$	(1.84	)

Weighted-average common shares used in calculating:
Basic earnings (loss) per share attributable to common stockholders		52,064,809			41,308,242			30,490,783
Diluted earnings (loss) per share attributable to common stockholders		53,622,904			41,308,242			30,490,783

The accompanying notes are an integral part of these consolidated financial statements.

The accompanying notes are an integral part of these consolidated financial statement

	Common Stock $0.0001 Par Value					Additional Paid-In			Accumulated Other Comprehensive			Accumulated			Total Stockholders' Equity			Common Stock $0.0001 Par Value				Additional Paid-In			Accumulated Other Comprehensive			Accumulated			Total Stockholders' Equity
	Shares			Amount		Capital			Income (Loss)			Deficit			(Deficit)			Shares		Amount		Capital			Income (Loss)			Deficit			(Deficit)
BALANCE--January 1, 2017		18,215,181			2		389,374			56			(305,293	)		84,139
Proceeds from follow on offering, net of offering cost of $3,665		3,950,190			—		48,675			—			—			48,675
Proceeds from exercise of stock options		46,680			—		277			—			—			277
Vesting of restricted stock		8,543			—		59			—			—			59
Stock-based compensation expense		—			—		5,450			—			—			5,450
Proceeds from "At-the-market" offering, net		148,421			—		1,705			—			—			1,705
Unrealized losses on short-term investments		—			—		—			(199	)		—			(199	)
Employee withholdings ESPP		—			—		97			—			—			97
Cumulative effect adjustment of adoption ASU 2016-09		—			—		16			—			(16	)		-
Proceeds from direct stock placement, net		2,021,018			—		24,918			—			—			24,918
Net loss		—			—		—			—			(60,802	)		(60,802	)
Balance—December 31, 2017		24,390,033		$	2	$	470,571		$	(143	)	$	(366,111	)	$	104,319
Proceeds from "At-the-market" offering, net of offering cost of $67		2,114,169			—		15,497			—			—			15,497
Proceeds from exercise of stock options		7,850			—		26			—			—			26
Stock issuance due to warrant exercise, cashless		299,215			—		—			—			—			—
Stock purchase under ESPP		24,684			—		—			—			—			—
Stock-based compensation expense		—			—		6,201			—			—			6,201
Unrealized gains on short-term investments		—			—		—			118			—			118
Employee withholdings ESPP		—			—		198			—			—			198
Cumulative effect adjustment of adoption ASU 2014-09		—			—		—			—			649			649
Retirement of common stock in exchange for common stock warrant		(2,000,000	)		—		(16,780	)		—			—			(16,780	)
Issuance of common stock warrant in exchange for retirement of common stock		—			—		16,780			—			—			16,780
Net loss		—			—		—			—			(73,961	)		(73,961	)
Balance—December 31, 2018		24,835,951		$	2	$	492,493		$	(25	)	$	(439,423	)	$	53,047
Proceeds from "At-the-market" offering, net of $34 offering expense		140,819			—		830			—			—			830
Balance—January 1, 2019																			24,835,951	$	2	$	492,493		$	(25	)	$	(439,423	)	$	53,047
Proceeds from At-the-market offering, net of $34 offering expense																			140,819		—		830			—			—			830
Proceeds from direct offering, net of $1,571 in common stock warrants, $98 offering expenses		2,095,039			1		10,901			—			—			10,902			2,095,039		1		10,901			—			—			10,902
Proceeds from pre-funded common stock warrant from direct offering, net of $1,875 in common stock warrants, $93 offering expenses		—			—		13,032			—			—			13,032			—		—		13,032			—			—			13,032
Issuance of common stock warrant with direct offering		—			—		3,446			—			—			3,446			—		—		3,446			—			—			3,446
Stock purchase under ESPP		42,818			—		—			—			—			—			42,818		—		—			—			—			—
Stock-based compensation expense		—			—		6,005			—			—			6,005			—		—		6,005			—			—			6,005
Unrealized gains on short-term investments		—			—		—			25			—			25			—		—		—			25			—			25
Employee withholdings ESPP		—			—		182			—			—			182			—				182			—			—			182
Proceeds from exercise of stock options		25,857			—		178			—			—			178			25,857				178			—			—			178
Net loss		—			—		—			—			(56,047	)		(56,047	)		—		—		—			—			(56,047	)		(56,047	)
Balance—December 31, 2019		27,140,484		$	3	$	527,067		$	-		$	(495,470	)	$	31,600			27,140,484	$	3	$	527,067		$	—		$	(495,470	)	$	31,600
Proceeds from direct offering, net of $93 offering expenses																			3,036,719		—		24,201			—			—			24,201
Proceeds from pre-funded common stock warrant from direct offering, net of $41 offering expenses																			—		—		10,665			—			—			10,665
Proceeds from direct offering, net of $7,132 offering expenses																			6,388,889		1		107,867			—			—			107,868
Proceeds from direct offering, net of $8,770 offering expenses																			6,250,000		1		134,980			—			—			134,981
Deemed dividend from repricing Series 1 and 2 warrants																			—		—		3,906			—			—			3,906
Repricing Series 1 and 2 warrants																			—		—		(3,906	)		—			—			(3,906	)
Stock purchase under ESPP																			33,706		—		—			—			—			—
Pre-funded warrant exercise																			2,280,318		—		—			—			—			—
Stock-based compensation expense																			—		—		9,057			—			—			9,057
Unrealized losses on short-term investments																			—		—		—			(4	)		—			(4	)
Exercise of Series 1 and Series 2 warrants																			1,995,941		—		—			—			—			—
Employee withholdings ESPP																			—		—		345			—			—			345
Proceeds from exercise of stock options																			755,166		—		6,633			—			—			6,633
Net loss																			—		—		—			—			(73,158	)		(73,158	)
Balance—December 31, 2020																			47,881,223		5	$	820,815		$	(4	)	$	(568,628	)	$	252,188
Proceeds from At-the-market offering, net of $159 offering expenses																			277,629		—		5,131			—			—			5,131
Proceeds from direct offering, net of $5,332 offering expenses																			3,802,144		1		81,205			—			—			81,206
Stock purchase under ESPP																			26,878		—		—			—			—			—
Pre-funded warrant exercise																			725,784		—					—			—			—
Proceeds from Incyte Share Purchase Agreement																			1,421,523		—		24,848									24,848
Stock-based compensation expense																			—		—		13,317			—			—			13,317
Unrealized losses on short-term investments																			—		—		—			49			—			49
Vesting of RSU																			5,500		—		—			—			—			—
Employee withholdings ESPP																			—		—		367			—			—			367
Proceeds from exercise of stock options																			842,424		—		6,336			—			—			6,336
Net income																			—		—		—			—			24,926			24,926
Balance—December 31, 2021																			54,983,105	$	6	$	952,019		$	45		$	(543,702	)	$	408,368

The accompanying notes are an integral part of these consolidated financial statements.

	Years Ended December 31,									Years Ended December 31,
	2019			2018			2017			2021			2020			2019
CASH FLOWS FROM OPERATING ACTIVITIES:
Net loss	$	(56,047	)	$	(73,961	)	$	(60,802	)
Adjustments to reconcile net loss to net cash used in operating activities:
Net income (loss)										$	24,926		$	(73,158	)	$	(56,047	)
Adjustments to reconcile net loss to net cash provided by (used in) operating activities:
Depreciation		92			78			76			43			89			92
Amortization and accretion of investments		(780	)		(558	)		223			644			(130	)		(780	)
Non-cash operating lease expense		359			—			—			413			426			359
Non-cash interest expense											(225	)		389			—
Changes in fair value of derivate liability											(389	)		—			—
Stock-based compensation		6,005			6,201			5,450			13,317			9,057			6,005
Other		—			11			8			(1	)		1			—
Changes in operating assets and liabilities:
Prepaid expenses and other assets		(52	)		1,033			(329	)		(1,394	)		(4,314	)		(52	)
Accounts payable		4,739			(792	)		(194	)		2,161			(2,670	)		4,739
Deferred revenue		(1,517	)		(1,517	)		2,892			(13,133	)		(1,517	)		(1,517	)
Accrued expenses and other liabilities		(3,411	)		974			5,305			2,769			567			(3,411	)
Net cash used in operating activities		(50,612	)		(68,531	)		(47,371	)
Net cash provided by (used in) operating activities											29,131			(71,260	)		(50,612	)
CASH FLOWS FROM INVESTING ACTIVITIES:
Purchases of property and equipment		—			(187	)		(84	)		(129	)		—			—
Purchases of short-term investments		(104,018	)		(78,844	)		(152,263	)		(294,719	)		(278,937	)		(104,018	)
Proceeds from sales and maturities of short-term investments		116,799			130,429			135,275			253,975			136,407			116,799
Net cash provided by (used in) investing activities		12,781			51,398			(17,072	)
Net cash (used in) provided by investing activities											(40,873	)		(142,530	)		12,781
CASH FLOWS FROM FINANCING ACTIVITIES:
Proceeds from issuance of common stock in follow on public offering, net		—			—			48,675
Proceeds from issuance of common stock in follow on public offerings, net											81,206			242,849			—
Proceeds from issuance of common stock in at-the-market offering, net		830			15,497			1,755			5,131			—			830
Allocation of proceeds to common stock issued under the Incyte Share Purchase Agreement											24,848			—			—
Allocation of proceeds to derivative liability recorded under the Incyte Share Purchase Agreement											576			—			—
Proceeds from issuance of common stock in direct placement offering, net		27,380			—			24,918			—			34,866			27,380
Proceeds from term loan agreement, net											—			19,730			—
Proceeds from Employee Stock Purchase Plan		182			198			97			367			345			182
Proceeds from exercise of stock options		178			26			277			6,336			6,633			178
Other		—			8			—			—			1			—
Net cash provided by financing activities		28,570			15,729			75,722			118,464			304,424			28,570
NET (DECREASE) INCREASE IN CASH, CASH EQUIVALENTS AND RESTRICTED CASH		(9,261	)		(1,404	)		11,279
NET INCREASE (DECREASE) IN CASH, CASH EQUIVALENTS AND RESTRICTED CASH											106,722			90,634			(9,261	)
CASH, CASH EQUIVALENTS AND RESTRICTED CASH—beginning of year		33,985			35,389			24,110			115,358			24,724			33,985
CASH, CASH EQUIVALENTS AND RESTRICTED CASH—end of year	$	24,724		$	33,985		$	35,389		$	222,080		$	115,358		$	24,724

The following table provides a reconciliation of cash, cash equivalents, and restricted cash equivalents reported within the consolidated balance sheets that sum to the total of the amounts shown in the consolidated statements of cash flows:

	Years Ended December 31,						Years Ended December 31,
	2019		2018		2017		2021		2020		2019
	(In thousands)						(In thousands)
Cash and cash equivalents	$	24,609	$	33,769	$	35,168	$	221,965	$	115,243	$	24,609
Restricted cash included in current and noncurrent assets		115		216		221		115		115		115
Cash, cash equivalents and restricted cash	$	24,724	$	33,985	$	35,389	$	222,080	$	115,358	$	24,724

The accompanying notes are an integral part of these consolidated financial statements.

Syndax Pharmaceuticals, Inc. (“the Company” or “Syndax”) is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. The Company is developing its lead product candidate, entinostat, a once-weekly, oral, small molecule, Class I HDAC inhibitor, in combination with exemestane and several approved PD-1/PD-L1 antagonists. The Company’s pipeline also includes SNDX-6352, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor, as well as SNDX-5613, ~~a selective inhibitor~~ targeting the binding interaction of menin with the mixed lineage leukemia ~~(“MLL”) protein.~~1 (MLL1) protein for the treatment of MLL-rearranged, or MLLr, acute leukemias and nucleophosmin 1, or NPM1, mutant acute myeloid leukemia (AML), as well as axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1, or CSF-1 receptor. The Company has deprioritized the development of entinostat, a once-weekly, oral, small molecule, Class I HDAC inhibitor, to focus resources on advancing the remainder of our pipeline. The Company plans to continue to leverage the technical and business expertise of its management team and scientific collaborators to license, acquire and develop additional cancer therapies to expand its pipeline.

Since its inception, the Company has devoted its efforts principally to research and development and raising capital. The Company is subject to risks common to companies in the development stage, including, but not limited to, successful development of therapeutics, obtaining additional funding, protection of proprietary therapeutics, compliance with government regulations, fluctuations in operating results, dependence on key personnel and collaborative partners, and risks associated with industry changes. The Company’s long-term success is dependent upon its ability to successfully develop and market its product candidates, expand its oncology drug pipeline, earn revenue, obtain additional capital when needed, and ultimately, achieve profitable operations. The Company anticipates that it will be several years before any of its product candidates is approved, if ever, and the Company begins to generate revenue from sales of such product candidates. Accordingly, management expects to incur substantial losses on the ongoing development of its product candidates and does not expect to achieve positive cash flow from operations for the foreseeable future, if ever. As a result, the Company will continue to require additional capital to move forward with its business plan. While certain amounts of this additional capital were raised in the past, there can be no assurance that funds necessary beyond these amounts will be available in amounts or on terms sufficient to ensure ongoing operations.

The Company’s management believes that the cash, cash equivalents and short-term investments balances as of December 31, ~~2019, in combination with the net proceeds of its January 2020 equity financing and February 2020 debt financing (see Note 19),~~2021, should enable the Company to maintain its planned operations for at least twelve months from the date these financial statements were issued. The Company’s ability to fund all of its planned operations internally beyond that date, including the completion of its ongoing and planned clinical trial activities, may be substantially dependent upon whether the Company can obtain sufficient funding on terms acceptable to the Company. Proceeds from additional capital transactions would allow the Company to accelerate and/or expand its planned research and development activities. In the event that sufficient funds were not available, the Company may be required to delay or reduce expenditures to conserve cash, which could involve scaling back or curtailing development and general and administrative activities.

With the global spread of the ongoing COVID-19 pandemic in 2021, the Company has implemented business continuity plans designed to address and mitigate the impact of the COVID-19 pandemic on its business. The Company anticipates that the COVID-19 pandemic could have an impact on the clinical development timelines for one or more of its clinical programs. The extent to which the COVID-19 pandemic impacts the Company’s business, clinical development, manufacturing of clinical and commercial drug substance and drug product, and regulatory efforts, the corporate development objectives and the value of and market for the Company’s common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the United States, Europe and other countries, and the effectiveness of actions taken globally to contain and treat the disease. The global economic slowdown, the overall disruption of global healthcare systems and the other risks and uncertainties associated with the pandemic could have a material adverse effect on its business, financial condition, results of operations and growth prospects.

In addition, the Company is subject to other challenges and risks specific to its business and ability to execute on the strategy, as well as risks and uncertainties common to companies in the pharmaceutical industry with

development and commercial operations, including, without limitation, risks and uncertainties associated with: obtaining regulatory approval of the Company’s late-stage product candidate; delays or problems in the supply of the Company’s products, loss of single source suppliers or failure to comply with manufacturing regulations; identifying, acquiring or in-licensing additional products or product candidates; pharmaceutical product development and the inherent uncertainty of clinical success; and the challenges of protecting and enhancing the Company’s intellectual property rights; complying with applicable regulatory requirements. In addition, to the extent the ongoing COVID-19 pandemic adversely affects the Company’s business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties discussed above.

The Company has prepared the accompanying consolidated financial statements in conformity with accounting principles generally accepted in the United States of America (“U.S. GAAP”).

In 2011, the Company established a wholly owned subsidiary in the United Kingdom. There have been no activities for this entity to date. In 2014, the Company established a wholly owned U.S. subsidiary, Syndax Securities Corporation. The consolidated financial statements include the accounts of the Company and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation.

The preparation of consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of

contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of costs and expenses during the reporting period. The Company bases estimates and assumptions on historical experience when available and on various factors that it believes to be reasonable under the circumstances. The Company evaluates its estimates and assumptions on an ongoing basis. The Company’s actual results may differ from these estimates under different assumptions or conditions.

Estimates and assumptions about future events and their effects cannot be determined with certainty and therefore require the exercise of judgment. As of the date of issuance of these financial statements, the Company is not aware of any specific event or circumstance that would require the Company to update its estimates, assumptions and judgments or revise the carrying value of its assets or liabilities. These estimates may change as new events occur and additional information is obtained and are recognized in the consolidated financial statements as soon as they become known. Actual results could differ from those estimates and any such differences may be material to the Company’s financial statements.

Cash equivalents include all highly liquid investments maturing within 90 days or less from the date of purchase. Cash equivalents include money market funds, corporate debt securities, U.S. government agency notes, and overnight deposits.

The Company classifies as restricted cash all cash pledged as collateral to secure long-term obligations and all cash whose use is otherwise limited by contractual provisions. Amounts are reported as non-current unless restrictions are expected to be released in the next 12 months.

Short-term investments include marketable securities with maturities of less than one year or where management’s intent is to use the investments to fund current operations or to make them available for current operations. ~~Long-term investments include marketable securities with remaining maturities greater than one year or that are due after one year from the balance sheet date.~~ All investments in marketable securities are classified as available-for-sale and are reported at fair value with unrealized gains and losses excluded from earnings and reported net of tax in accumulated other comprehensive income, which is a component of stockholders’ ~~equity (deficit).~~equity. Unrealized losses that are determined to be other-than-temporary, based on current and expected market conditions, are recognized in earnings. Declines in fair value determined to be credit related are charged to earnings. The cost of marketable securities sold is determined by the specific identification method.

Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision maker, or decision-making group, in making decisions regarding resource allocation and assessing performance. The Company has ~~one~~1 operating segment.

Cash and cash equivalents, restricted cash, and short-term ~~and long-term~~ investments are financial instruments that potentially subject the Company to concentrations of credit risk. Substantially all of the Company’s cash, cash equivalents, and short-term investments were deposited in accounts at two financial institutions, and at times, such deposits may exceed federally insured limits. The Company has not experienced any losses in such accounts, and management believes that the Company is not exposed to significant credit risk due to the financial position of the depository institutions in which those deposits are held. The Company’s available-for-sale investments primarily consist of government money market funds, corporate debt securities, commercial paper, credit card asset-backed securities and overnight deposits and potentially subject the Company to concentrations of credit risk.

Property and equipment are recorded at cost. Depreciation is recorded using the straight-line method over the estimated useful lives of the assets (three to five years). Assets under capital leases are amortized over the shorter of their useful lives or lease term using the straight-line method. Major replacements and improvements are capitalized, while general repairs and maintenance are expensed as incurred.

Long-lived assets are reviewed for impairment whenever events or changes in circumstances indicate that the carrying amount of the asset may not be recoverable. When such events occur, the Company compares the carrying

amounts of the assets to their undiscounted expected future cash flows. If this comparison indicates that there is impairment, the amount of impairment is calculated as the difference between the carrying value and fair value. To date, no0 such impairments have been recognized.

Debt issuance costs consist of payments made to secure commitments under certain debt financing arrangements. These amounts are recognized as interest expense over the period of the financing arrangement using the effective interest method. If the financing arrangement is cancelled or forfeited, or if the utility of the arrangement to the Company is otherwise compromised, these costs are recognized as interest expense immediately. The Company’s consolidated financial statements present debt issuance costs related to a recognized debt liability as a direct reduction from the carrying amount of that debt liability.

The Company ~~adopted~~accounts for derivative financial instruments as either equity or liabilities in accordance with Accounting Standards Codification ~~(“ASC”) Rule 606 Revenue from Contracts~~Topic 815, Derivatives and Hedging, based on the characteristics and provisions of each instrument. The derivative liability is recorded at fair value, which is estimated using a Black Scholes model. The liability is measured quarterly with ~~Customers (ASC 606), on January 1, 2018, using~~any change in fair value being recognized in the ~~modified retrospective method~~statement of operations. We do not hold or issue derivative instruments for all contracts not completed as of the date of adoption. The reported results for 2018 reflect the application of ASC 606 guidance while the reported results for 2017 were prepared under the guidance of ASC 605, trading or speculative purposes.

Revenue Recognition (ASC 605). As of January 1, 2018, the Company had only one contract within the scope of ASC 606, a license agreement with Kyowa Kirin Co., Ltd. (“KKC”), under which the Company granted KKC an exclusive license to develop and commercialize entinostat in Japan and Korea (the “KKC License Agreement”). The KKC License Agreement is discussed further in Note 4.

The Company enters into license agreements for the development and commercialization of its product candidates. License agreements may include non-refundable upfront payments, contingent payments based on the occurrence of specified events under the Company’s license arrangements, partial or complete reimbursement of research and development expenses, license fees and royalties on sales of entinostat if they are successfully approved and commercialized. The Company’s performance obligations under the license agreements may include the transfer of intellectual property rights in the form of licenses, obligations to provide research and development services and related materials and participation on certain development and/or commercialization committees.

~~Revenue is recognized~~The Company recognizes revenue when ~~or as, performance obligations are satisfied, which occurs when~~our customer obtains control of ~~the~~ promised ~~products~~goods or services, ~~is transferred to customers. Revenue is measured as~~in an amount that reflects the ~~amount of~~ consideration ~~the Company expects~~which we expect to receive in exchange for ~~transferring products~~those goods or ~~services to a customer (“~~services. We recognize revenue following the five – step model prescribed under FASB Accounting Standards Codification (ASC 606), Revenue from Contracts with Customers: (i) identify contract(s) with customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction ~~price”). To the extent that~~price; (iv) allocate the transaction price ~~includes variable consideration,~~to the ~~Company estimates the amount of variable consideration that should be included~~performance obligations in the ~~transaction price utilizing~~contract; and (v) recognize revenue when (or as) we satisfy the most likely amount method. Variable consideration is included in the transaction price if, in the Company’s judgment, it is probable that a significant future reversal of cumulative revenue under the contract will not occur. Estimates of variable consideration and determination of whether to include estimated amounts in the transaction price are based largely on an assessment of the Company’s anticipated performance ~~and all information (historical, current and forecasted) that is reasonably available.~~obligations.

The Company assesses the promises to determine if they are distinct performance obligations. Once the performance obligations are determined, the transaction price is allocated based on a relative standalone selling price basis. Milestone payments and royalties are typically considered variable consideration at the outset of the contract and are recognized in the transaction price either upon occurrence or when the constraint of a probable reversal is no longer applicable.

Licenses of intellectual property: If the license to the Company’s intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, the Company recognizes revenues from non-refundable, up-front fees allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, the Company utilizes judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from non-refundable, up-front fees. Arrangements containing licenses to the Company’s intellectual property typically provide for a know-how transfer period. These arrangements may or may not also include rights to future updates of that intellectual property and related know-how. Revenues from non-refundable, up-front fees allocated to the licenses are recognized as the license is transferred to the customer and the customer is able to use and benefit from the license. This generally takes place over the related know-how transfer period, or if applicable, over the term of transfer of future updates to the intellectual property.

Development Milestone Payments: At the inception of each arrangement that includes development milestone payments, the Company evaluates whether the milestones are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the control of the Company or the licensee, such as regulatory approvals, are generally not considered probable of being achieved until those approvals are received. The transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis, for which the Company recognizes revenue as or when the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, the Company re-evaluates the probability of achievement of such development milestones and any related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect license fees and earnings in the period of adjustment. For development milestones related to the KKC Agreement, the Company does not take a substantive role or control the research, development or commercialization of any products generated by KKC. Therefore, the Company is not able to reasonably estimate when, if at all, any development milestone payments may be payable to the Company. As such, the development milestone payments associated with the KKC Agreement involve a substantial degree of uncertainty and risk that they may never be received.

Commercial Milestone Payments and Royalties: For arrangements that include sales-based royalties, including milestone payments based on the level of commercial sales, and the license is deemed to be the predominant item to which the royalties or commercial milestones relate, the Company will recognize revenue at the later of when the related sales occur or when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date no commercial milestone payments or royalties have been achieved.

When no performance obligations are required of the Company, or following the completion of the performance obligation period, such amounts are recognized as revenue upon transfer of control of the goods or services to the customer. Generally, all amounts received or due other than sales-based milestones and royalties are classified as license fees. Sales-based milestones and royalties will be recognized as royalty revenue at the later of when the related sales occur or when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).

resulting from the Company’s license agreements do not represent a financing component as the payment is not financing the transfer of goods or services, and the technology underlying the licenses granted reflects research and development expenses already incurred by the Company.

For additional information on our collaboration and license arrangements, please read Note 4, Collaboration and License Agreements, to these consolidated financial statements.

Research and development costs are expensed as incurred. Research and development expenses include payroll and personnel expenses, consulting costs, external contract research and development expenses, and allocated overhead, including rent, equipment depreciation, and utilities. Research and development costs that are paid in advance of performance are capitalized as a prepaid expense and amortized over the service period as the services are provided. The Company expenses upfront license payments related to acquired technologies that have not yet reached technological feasibility and have no alternative future use.

In instances where the Company enters into cost-sharing arrangements, all research and development costs reimbursed by the collaborators are accounted for as reductions to research and development expense. During the year ended December 31, 2021 and 2020, the Company incurred 0 external costs related to cost-sharing collaborations. During the year ended December 31, 2019, the Company incurred $2.0 million in external costs related to cost-sharing collaborations, of which $1.0 million has been recorded as a reduction to research and development expense. During the year ended December 31, 2018, the Company incurred $4.7 million in external costs related to cost-sharing collaborations, of which $2.4 million has been recorded as a reduction to research and development expense. During the year ended December 31, 2017, the Company incurred $3.0 million in external costs related to cost-sharing collaborations, of which $1.4 million has been recorded as a reduction to research and development expense.

Clinical trial costs are a component of research and development expenses. The Company accrues and expenses clinical trial activities performed by third parties based on an evaluation of the progress to completion of specific tasks using data such as patient enrollment, clinical site activations, or other information provided to us by our vendors.

The Company records deferred tax assets and liabilities for the expected future tax consequences of temporary differences between the Company’s financial statement carrying amounts and the tax bases of assets and liabilities and for loss and credit carryforwards using enacted tax rates expected to be in effect in the years in which the differences reverse. A valuation allowance is provided to reduce the net deferred tax assets to the amount that will more likely than not be realized. The Company determines whether it is more likely than not that a tax position will be sustained upon examination. If it is not more likely than not that a position will be sustained, none of the benefit attributable to the position is recognized. The tax benefit to be recognized for any tax position that meets the more-likely-than-not recognition threshold is calculated as the largest amount that is more than 50% likely of being realized upon resolution of the contingency. The Company accounts for interest and penalties related to uncertain tax positions as part of its provision for income taxes.

As permitted under Delaware law, the Company indemnifies its officers, directors, and employees for certain events or occurrences that happen by reason of the relationship with, or position held at, the Company. The Company has standard indemnification arrangements under office leases (as described in Note ~~14)~~5) that require it to indemnify the landlord against all costs, expenses, fines, suits, claims, demands, liabilities, and actions directly resulting from any breach, violation, or nonperformance of any covenant or condition of the Company’s lease. Through December 31, ~~2019,~~2021, the Company had not experienced any losses related to these indemnification obligations and no0 claims were outstanding. The Company does not expect significant claims related to these indemnification obligations, and consequently, concluded that the fair value of these obligations is negligible, and no0 related reserves were established.

The Company accounts for all stock option awards granted to employees and non-employees using a fair value method. Stock-based compensation is measured at the grant date fair value of the stock option grants and is recognized over the requisite service period of the awards (usually the vesting period) on a straight-line basis. For equity awards that have a performance condition, the Company recognizes compensation expense based on its assessment of the probability that the performance condition will be achieved. The Company accounts for forfeitures as they occur.

Basic earnings per share is computed by dividing undistributed net income attributable to Syndax by the weighted-average number of common shares outstanding during the period. Diluted earnings per share is computed based on the treasury method by dividing net income by the weighted-average number of common shares outstanding during the period plus potentially dilutive common equivalent shares outstanding.

~~In February 2016,~~From time to time, new accounting pronouncements are issued by the Financial Accounting Standards Board ~~(“FASB”)~~FASB or other accounting standard setting bodies that we adopt as of the specified effective date. Unless otherwise discussed below, we do not believe that the adoption of recently issued standards have or may have a material impact on our consolidated statements or disclosures.

Income Taxes: In December 2019, the FASB issued Accounting Standards Update (“ASU”) ~~2016-02, Leases~~2019-12, Income Taxes (Topic ~~842) (“ASU 2016-02”). The Company adopted ASU 2016-02~~740):Simplifying the Accounting for Income Taxes. This standard removes certain exceptions to the general principles in Topic 740 and ~~its related amendments (collectively known as ASC 842) using~~simplifies certain other aspects of the ~~prospective method,~~accounting for income taxes. This standard became effective for us on January 1, ~~2019. See Note 5 “Leases” to our consolidated financial statements included elsewhere herein for the required disclosures related to the impact of adopting this standard~~2021 and ~~a discussion of the Company’s updated policies related to leases. The Company adopted ASU 2016-02 on January 1, 2019, and it~~ did not have a material impact on ~~its~~our consolidated ~~balance sheet, consolidated statement of comprehensive loss or consolidated statement of cash flows.~~financial statements and related disclosures.

In September 2021, the Company entered into the Incyte License and Collaboration Agreement with Incyte covering the worldwide development and commercialization of SNDX-6352 (axatilimab). Also, in September 2021 the Company entered into a share purchase agreement with Incyte, or Incyte Share Purchase Agreement. These agreements are collectively referred to as the Incyte Agreements. Under the terms of the Incyte Agreements, Incyte will receive exclusive commercialization rights outside of the United States, subject to its royalty payment obligations set forth below. In the United States, Incyte and the Company will co-commercialize axatilimab, with the Company having the right to co-promote axatilimab with Incyte, subject to the Company’s exercise of its co-promotion option. Incyte will be responsible for leading all aspects of commercialization of axatilimab in the United States. The Company and Incyte will share equally the profits and losses from ~~Contracts~~co-commercialization efforts in the United States. The Company and Incyte have agreed to co-develop axatilimab and to share development costs associated with ~~Customers~~global and U.S. – specific clinical trials, with Incyte responsible for 55% of such costs and the Company responsible for 45% of such costs. Incyte is responsible for 100% of future development costs for trials that are specific to ex-U.S. countries. Each company will be responsible for funding any of its own independent development activities. All development costs related to the collaboration will be subject to a joint development plan.

Under the terms of the Incyte Agreement, Incyte paid the Company a non-refundable cash payment of $117 million. The Company is eligible to receive up to $220 million in future contingent development and regulatory milestones and up to $230 million in commercialization milestones as well as tiered royalties ranging in the mid-teens percentage on net sales of the licensed product comprising axatilimab in Europe and Japan and low double digit percentage in the rest of the world outside of the United States. The Company’s right to receive royalties in any particular country will expire upon the last to occur of (a) the expiration of licensed patent rights covering the licensed product in that particular country, (b) a specified period of time after the first post – marketing authorization sale of a licensed product in that country, and (c) the expiration of any regulatory exclusivity for that licensed product in that country.

In December 2021, the Company and Incyte signed a Letter Agreement. Upon the signing of the Letter Agreement both the Incyte Agreement and Incyte Share Purchase Agreement became effective. As a result, the Company received the upfront fee of $117 million and the Company issued 1,421,523 shares of common stock for an aggregate purchase price of $35 million, or $24.62 per share, for total cash consideration $152 million.

The Incyte Agreement and the Incyte Share Purchase Agreement were executed on the same date and negotiated simultaneously. Management therefore concluded that the Incyte Agreements are to be combined for accounting purposes and therefore allocated the total consideration to the units of account identified. The common stock issued to Incyte was recorded at fair value of $24.8 million. Pursuant to the Letter Agreement, Incyte is permitted to terminate the Incyte Agreement, if, prior to March 23, 2022 either Incyte or the Company receives a notification from any governmental authority (including the Federal Trade Commission or the Department of Justice, Antitrust Division), challenging the transactions completed by the Incyte Agreements, hereafter referred to as the Termination Right. If such challenge occurs and Incyte exercises the Termination Right, the Incyte Agreement will be rescinded, and the Company will return the $117 million upfront payment to Incyte. In addition, Incyte will be required to sell the Syndax common shares that it received under the Incyte Share Purchase Agreement and remit the net proceeds to the Company. To the extent that the net proceeds from the sale of the Syndax common stock by Incyte is greater or less than the proceeds received by the Company in the Incyte Share Purchase Agreement, or $35 million, a cash payment will be made to make the parties whole. The Company determined that the cash settlement feature of the Letter Agreement represents an embedded derivative requiring bifurcation and separate accounting recognition at fair value. Accordingly, the Company allocated $0.6 million of the total consideration received to the derivative liability, see Note 9 for further discussion of the derivative liability.

The Company evaluated the terms of the Incyte Agreement and determined it is within the scope of Accounting Standard Update 2018-18, Collaborative Arrangements (Topic 808), and has elements that are within the scope of Topic 606 and Topic 808.

The Company identified the following promises in the Incyte Agreements that were evaluated under the scope of Topic 606: (i) delivery of a license for SNDX-6532 to develop, commercialize, and conduct medical affairs and (ii) services to be performed in accordance with the development plan. The Company also evaluated whether certain options outlined within the Incyte Agreements represented material rights that would give rise to a performance obligation and concluded that none of the options convey a material right to Incyte and therefore are not considered separate performance obligations within the Incyte Agreements.

The Company assessed the above promises and determined that the license for SNDX-6532 represents the only performance obligation within the scope of Topic 606. The license for SNDX-6532 is considered functional intellectual property and distinct from other promises under the contract as Incyte can benefit from the license on its own or together with other readily available resources. The services performed by the Company to obtain regulatory approval of SNDX-6532 are not complex or specialized, could be performed by another qualified third party, are not expected to significantly modify or customize the license given that SNDX-6532 is late-stage intellectual property that has completed its Phase 1/2 trial and is currently enrolling in a global pivotal Phase 2 trial, and the services are expected to be performed over a short period of time. Therefore, the license represents a separate performance obligation within a contract with a customer under the scope of Topic 606 at contract inception.

The Company considers the collaborative research and development activities and manufacturing activities to be separate units of account within the scope of Topic 808 and are not deliverables under Topic 606. The Company and Incyte are both active participants in the activities and are exposed to significant risks and rewards that are dependent on the commercial success of the activities in the arrangement.

Under the scope of Topic 606, the Company identified contract promises for the license of intellectual property and know-how rights for SNDX-6352. The Company determined that the license was capable of being distinct from the ongoing collaboration activities. After the allocation to the common stock and derivative liability, the total transaction price to be allocated to the Incyte Agreement is $126.6 million. The Company estimated the

standalone selling price of the license to be the entire $126.6 million, based on an application of the income approach by measuring the fair value of the discounted cash flows from commercialization. Significant assumptions included in the valuation included judgments relating to the probability of achieving both regulatory and commercial milestones, forecasted future cash flows and the election of the discount rate. As the Company concluded the license was distinct, revenue of $126.6 million was recognized upon transfer of the license to Incyte in the year ended December 31, 2021.

The Company used the most likely amount method to estimate variable consideration and estimated that the most likely amount for each potential preclinical, development, and regulatory variable consideration milestone payment under this agreement is zero, as achievement of those milestones is uncertain and highly susceptible to factors outside the Company’s control. Accordingly, all such milestone payments were excluded from the transaction price. Management will reevaluate the transaction price at the end of each reporting period and as uncertain events are resolved or other changes in circumstances occur, will adjust the transaction price as necessary. Sales based royalties, including milestones based on the level of sales, were also excluded from the transaction price, as the license is deemed to be the predominant item to which the royalties relate. The company will recognize such revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).

On December 19, 2014 (the “Effective Date”), the Company entered into the KKC License Agreement, under which the Company granted KKC an exclusive license to develop and commercialize entinostat in Japan and Korea.

Under the terms of the KKC License Agreement, the Company will be responsible for the manufacture and supply of the products during the development activities. In addition to the license and manufacturing obligations, the Company is obligated to provide KKC access to know-how and regulatory information the Company may develop over the life of the entinostat patent. Lastly, to the extent additional intellectual property is developed during the term of the agreement, KKC will receive the right to the intellectual property when and if available. KKC will conduct the development, regulatory approval filings, and commercialization activities of entinostat in Japan and Korea. KKC paid the Company $25.0 million upfront, which included a $7.5 million equity investment and a $17.5 million non-refundable cash payment. In addition, to the extent certain development and commercial milestones are achieved, KKC will be required to pay the Company up to $75.0 million in milestone payments over the term of the license agreement. The term of the agreement commenced on the Effective Date and, unless earlier terminated in accordance with the terms of the agreement, will continue on a country-by-country and product-by-product basis, until the later of: (i) the date all valid claims of the last effective patent among the Company’s patents expires or is abandoned, withheld, or is otherwise invalidated in such country; and (ii) 15 years from the date of the first commercial sale of a product in the Japan or Korea.

The equity purchase and the up-front payment of the license fee were accounted for separately. The Company allocated the amount of consideration equal to the fair value of the shares on the Effective Date, which resulted in $7.7 million of proceeds allocated to the equity purchase and the remaining consideration of $17.3 million allocated to the up-front license fee.

In October 2017, the Company announced that KKC enrolled the first Japanese patient into a local pivotal study of entinostat for the treatment of hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. In accordance with the terms of the license agreement, KKC paid the Company a $5.0 million milestone payment which the Company received in December 2017.

The Company determined that the performance obligations associated with the KKC License Agreement include (i) the combined license, rights to access and use materials and data, and rights to additional intellectual property, and (ii) the clinical supply obligation. All other goods or services promised to KKC are immaterial in the context of the agreement. Under ASC 606, the identification of the clinical supply obligation as a distinct performance obligation separate and apart from the license performance obligation resulted in a change in the performance period. The start of the performance period under ASC 606 was determined to be the contract inception date, December 19, 2014. The clinical supply was identified as a separate performance obligation under ASC 606 as (i) the Company is not providing a significant service of integration whereby the clinical supply and other promises are inputs into a combined output, (ii) the clinical supply does not significantly modify or customize the other

promises nor is it significantly modified or customized by them, and (iii) the clinical supply is not highly interdependent or highly interrelated with the other promises in the agreement as KKC could choose not to purchase the clinical supply from the Company without significantly affecting the other promised goods or services. The Company further concluded that the clinical supply represented an immaterial performance obligation and therefore the entire $17.3 million allocated to the upfront payment was allocated to the combined license and will be recognized ratably over the performance period, representing contract inception though 2029. In 2017, KKC achieved a development milestone, and was required to pay the Company $5.0 million. The Company is recognizing the development milestone consideration over the performance period coinciding with the license to intellectual property. As the Company determined that its performance obligations associated with the KKC Agreement at contract inception were not distinct and represented a single performance obligation, and that the obligations for goods and services provided would be completed over the performance period of the agreement, any payments received by the Company from KKC, including the upfront payment and progress-dependent development and regulatory milestone payments, are recognized as revenue using a time-based proportional performance model over the contract term (December 2014 through 2029) of the collaboration, within license fees. To date no commercial milestone payments or royalties have been achieved.

~~Contract liabilities consisted~~In September 2021, KKC informed the Company that it is discontinuing its development of ~~deferred revenue, as presented on the consolidated balance sheet, as of December 31, 2019. Deferred revenue related to~~entinostat in Japan and Korea and terminating the KKC License ~~Agreement was $14.7 million as of December 31, 2019 and will be recognized over the remainder of the contract term.~~

~~The Company adopted ASC 842 on January 1, 2019, using the prospective approach which provides~~Agreement. As a method for recording existing leases at adoption using the effective date of the standard as its initial application date. ASC 842 generally requires all leases to be recognized on the balance sheet. In addition,result, the Company ~~elected the relief package~~recognized all remaining deferred revenue of practical expedients permitted under the transition guidance within the new standard, which among other things, allowed the Company not to reassess whether any expired or existing contracts are or contain leases, the lease classification for any expired or existing leases and initial direct costs for any existing leases. The reported results for 2019 reflect the application of ASC 842 guidance while the reported results for 2018 were prepared under the guidance of ASC 840, Leases. The adoption of ASC 842 resulted$12.4 million in the recording of a lease asset and lease liability of approximately $1.3 million as of January 1, 2019. ASC 842 did not materially impact the Company’s consolidated results of operations, equity or cash flows as of the adoption date or for the periods presented.September 2021.

The Company accounts for leases in accordance with ASC 842, Leases, and determines whether an arrangement is a lease at inception. Operating lease right-of-use (“ROU”) assets and lease liabilities are recognized based on the present value of the future minimum lease payments over the lease term at commencement date. Lease agreements with lease and non-lease components are accounted for separately. For leases that do not provide an implicit rate, the Company uses the incremental borrowing rate based on the information available at commencement date in determining the present value of future payments. The ROU asset also includes any lease payments made and excludes lease incentives and initial direct costs incurred. The lease terms may include options to extend or terminate the lease when it is reasonably certain that the Company will exercise that option. Leases with an initial term of 12 months or less are not recorded on the balance sheet as the Company has elected to apply the short-term lease exemption. Lease expense for minimum lease payments is recognized on a straight-line basis over the lease term.

The Company identified two existing long-term building leases on the adoption date of ASC 842 that are classified as operating leases. In September 2016, the Company entered into a five-year operating lease for 12,207 square feet of office space in Waltham, Massachusetts, with a lease commencement date of March 1, 2017. On August 17, 2021, the Company signed a 36-month extension to the lease for the Waltham, Massachusetts office with aggregate payments of $1.6 million, with a lease commencement date of March 1, 2022.

In December 2015, the Company entered into a 62-month operating lease for 4,039 square feet of space in New York, New York, which commenced on January 1, 2016. ~~The~~In February 2021, the Company signed an 18-month extension to the lease for the New York office, with aggregate payments of $270,000, with a lease commencement date of March 1, 2021.The remaining lease terms as of December 31, ~~2019~~2021, for the facility in Waltham, Massachusetts and New York, New York, were 2638 months and 148 months, respectively.

As of December 31, ~~2019,~~2021, the consolidated balance sheet includes a ~~$0.7~~$1.0 million operating lease ROU asset and a ~~$0.9~~$1.1 million ROU liability. The Company used a weighted average discount rate of 14% to calculate its lease obligations, and an increase or decrease in the rate does not have a significant impact on the ROU asset or ROU liability. The ROU asset is amortized on a straight-line basis over the remainder of the lease term. For the year ended December 31, ~~2019,~~2021, the Company recorded approximately ~~$447,000~~$413,000 in operating lease expense and made approximately ~~$566,000~~$544,000 in lease payments.

Future minimum lease payments under the Company’s operating leases, ~~as of December 31, 2019 and 2018,~~ were as follows:

Maturity of lease liabilities	As of			As of		As of			As of
(in thousands)	December 31, 2019			December 31, 2018		December 31, 2021			December 31, 2020
2019	$	—		$	569
2020		585			588
2021		394			395				$	394
2022		59			59	$	473			59
2023							376			—
Thereafter		—			—		454			—
Total lease payments	$	1,038		$	1,611	$	1,303		$	453
Less: imputed interest		(141	)				(231	)		(36	)
Total operating lease liability	$	897				$	1,072		$	417

Future minimum lease payments under the Company’s capital leases as of December 31, ~~2019~~2021, and ~~2018,~~2020, were ~~$9,000~~$ 1,000 and ~~$14,000,~~$5,000, respectively.

6. ~~Net Loss~~Earnings (Loss) per Share ~~Attributable to Common Stockholders~~

Basic ~~net loss attributable to common stockholders~~and diluted earnings (loss) per share is computed by dividing the net loss attributable to common stockholders by the weighted-average number of common shares outstanding for the period. Because the Company has reported a net loss for the three years ended December 31, 2019, 2018, and 2017, diluted net loss per common share is the sameare calculated as ~~basic net loss per common share for those periods. The following table summarizes the computation of basic and diluted net loss per share attributable to common stockholders of the Company~~follows (in ~~thousands, except per share data)~~000s):

The following potentially dilutive securities have been excluded from the computation of diluted weighted-average shares outstanding for 2020 and 2019, because such securities have an antidilutive impact due to losses reported (in common stock equivalent shares):

As discussed in Note 12, in June 2018, the Company signed an exchange agreement with an investor under which the investor exchanged 2,000,000 shares of common stock for 2,000,000 pre-funded warrant shares. Further, in March 2019, the Company sold an additional 2,500,000 pre-funded warrant shares. The pre-funded warrants are exercisable into shares of common stock for $0.0001 per share. The shares of common stock into which the pre-funded warrants may be exercised are considered outstanding for the purposes of computing earnings per share. In January 2020, the Company sold 3,036,719 shares of common stock at a price of $8.00 per share and pre-funded warrants to purchase 1,338,287 shares of our common stock. During the year ended December 31, 2021, 475,784 pre-funded warrants were exchanged for shares of common stock in a cashless exercise and 250,000 pre-funded warrants were exchanged for shares of common stock in a cash excercise. As of December 31, 2021, 3,975,024 pre-funded warrants were considered issued and outstanding.

In October 2017, the Company entered into a license agreement (the “Allergan License Agreement”) with Vitae Pharmaceuticals, Inc., a subsidiary of Allergan (“Allergan”), under which Allergan granted the Company an exclusive, sublicensable, worldwide license to a portfolio of preclinical, orally available, small molecule inhibitors of the interaction of menin with Mixed Lineage Leukemia (“MLL”) protein (the “Menin Assets”). The Company made a nonrefundable upfront payment of $5.0 million to Allergan in the fourth quarter of 2017. Additionally, subject to the achievement of certain milestone events, the Company may be required to pay Allergan up to $99.0 million in one-time development and regulatory milestone payments over the term of the Allergan License Agreement. In the event that the Company or any of its affiliates or sublicensees commercializes the Menin Assets, the Company will also be obligated to pay Allergan low single to low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $70.0 million in potential one-time, sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, the Company may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with Allergan. The Company is solely responsible for the development and commercialization of the

Menin Assets. Each party may terminate the Allergan License Agreement for the other party’s uncured material breach or insolvency; and the Company may terminate the Allergan License Agreement at will at any time upon advance written notice to Allergan. Allergan may terminate the Allergan License Agreement if the Company or any of its affiliates or sublicensees institutes a legal challenge to the validity, enforceability, or patentability of the licensed patent rights. Unless terminated earlier in accordance with its terms, the Allergan License Agreement will continue on a country-by-country and product-by-product basis until the later of: (i) the expiration of all of the licensed patent rights in such country; (ii) the expiration of all regulatory exclusivity applicable to the product in such country; and (iii) 10 years from the date of the first commercial sale of the product in such country.

As of the date of the Allergan License Agreement, the asset acquired had no alternative future use nor had it reached a stage of technological feasibility. As the processes or activities that were acquired along with the license do not constitute a “business,” the transaction has been accounted for as an asset acquisition. As a result, in 2017, the upfront payment of $5.0 million was recorded as research and development expense in the consolidated statements of operations. In June 2019, the Company achieved certain development and regulatory milestones. As a result, in June 2019, the Company recorded $4.0 million as research and development expense. The amount ~~payable has been recorded~~was paid in ~~accounts payable as of December 31, 2019.~~2020.

In July 2016, the Company entered into a license agreement (the “UCB License Agreement”) with UCB Biopharma Sprl (“UCB”), under which UCB granted to the Company a worldwide, sublicenseable, exclusive license to UCB6352, which the Company refers to as SNDX-6352 or axatilimab, an IND-ready anti-CSF-1R monoclonal antibody. The Company made a nonrefundable upfront payment of $5.0 million to UCB in the third quarter of 2016. Additionally, subject to the achievement of certain milestone events, the Company may be required to pay UCB up to $119.5 million in one-time development and regulatory milestone payments over the term of the UCB License Agreement. In the event that the Company or any of its affiliates or sublicensees commercializes SNDX-6352, the Company will also be obligated to pay UCB low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $250.0 million in potential one-time, sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, the Company may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with UCB. The Company will be solely responsible for the development and commercialization of SNDX-6352, except that UCB is performing a limited set of transitional chemistry, manufacturing and control tasks related to SNDX-6352. Each party may terminate the UCB License Agreement for the other party’s uncured material breach or insolvency; and the Company may terminate the UCB License Agreement at will at any time upon advance written notice to UCB. UCB may terminate the UCB License Agreement if the Company or any of its affiliates or sublicensees institutes a legal challenge to the validity, enforceability, or patentability of the licensed patent rights. Unless terminated earlier in accordance with its terms, the UCB License Agreement will continue on a country-by-country and product-by-product basis until the later of: (i) the expiration of all of the licensed patent rights in such country; (ii) the expiration of all regulatory exclusivity applicable to the product in such country; and (iii) 10 years from the date of the first commercial sale of the product in such country.

As of the date of the UCB License Agreement, the asset acquired had no alternative future use nor had it reached a stage of technological feasibility. As the processes or activities that were acquired along with the license do not constitute a “business,” the transaction has been accounted for as an asset acquisition. As a result, in 2016, the upfront payment of $5.0 million was recorded as research and development expense in the consolidated statements of operations. In July 2020, the Company achieved certain development and regulatory milestones. As a result, in July 2020, the Company recorded $2.0 million as research and development expense, which has been fully paid. In March and September 2021, the Company recorded $2.0 million, respectively, as research and development expenses for the achievement of certain development milestones. The Company fully paid the March 2021 milestone in the second quarter of 2021. The September 2021 milestone of $2.0 million is recorded as an accrued expense as of December 31, 2021.

In March 2014, the Company entered into the “ECOG Agreement with Eastern Cooperative Oncology Group, a contracting entity for the Eastern Cooperative Oncology Group—American College of Radiology Imaging Network Cancer Research Group (“ECOG-ACRIN”), that describes the parties’ obligations with respect to the NCI-sponsored pivotal Phase 3 clinical trial of entinostat. Under the terms of the ECOG Agreement, ECOG-ACRIN will perform this clinical trial in accordance with the clinical trial protocol and a mutually agreed scope of work. The Company will provide a fixed level of financial support for the clinical trial through an upfront payment of $0.7 million and a series of payments of up to $1.0 million each that are comprised of milestone payments through the completion of enrollment and time-based payments through the completion of patient monitoring post-enrollment.

In addition, the Company is obligated to supply entinostat and placebo to ECOG-ACRIN for use in the clinical trial. From the second quarter of 2016 through the fourth quarter of 2018, the Company has entered into a number of amendments to the agreement to provide for additional study activities resulting in an increase of the contractual obligation of ~~$5.1~~$5.3 million. The ~~total contractual costs~~Company has agreed to provide this additional financial support to fund the additional activities required to ensure that the E2112 clinical trial will satisfy FDA registration requirements.

In May 2020, the Company announced that the E2112 trial did not achieve the primary endpoint of demonstrating a statistically significant overall survival benefit over hormone therapy alone. As a result, the Company has decided to deprioritize the entinostat program to focus resources on advancing the remainder of its pipeline. As of December 31, 2021, the Company’s aggregate payment obligations under this agreement are ~~$24.5 million. As of December 31, 2019, the Company’s~~approximately $24.7 million; and its maximum ~~aggregate~~ remaining payment obligations ~~under the agreement~~ are ~~approximately $6.7~~$3.2 million, which are estimated to be paid over a period of approximately ~~two years.~~one year. As of December 31, 2021, the Company has accrued $3.0 million related to the ECOG Agreement.

Data and inventions from the Phase 3 clinical trial are owned by ECOG-ACRIN. The Company has access to the data generated in the clinical trial, both directly from ECOG-ACRIN under the ECOG Agreement as well as from the NCI. Additionally, ECOG-ACRIN has granted the Company a non-exclusive royalty-free license to any inventions or discoveries that are derived from entinostat as a result of its use during the clinical trial, along with a first right to negotiate an exclusive license to any of these inventions or discoveries. Either party may terminate the ECOG Agreement in the event of an uncured material breach by the other party or if the ~~FDA~~U.S. Food and Drug Administration (“FDA”) or ~~NCI~~National Cancer Institute (“NCI”) withdraws the authorization to perform the clinical trial in the United States. The parties may jointly terminate the ECOG Agreement if the parties agree that safety-related issues support termination of the clinical trial.

~~The Company records the appropriate clinical trial expenses in its financial statements by matching those expenses with the period in which the services and efforts are expended.~~ The Company accounts for these expenses according to the progress of the clinical trial as measured by patient enrollment and the timing of various aspects of the clinical trial. The Company determines accrual estimates through financial models,taking into account discussion with applicable personnel and ECOG-ACRIN as to the progress ~~or state~~ of consummation of the clinical trial or the services completed.

In March 2007, the Company entered into a license agreement (the “Bayer Agreement”) with Bayer Schering Pharma AG (“Bayer”) for a worldwide, exclusive license to develop and commercialize entinostat and any other products containing the same active ingredient. Under the terms of the Bayer Agreement, the Company paid a nonrefundable up-front license fee of $2.0 million and is responsible for the development and marketing of entinostat. The Company recorded the $2.0 million license fee as research and development expense during the year ended December 31, 2007, as it had no alternative future use. The Company will pay Bayer royalties on a sliding scale based on net sales, if any, and make future milestone payments to Bayer of up to $150.0 million in the event that certain specified development and regulatory goals and sales levels are achieved. ~~In June 2014, a development milestone was achieved, and the Company recorded $2.0 million of research and development expense, which has been fully paid.~~

In connection with the Bayer Agreement, the Company issued to Bayer a warrant to purchase the number of shares of the Company’s common stock equal to 1.75% of the shares of common stock outstanding on a fully diluted basis as of the earlier of the date the warrant was exercised or the closing of the IPO. The warrant contained anti-dilution protection to maintain Bayer’s potential ownership at 1.75% of the shares of common stock outstanding on a fully diluted basis, requiring that the actual number of shares of common stock issuable pursuant to the warrant be increased or decreased for any changes in the fully diluted shares of common stock outstanding. The warrant was exercisable at an exercise price of $1.54 per share and would have expired upon the earlier of the 10-year anniversary of the closing of the IPO or the date of the consummation of a disposition transaction. The warrant was classified as a long-term liability and recorded at fair value with the changes in the fair value recorded in other expense. The Company used the Black-Scholes option-pricing model to determine the fair value of the warrant. Upon the closing of the IPO, the anti-dilution protection for the warrant expired, resulting in the reclassification of the warrant liability to additional paid-in capital. The warrant was re-measured using current assumptions just prior to the reclassification. On March 1, 2018, Bayer notified the Company of its election to exercise the warrant utilizing the net exercise feature contained therein, resulting in the Company’s issuance to Bayer of 299,215 shares of the Company’s common stock for no net cash proceeds.

Depreciation expense was $43,000 and $90,000 for years ended December 31, 2021 and 2020.

The carrying amounts of cash and cash equivalents, restricted cash, accounts payable, and accrued expenses approximated their estimated fair values due to the short-term nature of these financial instruments. Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. Valuation techniques used to measure fair value are performed in a manner to maximize the use of observable inputs and minimize the use of unobservable inputs.

The accounting standard describes a fair value hierarchy based on three levels of inputs, of which the first two are considered observable and the last unobservable, that may be used to measure fair value, which are the following:

Level 1—Quoted prices (unadjusted) in active markets that are accessible at the market date for identical unrestricted assets or liabilities.

Level 2—Inputs other than Level 1 that are observable, either directly or indirectly, such as quoted prices for similar assets or liabilities; quoted prices in markets that are not active; or other inputs for which all significant inputs are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities.

Level 3—Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities.

~~During~~The table below presents information about the ~~years presented, the Company has not changed the manner in which it values~~Company’s assets and liabilities that are regularly measured and carried at fair value ~~using Level 3 inputs. The Company recognizes transfers between levels of~~and indicate the level within the fair value hierarchy as of valuation techniques the ~~end~~Company utilized to determine such fair values (in thousands):

There have been no material impairments of ~~the reporting period. There were no transfers within the hierarchy~~our assets measured and carried at fair value during the years ended December 31, ~~2019, 2018~~2021, and ~~2017.~~

~~A summary of~~2020. In addition, there have been no changes in valuation techniques during the ~~assets~~years ended December 31, 2021, and ~~liabilities carried at~~2020. The fair value ~~in accordance with the hierarchy defined above is as follows (in thousands):~~

~~Cash equivalents~~ of ~~$23.4 million as of December 31, 2019 and $29.3 million as of December 31, 2018 consisted of overnight investments and money market funds and are classified within~~ Level 1 ~~of the fair value hierarchy because they~~instruments classified as cash equivalents are valued using quoted market prices in active markets. ~~Cash equivalents~~The fair value of ~~$1.2 million as of December 31, 2019 and $4.5 million as of December 31, 2018 consisted of highly rated corporate bonds and commercial paper and are classified within~~ Level 2 ~~of the fair value hierarchy because pricing inputs are~~instruments classified as cash equivalents and short-term investments was determined other than quoted prices in active markets, which are either directly or indirectly observable as of the reporting ~~date;~~date and fair value is determined ~~through the use of~~using models or other valuation methodologies. The fair value of the Level 3 instrument is determined using unobservable inputs and the Company utilized a Black Scholes valuation model as of December 9, 2021 (initial recognition) and December 31, 2021 respectively.

~~Short-term investments~~The following table summarizes the significant unobservable inputs in the fair value measurement of ~~$35.2 million~~the Company’s contingent consideration obligations as of December 31, ~~2019 and $47.1 million as of December 31, 2018, consisted of commercial paper and highly rated corporate bonds and are classified within Level 2 of~~2021:

The following table summarizes the fair value hierarchy because pricing inputs are other than quoted prices in active markets, which are either directly or indirectly observable as of the reporting date; and fair value is determined through the use of models or other valuation methodologies.rollforward (in thousands):

The short-term investments are classified as available-for-sale securities. As of December 31, ~~2019,~~2021, the remaining contractual maturities of the available-for-sale securities were less than 12 months, and the balance in the Company’s accumulated other comprehensive income was comprised solely of activity related to the Company’s available-for-sale securities. There were no0 realized gains or losses recognized on the sale or maturity of available-for-sale securities during the three years ended December 31, ~~2019.~~2021. As a result, the Company did not reclassify any amounts out of accumulated other comprehensive income for the same periods. The Company has a limited number of available-for-sale securities in insignificant loss positions as of December 31, ~~2019,~~2021, which the Company does not intend to sell and has concluded it will not be required to sell before recovery of the amortized cost for the investment at ~~maturity.~~ maturity

The following table summarizes the available-for-sale securities (in thousands):

	Amortized Cost		Unrealized Gains		Unrealized Losses			Fair Value		Amortized Cost		Unrealized Gains		Unrealized Losses			Fair Value
December 31, 2019
December 31, 2021
Commercial paper	$	15,675	$	5	$	—		$	15,680	$	306,715	$	70	$	(17	)	$	306,768
Corporate bonds		18,361		—		(5	)		18,356		22,147		—		(6	)		22,141
Asset back securities		2,300		—		—			2,300
US treasury											14,212		—		(2	)		14,210
	$	36,336	$	5	$	(5	)	$	36,336	$	343,074	$	70	$	(25	)	$	343,119
December 31, 2018
December 31, 2020
Commercial paper	$	22,619	$	—	$	(15	)	$	22,604	$	154,176	$	13	$	(16	)	$	154,173
Corporate bonds		29,047		2		(12	)		29,037		22,617		2		(3	)		22,616
US treasury											6,030		—		—			6,030
	$	51,666	$	2	$	(27	)	$	51,641	$	182,823	$	15	$	(19	)	$	182,819

Prepaid expenses and other current assets consisted of the following (in thousands):

	December 31,				December 31,
	2019		2018		2021		2020
Short-term deposits	$	1,297	$	663	$	6,894	$	4,683
Prepaid insurance						642		427
Interest receivable on investments						429		175
Prepaid clinical supplies		166		101		-		58
Interest receivable on investments		116		253
Reimbursable costs		416		797		-		24
Prepaid insurance		214		188
Other		347		332		380		317
Total prepaid expenses and other current assets	$	2,556	$	2,334	$	8,345	$	5,684

Accrued expenses and other current liabilities consisted of the following (in thousands):

In connection with the closing of the Company’s IPO, the Company filed an amended and restated certificate of incorporation and adopted amended and restated bylaws; and pursuant to the amended and restated certificate of incorporation, theThe Company is authorized to issue 100,000,000 shares of common stock. The holders of each share of common stock are entitled to one vote per share held and are entitled to receive dividends, if and when declared by the Board, and to share ratably in the Company’s assets available for distribution to stockholders, in the event of liquidation.

In April 2017, the Company entered into a sales agreement with Cowen under which the Company may issue and sell shares of our common stock having aggregate sales proceeds of up to $50.0 million from time to time through Cowen, acting as agent, in a series of one or more ATM equity offerings (the “2017 ATM Program”). Since inception of the ATM program in 2017, the Company has sold 2,403,409 shares of common stock pursuant to the ATM program, at an average price of $7.82 per share for gross proceeds of $18.8 million, resulting in net proceeds

~~of $18.2 million after deducting sales commissions and offering expenses. The 2017 ATM Program was replaced by the 2019 ATM Program.~~

~~In August 2019,~~March 2021, the Company entered into a new sales agreement with Cowen and Company, LLC (“Cowen”) under which the Company may issue and sell shares of its common stock having aggregate sales proceeds of up to ~~$50.0~~$75.0 million from time to time through Cowen, acting as agent, in a series of one or more ~~at-the-market (“ATM”)~~ATM equity offerings (the ~~“2019~~“2021 ATM Program”). Cowen is not required to sell any specific amount but acts as the Company’s sales agent using commercially reasonable efforts consistent with its normal trading and sales practices. Shares sold pursuant to the sales agreement will be sold pursuant to a shelf registration statement on Form ~~S-3~~S-3ASR (Registration No. ~~333-233564)~~333-254661), which ~~was declared~~became automatically effective upon filing on ~~September 10, 2019.~~March 24, 2021. The Company’s common stock will be sold at prevailing market prices at the time of ~~the~~ sale; and as a result, prices may vary. ~~The Company pays Cowen up to 3% of~~For the ~~gross proceeds from any common stock sold through this sales agreement. In 2019, prior to the effectiveness of the 2019 ATM Program,~~year ended December 31, 2021, the Company sold ~~140,819~~277,629 common shares of common stock under the ~~2017~~2021 ATM ~~program for~~Program, with net proceeds of ~~$0.8~~approximately $5.1 million. No

On June 18, 2018, the Company signed an exchange agreement with Biotechnology Value Fund and certain affiliated funds (“BVF”) under which BVF exchanged 2,000,000 shares of common stock ~~have been sold under~~for 2,000,000 Pre-Funded Warrant shares. The Company recorded the ~~2019 ATM program.~~issuance of the pre-funded warrants and the retirement of the common stock at fair value within additional paid-in capital. BVF can exercise the Pre-Funded Warrants at an exercise price per share equal to $0.0001 per share and the Pre-Funded Warrants expire 20 years from issuance. Per the terms of the warrant agreement, the outstanding Pre-Funded Warrants may not be exercised if the holder's ownership of the Company’s common stock would exceed 9.99 % following such exercise.

In March 2019, the Company issued 2,095,039 shares of its common stock and pre-funded warrants to purchase 2,500,000 shares of common stock (the “Pre-Funded Warrants”) to certain investors in a registered direct offering. The Pre-Funded Warrants are exercisable immediately upon issuance at an exercise price of $0.0001 per share and have a term of 20 years. The Company sold the shares of common stock and Pre-Funded Warrants together with ~~two~~2 series of warrants, Series 1 Warrants and Series 2 Warrants, to purchase an aggregate of 4,595,039 shares of the Company’s common stock (the “Series Warrants”). The offering price for the securities was $6.00 per share (or $5.9999 for each Pre-Funded Warrant). The aggregate gross proceeds to the Company from this offering were $27.6 million, excluding any proceeds the Company may receive upon exercise of the Pre-Funded Warrants and Series Warrants and offering costs of $0.2 million. No underwriter or placement agent participated in the offering.

The Series Warrants are immediately exercisable. Each Series 1 Warrant has an initial exercise price of $12.00 per share of common stock and each Series 2 Warrant has an initial exercise price of $18.00 per share of common stock, in each case subject to certain adjustments (as described below). The Series Warrants expire on the earlier of (i) 90 days following the Company’s confirmation to holders of the Company’s release of positive data confirming the achievement of the specified primary endpoint of overall survival benefit in the E2112 clinical trial in breast cancer patients, or (ii) December 31, 2020.

If, prior to the expiration date of the Series Warrant, the Company sells additional capital stock or derivative securities convertible into or exercisable for capital stock (other than Exempted Securities as defined by the Series Warrant) in one or more related transactions primarily for the purpose of raising capital at a Weighted-Average Price (as described below) below $12.00 per share, then the initial exercise price of the Series Warrants will be automatically reset upon exercise to an exercise price (the “Adjusted Exercise Price”) that is the midpoint between the initial exercise price and the lowest Weighted-Average Price per share at which the Company sells capital stock or derivative securities convertible into or exercisable for capital stock in a subsequent offering prior to the exercise date; provided, however, that the Adjusted Exercise Price will not be reduced below $6.00 per share. The Weighted-Average Price shall be calculated as the weighted-average common stock equivalent price of the equity securities sold in such transaction(s) (excluding any derivative securities with an exercise or conversion price that is above the closing sale price as of the time of pricing such offering(s)). In no event will the exercise price for the Series Warrants be adjusted more than once pursuant to this adjustment mechanism.

In January 2020, the Company sold 3,036,719 shares of common stock, par value $0.0001 per share (“Common Stock”) and Pre-Funded Warrants to purchase 1,338,287 shares of Common Stock (the “Pre-Funded Warrants”). The offering price for the securities was $8.00 per share or $7.9999 for each Pre-Funded Warrant. As a result of this offering, the exercise price ofadjustments. All Series 1 and Series 2 ~~Warrants outstanding reset from $12.00 per share to $10.00 per share and from $18.00 per share to $13.00, respectively.~~warrants were exercised in 2020.

The Pre-Funded Warrants and the Series Warrants may not be exercised by the holder to the extent that the holder, together with its affiliates, would beneficially own, after such exercise more than 9.99% of the shares of the Company’s common stock then outstanding (subject to the right of the holder to increase or decrease such beneficial ownership limitation upon notice to the Company, provided that such limitation cannot exceed 19.99%) and provided that any increase in the beneficial ownership limitation shall not be effective until 61 days after such notice is delivered.

The Series Warrants were classified as a component of permanent equity and were recorded at the issuance date using a relative fair value allocation method. The Series Warrants are equity classified because they are freestanding financial instruments that are legally detachable and separately exercisable from the equity instruments, are immediately exercisable, do not embody an obligation for the Company to repurchase its shares, and permits the holders to receive a fixed number of common shares upon exercise. In addition, such warrants do not provide any guarantee of value or return. The Company valued the Series Warrants at issuance using the Black Scholes option pricing model and determined the fair value of the 4,595,039 Series Warrants at $3.4 million. The key inputs to the valuation model included the weighted average volatility of 89.1% and the weighted average expected term of 1.4 years. During 2020, holders of Series 1 warrants and Series 2 warrants exercised 4,595,039 Series Warrants in exchange for 1,995,941 shares of the Company’s common stock. As of December 31, 2020, all Series Warrants have been exercised.

~~On June 18, 2018,~~In January 2020, the Company ~~signed an exchange agreement with Biotechnology Value Fund and certain affiliated funds (“BVF”) under which BVF exchanged 2,000,000~~sold 3,036,719 shares of common stock, par value per share $0.0001 and Pre-Funded Warrants to purchase 1,338,287 shares of common stock. The offering price for ~~2,000,000~~the securities was $8.00 per share or $7.9999 for each pre-funded warrant. As a result of this offering, the exercise price of Series 1 and Series 2 Warrants outstanding reset from $12.00 per share to $10.00 per share and from $18.00 per share to $13.00, respectively. The Company recorded $3.9 million as a deemed dividend which represents the value transferred to the warrant holders due to the Series Warrant adjustment mechanisms being triggered. The deemed dividend was recorded as both an increase and a decrease in Additional Paid in Capital and reduced net income available to common stockholders by the same amount. The key inputs to the validation model included the weighted volatility of 96.74% and weighted average expected term of 0.4 years.

In May 2020, the Company sold 6,388,889 shares of common stock, par value $0.0001 per share, at $18.00 per share, with net proceeds of approximately $107.9 million.

In December 2020, the Company sold 6,250,000 shares of common stock, par value $0.0001 per share, at $23.00 per share, with net proceeds of approximately $135.0 million.

In December 2021, the Company issued 3,802,144 shares of common stock and Pre-Funded Warrants to purchase 1,142,856 shares of common stock. The offering price for the securities was $17.50 per share or $17.4999 for each Pre-Funded Warrant, ~~shares.~~with net proceeds of approximately $81.2 million.

In December 2021, in connection with the Incyte License and Collaboration Agreement and Share Purchase Agreement, the Company issued 1,421,523 shares of common stock, with net proceeds of approximately $35.0 million. The Company recorded the equity issuance at a fair value of $24.8 million based on the market price of the ~~Pre-Funded Warrants and~~stock on the ~~retirement~~date of the common stock at fair value within additional paid-in capital. BVF can exercise the Pre-Funded Warrants at an exercise price per share equal to $0.0001 per share and the Pre-Funded Warrants expire 20 years from issuance. Per the terms of the warrant agreement, the outstanding Pre-Funded Warrants may not be exercised if the holder's ownership of the Company's common stock would exceed 9.99 percent following such exercise.

The Company has reserved for future issuance the following shares of common stock related to the potential warrant exercise, exercise of stock options, and the employee stock purchase plan:

In September 2015, the Company’s board of directors adopted its 2015 Omnibus Incentive Plan (“2015 Plan”), which was subsequently approved by its stockholders and became effective upon the closing of the IPO on March 8, 2016. The 2015 Plan replaced the 2007 Stock Plan (“2007 Plan”) and allows for the granting of incentive stock options, nonqualified stock options, stock appreciation rights, restricted stock, unrestricted stock, stock units, dividend equivalent rights, performance awards, annual incentive awards, and other equity-based awards to the Company’s executives and other employees, non-employee members of the board of directors, and consultants of the Company. Any options or awards outstanding under the Company’s 2007 Plan ~~remain~~remains outstanding and effective. Any shares of common stock related to awards outstanding under the 2007 Plan that thereafter terminate by expiration, forfeiture, cancellation or otherwise without the issuance of such shares will be added to, and included in, the 2015 Plan reserve amount. The Company initially reserved 1,750,000 shares of its common stock for the issuance of awards under the 2015 Plan. As of December 31, ~~2019,~~2021, there were ~~586,554~~1,017,242 shares available for issuance under the 2015 Plan.

The 2015 Plan provides that the number of shares reserved and available for issuance under the 2015 Plan will automatically increase each January 1, beginning on January 1, 2017, by 4% of the outstanding number of shares of common stock on the immediately preceding December 31 or such lesser number of shares as determined by the Company’s board of directors. On January 1, ~~2020,~~2022, the shares available for issuance under the 2015 Plan were increased to ~~1,672,173.~~3,215,376.

The Company recognized stock-based compensation expense related to the issuance of stock option awards to employees and non-employees and related to the Employee Stock Purchase Plan in the consolidated statements of operations as follows (in thousands):

	Years Ended December 31,						Years Ended December 31,
	2019		2018		2017		2021		2020		2019
Research and development	$	2,061	$	1,910	$	1,363	$	4,398	$	2,400	$	2,061
General and administrative		3,944		4,291		4,087		8,919		6,657		3,944
Total	$	6,005	$	6,201	$	5,450	$	13,317	$	9,057	$	6,005

As of December 31, ~~2019,~~2021, there was ~~$10.1~~$25.7 million of unrecognized compensation cost related to employee and non-employee unvested stock options and restricted stock units (“RSU’s”) granted under the 2007 and 2015 Plans, which is expected to be recognized over a weighted-average remaining service period of ~~2.3~~2.8 years. Stock compensation costs have not been capitalized by the Company. As of December 31, ~~2019,~~2021, there was ~~$0.7~~$0.9 million of unrecognized compensation cost related to performance-based options, and ~~$9.4~~$24.8 million of unrecognized compensation expense related to ~~service based~~service-based options.

Our stock-based awards are subject to either service or performance-based vesting conditions. Compensation expense related to awards to employees, directors and non-employees with service-based vesting conditions is recognized on a straight-line basis based on the grant date fair value over the associated service period of the award, which is generally the vesting term. Compensation expense related to awards to employees with performance-based vesting conditions is recognized based on the grant date fair value over the requisite service period using the straight-line method to the extent achievement of the performance condition is probable.

In 2017, the Company granted 60,000 options with performance conditions (“2017 Performance Awards”), 13,333 of which ~~have~~ vested in 2019 and 6,667 of which ~~have been~~were cancelled as of December 31, 2019. On January 1, 2021, the Company determined that a second performance had not been achieved. As a result of this, the Company cancelled 20,000 options. In the years ended December 31, ~~2019, 2018~~2021, 2020 and ~~2017,~~2019 the Company recorded approximately ~~$88,000, $142,000~~$25,000, $9,000, and ~~$29,000,~~$88,000, respectively of stock compensation ~~expense~~ associated with these awards.

In 2019, the Company granted to certain employees 583,000 stock options that contain performance-based vesting criteria (“2019 Performance Awards”), primarily related to the achievement of certain clinical and regulatory development milestones related to product candidates. Recognition of stock-based compensation expense associated with these performance-based stock options commences when the performance condition is considered probable of achievement, using management’s best estimates, which consider the inherent risk and uncertainty regarding the future outcomes of the milestones.

~~The achievement~~In the fourth quarter of 2020 one of the performance milestones for the 2019 Performance Awards was ~~considered~~achieved and of the associated 194,331 stock options, 64,777 stock options vested, and 388,669 options were cancelled. In 2021, 64,780 stock options vested with the remaining 64,774 options to ~~be probable and the~~vest in 2022. The Company recorded approximately ~~$181,000~~$257,000 and $207,000 of stock compensation expense associated with these awards for the ~~year~~years ended December 31, ~~2019.~~2021 and 2020, respectively. For the remaining performance milestones, achievement of the performance conditions was ~~considered~~ not ~~probably, nor~~ met ~~and therefore no~~as of December 31, 2021. Therefore 0 expense has been recognized related to these ~~awards~~performance milestones for the year ended December 31, ~~2019.~~2021, and 0 options were cancelled in 2021.

In October 2021, in connection with the retirement of 2 employees, the Company entered into severance and consulting agreements. Under these agreements the Company extended vesting term for a total of 34,728 unvested options unvested options, which would not have otherwise vested and extended the exercise period of the vested

options post termination of the consulting agreement. The Company accounted for the change as a modification of an equity award under ASC 718. As a result of the modifications, the Company recognized approximately $0.8 million of incremental stock compensation expense in 2021.

The fair value of each option award is estimated on the date of grant using the Black-Scholes option-pricing model with the weighted-average assumptions noted in the table below. Expected volatility for the Company’s common stock was determined based on an average of the historical volatility of a peer group of similar public companies. The Company estimated the expected term of its employee stock options using the “simplified” method, whereby, the expected term equals the average of the vesting term and the original contractual term of the option. The contractual life of the option was used for the estimated life of the non-employee grants. The assumed dividend yield is based upon the Company’s expectation of not paying dividends in the foreseeable future. The risk-free interest rate for periods within the expected life of the option is based upon the U.S. Treasury yield curve in effect at the time of grant. The Company accounts for forfeitures when they occur. The grant date fair values of options issued to employees and non-employees were estimated using the Black-Scholes option-pricing model with the following assumptions:

	Years Ended December 31,									Years Ended December 31,
	2019			2018			2017			2021			2020			2019
Expected term (in years)		5.97			5.90			6.02			6.02			5.97			5.97
Volatility rate		76.95	%		76.28	%		73.86	%		85.84	%		81.59	%		76.95	%
Risk-free interest rate		2.29	%		2.69	%		2.02	%		0.67	%		1.20	%		2.29	%
Expected dividend yield		0.00	%		0.00	%		0.00	%		0.00	%		0.00	%		0.00	%

A summary of employee and non-employee option activity under the Company’s equity award plans is presented below (in thousands, except share data):

The weighted-average grant date fair value of options granted during the years ended December 31, 2021, 2020 and 2019, ~~2018~~was $14.70, $7.88, and ~~2017, was~~ $4.81 ~~$6.17, and $6.68~~ per share, respectively. The fair value is being expensed over the vesting period of the options (usually three to four years) on a straight-line basis as the services are being provided.

There were 842,424 options exercised for the year ended December 31, 2021, resulting in total proceeds of $6.3 million; 755,166 options exercised for the year ended December 31, 2020, resulting in total proceeds of $6.6 million; and 25,857 options exercised for the year ended December 31, 2019, resulting in total proceeds of $178,000; 7,850 options exercised for the year ended December 31, 2018, resulting in total proceeds of $26,000; and 46,680 options exercised for the year ended December 31, 2017, resulting in total proceeds of $0.3 million.$178,000. The intrinsic value of options exercised during the years ended December 31, 2021, 2020 and 2019 ~~2018 and 2017~~ was ~~$9,000, $0.1~~$10.1 million, $7.1 million, and ~~$0.2 million,~~$9,000, respectively. In accordance with the Company’s policy, the shares were issued from a pool of shares reserved for issuance under the 2007 and 2015 Plans.

RSUs awarded to Board of Directors or employees vest on either i) one – year anniversary date of the related grant or ii) 25% on each anniversary for 4 years. The following table summarizes our RSU activity:

(1) RSUs granted in 2021 primarily represent RSUs granted in conjunction with our annual awards made in February 2021granted to our Board of Directors.

RSU’s granted in 2021 and 2020 had a weighted average grant date fair value of $21.19 and $10.48, respectively. There were 0 RSU’s granted in 2019. The fair values of RSU’s vested in 2021 totaled $60,000. There were 0 RSU’s vested in 2020.

In September 2015, the Company’s Board adopted the Employee Stock Purchase Plan (the “ESPP”), which was subsequently approved by the Company’s stockholders in February 2016 and became effective upon the closing of the IPO on March 8, 2016. The ESPP authorizes the initial issuance of up to a total of 250,000 shares of common stock to the Company’s employees. The Company issued ~~42,818~~26,878 and 33,706 shares during ~~2019.~~2021 and 2020, respectively. On January 1, ~~2020,~~2022, the shares of common stock reserved for issuance under the ESPP was increased to ~~1,128,398.~~1,546,410. Under the terms of the ESPP, eligible employees can elect to acquire shares of the Company’s common stock through periodic payroll deductions during a series of six month offering periods. Purchases under the ESPP are ~~effected~~affected on the last business day of each offering period at a 15% discount to the lower of closing price on that day or the closing price on the first day of the offering period.

The ESPP is considered a compensatory plan with the related compensation cost expensed over the six-month offering period. For the years ended December 31, ~~2019, 2018~~2021, 2020 and ~~2017~~2019 the Company recorded stock-based compensation expense related to the ESPP of $175,000, $203,000 and $113,000 ~~$132,000 and $42,000~~ respectively.

The Company has a Section 401(k) defined contribution savings plan for its employees. The plan covers substantially all employees who meet minimum age and service requirements and allows participants to defer a portion of their annual compensation on a pretax basis, subject to legal limitations. Company contributions to the plan may be made at the discretion of the Board. For the years ended December 31, ~~2019, 2018~~2021, 2020 and ~~2017,~~2019, the Company made ~~$119,000, $126,000~~$444,000, $250,000 and ~~$106,000~~$119,000 contributions to the plan, respectively.

In February 2020, the Company entered into a loan and security agreement (the “Loan Agreement”) with Hercules Capital, Inc. (“Hercules”), which provided for aggregate maximum borrowings of up to $30.0 million, consisting of (i) a term loan of up to $20.0 million, which was funded on February 7, 2020 (the “Initial Advance”), and (ii) subject to Hercules’ investment committee approval, an additional term loan of up to $10.0 million, available for borrowing from February 7, 2020 to December 15, 2020 (the “Tranche 2 Advance”). The Company elected not to draw the additional term of $10.0 million. Borrowings under the Loan Agreement bear interest at an annual rate equal to the greater of (i) 9.85% or (ii) 5.10% plus the Wall Street Journal prime rate. The company paid a $100,000 facility charge upon closing, which is being expensed over the term of the debt. The final payment will be accrued over the term of the debt.

On December 22, 2021, the Company entered into Amendment No. 1 to the Company’s Loan and Security Agreement (the “FirstAmendment”) with the several banks and financial institutions or entities from time-to-time party thereto (collectively, the “Lender”) and Hercules Capital, Inc., in its capacity as administrative agent for itself and the Lender (in such capacity, the “Agent”). The First Amendment amended that certain Loan and Security

Agreement dated as of February 7, 2020 (the “LoanAgreement,” as amended by the First Amendment, the “Amended LoanAgreement”) among the Borrower, the Lender and the Agent. The First Amendment was accounted for a modification during the year ended December 31, 2021.

The First Amendment increases the amount that the Company may borrow by $50.0 million, from up to $30.0 million to up to $80.0 million, in multiple tranches. The First Amendment increases the second tranche (“Tranche 2”) from $10.0 million to $30.0 million with $15.0 million being available at the Company’s option through April 30, 2022 and another $15.0 million being available at the Company’s option through November 30, 2022, which availability period will be extended to April 30, 2023 if the first $15.0 million is drawn prior to April 30, 2022. The First Amendment also provides for a third tranche of $30.0 million (“Tranche 3”), which is available, subject to the Agent’s investment committee approval, through the Interest-Only Period (as defined below). The Company’s only borrowings to date under the Loan Agreement are the first tranche of $20.0 million, which the Company drew upon the closing of the Loan Agreement on February 7, 2020.

Additionally, the First Amendment, among other things, (i) extended the expiration of the period in which interest-only payments on borrowings under the Loan Agreement are required from October 1, 2021 to January 1, 2023, which is further extendable to December 31, 2023 upon the partial or full draw of Tranche 2 (the “Interest-Only Period”), (ii) extended the maturity date of Loan Agreement from September 1, 2023 to April 1, 2024, (iii) decreased the annual interest rate from the greater of (w) 9.85% or (x) 5.10% plus the Wall Street Journal prime rate to the greater of (y) 9.25% or (z) 6.00% plus the Wall Street Journal prime rate, (iv) applies a facility charge equal to 0.50% of any future draws, (v) applies a 4.99% end of term charge to any future draws payable on the maturity date, (vi) permits the entry into the Collaboration and License Agreement as previously disclosed with Incyte Corporation, and (vii) adds a minimum cash covenant applicable on the occurrence of certain events. The First Amendment also resets the prepayment premium requirements as of the date of the First Amendment so that any prepayments are subject to a prepayment premium equal to (i) 2.0% of the principal amount outstanding if the prepayment occurs during the first year following the First Loan Amendment, (ii) 1.5% of the principal amount outstanding if the prepayment occurs during the second year following the First Loan Amendment, and (iii) 1.0% of the principal amount outstanding at any time thereafter but prior to the Maturity Date.

Borrowings under the Amended Loan Agreement are collateralized by substantially all of the Company’s and its subsidiaries personal property and other assets, other than its intellectual property. The Amended Loan Agreement includes a minimum cash covenant of $12.5 million that has applied since October 1, 2020, subject to reduction upon satisfaction of certain conditions as set forth in the Amended Loan Agreement. As of December 31, 2020, the conditions set forth in the Loan Agreement were met. The cash covenant of $12.5 million was waived. In addition, the Amended Loan Agreement includes customary affirmative and restrictive covenants and representations and warranties, including a minimum cash covenant applicable on the occurrence of certain events, a covenant against the occurrence of a “change in control,” financial reporting obligations, and certain limitations on indebtedness, liens (including a negative pledge on intellectual property and other assets), investments, distributions (including dividends), collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, and deposit accounts. The Amended Loan Agreement also includes customary events of default, including payment defaults, breaches of covenants following any applicable cure period, the occurrence of certain events that could reasonably be expected to have a “material adverse effect” as set forth in the Amended Loan Agreement, cross acceleration to third-party indebtedness and certain events relating to bankruptcy or insolvency. Upon the occurrence of an event of default, a default interest rate of an additional 5.0% may be applied to the outstanding principal balance, and Hercules may declare all outstanding obligations immediately due and payable and take such other actions as set forth in the Amended Loan Agreement.

In connection with the Amended Loan Agreement, the Company was required to enter into separate deposit account control agreements with the lender in order to perfect the lender’s security interest in the cash collateral in the Company’s operating accounts. In the event of a default under the Amended Loan Agreement, the lender would have the right to take control of the operating accounts and restrict the Company’s access to the operating accounts and the funds therein.

During the year ended December 31, 2021 the Company recognized $1.9 million of interest expense related to the Initial Advance pursuant to the Amended Loan Agreement.

As of December 31, 2021, the Company’s maturities of principal obligations under its long-term debt are as follows:

The Company has not recorded any net tax provision for the periods presented due to the utilization of tax attributes to offset current year federal and state taxable income, the historical losses incurred, and the need for a full valuation allowance on deferred tax assets. The ~~difference between the income tax expense at the U.S. federal statutory rate~~Company’s current year profit and ~~the recorded provision is primarily due to the valuation allowance provided on all deferred tax assets. The Company’s loss~~historical losses before income tax for the periods presented was generated entirely in the United States.

A reconciliation of the provision for income taxes computed at the statutory federal income tax rate to the provision for income taxes as reflected in the financial statements is as follows:

The significant components of the Company’s deferred tax are as follows (in thousands):

	Years Ended December 31,						Years Ended December 31,
	2019			2018			2021			2020
Deferred tax assets (liabilities):
Net operating loss carryforwards	$	16,410		$	12,684		$	17,642		$	22,794
Research and development credits		4,156			3,443			6,113			4,856
Capitalized start-up and research and development costs, net		55,452			59,331
Capitalized start-up and other costs								34,898			28,854
Capitalized research and development costs								31,365			35,632
Deferred revenue		3,334			3,690			—			2,989
Depreciation and amortization of capitalized cost		13			(11,550	)
Equity based compensation								6,277			5,117
Accruals		828			630			845			1,657
Other temporary differences		4,223			3,423			10			29
Deferred tax assets before valuation allowance		84,416			71,651			97,150			101,928
Valuation allowances		(84,416	)		(71,651	)		(97,150	)		(101,928	)
Net deferred tax assets	$	—		$	—		$	—		$	—

The Company has provided a valuation allowance for the full amount of the net deferred tax assets as the realization of the deferred tax assets is not determined to be more likely than not. The valuation allowance decreased by $4.8 million in 2021 due to the decrease in deferred tax assets, primarily driven by the utilization of tax attributes to offset federal and state taxable income, partially offset by an increase to other deferred tax assets. The valuation allowance increased by ~~$12.8 million and $17.2~~$17.5 million in ~~2019 and 2018, respectively,~~2020 due to the increase in deferred tax assets, primarily ~~due to~~driven by net operating loss carryforwards and capitalized research and development costs.

As of December 31, ~~2019,~~2021, the Company had approximately ~~$68.0~~$73.5 million and ~~$33.1~~$34.6 million in federal and state Net Operating Losses (“NOLs”), respectively, which may be available to offset future taxable income. The Company has generated federal NOLs of $48.5 million which have an indefinite carryforward period. The remaining $25.0 million of federal NOLs and the Company’s state NOLs will begin to expire at various dates starting in ~~2025.~~ 2026.

As of December 31, ~~2019,~~2021, the Company had federal and state research credits of ~~$2.9~~$4.1 million and ~~$1.6~~$2.5 million, respectively, which begin to expire in ~~2021.~~2022.

Realization of future tax benefits is dependent on many factors, including the Company’s ability to generate taxable income within the net operating loss carryforward period. Under the Internal Revenue Code provisions, certain substantial changes in the Company’s ownership, including the sale of the Company or significant changes in ownership due to sales of equity, may have limited, or may limit in the future, the amount of net operating loss carryforwards which could be used annually to offset future taxable income. The Company completed an analysis through ~~March~~December 31, ~~2019~~2020 and determined that on March 30, 2007, ~~and~~ August 21, 2015 and May 4, 2020 ownership changes had occurred. The Company may also experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. As a result, its ability to use its pre-change NOLs to offset U.S. federal taxable income may be subject to limitations, which could potentially result in increased future tax liability. In addition, at the state level, there may be periods during which the use of NOLs is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.

As of December 31, ~~2019,~~2021, and ~~2018,~~2020, the Company had uncertain tax positions of $0.2 million related to ~~capitalized research and development costs and~~ research and development credits, which reduce the deferred tax assets with a corresponding decrease to the valuation allowance. The Company has elected to recognize interest and penalties related to income tax matters as a component of income tax expense, of which no0 interest or penalties were recorded for the years ended December 31, ~~2019~~2021 and ~~2018.~~2020. The Company expects none of the unrecognized tax benefits to decrease within the next 12 months related to expired statutes or settlement with the taxing authorities. Due to the Company’s valuation allowance as of December 31, ~~2019, none~~2021, NaN of the Company’s unrecognized tax benefits, if recognized, would affect the effective tax rate.

A reconciliation of the Company’s unrecognized tax benefits is as follows (in thousands):

	Years Ended December 31,							Years Ended December 31,
	2019		2018		2017			2021		2020		2019
Unrecognized tax benefit--beginning of year	$	163	$	163	$	241		$	163	$	163	$	163
Decreases related to prior period positions		—		—		(78	)		0		0		0
Unrecognized tax benefit--end of year	$	163	$	163	$	163		$	163	$	163	$	163

The Company files tax returns in the United States, Massachusetts, California, New Jersey, New York, Rhode Island and Pennsylvania. All tax years since inception (October 11, 2005) remain open to examination by major tax jurisdictions to which the Company is subject, as carryforward attributes generated in years past may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if they have or will be used in a future period. The Company is currently not under examination by the Internal Revenue Service or any other jurisdictions for any tax years.

Incyte – In September 2021, the Company entered into the Incyte Agreement and Incyte Stock Purchase Agreement. Under the terms of the Incyte Agreement, Incyte will receive exclusive commercialization rights of axatilimab outside of the United States. In the United States, Incyte and the Company will co-commercialize

axatilimab, with the Company having the right to co-promote the product with Incyte. In exchange for these rights, Incyte agreed to pay a non-refundable cash payment of $117 million and in addition a $35 million equity investment. In certain cases, the Company is required to assist Incyte and is responsible for 45% of development costs associated with global and U.S. specific clinical trials.

NovaMedica—In August 2013, in connection with the third tranche of its Series B-1 financing, the Company entered into a Technology Transfer Agreement (the “Tech Transfer Agreement”) with Domain Russia Investments Limited (“DRI”). Pursuant to the Tech Transfer Agreement, in exchange for nominal payment, the Company assigned to DRI certain patent applications and granted to DRI a license to develop and commercialize entinostat in certain Eastern European countries (the “Covered Territory”). The Company concurrently entered into a sublicense agreement with DRI (the “DRI Sublicense”) and a sublicense agreement (the “NovaMedica Sublicense”) with NovaMedica LLC (“NovaMedica”), which is jointly owned by Rusnano Medinvest LLC and DRI. Pursuant to the DRI Sublicense, the Company granted to DRI an exclusive sublicense to develop, manufacture and commercialize entinostat in the Russian Federation. Pursuant to the NovaMedica Sublicense, the Company granted to NovaMedica an exclusive sublicense to develop, manufacture and commercialize entinostat in the rest of the Covered Territory. Immediately thereafter, the Company, DRI and NovaMedica executed an assignment and assumption agreement, pursuant to which the assigned patents and all of DRI’s rights and obligations under the Tech Transfer Agreement and the DRI Sublicense were transferred to NovaMedica. Under the Tech Transfer Agreement, in certain cases, the Company is required to assist NovaMedica, and NovaMedica is required to reimburse the Company for any out-of-pocket expenses incurred in providing this assistance, including travel-related expenses.

Eddingpharm—In April 2013, the Company entered into a License and Development Agreement (the “Eddingpharm License Agreement”) and a Series B-1 purchase agreement (the “Eddingpharm Purchase Agreement”) with Eddingpharm International Company Limited (“Eddingpharm”). Under the terms of the Eddingpharm License Agreement, Eddingpharm, in exchange for rights to develop and commercialize entinostat in China and certain other Asian countries, purchased $5.0 million of Series B-1 and agreed to make certain contingent milestone and royalty payments based on revenue targets. In certain cases, the Company is required to assist Eddingpharm, and Eddingpharm is required to reimburse the Company for any out-of-pocket expenses incurred in providing this assistance, including reimbursement for person-hours above a certain cap.

On February 17, 2022, UCB Biopharma SRL (“UCB”) sent the Company a demand for payment alleging that the Company is obligated to pay a portion of the consideration that the Company has received or will receive in the future pursuant to the License Agreement as sublicensing revenue. The Company believes that it has fully satisfied its payment obligation and is in discussions with UCB regarding the matter.

From time to time, the Company may be subject to various claims and proceedings in the ordinary course of business. If the potential loss from any claim, asserted or unasserted, or proceeding is considered probable and the amount is reasonably estimable, the Company will accrue a liability for the estimated loss. There were 0 contingent liabilities recorded as of December 31, 2021 or 2020.

	Years Ended December 31,						Years Ended December 31,
		2019		2018	2017			2021		2020	2019
	(In thousands)						(In thousands)
Supplemental Disclosures of Cash Flow Information
Interest paid	$	—	$	—	$	—	$	1,997	$	1,631	$	—
Supplemental Disclosures of Non-Cash Investing and Financing Activities:
Issuance costs included in accounts payable and accrued expenses	$	—	$	—	$	50	$	134	$	43	$	—
Vesting of restricted stock	$	—	$	—	$	59

~~The adoption of ASC 842, “Leases”, resulted in the recording of a lease asset and a lease liability of approximately $1.3 million as of January 1, 2019.~~

In June 2015, the Company hired a Chief Executive Officer who was also appointed as a member of the Board. This individual is also a managing director at MPM Asset Management, LLC, which holds an investment in the Company’s common stock.

The following table contains quarterly financial information for 2019 and 2018. The Company believes that the following information reflects all normal recurring adjustments necessary for a fair statement of the information for the periods presented. The operating results for any quarter are not necessarily indicative of results for any future period.

Three Months Ended

2019

In thousands, except per share data

March 31

June 30

September 30

December 31

License fees

$
379

$
379

$
379

$
380

Operating expenses:

Research and development

11,279

12,290

9,923

9,502

General and administrative

3,911

3,463

3,605

5,083

Total expenses

15,190

15,753

13,528

14,585

Loss from operations

(14,811
)

(15,374
)

(13,149
)

(14,205
)
Other income

509

458

320

205

Net loss

$
(14,302
)

$
(14,916
)

$
(12,829
)

$
(14,000
)
Net loss per share attributable to common
stockholders—basic and diluted

$
(0.53
)

$
(0.47
)

$
(0.41
)

$
(0.44
)
Weighted-average shares--basic and diluted

27,023,466

31,605,279

31,630,639

31,640,484

Three Months Ended

2018

In thousands, except per share data

March 31

June 30

September 30

December 31

License fees

$
379

$
379

$
379

$
380

Operating expenses:

Research and development

15,339

14,851

14,095

15,821

General and administrative

4,791

4,479

4,125

3,892

Total expenses

20,130

19,330

18,220

19,713

Loss from operations

(19,751
)

(18,951
)

(17,841
)

(19,333
)
Other income

353

563

503

496

Net loss

$
(19,398
)

$
(18,388
)

$
(17,338
)

$
(18,837
)
Net loss per share attributable to common
stockholders—basic and diluted

$
0.79

$
0.74

$
0.68

$
0.70

Weighted-average shares--basic and diluted

24,478,269

24,705,441

25,471,587

26,804,089

On January 30, 2020, the Company entered into a securities purchase agreement (the “Purchase Agreement”) with five life sciences investors, including Biotechnology Value Fund, L.P., Boxer Capital and AI Life Sciences Investments LLC, an affiliate of Access Industries Inc. (the “Initial Purchasers”), relating to the issuance and sale (the “Offering”) of 3,036,719 shares of its Common Stock, par value $0.0001 per share (“Common Stock”) and pre-funded warrants to purchase 1,338,287 shares of Common Stock (the “Pre-Funded Warrants”). The Pre-Funded Warrants enable the holder to make a cash investment in the Company without increasing its beneficial ownership in the Common Stock because the shares of Common Stock underlying the Pre-Funded Warrant are not issued until the warrant is exercised. The Pre-Funded Warrants are exercisable immediately upon issuance at an initial exercise price of $0.0001 per share and expire on the date upon which the Pre-Funded Warrant is fully exercised. The shares of Common Stock and Pre-Funded Warrants will be issued separately.

The offering price for the securities is $8.00 per share (or $7.9999 for each Pre-Funded Warrant). The aggregate gross proceeds to the Company from this offering are expected to be approximately $35.0 million, excluding any proceeds the Company may receive upon exercise of the Pre-Funded Warrants.

The exercise price and the number of shares of Common Stock purchasable upon the exercise of the Pre-Funded Warrants are subject to adjustment upon the occurrence of specific events, including stock dividends, stock splits, reclassifications and combinations of the Company’s Common Stock. As a result of the offering, the initial exercise price of the Series 1 Warrants was reduced to $10.00 per share and the initial exercise price of the Series 2 Warrants was reduced to $13.00 per share.

On February 7, 2020, the Company entered into a loan and security agreement (the “Loan Agreement”) with Hercules Capital, Inc. (“Hercules”), which provided for aggregate maximum borrowings of up to $30.0 million, consisting of (i) a term loan of up to $20.0 million, which was funded on February 7, 2020, and (ii) subject to Hercules’ investment committee approval, an additional term loan of up to $10.0 million, available for borrowing from February 7, 2020 to December 15, 2020 (the “Tranche 2 Advance”). Borrowings under the Loan Agreement bear interest at an annual rate equal to the greater of (i) 9.85% or (ii) 5.10% plus the Wall Street Journal prime rate.

Borrowings under the Loan Agreement are repayable in monthly interest-only payments through October 1, 2021, or April 1, 2022 if the Phase 3 clinical trial of entinostat (E2112) in patients with advanced hormone receptor positive, human epidermal growth factor receptor 2 negative, breast cancer has achieved the primary efficacy endpoint sufficient to file an NDA as the next step in clinical development (“Performance Milestone”). After the interest-only payment period, borrowings under the Loan Agreement are repayable in equal monthly payments of principal and accrued interest until the maturity date of the loan, which is either (i) September 1, 2023, or (ii) March 1, 2024 upon achievement of the Performance Milestone (the “Maturity Date”). At the Company’s option, the Company may prepay all, but not less than all, of the outstanding borrowings, subject to a prepayment premium equal to (i) 2.0% of the principal amount outstanding if the prepayment occurs during the first year following the applicable loan being funded, (ii) 1.5% of the principal amount outstanding if the prepayment occurs during the second year following the applicable loan being funded, and (iii) 1.0% of the principal amount outstanding at any time thereafter but prior to the Maturity Date. In addition, the Company paid a $100,000 facility charge upon closing and will pay a $50,000 facility charge in connection with the Tranche 2 Advance. The Loan Agreement also provides for a final payment, payable upon maturity or the repayment in full of all obligations under the agreement, of up to 4.99% of the aggregate principal amount of the Term Loan Advances.

Borrowings under the Loan Agreement are collateralized by substantially all of the Company’s and its subsidiaries personal property and other assets, other than its intellectual property. The Loan Agreement includes a minimum cash covenant of $12.5 million that applies commencing on October 1, 2020, subject to reduction upon satisfaction of certain conditions as set forth in the Loan Agreement. In addition, the Loan Agreement includes customary affirmative and restrictive covenants and representations and warranties, including a covenant against the occurrence of a “change in control,” financial reporting obligations, and certain limitations on indebtedness, liens (including a negative pledge on intellectual property and other assets), investments, distributions (including dividends), collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, and deposit accounts. The Loan Agreement also includes customary events of default, including payment defaults, breaches of covenants following any applicable cure period, the occurrence of certain events that could reasonably be expected to have a “material adverse effect” as set forth in the Loan Agreement, cross acceleration to third-party indebtedness and certain events relating to bankruptcy or insolvency. Upon the occurrence of an event of default, a default interest rate of an additional 5.0% may be applied to the outstanding principal balance, and Hercules may declare all outstanding obligations immediately due and payable and take such other actions as set forth in the Loan Agreement.

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock	SNDX	The Nasdaq Stock Market, LLC


		Page
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS		ii

PART I
Item 1.	Business	1
Item 1A.	Risk Factors	23
Item 1B.	Unresolved Staff Comments	5955
Item 2.	Properties	5955
Item 3.	Legal Proceedings	5955
Item 4.	Mine Safety Disclosures	5955

PART II
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuers Purchases of Equity Securities	6056
Item 6.	Selected Financial Data	6157
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	6258
Item 7A.	Quantitative and Qualitative Disclosures about Market Risk	7469
Item 8.	Financial Statements and Supplementary Data	7470
Item 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	7470
Item 9A.	Controls and Procedures	7470
Item 9B.	Other Information	7572
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	72

PART III
Item 10.	Directors, Executive Officers and Corporate Governance	7673
Item 11.	Executive Compensation	7673
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	7673
Item 13.	Certain Relationships and Related Transactions, and Director Independence	7673
Item 14.	Principal Accountant Fees and Services	7673

PART IV
Item 15.	~~Exhibits~~Exhibit and Financial Statement Schedules	7774
Item 16.	Form 10-K Summary	8277

	Pages
Report of Independent Registered Public Accounting Firm	F-1
Consolidated Balance Sheets as of December 31, 2021 and 2020	F-4
Consolidated Statements of Operations for the Years Ended December 31, 2021, 2020 and 2019	F-5
Consolidated Statements of Comprehensive Income (Loss) for the Years Ended December 31, 2021, 2020 and 2019	F-7
Consolidated Statements of Stockholders’ Equity for the Years Ended December 31, 2021, 2020 and 2019	F-8
Consolidated Statements of Cash Flows for the Years Ended December 31, 2021, 2020 and 2019	F-9
Notes to Consolidated Financial Statements	F-11

Exhibit No.		Description

3.1		Amended and Restated Certificate of Incorporation of the Company (incorporated herein by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K (File No. 001-37708), as filed with the SEC on March 8, 2016).

3.2		Amended and Restated Bylaws of the Company (incorporated herein by reference to Exhibit 3.2 to the Company’s Current Report on Form 8-K (File No. 001-37708), as filed with the SEC on March 8, 2016).

4.1		Specimen Common Stock Certificate of the Company (incorporated herein by reference to Exhibit 4.1 to the Company’s Registration Statement on Form S-1/A (File No. 333-208861), as filed with the SEC on February 20, 2016).

4.2		Form of Pre-Funded Warrant to purchase Common Stock issued pursuant to the Exchange Agreement between the Company and Biotechnology Value Fund, L.P., Biotechnology Value Fund II, L.P. and Biotechnology Value Trading Fund OS, L.P., dated June 18, 2018 (incorporated by reference to Exhibit 4.1 to the Company’s Current Report on Form 8-K (File No. 001-37708), as filed with the SEC on June 20, 2018).

4.3		~~Form of Series Warrant to purchase Common Stock (incorporated by reference to Exhibit 4.1 to the Company’s Current Report on Form 8-K (File No. 001-37708), as filed with the SEC on March 29, 2019).~~

~~4.4~~		Form of Pre-Funded Warrant issued pursuant to the securities purchase agreement between the Company and Certain Purchasers, dated March 26, 2019 (incorporated by reference to Exhibit 4.2 to the Company’s Current Report on Form 8-K (File No. 001-37708), as filed with the SEC on March 29, 2019).

4.4		Form of Pre-Funded Warrant issued pursuant to the securities purchase agreement between the Company and Certain Purchasers, dated January 30, 2020 (incorporated by reference to Exhibit 4.1 to the Company’s Current Report on Form 8-K (File No. 001-37708), as filed with the SEC on February 4, 2020).

4.5		Description of Capital Stock (incorporated by reference to Exhibit 4.5 to the Company’s Annual Report on Form 10-K (File No. 001-37708), as filed with the SEC on March 5, 2020).

10.1*		2007 Stock Plan (incorporated herein by reference to Exhibit 10.3 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

Exhibit No.		Description

10.2*		2007 Stock Plan Amendment, dated as of March 8, 2013 (incorporated herein by reference to Exhibit 10.4 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.3*		2007 Stock Plan Amendment, dated as of July 10, 2013 (incorporated herein by reference to Exhibit 10.5 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.4*		2007 Stock Plan Amendment, dated as of January 23, 2014 (incorporated herein by reference to Exhibit 10.6 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

Large Accelerated Filer	☐☒	Accelerated Filer	☒☐

Non-accelerated Filer	☐	Smaller Reporting Company	☒

Emerging growth company	☒☐

	Years Ended December 31,
(In thousands, except share and per share data)	2019			2018			2017			2016			2015
Revenue	$	1,517		$	1,517		$	2,108		$	1,220		$	627
Operating expenses:
Research and development		42,994			60,106			48,201			31,665			9,549
General and administrative		16,062			17,287			15,861			13,321			11,591
Total operating expenses		59,056			77,393			64,062			44,986			21,140
Loss from operations		(57,539	)		(75,876	)		(61,954	)		(43,766	)		(20,513	)
Interest income (expense)		1,571			1,942			1,421			956			(1,414	)
Other expense		(79	)		(27	)		(269	)		(1,662	)		(2,192	)
Net loss	$	(56,047	)	$	(73,961	)	$	(60,802	)	$	(44,472	)	$	(24,119	)
Net loss attributable to common stockholders ⁽¹⁾	$	(56,047	)	$	(73,961	)	$	(60,802	)	$	(47,070	)	$	(103,845	)
Net loss per share attributable to common stockholders--basic and diluted ⁽¹⁾	$	(1.84	)	$	(2.92	)	$	(2.90	)	$	(3.22	)	$	(1,519.27	)
Weighted-average common shares outstanding--basic and diluted ⁽¹⁾		30,490,783			25,371,511			20,997,211			14,619,716			68,352

	Years Ended December 31,									2019 - 2018 Increase (Decrease)						2018 - 2017 Increase (Decrease)
(in thousands)	2019			2018			2017			$			%			$			%
Revenues:
License fees	$	1,517		$	1,517		$	2,108		$	-			0	%	$	(591	)		(28	)%
Total revenues		1,517			1,517			2,108			-			0	%		(591	)		(28	)%
Operating expenses:
Research and development		42,994			60,106			48,201			(17,112	)		(28	)%		11,905			25	%
General and administrative		16,062			17,287			15,861			(1,225	)		(7	)%		1,426			9	%
Total operating expenses		59,056			77,393			64,062			(18,337	)		(24	)%		13,331			21	%
Loss from operations		(57,539	)		(75,876	)		(61,954	)		(18,337	)		(24	)%		13,922			22	%
Other (expense) income:
Interest (expense) income, net		1,571			1,942			1,421			(371	)		(19	)%		521			37	%
Other (expense) income, net		(79	)		(27	)		(269	)		(52	)		(193	)%		242			90	%
Total other income		1,492			1,915			1,152			(423	)		(22	)%		763			66	%
Net loss	$	(56,047	)	$	(73,961	)	$	(60,802	)	$	(17,914	)		(24	)%	$	13,159			22	%

(in thousands)	Total		Less than 1 Year		1 to 3 Years		3 to 5 Years		More than 5 Years
Term loan ⁽¹⁾	$	24,235	$	1,883	$	22,352	$	—	$	—
Operating leases for office space⁽²⁾		1,303		473		376		454		—
Operating lease for office equipment ⁽³⁾		2		2		—		—		—
Capital lease for office equipment⁽⁴⁾		1		1		—		—		—
	$	25,541	$	2,359	$	22,728	$	454	$	—

Exhibit No.		~~Description~~


10.5*		2007 Stock Plan Amendment, dated as of December 17, 2014 (incorporated herein by reference to Exhibit 10.7 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.6*		2007 Stock Plan Amendment, dated as of May 28, 2015 (incorporated herein by reference to Exhibit 10.8 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.7*		2007 Stock Plan Amendment, dated as of August 20, 2015 (incorporated herein by reference to Exhibit 10.9 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.8*		Form of Incentive Stock Option Agreement under 2007 Stock Plan (incorporated herein by reference to Exhibit 10.10 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.9*		Form of Non-Statutory Stock Option Agreement under 2007 Stock Plan (incorporated herein by reference to Exhibit 10.11 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.10*		2015 Omnibus Incentive Plan (incorporated herein by reference to Exhibit 10.12 to the Company’s Registration Statement on Form S-8 (File No. 333-210412), as filed with the SEC on March 25, 2016).

10.11*		Form of Incentive Stock Option Agreement under 2015 Omnibus Incentive Plan (incorporated herein by reference to Exhibit 10.13 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.12*		Form of Non-Qualified Option Agreement under 2015 Omnibus Incentive Plan (incorporated herein by reference to Exhibit 10.14 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.13*		Form of Stock Unit Agreement under 2015 Omnibus Incentive Plan (incorporated herein by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on August 6, 2020).

10.14*		Form of Deferred Settlement Stock Unit Agreement under 2015 Omnibus Incentive Plan (incorporated herein by reference to Exhibit 10.14 to the Company’s Annual Report on Form 10-K (file No. 001-37708), as filed with the SEC on March 12, 2021).

10.15*		2015 Employee Stock Purchase Plan (incorporated herein by reference to Exhibit 4.16 to the Company’s Registration Statement on Form S-8 (File No. 333-210412), as filed with the SEC on March 25, 2016).

10.14*		Executive Employment Agreement by and between the company and Briggs W. Morrison, M.D., dated as of September 30, 2015 (incorporated herein by reference to Exhibit 10.16 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.15*		Executive Employment Agreement by and between the company and Michael A. Metzger, dated as of September 30, 2015 (incorporated herein by reference to Exhibit 10.17 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.16*		Amended and Restated Executive Employment Agreement by and between the Company and Briggs W. Morrison, M.D., dated as of February 2, 2022.

10.17*		Amended and Restated Executive Employment Agreement by and between the Company and Michael A. Metzger, dated as of February 2, 2022.

Exhibit No.		Description


10.18*		Amended and Restated Executive Employment Agreement by and between the Company and Michael L. Meyers, M.D., Ph.D., dated as of ~~October 1, 2015~~April 27, 2020 (incorporated herein by reference to Exhibit ~~10.18 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).~~

10.17*		~~Executive Employment Agreement by and between the Company and Richard P. Shea, dated as of February 9, 2017 (incorporated herein by reference to Exhibit 10.1~~10.6 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on ~~August 10, 2017)~~May 7, 2020).

10.1810.19		Non-employee Director Compensation Policy, as amended, dated as of February 2, 2022.

10.20*		Form of Indemnification Agreement by and between the company and each of its directors and officers (incorporated herein by reference to Exhibit 10.21 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.19†~~10.21†		License, Development and Commercialization Agreement by and between the company and Bayer Schering Pharma AG, dated as of March 26, 2007 (incorporated herein by reference to Exhibit 10.22 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

Exhibit No.		~~Description~~


~~10.20†~~10.22†		First Amendment to the License, Development and Commercialization Agreement by and between the company and Bayer Pharma AG, dated as of October 13, 2012 (incorporated herein by reference to Exhibit 10.23 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.21~~10.23		Second Amendment to the License, Development and Commercialization Agreement by and between the company and Bayer Pharma AG, dated as of February 1, 2013 (incorporated herein by reference to Exhibit 10.24 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.22†~~10.24†		Third Amendment to the License, Development and Commercialization Agreement by and between the company and Bayer Pharma AG, dated as of October 9, 2013 (incorporated herein by reference to Exhibit 10.25 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.23†~~10.25†		Letter Agreement by and between the company and Bayer Pharma AG, dated as of September 18, 2014 (incorporated herein by reference to Exhibit 10.26 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.24†~~		Clinical Trial Agreement by and between the company and Eastern Cooperative Oncology Group, dated as of March 14, 2014 (incorporated herein by reference to Exhibit 10.27 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.25†~~		Amendment No. 1 to Clinical Trial Agreement by and between the company and ECOG-ACRIN Cancer Research Group, dated as of January 30, 2015 (incorporated herein by reference to Exhibit 10.28 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

10.26†		Amendment No. 2 to Clinical Trial Agreement by and between the company and ECOG-ACRIN Cancer Research Group, dated as of July 31, 2015 (incorporated herein by reference to Exhibit 10.37 to the Company’s Registration Statement on Form S-1/A (File No. 333-208861), as filed with the SEC on February 22, 2016).

~~10.27†~~		Amendment No. 3 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated as of April 20, 2016 (incorporated herein by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on August 15, 2016).

~~10.28†~~		Amendment No. 4 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated as of April 20, 2016 (incorporated herein by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on August 15, 2016).

~~10.29†~~		Amendment No. 5 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated as of April 20, 2016 (incorporated herein by reference to Exhibit 10.3 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on August 15, 2016).

~~10.30†~~		Amendment No. 6 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated as of April 25, 2016 (incorporated herein by reference to Exhibit 10.4 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on August 15, 2016).

~~10.31†~~		Amendment No. 7 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated January 9, 2017 (incorporated herein by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on May 9, 2017).

Exhibit No.		~~Description~~

~~10.32†~~		Amendment No. 8 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated January 18, 2017 (incorporated herein by reference to Exhibit 10.3 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on May 9, 2017).

~~10.33†~~		Amendment No. 9 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated November 22, 2017 (incorporated herein by reference to Exhibit 10.34 to the Company’s Annual Report on Form 10-K (File No. 001-37708), as filed with the SEC on March 8, 2018).

~~10.34†~~		Amendment No. 10 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated October 15, 2018 (incorporated herein by reference to Exhibit 10.35 to the Company’s Annual Report on Form 10-K (File No. 001-37708), as filed with the SEC on March 7, 2019).

~~10.35†~~		Amendment No. 11 to Clinical Trial Agreement by and between the Company and ECOG-ACRIN Cancer Research Group, dated July 1, 2019 (incorporated herein by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on November 7, 2019).

~~10.36†~~		Clinical Trial Collaboration and Supply Agreement by and between the company and MSD International GmbH, dated as of March 27, 2015 (incorporated herein by reference to Exhibit 10.32 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.37†~~		First Amendment to Clinical Trial Collaboration and Supply Agreement by and between the company and MSD International GmbH, dated as of August 13, 2015 (incorporated herein by reference to Exhibit 10.38 to the Company’s Registration Statement on Form S-1/A (File No. 333-208861), as filed with the SEC on February 22, 2016).

~~10.38†~~		Amendment #1 to Clinical Trial Collaboration and Supply Agreement by and between the Company, Merck Sharp & Dohme B.V., and MSD International GmbH, dated as of April 26, 2017 (incorporated herein by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on August 10, 2017).

~~10.39†~~		License, Development and Commercialization Agreement by and between the company and Kyowa Hakko Kirin Co., Ltd., dated December 19, 2014 (incorporated herein by reference to Exhibit 10.33 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.40†~~		Side Letter by and between the company and Kyowa Hakko Kirin Co., Ltd., dated December 19, 2014 (incorporated herein by reference to Exhibit 10.34 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.41†~~		Amendment #1 to License, Development and Commercialization Agreement by and between the company and Kyowa Hakko Kirin Co., Ltd., dated September 18, 2015 (incorporated herein by reference to Exhibit 10.39 to the Company’s Registration Statement on Form S-1/A (File No. 333-208861), as filed with the SEC on February 22, 2016).

~~10.42†~~		Amendment #2 to License, Development and Commercialization Agreement by and between the company and Kyowa Hakko Kirin Co., Ltd., dated January 16, 2017 (incorporated herein by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on May 9, 2017).

~~10.43†~~		Combination Study Collaboration Agreement by and between the company and Genentech, Inc. dated August 24, 2015 (incorporated herein by reference to Exhibit 10.35 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

Exhibit No.		~~Description~~

~~10.44†~~		Clinical Trial Collaboration and Supply Agreement by and between the company, Pfizer Inc. and Ares Trading S.A., dated as of December 31, 2015 (incorporated herein by reference to Exhibit 10.36 to the Company’s Registration Statement on Form S-1/A (File No. 333-208861), as filed with the SEC on January 11, 2016).

~~10.45†~~		License Agreement by and between the Company and UCB Biopharma Sprl, dated as of July 1, 2016 (incorporated herein by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K (File No. 001- 37708), as filed with the SEC on October 7, 2016).

~~10.46†~~10.27†		Side Agreement by and between the Company and UCB Biopharma Sprl, dated March 8, 2017 (incorporated herein by reference to Exhibit 10.4 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on May 9, 2017).

~~10.47†~~10.28†		Amendment No. 1 to License Agreement by and between the Company and UCB Biopharma Sprl, dated as of July 9, 2019 (incorporated herein by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on November 7, 2019).

~~10.48~~10.29		Third Amended and Restated Investors’ Rights Agreement by and among the company and the parties thereto, dated as of August 21, 2015 (incorporated herein by reference to Exhibit 10.1 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016).

~~10.49†~~10.30†		License Agreement by and between the Company and Vitae Pharmaceuticals, Inc., dated as of October 13, 2017 (incorporated herein by reference to Exhibit 10.47 to the Company’s Annual Report on Form 10-K (File No. 001-37708), as filed with the SEC on March 8, 2018).

Exhibit No.		Description

~~10.50†~~10.31†		Amendment No. 1 to License Agreement by and between the Company and Vitae Pharmaceuticals, Inc., dated as of January 25, 2019 (incorporated herein by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on May 8, 2019).

~~10.51~~10.32†		~~Exchange~~Collaboration and License Agreement by and between the Company and ~~Biotechnology Value Fund, L.P., Biotechnology Value Fund II, L.P. and Biotechnology Value Trading Fund OS, L.P.,~~Incyte Corporation, dated ~~June 18, 2018~~as of September 24, 2021 (incorporated herein by reference to Exhibit 10.1 to the Company’s ~~Periodic~~Quarterly Report on Form ~~8-K~~10-Q (File No. 001-37708), as filed with the SEC on ~~June 20, 2018)~~November 15, 2021).

10.33		Purchase Agreement by and between the Company and Incyte Corporation, dated as of September 24, 2021 (incorporated herein by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on November 15, 2021).

10.34		Loan and Security Agreement dated February 7, 2020 between Syndax Pharmaceuticals, Inc. and Hercules Capital, Inc. (incorporated herein by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q (File No. 001-37708), as filed with the SEC on May 7, 2020).

10.35		First Amendment to the Company’s Loan and Security Agreement with the several banks and financial institutions or entities from time-to-time party thereto and Hercules Capital, Inc., in its capacity as administrative agent for itself and the Lender, dated December 22, 2021.

21.1		Subsidiaries of the Registrant ~~(incorporated herein by reference to Exhibit 21.1 to the Company’s Registration Statement on Form S-1 (File No. 333-208861), as filed with the SEC on January 4, 2016)~~.

23.1		Consent of Independent Registered Public Accounting Firm

24.1		Power of Attorney (included on the signature page to this report).

31.1		Certification of the Principal Executive Officer pursuant to Rule 13a-14(a) or 15d-14(a) of the Securities Exchange Act of 1934.

31.2		Certification of the Principal Financial Officerand Principal Accounting Officer pursuant to Rule 13a-14(a) or 15d-14(a) of the Securities Exchange Act of 1934.

32.1+		Certification of Principal Executive Officer and Principal Financial Officer pursuant to Rule 13a-14(b) or 15d-14(b) of the Exchange Act and 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.

101.INS		Inline XBRL Instance Document.

101.SCH		Inline XBRL Taxonomy Extension Schema Document.

101.CAL		Inline XBRL Taxonomy Extension Calculation Linkbase Document.

101.DEF		Inline XBRL Taxonomy Extension Definition Linkbase Document

101.LAB		Inline XBRL Taxonomy Extension Label Linkbase Document.

Exhibit No. 101.PRE		~~Description~~ Inline XBRL Taxonomy Extension Presentation Linkbase Document.

~~101.PRE~~104		Cover Page Interactive Data File (formatted as Inline XBRL ~~Taxonomy Extension Presentation Linkbase Document.~~and contained in Exhibit 101)


	SYNDAX PHARMACEUTICALS, INC.

Date: March ~~5, 2020~~1, 2022	By:	/s/ ~~Briggs W. Morrison, M.D.~~Michael A. Metzger
		~~Briggs W. Morrison, M.D.~~Michael A. Metzger
		Chief Executive Officer


Signature	Title	Date

/s/ ~~Briggs W. Morrison, M.D.~~Michael A. Metzger	Chief Executive Officer and Director (Principal Executive Officer)	March ~~5, 2020~~1, 2022
~~Briggs W. Morrison, M.D.~~Michael A. Metzger		March ~~5, 2020~~1, 2022

/s/ ~~Richard P. Shea~~Alexander Nolte	Chief ~~Financial~~Accounting Officer ~~and Treasurer~~ (Principal ~~Financial~~Accounting Officer, ~~and~~ Interim Principal ~~Accounting~~Financial Officer)	March ~~5, 2020~~1, 2022
~~Richard P. Shea~~		March ~~5, 2020~~1, 2022

~~/s/ Michael A. Metzger~~	~~Chief Operating Officer and Director~~	~~March 5, 2020~~
~~Michael A. Metzger~~	Alexander Nolte

/s/ Dennis G. Podlesak	Chairman of the Board of Directors	March ~~5, 2020~~1, 2022
Dennis G. Podlesak	Chairman of the Board of Directors	March ~~5, 2020~~1, 2022

/s/ ~~Pierre Legault~~Martin H. Huber, M.D.	Director	March ~~5, 2020~~1, 2022
~~Pierre Legault~~Martin H. Huber, M.D.

/s/ ~~Fabrice Egros, PharmD, Ph.D.~~Jennifer Jarrett	Director	March ~~5, 2020~~1, 2022
~~Fabrice Egros, PharmD, Ph.D.~~Jennifer Jarrett	Director	March ~~5, 2020~~1, 2022

/s/ Keith A. Katkin	Director	March ~~5, 2020~~1, 2022
Keith A. Katkin	Director	March ~~5, 2020~~1, 2022

/s/ ~~Jennifer Jarrett~~Pierre Legault	Director	March ~~5, 2020~~1, 2022
~~Jennifer Jarrett~~Pierre Legault	Director	March ~~5, 2020~~1, 2022

/s/ William Meury	Director	March ~~5, 2020~~1, 2022
William Meury	Director	March ~~5, 2020~~1, 2022

			Fair Value Measurements Using
	Total Carrying Value		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
December 31, 2021
Assets:
Cash equivalents	$	221,964	$	96,816	$	125,148	$	—
Short-term investments		217,971		—		217,971		—
Total assets	$	439,935	$	96,816	$	343,119	$	—

Liabilities:
Derivative Liability		187		—		—		187
Total Liabilities	$	187	$	—	$	—	$	187

December 31, 2020
Assets:
Cash equivalents	$	115,243	$	110,246	$	4,997	$	—
Short-term investments		177,822		—		177,822		—
Total assets	$	293,065	$	110,246	$	182,819	$	—

			As of December 31, 2021
	Fair Value		Unobservable Input	Range	Weighted Average
(in thousands)
Liabilities:
Derivative Liability	$	187	Discount Rate Volatility Expected timing of the Termination Right	4-5% 58-61% 9 months	4.5% 59.5% 9 months

	Fair Value
Derivative Liability:
Beginning Balance 1/1/2021	$	0
Additions		576
Change in fair value		(389	)
Ending Balance 12/31/2021	$	187

	December 31, ~~2019~~2021
Common stock issuable under pre-funded warrants		~~4,500,000~~
~~Series 1 and 2 warrants~~		~~4,595,039~~3,975,024
Options to purchase common stock		~~6,643,565~~8,071,089
Employee Stock Purchase Plan		~~856,994~~1,296,410
Total		~~16,595,598~~13,342,523

	Number of Options			Weighted Average Exercise Price		Weighted Average Remaining Contractual Term (in years)		Aggregate Intrinsic Value
Outstanding—January 1, 2019		4,252,983		$	9.23		7.3	$	66
Granted		1,964,025		$	6.99
Exercised		(25,857	)	$	6.86
Canceled or forfeited		(134,140	)	$	9.85
Outstanding—December 31, 2019		6,057,011		$	8.50		7.2	$	6,306
Exercisable—December 31, 2019		3,620,626		$	8.93		6.1	$	3,114
Options vested, exercisable or expected to vest—December 31, 2019		5,655,008		$	8.64		7.1	$	5,373

	Number of Shares			Weighted Average Grant Date Fair Value
Unvested—December 31, 2020		18,500		$	10.48
Granted		119,333		$	21.19
Vested		(5,500	)	$	11.17
Forfeited		-		$	-
Unvested—December 31, 2021		132,333

	Three Months Ended
	2019
In thousands, except per share data	March 31			June 30			September 30			December 31
License fees	$	379		$	379		$	379		$	380
Operating expenses:
Research and development		11,279			12,290			9,923			9,502
General and administrative		3,911			3,463			3,605			5,083
Total expenses		15,190			15,753			13,528			14,585
Loss from operations		(14,811	)		(15,374	)		(13,149	)		(14,205	)
Other income		509			458			320			205
Net loss	$	(14,302	)	$	(14,916	)	$	(12,829	)	$	(14,000	)
Net loss per share attributable to common stockholders—basic and diluted	$	(0.53	)	$	(0.47	)	$	(0.41	)	$	(0.44	)
Weighted-average shares--basic and diluted		27,023,466			31,605,279			31,630,639			31,640,484

	Three Months Ended
	2018
In thousands, except per share data	March 31			June 30			September 30			December 31
License fees	$	379		$	379		$	379		$	380
Operating expenses:
Research and development		15,339			14,851			14,095			15,821
General and administrative		4,791			4,479			4,125			3,892
Total expenses		20,130			19,330			18,220			19,713
Loss from operations		(19,751	)		(18,951	)		(17,841	)		(19,333	)
Other income		353			563			503			496
Net loss	$	(19,398	)	$	(18,388	)	$	(17,338	)	$	(18,837	)
Net loss per share attributable to common stockholders—basic and diluted	$	0.79		$	0.74		$	0.68		$	0.70
Weighted-average shares--basic and diluted		24,478,269			24,705,441			25,471,587			26,804,089