TABLE OF CONTENTS

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CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

Statements made in this Annual Report on Form 10-K for the fiscal year ended December 31, 2020 (this “Annual Report”) that are not statements of historical2023, or current facts, such as those under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” arethis Annual Report, may include “forward-looking statements” within the meaning of the federal securities laws, which statements are subject to considerable risks and uncertainties. These forward-looking statements are intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. Forward-lookingAll statements discuss our business, operations and financial performance and conditions, as well as our plans, objectives and expectations for our business operations and financial performance and condition. In some cases, youincluded or incorporated by reference in this Annual Report, other than statements of historical fact, are forward-looking statements. You can identify forward-looking statements by terminologythe use of words such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “predict,” “positioned,” “potential,” “seek,” “should,” “suggest,” “target,” “will,” “would” and similar statements of a future or forward-looking nature and identify forward-looking statements. In particular, forward-looking statements contained in this Annual Report relate to, among other similar expressionsthings, the process of discovering, developing and commercializing medicines that are predictionssafe and effective for use as human therapeutics, and in the endeavor of or indicate future events and future trends, orbuilding a business around such medicines. We caution you that the negativeforegoing may not encompass all of these terms or other comparable terminology intended to identifythe forward-looking statements about the future.made in this Annual Report. In addition, statements that “we believe” orand similar statements reflect our current beliefs and opinions on the relevant subject. These forward-looking statements beliefsare based upon information available to us as of the date of this Annual Report on Form 10-K, and opinions,while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information.

Forward-looking statements are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are subject to risks, uncertainties and assumptions about us, may include or otherwise be dependent on projectionsoutside of our future financial performance, our anticipated growth strategies and anticipated trends in our business.

The followingcontrol. There are or will be important factors could affect our future results and other outcomes, andthat could cause thoseactual results or other outcomes to differ materially from those expressed or implied in our forward-looking statements:

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Risks Related to Our Discovery, Development and Regulatory Approval of Development Candidates

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Risks Related to Government Regulation

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Risks Related to Manufacturing, Commercialization and Reliance on Third Parties.

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Risks Related to Our Intellectual Property

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Risks Related to Our Business Operations and Industry

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Risks Related to Our Common Stock

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PART I

Item 1. Business

OverviewGeneral

We are a biopharmaceutical company utilizing our proprietary human memory B cell platform to discover and develop first-in-class antibody therapeutics designed to changefocused on the way diseases are currently being treated. Our proprietary discovery engine identifies novel therapeutic antibodies and their targets by leveraging highly educated componentsdevelopment of the immune system, memory B cells, from patients who have learned to fight off their disease. B cells are key elements in the human immune system response because they produce specific, high-affinity antibodies that bind to pathogens or cancer cells and target them for destruction by other immune effector cells. Our platform is different from those of other biotechnology companies because of our unbiased, broad, deep and efficient approach to identifying novel antibody-target pairs that may be useful in treating cancer and infectious diseases. Unlike other approaches that use deep sequencing of B cells to identify dominant clones that are common within and across patients, and which assume those clones are therapeutically relevant, we do not assume that any such genomic dominance is necessarily the hallmark of therapeutic utility.

Our primary focus areas aretargeted oncology and infectious disease. Despite many elements that distinguish oncology from infectious diseases, we believe that our platform will enable the discovery of novel antibodies in both these therapeutic areas because of our interrogation of memory B cells from patients who have learned to fight off these diseases. We anticipate screening for novel antibodies that bind viral or bacterial antigens may be simpler relative to oncology. As an example, viral diseases, such as COVID-19, involve fewer potential target antigens represented in the much smaller viral genome, compared to possible oncology targets in humans.

To date, we have processed more than 150 cancer patient memory B cell samples and have generated and screened more than 300,000 hybridomas, or stable, immortalized forms of B cell clones that produce a single antibody for extended periods of time. We have so far successfully identified approximately 1,300 individual antibodies, which we refer to as hits, that appear to bind to either a cancer cell or a tumor extract with high-affinity and specificity. Using this approach, we have identified over 50 potentially novel cancer targets.therapies. We believe that severalthe pursuit of these antibody-target pairs could potentially formnovel or underexplored targets will be central to the basisnext generation of transformative therapies. For that reason, we pursue therapeutics that we believe have best-in-class or first-in-class potential. Our goal is to establish a therapeutic interventionbroad pipeline of preclinical and clinical assets which we can efficiently develop through successive value inflection points. To support that goal, we pair business development activity with significant investment in our internal discovery programs.

Our named pipeline comprises one clinical and three preclinical assets. Our clinical asset is AL102, an investigational gamma secretase inhibitor, or a diagnostic to detect such targetsGSI, currently under evaluation in a broader patient population. OnePhase 3 trial for the treatment of these unique targets is interleukin-38,desmoid tumors. We acquired AL102 and related assets pursuant to an Asset Purchase Agreement, or IL-38, a novel immune checkpoint inhibitor, which is the current focus of our lead discovery program, IMM-ONC-01, which is in preclinical stage. If our preclinical evaluation is successfully completed, we expect to file an Investigational New Drug,Ayala Purchase Agreement, with Ayala Pharmaceuticals, Inc., or IND, application with the U.S. Food & Drug Administration, or FDA, in connection with this program in the second half of 2021.

We believe that our platform is useful in uncovering new insights into cancer biology itself. In analyzing more than 50 cancer targetsAyala, that we have identified to date, we observed a “functional clustering” of targets, indicating that different tumor patients appear to mount an immune response directed towards specific processes in cancer biology. We are leveraging these insights to guideentered into on February 5, 2024, and the discovery of future oncology pipeline assets and to perhaps enable future strategic collaborations and additional value creation.

transaction closed on March 25, 2024. Based on our evaluation of Phase 2 data, we believe that AL102 has the potential, if approved, to establish a new standard of care for patients with desmoid tumors.

Our scientific founder, Scott Dessain, M.D.preclinical pipeline is centered on IM-1021, a receptor tyrosine kinase-like orphan receptor 1, or ROR1, antibody-drug conjugate, or ADC; IM-3050, a fibroblast activation protein, or FAP, targeted radioligand therapy, or RLT, candidate; and IM-4320, an anti-IL-38 immunotherapy candidate. We anticipate submitting investigational new drug applications, or INDs, for IM-3050 and IM-1021 in the first quarter of 2025 and for IM-4320 at a later date. We believe that each of these drugs has the potential to improve outcomes for patients across multiple indications.

Our business model is built upon our expertise in discovering and developing targeted therapies as well as our ability to evaluate and acquire high- potential assets. We believe that the successful track record of our leadership team will make us more attractive to companies selling assets, especially early-stage biotechnology companies that lack resources to efficiently develop their assets.

Our perspective is that the most important considerations when acquiring an asset are the quality of its preclinical or clinical data and the economic terms on which it can be acquired. Accordingly, we are willing to consider assets across multiple modalities, including ADCs, RLTs, naked antibodies, small molecules and more. We believe that effectively pursuing a novel target requires selecting a modality that is appropriate to the target biology.

At present, our internal discovery efforts are centered on ADCs and RLTs. We believe that a broad toolbox of linkers and payloads is necessary to design and develop a broad pipeline of ADCs, as different targets may require different payloads to achieve optimal efficacy and therapeutic index. The novel linker-payload unit we exclusively licensed from Zentalis Pharmaceuticals, Inc., Ph.D., has used ouror Zentalis, is an important component of this toolbox, and we have efforts underway to develop additional linkers and payloads. We also believe that the incorporation of albumin binders into radioligand therapies provides a differentiated approach that can increase the dose of radiation absorbed by patient tumors.

Our discovery platform provides us with a proprietary hybridoma technology to successfully interrogate theimmortalize memory B cells isolated from oncology patient samples. This enables the production of poliosufficient quantities of antibodies to perform high-throughput functional screening, allowing for the recognition of antibodies and targets whose role in cancer was not previously appreciated. In January 2023, we announced an agreement with AbbVie under which AbbVie paid us $30 million upfront for access to up to 10 targets identified through our discovery platform.

On October 2, 2023, we completed a merger with Morphimmune Inc, or the Merger. As a result of the Merger, our corporate strategy has shifted significantly. At the close of the Merger, Clay Siegall, Ph.D. became our President and Chief Executive Officer. Three additional Morphimmune Inc, or Morphimmune, executives joined our leadership at the time of the Merger and, since that time, we have continued to expand our executive management team. We believe that these new hires, in combination with our existing management, have the experience and skills necessary to execute our post-Merger strategy.

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Immunome Pipeline

AL102 (Gamma Secretase Inhibitor)

On February 5, 2024, we entered into the Ayala Purchase Agreement with Ayala, pursuant to which we acquired assets including the rights to AL102, a GSI, currently under evaluation in a Phase 3 trial for the treatment of desmoid tumors. We closed the transaction contemplated by the Ayala Purchase Agreement, including the purchase of AL102, on March 25, 2024.

Our interest in AL102 was largely a response to Phase 2 data, a preliminary version of which was shared by Ayala at European Society for Medical Oncology congress, or ESMO, in October 2023. Ayala’s data showed an objective response rate, or ORR, of 64% in the intent-to-treat population and 75% among evaluable patients. Other measures of response, including tumor volume as measured by MRI and cellularity as estimated via T2 imaging, also showed deep responses. 

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Disease background

Desmoid tumors, also known as aggressive fibromatosis or desmoid-type fibromatosis, are debilitating, painful and aggressive non-metastatic soft tissue tumors that are prone to recurrence. Depending on where in the body they occur, desmoid tumors can cause debilitating pain, deformity and, in some cases, life threatening organ damage. These tumors are rare, with approximately 1,000-1,650 patients diagnosed each year and has identified novel antibodies directedapproximately 5,500-7,000 actively managed patients in the United States. They typically occur in people between the ages of 15 and 60 and are most common in early adolescence, with a peak around 30 years of age, and they are more common in women than men.

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Desmoid tumors arise in connective tissue and can occur anywhere in the body where connective tissue is found. These tumors are locally aggressive, which means that while they do not metastasize to other parts of the body, they can grow into the surrounding or adjacent tissue. While some people with desmoid tumors do not experience symptoms, others may experience pain, swelling, difficulty sleeping, and reduced mobility. Symptoms largely depend on the location of the tumor and the extent of invasion or compression of surrounding tissue. The pain and physical limitations associated with desmoid tumors lead to high clinical burdens and reduced quality of life. Additionally, a study conducted in Denmark found that patients with desmoid tumors have substantially higher healthcare resource utilization compared with matched patients at 1- and 3- years post-diagnosis, including increases in both in-patient and out-patient visits as well as days of hospitalization.

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The vast majority (85-90%) of desmoid tumors are sporadic and result from somatic mutations in the CTNNB1 gene, which encodes β-catenin protein. Desmoid tumors may also result from germline mutation of the APC gene, which is also associated with familial adenomatous polyposis, that virus.leads to accumulation of β-catenin in the nucleus and drives overexpression of its target genes. Risk factors for developing desmoid tumors in patients with these mutations include trauma (especially abdominal surgery), estrogen, and pregnancy.

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Desmoid tumors exhibit a variable clinical course, but evidence suggests that the initial period of tumor growth is followed by a long period during which the tumor is stable or may even regress. The recurrence rate of desmoid tumors is associated with tumor location and underlying genetic mutation. For example, tumors on the extremities have recurrence rates of up to 77% and intra-abdominal tumors recur much more frequently than extra-abdominal tumors in patients with familial adenomatous polyposis. Risk factors for the initial development of desmoid tumors can also increase the risk of recurrence.

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Prior to the November 2023 U.S. Food & Drug Administration, or FDA, approval of the GSI nirogacestat for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, the treatment landscape for desmoid tumors included watchful waiting, surgery, radiation therapy, low-dose or conventional chemotherapy, or tyrosine kinase inhibitors. Treatment considerations include tumor progression, symptoms, risk of morbidity, surgical risk, and the need for a fast response. Active surveillance is now the preferred management approach for patients whose tumors are in non-critical anatomic locations. We are buildingbelieve GSIs may ultimately capture much of the market for first-line desmoid tumor therapy.

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Mechanism of action

AL102 is an investigational, oral, once-daily GSI. GSIs alter signaling through the Notch pathway, which is involved in embryonic development and the renewal and maintenance of adult tissues. Notch plays a critical role in the proliferation, survival, migration, invasion, and metastasis of cancer cells, which contribute to the development and progression of cancer. Notch also contributes to resistance to cancer therapeutics. Gamma secretase-mediated cleavage of Notch releases the Notch intracellular domain which travels to the nucleus and activates the genes that mediate oncologic behavior. Inhibition of gamma secretase by AL102 blocks this cleavage and inhibits Notch pathway activation.

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Clinical development

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Prior to the initiation of the Phase 3 trial of AL102 in desmoid tumors (RINGSIDE Part B), AL102 clinical activity was observed in two clinical trials that enrolled adult desmoid tumor patients. A Phase 1 dose-escalation clinical trial was conducted by Bristol-Myers Squibb, or BMS, in patients with solid tumors. In this trial, one patient with desmoid fibromatosis was enrolled. This patient demonstrated tumor shrinkage of 16.5% while on study. Based on these data and responses demonstrated with other GSIs, Ayala designed a seamless Phase 2/3 study called RINGSIDE to specifically evaluate the activity of AL102 in patients with progressing desmoid tumors who required therapy. RINGSIDE Part A enrolled 42 patients at three different dosing regimens of AL102: 2 mg once a day for two days every week, 4 mg once a day for two days every week or 1.2 mg once a day daily. Overall, the ORR in evaluable patients as measured by RECIST v1.1 by an independent radiologist was 61% for all doses tested. The 1.2 mg daily dosing cohort had an ORR of 75% in

the evaluable population. AL102 was well tolerated overall with a safety profile consistent with that proofreported with other GSIs. These data were reported at ESMO in 2023.

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Phase 3 RINGSIDE Part B trial in desmoid tumors

Based upon the clinical activity observed in RINGSIDE Part A at the dose of concept to advance a potential product for another virus, SARS-CoV-2, which causes COVID-19. In collaboration1.2 mg given once daily, and following consultation with the United States DepartmentFDA, the phase 3 randomized registration trial, RINGSIDE Part B (NCT04871282) was initiated by Ayala in November 2022. Enrollment was completed in February of Defense,2024.

RINGSIDE Part B is a registrational Phase 3, global, double-blind, randomized, placebo-controlled clinical trial, conducted at 61 clinical sites in North America, Europe, Asia and Australia. It will evaluate the efficacy, safety and tolerability of AL102 compared to placebo in patients with progressing desmoid tumors. One hundred fifty-six patients with histologically confirmed desmoid tumors with progressive disease (defined as tumor growth of at least 20% within the past 12 months as measured by RECIST v1.1) were enrolled. Patients were either treatment-naïve with desmoid tumors not amenable to surgery or DoD, we are pursuing an innovative therapeutic approach against the SARS-CoV-2 virus by seeking to identify effective anti-viral antibodies produced by the memory B cells from “super-responders.” These COVID-19 convalescent patients have cleared their infections and have high levelshad refractory or recurrent disease after at least one line of circulating, high-affinity anti-viral antibodies. Our aim is to interrogate their memory B cells to identify and then reconstitute a mixture of likely four (but up to six) anti-viral antibodies as a “cocktail”, or IMM-BCP-01. The IMM-BCP-01 program was initially focused on original variants of SARS-CoV-2. However,therapy. Patients in the intereststudy were randomized to receive either AL102 at a dose of public health, our current efforts now also include testing1.2 mg given once daily or placebo and evaluated for tumor progression using RECIST v1.1. Patients who progress while on study are eligible to enter an open-label extension whereby they may receive AL102 at a dose of our antibodies against the emerging SARS-CoV-2 variants. 1.2 mg once daily until disease progression or unacceptable toxicity. The primary endpoint of RINGSIDE Part B is progression free survival with secondary endpoints of ORR, duration of response and specific patient-reported outcomes.

We expect to progress IMM-BCP-01publish topline data for RINGSIDE Part B in the first quarter of 2025. In parallel, we are evaluating and performing the additional manufacturing and pharmacology work required to support an NDA submission.

IM-1021 (ROR1 ADC)

On January 8, 2024, we announced that we had entered into an exclusive, worldwide license agreement with Zentalis, or the Zentalis License Agreement, under which we licensed from Zentalis ZPC-21 (now IM-1021), a preclinical-stage ADC targeting ROR1. ROR1 has an oncofetal expression pattern, with little or no expression in healthy tissue, and it is expressed on solid and liquid tumors. We believe ROR1 has been validated as an ADC target through clinical trials of a competitor ADC in multiple B-cell malignancies.

ROR1 as a therapeutic target in multiple oncology indications

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ROR1 is expressed during normal embryonic and fetal development but is largely absent in most mature tissues. While low ROR1 expression is seen in some adult tissues (adipose, pancreas, lung, and a subset of intermediate B cells), high expression has been observed in a variety of blood malignancies and solid tumors. High expression of ROR1 was initially detected in B-cell chronic lymphocytic leukemia, or CLL, and subsequently identified in acute lymphocytic leukemia, non-Hodgkin lymphomas, and myeloid malignancies. Strong expression of ROR1 has also been reported in >30% of primary colon, lung, and pancreatic tumor samples, with more moderate expression seen in the majority of ovarian, lymphoma, skin, testicular, uterine, prostate, and adrenal cancers. Given this pattern of expression, ROR1 may have clinical utility as a therapeutic target in multiple solid and liquid tumor indications, including diseases with large patient populations and high unmet need.

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ROR1 is an ADC target with demonstrated clinical activity. Clinical data from two competitor programs support the potential of ROR1-targeted ADCs. MK-2140 (formerly known as VLS-101) is a ROR1-targeted ADC which is currently being evaluated in four phase 2 trials for B-cell malignancies. In a Phase 1 dose escalation study of MK-2140 in heavily pre-treated patients (median prior lines of therapy = 4, range 1-9), objective tumor responses were observed in patients with mantle cell lymphoma, or MCL, or diffuse large B-cell lymphoma, or DLBCL, but not in patients with CLL,

A retrospective analysis of images obtained from PET/CT imaging using 68Ga-FAPI, a FAP-targeted radiodiagnostic, found tumor-specific uptake across fifteen types of solid tumors with the highest uptake in lung, breast and esophageal cancers, cholangiocellular carcinoma and sarcoma. 

FAP is a membrane-bound serine protease that promotes tumor development and metastasis by influencing extracellular matrix remodeling, intracellular signaling, angiogenesis, epithelial-to-mesenchymal transition, and immunosuppression. The broad distribution of FAP across tumor types and the specificity of its expression in tumors make it an attractive target for the development of therapeutics and diagnostics. 

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FAP-specific inhibitors, such as talabostat, also known as BXCL701, have been investigated in clinical trials since at least 2005; however, none have been approved by the FDA to treat cancer. Other product candidates that have been investigated in the clinic have used FAP to target PET tracers for tumor imaging and cytotoxic molecules and radionuclides as antitumor agents. 

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Emerging field of targeted radiotherapies

Two targeted radiotherapies have been approved by the FDA in the past few years: Luthera® for gastroenteropancreatic neuroendocrine tumors, or GEP-NETs, that express the somatostatin receptor; and Pluvicto® for metastatic castration-resistant prostate cancer, or mCRPC. There has also been strong interest from pharmaceutical companies in acquiring radiotherapies, exemplified by the $4.1 billion dollar acquisition of RayzeBio, Inc. by BMS in 2024; the $2.1 billion acquisition of Endocyte, Inc. by Novartis AG in 2018; a $260 million upfront payment from Lantheus Holdings, Inc. to license two radiotherapeutics from Point Biopharma, Inc.; and a $50 million upfront payment from Novartis AG to license FAP-2286, a FAP-targeted radiotherapy Phase 1 clinical candidate originally developed by Clovis Oncology, Inc.

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Published clinical results from IM-3050 competitor product candidates have demonstrated both the potential therapeutic benefits of this class of therapeutics and the limitations of current candidates. Among eleven patients with advanced or metastatic solid tumors treated with 177Lu-FAP-2286, one patient achieved a PR after six treatments, and that patient’s disease did not progress for more than 12 months after their first dose. However, most patients did not achieve a PR, highlighting the potential for FAP-targeted therapies with improved activity. 

Our approach

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IM-3050, our lead FAP-targeted RLT, has four functional domains:

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IL-38 mRNA expression data from The Cancer Genome Atlas, or TCGA, show that IL-38 expression is significantly higher in head and neck squamous carcinoma, or HNSC, compared to normal tissues. IL-38 transcripts were also detectable in multiple squamous tumor types among the 30 types tested. Notably, carcinomas with squamous cell morphology have exhibited the highest IL-38 expression and highest frequency of IL-38 positive patient samples. Results of the mRNA expression analysis were further confirmed by screening primary tumor samples from patients with HNSC, lung cancer therapeutics(adenocarcinoma and squamous cell carcinoma), and cervical squamous cell carcinoma for the presence of IL-38 protein, which was found to be present in the majority of samples.

In addition to the studies noted above demonstrating that overexpression of IL-38 is associated with reduced intra-tumoral immunity, the potential for IL-38 as an immuno-oncology, or I/O, target is supported by data showing that down-regulation of IL-38 promotes activation of the innate immune system. For example, IL-38 knockout mice exhibited increased pro-inflammatory cytokine levels and delayed tumor growth. Moreover, the IL-38 pathway has been validated as a therapeutic target for treating psoriasis, a disease in which low levels of IL-38 promote a pro-inflammatory immune state. Spesolimab-sbzo, an antibody therapy that received FDA approval in 2022 for the treatment of adults with generalized pustular psoriasis, binds to IL36R and prevents the binding of other ligands that can induce downstream immune activation.

We believe these findings provide compelling evidence that IL-38 inhibition has potential as a novel I/O strategy. While immune checkpoint inhibitors that target T-cells, such as anti-CTLA-4, anti-PD-1 and anti-PD-L1, show great promise in diverse cancer indications, most patients receiving these therapies do not experience meaningful or sustained clinical responses. This is believed to be due to limited infiltration of immune cells, low tumor mutational burden, or the absence of a sustained immune response to the tumor. IL-38 inhibition may reverse the inhibitory mechanisms that regulate innate immune cells, providing a novel approach to leveraging the immune system to treat cancer.

Development of IM-4320 as a potential I/O therapy

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To pursue IL-38, we generated anti-IL-38 antibodies and evaluated them for therapeutic potential. Through these evaluations, we found that:

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We believe that IM-4320, our lead anti-IL-38 antibody, shows in vivo anti-tumor activity consistent with an active I/O agent. Our data indicate that IM-4320 selectively binds to IL-38, inhibiting its binding ILRAPL1 and IL-36R. Furthermore, it inhibited tumor growth in an immune cold melanoma model.

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We intend to submit an IND for this program to the FDA subsequent to our anticipated IND submissions for IM-3050 and IM-1021.

ADC Strategy

We are pursuing a target-driven development strategy intended to establish a broad pipeline of next-generation ADCs focused on oncology indications with high unmet need. We are working to identify novel or under-explored targets that we believe will enable the development of first-in-class ADCs. We also are working to identify clinically validated ADC targets for which competitor programs have shown suboptimal efficacy and/or safety, with the goal of advancing best-in-class ADCs against these targets that overcome these limitations. Our ability to achieve these goals is predicated on our deep understanding of ADC target biology and our ability to deploy a broad toolbox of antibodies, linkers, and payloads in combinations that best match this biology.

Our development process is intended to efficiently advance ADC pipeline candidates through clinical proof-of-concept. We believe that key steps in this process include:

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with our proprietary payload provided improved activity compared with a deruxtecan-containing HER2 ADC when dosed intravenously weekly for three weeks.

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We believe that camptothecin derivatives are well-suited for ADCs targeting solid tumor because they achieve a higher DAR and higher clinical doses. Additionally, a third-party comparison of two FDA-approved HER2 ADCs that contain the same antibody (trastuzumab) but different payloads showed that percentage of patients with progression-free survival was significantly higher for the ADC containing the camptothecin derivative.

In addition to our portfolio of targets, antibodies, and payloads, we also have access to novel linker technologies under our exclusive worldwide license agreement with Zentalis.

Immunome Discovery Platform

Immunome’s discovery platform provides a proprietary approach to identifying cancer-associated targets. Although many of newthese targets and novel therapeuticsare known in scientific literature, many of them were not previously known to neutralize them represent vitally important opportunities to help identify innovative and more effective cancer treatments. We are guided in our efforts by those patients who have effectively mounted a defense against their disease, and we leverage the wisdom of their memory B cells to illuminate the best routes forward.

Our Solution: Immunome’s Discovery Enginebe associated with cancer.

The below graphic in Figure 1 demonstrates the key components of our approach and discovery process using our proprietary discovery engine.

Figure 1. Key components ofworkflow for our discovery engineplatform is as follows: 

Patient Sampling: Our discovery process begins with obtaining a patient’s lymph node, tumor or blood sample and then purifying and expanding the memory B cell population. In oncology, patients sampled include those who are treatment naïve, treated with standard regimens, or have shown clinical signs of response to immunity enhancing therapies. In infectious diseases, such as COVID-19, we include samples from patients who have successfully cleared the infection.been treated with immunotherapies.

Patient Response: We fuse and immortalize thousands of these patient-derived memory B cells using proprietary methods, capturing them as hybridomas, thateach of which typically express an individual antibody in quantities sufficient for extensive functional screening.

Antibody Screening: For oncology, we screen individual antibodies by assessing their binding to intact cancer cells or normal cells, or by assessing their binding to a large number (typically 100) of different extracts of authentic tumor samples and cancer cell lines (Figure 2).lines. Using our proprietary approach, we can screen up to 20,00018,400 antibodies on a single array. For infectious diseases, such as COVID, we screen against defined sets of antigens expressed by the infectious agent. Hybridomas producing antibodies that show both high-affinity binding, by typically binding at single digit nanomolar concentrations, and specific binding, by showing much higher binding to a subset of tumor cells compared to normal cells, or to irrelevant viral proteins, are designated as screening “hits.” Hybridomas producing those hits can be sequenced, their immunoglobulin genes can be cloned into expression vectors, and the individual antibodies can then be produced recombinantly.

method involves an assessment of antibody binding to known human proteins spotted on a protein microarray with high selectivity (for example, as shown in Figure 3, where a single antigen is identified).selectivity. If the target is not represented on the array or no specific binding is seen, we attempt to use the antibody to “pull out” the antigen from its source using immunoprecipitation, and then identify the antigen sequence using mass spectrometry. Using these two approaches we are usuallylargely successful in identifying the antigen to which newly identified antibodies are binding. We then conduct experiments to assess whether the binding of the antibody to the specific antigen can produce a change in the biology of a cancer cell expressing the target, which we refer to as target validation. Additional tests, such as measurements of changes in cell growth, cell survival, cell migration, or internalization of the antigen after it has been bound by the antibody, are used to further assess the potential that the antibody could be of therapeutic interest.

Figure 3. An example of human protein microarray-based target identificationOur Management Team

Engine Output:   So far, we have screenedWe are led by Clay Siegall, Ph.D., President and Chief Executive Officer. Dr. Siegall previously served as CEO of Seagen, Inc., which he co-founded in 1997 and led for nearly 25 years. During his tenure, Seagen earned FDA approvals for four cancer therapies. Pfizer purchased Seagen in December 2023. Dr. Siegall joined us in connection with our acquisition of Morphimmune, a preclinical biotechnology company led by Dr. Siegall, in October 2023.

In addition to Dr. Siegall, three members of our current management team joined us from Morphimmune in October 2023. Jack Higgins, Ph.D., our Chief Scientific Officer, held the same role at Morphimmune. He was previously the Chief Development Sciences Officer at Molecular Templates, Inc., where he led discovery and development efforts for multiple clinical candidates and co-invented the company’s Engineered Toxin Body platform. Bruce Turner, MD, Ph.D., our Chief Strategy Officer, held the same role at Morphimmune and previously founded several biotechnology companies including Xanadu Bio, Inc. and Gennao Bio, Inc. Max Rosett, our Executive Vice President, Operations, and Interim Chief Financial Officer, served as Acting Chief Operating Officer at Morphimmune. Mr. Rosett previously served as a Principal at Research Bridge Partners, where he led Research Bridge Partners’ investment in Morphimmune’s Series A financing.

Bob Lechleider, M.D. serves as our Chief Medical Officer. Dr. Lechleider was most recently the Chief Medical Officer of OncoResponse, Inc. and previously worked with Dr. Siegall at Seagen, where he was responsible for directing the development of early and late-stage portfolios. Phil Roberts serves as our Chief Technical Officer. Mr. Roberts previously served as SVP, Technical Operations at Mirati Therapeutics, Inc., where he led the CMC development of Krazati, Mirati’s first approved product. Sandra Stoneman, J.D., serves as our Chief Legal Officer. She joined us from Duane Morris LLP, where she was an equity partner. Kinney Horn serves as our Chief Business Officer. He previously served in the same role at Olema Oncology, Inc. and spent more than 300,000 hybridomas15 years at Genentech, Inc.

Strategic Transactions

Acquisition of Assets from Ayala Pharmaceuticals, Inc.

On February 5, 2024, we entered into the Ayala Purchase Agreement with Ayala, pursuant to which we acquired Ayala’s AL101 and identified 1,300 “hit” antibodiesAL102 programs and assumed certain of Ayala’s liabilities associated with the acquired assets, or the Ayala Asset Purchase. The Ayala Asset Purchase closed on March 25, 2024, or the Ayala Closing. At the Ayala Closing we (i) paid Ayala $20,000,000, less certain adjustments, (ii) issued Ayala 2,175,489 shares of Company common stock, or the Ayala Shares, with the shares valued at the trailing 30-day volume-weighted average price and (iii) assumed specified liabilities. Pursuant to the Ayala Purchase Agreement, we are obligated to pay Ayala up to $37,500,000 in development and commercial milestones. No legal entities or employees were acquired from Ayala.

The Ayala Purchase Agreement also provides that binduntil the six-month anniversary of the Ayala Closing, Ayala will hold and not sell 50% of the Ayala Shares, subject to certain exceptions. Further, Ayala has agreed, subject to certain exceptions, that until the one-year anniversary of the Ayala Closing, any transfer of the Ayala Shares by Ayala that exceed 15% of the average daily trading volume of our stock over the five-trading day period ending on the trading day immediately prior to such trading date shall be made pursuant to a cancer cellblock trade or other disposition through a tumor extract with high affinity and specificity. To date, while only a fraction of these hits has been assessed further, we have already identified from this fraction of available hits antibodies directed at more than 50market participant designated by us.

We have agreed to use our commercially reasonable efforts to (x) file a resale registration statement with the SEC registering the Ayala Shares for resale on or before the date seven days following the earlier of (i) April 1, 2024 and (ii) the date of this Annual Report and (y) cause such resale registration statement to be declared effective as soon as practicable after the filing thereof but no later than 90 calendar days after the filing thereof or by five trading days from when we are notified that the SEC will not review the resale registration statement or that it will not be subject to further review.

Merger with Morphimmune

On October 2, 2023, we completed our merger with Morphimmune. Under the terms of the Agreement and Plan of Merger and Reorganization dated as of June 28, 2023, or the Merger Agreement, among us, Morphimmune and Ibiza Merger Sub, Inc., a wholly owned subsidiary of the Company, or Merger Sub, Morphimmune merged with and into Merger Sub, with Morphimmune surviving as a wholly-owned subsidiary of us, or the Merger. In connection with the Merger, on October 2, 2023, we issued and sold 21,690,871 shares of our common stock pursuant to the subscription agreements in a Private Investment in Public Equity, or PIPE, transaction which provided us with gross proceeds of $125.0 million.

Acquisition of Assets from Atreca, Inc.

On December 22, 2023, we entered into an asset purchase agreement with Atreca, pursuant to which we will acquire certain antibody-related assets and materials for an upfront payment of $5.5 million and up to $7.0 million in clinical development milestones. The closing of the transaction is subject to customary conditions, including the approval of Atreca’s stockholders. We expect the closing to occur in the second quarter of 2024.

Strategic Collaborations, License Agreements and Other Material Agreements

BMS License Agreement

In connection with the Ayala Closing, we assumed the License Agreement dated as of November 29, 2017, with BMS, as amended by that certain First Amendment to License Agreement dated as of May 4, 2020, or the BMS License.

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Under the BMS License, BMS has granted us a worldwide, non-transferable, exclusive, sublicensable license under certain patent rights and know-how controlled by BMS to research, discover, develop, make, have made, use, sell, offer to sell, export, import and commercialize AL101 and AL102, or the BMS Licensed Compounds, and products containing AL101 or AL102, or the BMS Licensed Products, for all uses including the prevention, treatment or control of any human or animal disease, disorder or condition.  

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Under the BMS License, we are obligated to use commercially reasonable efforts to develop at least one BMS Licensed Product. We have sole responsibility for, and bear the cost of, conducting research and development and preparing all regulatory filings and related submissions with respect to the BMS Licensed Compounds and/or BMS Licensed Products. Ayala has assigned and transferred to us all INDs for the BMS Licensed Compounds originally assigned by BMS to Ayala. We are also required to use commercially reasonable efforts to obtain regulatory approvals in certain major market countries for at least one BMS Licensed Product, as well as to affect the first commercial sale of and commercialize each BMS Licensed Product after obtaining such regulatory approval. Immunome has sole responsibility for, and bears the cost of, commercializing BMS Licensed Products. For a limited period of time, we may not engage directly or indirectly in the clinical development or commercialization of a Notch inhibitor molecule that is not a BMS Licensed Compound.

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We are obligated to pay BMS up to approximately $142 million in the aggregate upon the achievement of certain clinical development and regulatory milestones by products containing the BMS Compounds.  Furthermore, we are obligated to pay up to $50 million per BSM Licensed Product containing a BMS Compound upon the achievement of certain commercial milestones for that product. In addition, we are obligated to pay BMS tiered royalties ranging from a high single-digit to a low teen percentage on worldwide net sales of all BMS Licensed Products.

cancer targets.​

BMS has the right to terminate the BMS License in its entirety upon written notice to us (a) for insolvency-related events involving us, (b) for our material breach of the BMS License if such breach remains uncured for a defined period of time, (c) for our failure to fulfil our obligations to develop or commercialize the BMS Licensed Compounds and/or BMS Licensed Products not remedied within a defined period of time following written notice by BMS, or (d) if we or our affiliates commence any action challenging the validity, scope, enforceability or patentability of any of the licensed patent rights. We concomitantly identifyhave the antibody,right to terminate the BMS License (a) for convenience upon prior written notice to BMS, the length of notice dependent on whether a BMS Licensed Product has received regulatory approval, (b) upon immediate written notice to BMS for insolvency-related events involving BMS, (c) for BMS’s material breach of the BMS License if such breach remains uncured for a defined period of time, or (d) on a BMS Licensed Compound-by-BMS Licensed Compound and/or BMS Licensed Product-by-BMS Licensed Product basis upon immediate written notice to BMS if we reasonably determine that there are unexpected safety and public health issues relating to the potential therapeutic, andapplicable BMS Licensed Compounds and/or BMS Licensed Products. Upon termination of the BMS License in its antigen target. Furthermore,entirety by us for convenience or by BMS, we grant an exclusive, non-transferable, sublicensable, worldwide license to BMS under certain of our patent rights that are necessary to develop, manufacture or commercialize BMS Licensed Compounds or BMS Licensed Products. In exchange for such license, BMS must pay us a low single-digit percentage royalty on net sales of the antibody may also be used inBMS Licensed Compounds and/or BMS Licensed Products by it or its affiliates, licensees or sublicensees, provided that the termination occurred after a diagnostic testspecified developmental milestone for such BMS Licensed Compounds and/or BMS Licensed Products.

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Zentalis License Agreement

In January 2024, we entered into the Zentalis License Agreement with Zentalis, pursuant to determine if a patient’s disease is over-expressing the antigen it is directed at. Our focus is on unmodified antibodies as therapeutic candidates which we believe, enablesreceived an exclusive, worldwide, royalty-bearing, sublicensable license under certain intellectual property relating to Zentalis’ proprietary ADC platform technology, ROR1 antibodies and ADCs targeting ROR1 to exploit products covered by or incorporating the licensed intellectual property rights. Under the Zentalis License Agreement, we are required to use commercially reasonable efforts to develop an ADC targeting ROR1, two additional ADCs, and commercialize any product that receives regulatory approval.

Under the Zentalis License Agreement, we paid to Zentalis upfront consideration totaling $15 million in cash and $20 million in shares of our common stock, with the shares valued at the trailing 30-day volume-weighted average price. We are obligated to pay Zentalis an aggregate of up to $150 million in development and regulatory milestones on the first product containing an ADC targeting ROR1, or a simpler development path.ROR1 ADC Product, to achieve such milestones and commercial milestones on ROR1 ADC Products. We are also obligated to pay to Zentalis mid-to-high single digit royalties on ROR1 ADC Products. In addition, we contemplate forming strategic partnershipsare obligated to pay Zentalis $25 million in development and regulatory milestones for the first product from each of the first five additional development programs using the licensed platform technology to generate products, and mid-single digit royalties on products from each such program. Our royalty payment obligation will commence, on a product-by-product and country-by-country basis, on the first commercial sale of such product in such country and will expire on the latest of (a) the ten (10)-year anniversary of such first commercial sale for such product in such country, (b) the expiration of regulatory exclusivity for such product in such country, and (c) the expiration of the last-to-expire valid claim of a licensed patent covering such product in such country.

The Zentalis License Agreement will continue until the expiration of all royalty payment obligations. The Zentalis License Agreement may be terminated early by (a) either party in its entirety upon (i) the other party’s uncured material breach, subject to a notice and cure period, (ii) any insolvency event of the other party or (iii) prolonged force majeure, (b) us, either in its entirety or in part, for convenience upon a specified period prior written notice, or (c) Zentalis (i) in its entirety if we challenge one of the licensed patents or (ii) fail to meet certain development activity benchmarks within specified time periods.

Collaboration with others who may seekAbbVie

On January 4, 2023, we entered into a collaboration and option agreement, or the Collaboration Agreement, with AbbVie Global Enterprises Ltd., or AbbVie, pursuant to use our antibodies as the basis for more complex modalities, such as engineered T cells or ADCs. For COVIDwhich we collected B cells from 30 super responder donors and identified over 400 antibodies specific for both spike and non-spike viral proteins. We anticipate the output from will useour discovery engine may potentially translate into oneplatform to two programs entering IND-enabling studies per year.

A Key Output from Our Discovery Platform: Functional Clustering

Our platform enables us to identify clusters as informed by the patient memory B cell response to gain additional insights into the biology of cancerdiscover and may allow the identification of new targets. The limited data available on each antigen we have identified to date have revealed a “functional clustering” of targets, or clusters of targets with functional similarities, which highlights those patients who mount a specific immune response. We believe these functional clusters, as shown in the illustration in Figure 4, may provide critical clues to the important tumor-driven processes that must be attacked by the immune system to effectively eliminate the disease.

Figure 4. To date, the Immunome discovery engine has identified 71 antibodies from patient memory B cells directed at more than 50 innovative cancer targets. These targets appear to cluster around six biological functions that might be of therapeutic importance in cancer.

As an example, when looking at clusters of targets with functional similarity, as shown in the above illustration, Target Cluster 1 contains several proteins that tumors appear to produce to modify their microenvironments. Prominent among these are several structural and catalytic proteins that regulate the formation and the function of exosomes, small vesicles packed with material used by cancer cells to create a pro-growth, pro-survival and anti-immune tumor niche. The tumor uses exosomes to change the functions of stromal cells, endothelial cells and immune effector cells, by taking control of those normal cells and using them to generate an environment in which cancer can thrive. We are actively exploring the concept that antibodies directed at some of these exosomal components may have therapeutic utility.

Similarly, Target Cluster 3 presently contains two proteinvalidate targets that may be classified as immune checkpoints serving as functional inhibitors of anti-tumor-immunity. One of the generally regarded great advances in cancer biology in the past 20 years is related to checkpoint inhibition, or the observation that tumors co-opt the very same mechanisms that the immune system uses to down-regulate itself after a response. A well-known checkpoint inhibitor is programmed death ligand 1, or PD-L1, a protein that normally binds to T cells and other immune effectors to “check” or turn down their activity after a physiological immune response has been completed. When a tumor produces this same protein, it results in immune suppression. Eliminating a tumor’s ability to down-regulate the immune system by targeting tumor-derived checkpoints enables patients’ immune systems to respond to and potentially clear their diseases. Checkpoint inhibitors have rapidly become a mainstay in cancer treatment and are now part of the standards of care for multiple solid tumors, with a worldwide market predicted to reach $25 billion by 2022. Most well-known among these are PD-L1 pathway-directed antibodies from Bristol-Myers Squibb Company, Merck & Co. Inc., AstraZeneca plc, or AstraZeneca, and F. Hoffmann-La Roche Ltd. However, these immuno-therapeutics are effective in only a minority of patients with solid malignancies, suggesting that tumors may suppress immunity through multiple interdependent mechanisms, beyond the PD-L1 pathway. Consistent with the two targets that have emerged in this cluster, our data appear to indicate that the B cells of cancer patients react to the proteins that tumors secrete to subvert immunity. One such immune checkpoint, which was identified by our platform, is IL-38, a heretofore obscure member of the interleukin one, or IL-1, family of immune regulatory proteins. We believe that an antibody directed at IL-38, if successful, could restore anti-tumor immunity when used alone or in combination with other checkpoint inhibitors.

Our Multiple Product Development Opportunities in Cancer

We believe our approach to the discovery of novel antibodies enables the following therapeutic modalities:

July 2020. Since August 2017, MIT ceased to be On November 17, 2022, we entered into a Letter Agreement, or Letter Agreement, with Whitehead, which became effective on January 4, 2023, upon the licensing agent for Whitehead and is no longer a party tosatisfaction of the conditions described therein. The Letter Agreement supplements the Whitehead Agreement.

Under the Whitehead Agreement, as amended, we are required to use diligent efforts to develop licensed products or licensed processes and to introduce licensed product or licensed processes into the commercial market and, thereafter, make licensed products and licensed processes reasonably available to the public. We are also obligated to achieve certain specified diligence milestones.

In connection with the Whitehead Agreement, we are required to make an annual license maintenance payment in the high five figures, which amount may be credited against royalties payable in the same calendar year.

Pursuant to the WhiteheadLetter Agreement, we are obligated to pay Whitehead up to $725,000 in the aggregate for certain development, regulatory and commercial milestones and up to $275,000 for each product or derivative that we discover using the licensed product or processes, or Discovered Products. We are also obligated to pay Whitehead a low single digit royalty on net sales of licensed products and licensed processes when sold as a therapeutic or diagnostic product, a mid-single digit royalty on net sales of such licensed products or processes when sold as a research reagent, and a less than one percent royalty on net sales of Discovered Products when sold as a therapeutic or diagnostic product. Our obligation to pay royalties on net sales of licensed products and licensed processes is limited to such products and processes the manufacture, use, sale, and/or import of which, absent the license granted under the Whitehead Agreement, would infringe a claim of a licensed patent. Our obligation to pay royalties on net sales of Discovered Products is limited to a period of seven years from the first commercial sale of each Discovered Product. We are obligated to pay Whitehead a high single digit royalty on service income received in connection with the provision of licensed services the provision of which, absent the license granted under the Whitehead Agreement, would infringe a claim of a licensed patent. We are obligated to pay Whitehead a high first decile percentage of certain payments received by us from sublicensees, subjectthe Collaborator (as defined in the Letter Agreement) (i.e., a corporate partner, as defined in the License Agreement) would be excluded from our payment obligations to certain reductions to single-digit percentages, andWhitehead. Further, we are obligated to pay Whitehead a mid-teen percentage royalty onwill make certain payments received from non-sublicensee corporate partners.

We have the right to terminate the Whitehead Agreement upon specified prior written notice to Whitehead. Whitehead may terminate the Whitehead Agreement(i) as Net Sales (as defined in the eventLicense Agreement) as long as we receive those payments from the Collaborator on a specified number of our uncured material breachproducts purchased by the Collaborator and (ii) upon the achievement of certain milestones whether by us or insolvency. Additionally, Whitehead may terminate the agreement if we or any of our affiliates or sublicensees challenges the validity, patentability, enforceability or non-infringement of the licensed patents.Collaborator.

TJU License Agreement with Purdue Research Foundation

In June 2012, weJanuary 2022, Morphimmune entered into ana Master License Agreement, or the Purdue License Agreement, with Purdue Research Foundation, or PRF. Under the Purdue License Agreement, PRF granted Morphimmune a royalty-bearing, transferable, worldwide, exclusive license, agreement, or the TJU Agreement, with Thomas Jefferson University, or TJU, pursuant to which we obtained from TJU a worldwide, royalty-bearing exclusive licensesublicensable through multiple tiers, under certain patent rights, know-how,patents and materials of TJU that relatetechnology owned by PRF relating to, our antibody screening platform, in each caseamong other subject matter, drugs to target FAP, to research, develop, manufacture, use,and commercialize and improve licensed products and to practice licensed processes for all purposes. The foregoing license grant included the right to grant sublicenses with certain restrictions. The TJU Agreement was subsequently amended in October 2017 and July 2020.

Under the TJU Agreement, we are required to use commercially reasonable diligent efforts to introduce licensed products and/or licensed processes into the commercial market and must endeavor to keep them reasonably available to the public.

In connection with the TJU Agreement, we are currently required to make an annual license maintenance payment in the low five figures, which amount may be credited against royalties payable in the same calendar year. We are also obligated to pay TJU $950,000 in the aggregate for certain development, regulatory and commercial milestones for licensed products. We are obligated to pay TJU a low single digit royalty on net sales of licensed products and licensed processes. Our obligation to pay royalties on net sales of licensed products and licensed processes is limited to net sales generated in countries in which a valid claim under licensed patent exists, and after expiration ofcovered by the licensed patents a lower royalty applies.in all fields of use with limited exceptions. The royalty ratelicense is subject to certain specified reductions. Royalties are payable under the agreement until expirationrights of the TJU Agreement. We are also obligatedU.S. government and rights retained by PRF (i) to pay TJUpractice and to license any government agencies, universities or other educational institutions to practice, make, and use the intellectual property licensed to Morphimmune on a high first decile percentage of any non-royalty sublicensing income received by us, subjectroyalty-free basis for non-commercial uses, (ii) to certain specified reductions.

manufacturers to produce, package, label, test and release bulk drug substance and drug product for clinical and non-clinical testing and for future commercial use, as needed. We expect to continue to rely on such third parties to manufacture our products for the foreseeable future. Our expected future contractual manufacturing organizations will each have successful track records of producing clinical and commercial products for other companies under applicable compliance regulations, such as cGMP compliance in the case of the FDA,FDA.

Competition

The development and will have previously been inspected by regulatory authorities for compliance with cGMP standards. As noted above, we have selected Abzena as our manufacturercommercialization of new product candidates is highly competitive. We compete in the segments of the antibodies for IND-enabling toxicologypharmaceutical, biotechnology and clinical supplies in IMM-ONC-01 and IMM-BCP-01. We plan to continue to work with such third parties located in United States or from time to time, located outside of the United States.

Competition

We are aware of several companiesother related markets that are developing antibodiesdevelop therapies for the treatment of cancer, and infectious diseases. Manywhich is highly competitive with rapidly changing standards of these companies are well-capitalized and, in contrast to us, have significant clinical experience, and may includecare. As such, our potential future strategic partners. In addition, these companies compete with us in recruiting scientific and managerial talent. Our success will partially depend on our ability to obtain, maintain, enforce and defend patents and other intellectual property rights with respect to our antibodies that are proven to be safer and/or more effective or are less expensive than competing products. Our commercial opportunity and success willcould be reduced or eliminated if competingour competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient, or are less expensive than the antibodiesany products that we may develop or if suchthat would render any products become availablethat we may develop obsolete or non-competitive. Our competitors also may obtain marketing approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the future.market.

In oncology, weWe expect to compete with antibody, biologiconcology companies advancing antibodies, ADCs, small molecules, targeted radiotherapies, and other therapeutic platforms and development companiesmodalities. We are aware of competitors who are also pursuing similar antibody-based discovery approaches, including, but not limited to, companies such as AbCellera Biologics, Inc.; Adaptive Biotechnologies Corporation, or Adaptive; AIMM Therapeutics B.V.; Atreca,IGM Biosciences, Inc.; IGM Biociences, Inc.;and OncoReponse, Inc. We also expect to compete with companies pursuing targeted radiotherapies, including, but not limited to, RayzeBio, Fusion Pharmaceuticals, POINT Biopharma, Aktis Oncology, Actinium Pharmaceuticals, and Yantai LNC Biotechnology. In addition, we expect to compete with large, multinational pharmaceutical companies that discover, develop and commercialize antibodies, ADCs, small molecules, targeted radiotherapies, and other therapeutics for use in treating

products than we expect the future market potentialhave. These competitors also compete with us in recruiting and needretaining qualified scientific and management personnel and establishing clinical study sites and patient registration for clinical studies, as well as in acquiring technologies complementary to, or necessary for, our antibody cocktailprograms. In addition, these larger companies may be able to use their greater market power to obtain more favorable supply, manufacturing, distribution and sales-related agreements with third parties, which could give them a competitive advantage over us.

Further, as more product candidates within a particular class of drugs proceed through clinical development to regulatory review and approval, the amount and type of clinical data that may be required by regulatory authorities may increase or change. Consequently, the results of our clinical trials for product candidates in that class will likely need to show a risk benefit profile that is competitive with or more favorable than those products and product candidates in order to obtain marketing approval or, if approved, a product label that is favorable for commercialization. If the risk benefit profile is not competitive with those products or product candidates, or if the approval of other agents for an indication or patient population significantly alters the standard of care with which we tested our product candidates, we may have developed a product that is not commercially viable, that we are not able to sell profitably or that is unable to achieve favorable pricing or reimbursement. In such circumstances, our future product revenue and financial condition would be negatively influenced should anymaterially and adversely affected.

Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of the numerous vaccine products, byour competitors. Smaller and other early-stage companies including Moderna, Inc.; Pfizer Inc. and BioNTech SE (in collaboration), AstraZeneca and Johnson and Johnson, continuemay also prove to be safesignificant competitors, particularly through collaborative arrangements with large and efficacious against COVID-19established companies. These third parties compete with us in recruiting and emerging variants of the virus.retaining qualified scientific and management personnel, establishing clinical study sites and subject enrollment for clinical studies, as well as in acquiring technologies complementary to, or necessary for, our current or future products or programs.

Intellectual Property

Intellectual property is of vital importance in our field and in biotechnology generally. We seek to protect and enhance proprietary technology, inventions, and improvements that are commercially important to the development of our business by seeking, maintaining, and defending patent rights, whether developed internally, acquired or licensed from third parties. We will also seek to rely on regulatory protection afforded through orphan drug designations, inclusion in expedited development and review, data exclusivity, market exclusivity and patent term extensions where available.

We utilize various types of intellectual property assets to provide multiple layers of protection. For example, we seek a variety of patents to protect our inventions including, for example, compositions of matter and uses in treatment and diagnostic and methods for novel antibodies, including methods of treatment for diseases expressing novel targets. We believe our current layered patent estate, together with our efforts to develop and patent next generation technologies, provides us with substantial intellectual property protection.

We have filed or will file for patent protection in the United States and internationally for our lead antibodies and the targets to which they bind, as well as for process improvements. As of February 25, 2021,March 28, 2024, we own national phaseor exclusively in-license (a) 139 issued or granted patents, including 6 issued U.S. patents, 74 EP validations, 2 Australian patents, 2 Canadian patents, 2 Chinese patents, 3 Indian patents, 2 Japanese patents, and 2 Korean patents; (b) 3 pending U.S. provisional patent applications in 11 countries or regional patent jurisdictions, including the United States, based on a Patent Cooperation Treaty, or PCT, application filed in 2019,applications; (c) 3 pending PCT applicationsapplications; (d) 19 pending U.S. non-provisional patent applications; and 6(e) 148 pending US provisionalforeign patent applications, withincluding 10 in Australia, 12 in Canada, 12 in China, 15 in Europe, 7 in India, 11 in Japan and 10 in Korea, all across 24 patent families, covering our IM-4320 (IL-38), IM-1021 (ROR1), IM-3050 (FAP), AL102 and AL101 product candidates. Our portfolio includes issued and/or pending claims directed to the composition of matter and methods of use for antibodies, including IMM-ONC-01IM-4320, IM-1021, IM-3050, AL102 and IMM-BCP-01, targeting identified antigens.AL101. Patent applications claiming the benefit of these PCT applications, if issued, are expected to expire between 2039 and 2040. Patent applications claiming priority to and the benefit of these provisional applications,covering IM-4320, if issued, are expected to expire between 2040 and 2042. However, we2042, absent any patent term extensions or adjustments and without accounting for terminal disclaimers. Patent applications covering IM-1021, if issued, are expected to expire in 2042, absent any patent term extensions or adjustments and without accounting for terminal disclaimers. Patent applications covering IM-3050, if issued, are expected to expire in 2045, absent any patent term extensions or adjustments and without accounting for terminal disclaimers. The US composition of matter patent covering AL102 will expire in 2038, which includes 5 years of expected patent term extension. Patent applications covering AL102 and various derivatives, if issued, are expected to expire between 2033-2043, absent any patent term extensions or adjustments and without accounting for terminal

disclaimers. The US composition of matter patent covering AL-101 will expire in 2037, which includes 5 years of expected patent term extension; patent applications covering AL-101, if issued, are expected to expire between 2032-2042, absent any patent term extensions or adjustments and without accounting for terminal disclaimers. We recognize that the area of patent and other intellectual property rights in biotechnology is an evolving one with many risks and uncertainties, which may affect those rights.the validity, enforceability and expiration of the aforementioned patents and patent applications.

Our commercial success will depend in significant part upon obtaining and maintaining patent protection and trade secret protection offor our current and future product candidatestargeted therapeutics and the methods used to develop and manufacture them, as well as successfully defending these patents against third-party challenges and operating without infringing on the proprietary rights of others. Our ability to stop third parties from making, using, selling, offering to sell or importing our products depends on the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities. We cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents, or any patents granted to us in the future will be commercially useful in protecting our product candidates, discoverytargeted therapeutics, current programs and processes. For this and more comprehensive risks related to our intellectual property, please see the section titled “Risk Factors — Risks Related to Our Intellectual Property.”

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, including the United States, the patent term is 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent’s term may potentially be lengthened by patent term adjustment, or PTA, which compensates a patentee for administrative delays by the USPTO in examining and granting a patent taking into account delays on the part of the patentee, or may be shortened if a patent is terminally disclaimed over an earlier expiring patent. In the United States, the patent term of a patent that covers an FDA-approved

patentability opinion which can be used to evaluate the chances of success for the national applications in foreign countries prior to having to incur the filing fees. Although a PCT application does not issue as a patent, it allows the applicant to establish a patent application filing date in any of the member states and then seek patents through later-filed national-phase applications. No later than either 30 or 31 months from the firstearliest priority date of the PCT application, separate national phase patent applications can be pursued in any of the PCT member states, depending on the deadline set by individual contracting states. National phase entry can generally be accomplished through direct national filing or, in some cases, through a regional patent organization, such as the European Patent Organization. The PCT system delays application filing expenses, allows a limited evaluation of the chances of success for national/regional patent applications and allows for substantial savings in comparison to having filed individual countries rather than a PCT application in the event that no national phase applications are filed.

For all patent applications, we determine claiming strategy on a case-by-case basis. Advice of counsel and our business model and needs are always considered. We file patentspatent applications containing claims for protection of all useful applicationscommercially relevant uses of our proprietary technologies and any products, as well as all new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable. We may periodically reassess the number and type of patent applications, as well as the pending and issued patent claims to ensure that coverage and value are obtained for our processes, and compositions, given existing patent law and court decisions. Further, claims may be modified during patent prosecution to meet our intellectual property and business needs.

We recognize that the ability to obtain patent protection and the degree of such protection depends on a number of factors, including the extent of the prior art, the novelty and non-obviousness of the invention, and the ability to satisfy subject matter, written description, and enablement requirements of the various patent jurisdictions. In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted or further altered even after patent issuance. Consequently, we may not obtain or maintain adequate patent

applications in the United States that also claim technology to which we have rights, we may have to participate in interference or derivation proceedings in the USPTO to determine priority of invention.

When available to expand market exclusivity, our strategy is to obtain, or license additional intellectual property related to current or contemplated development platforms, core elements of technology and/or product candidates.programs and targeted therapeutics.

For more information regarding the risks related to our intellectual property, see the section titled “Risk Factors — Risks Related to Our Intellectual Property.”

Government Regulation

The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics such as those we are developing.drugs and biologics. We, along with our third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of our productprograms and development candidates.

U.S. Government Regulation of Biological Products

In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its implementing regulations and biologics under the FDCA, the Public Health Service Act, or PHSA, and their implementing regulations. Both drugs and biologics also are subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state and local statutes and regulations requires the expenditure of substantial time and financial resources.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with Good Clinical Practices, or GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial

In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product. These so-called Phase 4 studies may be made a condition to approval of the BLA. FailureNDA or BLA; failure to exhibit due diligence with regard to conducting these Phase 4 clinical trials could result in withdrawal of approval for products. Concurrent with clinical trials, companies may complete additional animalnonclinical studies and develop additional information about the biological characteristics of the investigational product candidate and must 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 product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final product, or for biologics, the safety, purity and potency. 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.

BLA Submission and Review

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials, along with information relating to the product’s chemistry, manufacturing, and controls and proposed labeling, are submitted to the FDA as part of aan NDA or BLA requesting approval to market the product for one or more indications. TheAn NDA or BLA must include all relevantcontain sufficient evidence of the candidate’s safety, purity, potency and efficacy for its proposed indication or indications. Data may come from company-sponsored clinical trials or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data available from pertinent preclinicalsubmitted must be sufficient in quality and clinical studies, including negative or ambiguous results as well as positive findings, together with detailed information relatingquantity to establish the safety and efficacy of the investigational product to the product’s chemistry, manufacturing, controls,satisfaction of the FDA. The testing and proposed labeling,

 Before approving aan NDA or BLA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliancecomply with cGMP requirements and are adequate to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will typically inspect one or more treatmentclinical trial sites to assure that the clinical trials were conducted in compliance with good clinical practices, or GCP. If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficienciesTo assure cGMP and GCP compliance, an applicant must incur significant expenditure of time, money and effort in the submissionareas of training, record keeping, production, and often will request additional testing or information. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.quality control.

After the FDA evaluates aan NDA or BLA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response letter.Letter, or CRL. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A Complete Response letterCRL indicates that the review cycle of the application is complete, and the application will describe all ofnot be approved in its present form. A CRL generally outlines the deficiencies that the FDA has identified in the BLA,application, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the Complete Response letterCRL without first conducting required inspections, testing submitted product lots, and/or reviewing proposed labeling. In issuing the Complete Response letter,CRL, the FDA may recommend actions that the applicant might take to place the BLAapplication in condition for approval, including requests for additional informationclinical or clarification.other data, additional clinical trial(s) and/or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. If a CRL is issued, the applicant may choose to either resubmit the NDA or BLA addressing all of the deficiencies identified in the letter or withdraw the application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA or BLA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in response to an issued CRL in either two or six months depending on the type of information included. Even with the submission of this additional information, however, the FDA ultimately may delay or refuse approval of a BLA if applicabledecide that the application does not satisfy the regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.for approval.

If the FDA grants regulatory approval of a product, is granted, such approval will be granted for particular indicationsis limited to the conditions of use (e.g., patient population, indication) described in the application and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLAproduct with a Risk Evaluationrisk evaluation and Mitigation Strategy,mitigation strategy, or REMS, to ensure the benefits of the product outweigh its risks.risks and to assure the safe use of the drug or biological product. A REMS is a safety strategy to manage a known or potential serious risk associated with a product and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis. If the FDA concludes a REMS is needed, the sponsor of the NDA or BLA must submit a proposed REMS. The FDA will not approve the application without a REMS, if required. The FDA also may condition approval on, among other things, changes to proposed labeling (e.g., the addition of specific contraindications, warnings or precautions) or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace. The FDA may require one or more Phase 4 post a-market studiespost-market trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Expedited DevelopmentFast Track, Breakthrough Therapy and Priority Review ProgramsDesignations

The FDA offers a number ofis authorized to designate certain products for expedited development andor review programs for qualifying product candidates. The fast track program isif they are intended to expediteaddress an unmet medical need in the treatment of a serious or facilitate the process for reviewing new products that meet certain criteria. Specifically, new products are eligible forlife-threatening disease or condition. These programs include fast track designation, if they arebreakthrough therapy designation and priority review designation.

 To be eligible for a fast track designation, the FDA must determine, based on the request of a sponsor, that a product is intended to treat a serious or life-threatening disease or condition and demonstratedemonstrates the potential to address an unmet medical needsneed for the diseasesuch diseases or condition. Fast track designation appliesprovides opportunities for more frequent interactions with the FDA review team to the combinationexpedite development and review of the product andproduct. The FDA may also review

sections of the specific indicationNDA or BLA for which it is being studied. The sponsor of a fast track product has opportunities for frequent interactions with the review team during product development and, once a BLA is submitted, the product may be eligible for priority review. A fast track product may also be eligible for rolling review, where the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor providesand the FDA agree on a schedule for the submission of the application sections of the BLA,

A designated orphan drug may not receive orphan drug exclusivity if itdevelopment candidate approved on this basis is approved for a use that is broader thantypically subject to rigorous post-marketing compliance requirements, including the indication for which it received orphan designation. In addition, exclusive marketing rights incompletion of Phase 4 or post-approval clinical trials to establish the United States may be lost ifeffect on the FDA later determines thatclinical endpoint. Failure to conduct required post-approval studies, or to confirm the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantitiespredicted clinical benefit of the product during post-marketing studies, may allow the FDA to meetwithdraw approval of the needsdrug. The FDA may require the sponsor of patients witha product granted accelerated approval to have a confirmatory trial underway prior to approval. The sponsor must also submit progress reports on a confirmatory trial every six months until the rare disease or condition.trial is complete, and such reports are published on FDA’s website.

 All promotional materials for products approved under the accelerated approval program are subject to prior review by the FDA.

Pediatric Trials

Under the Pediatric Research Equity Act, or PREA, aan NDA or BLA or supplement to a BLAthereto must contain data to assess the safety and efficacy of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may grant deferrals for submission of such data or full or partial waivers. The FDCA requires that a sponsor who is planning to submit a marketing application for a drug or biologic product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan, or PSP, within sixty days of an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA.FDA, if there is no such meeting, as early as practicable before the initiation of Phase 3 or Phase 2/3 clinical trials. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information. The FDA and the sponsor must reach agreement on the PSP. A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from nonclinical studies, early phase clinical trials, and/or other clinical development programs. TheUnless otherwise required by regulation, the PREA does not apply to any product for an indication for which orphan designation has been granted. However, if only one indication for a product has orphan designation, a pediatric assessment may still be required for any applications to market that same product for the non-orphan indication(s).

Orphan Drug Designation and Exclusivity

Under the Orphan Drug Act, the FDA may on its own initiativegrant orphan drug designation to a drug or atbiologic product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the requestUnited States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug or biologic for this type of disease or condition will be recovered from sales in the United States for that drug or biologic. Orphan drug designation must be requested before submitting an NDA or BLA. After the FDA grants orphan drug designation, the identity of the applicant, grant deferralstherapeutic agent and its potential orphan use will be disclosed publicly by the FDA; the posting will also indicate whether the drug or biologic is no longer designated as an orphan drug. More than one program or development candidate may receive an orphan drug designation for submissionthe same indication. Orphan drug designation does not convey any advantage in or shorten the duration of datathe regulatory review and approval process.

 If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to seven years of orphan product exclusivity. During the seven-year exclusivity period, the FDA may not approve any other applications to market a product containing the same active moiety for the same disease, except in very limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity. A product is clinically superior if it is safer, more effective or fullmakes a major contribution to patient care. Thus, orphan drug exclusivity could block the approval of one of our potential products for seven years if a competitor obtains approval of the same product as defined by the FDA and we are not able to show the clinical superiority of our program or partial waivers.development candidate or if our program or development candidate’s indication is determined to be contained within the competitor’s product orphan indication. In addition, the FDA will not recognize

orphan drug exclusivity if a sponsor fails to demonstrate upon approval that the product is clinically superior to a previously approved product containing the same active moiety for the same orphan condition, regardless of whether or not the previously approved product was designated an orphan drug or had orphan drug exclusivity. A product that has received orphan drug designation may not receive orphan exclusivity if it is approved for a use that is broader than the indication for which it received the designation. Orphan exclusivity does not prevent the FDA from approving a different drug or biological product for the same disease or condition, or the same product for a different disease or condition.

Post-Approval Requirements

Any products manufacturedthat we may manufacture or distributed by usdistribute pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to monitoring and record-keeping requirements, reporting of adverse experiences with the product, periodic reporting requirements, providing the FDA with updated safety and efficacy information, product sampling and distribution andrequirements, as well as advertising and promotion ofrequirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product.product’s approved uses (known as off-label use), limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the Internet. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. Thereapproval of a new application or supplement, which may require the applicant to develop additional data or conduct additional pre-clinical studies and clinical trials. The FDA may also are continuing user feeplace other conditions on approvals, including the requirement for a REMS, to assure the safe use of the product. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.

 In addition, quality control and manufacturing procedures must continue to conform to applicable manufacturing requirements under whichafter approval to ensure the quality and long-term stability of the product. The cGMP regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports and returned or salvaged products. The manufacturing facilities for our programs and development candidates must meet cGMP requirements and satisfy the FDA assesses an annual program fee for eachor comparable foreign regulatory authorities before any product identified in anis approved BLA. Biologicand our commercial products can be manufactured. Third-party manufacturers must comply with cGMP regulations that require, among other things, quality control and quality assurance, the maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP. Manufacturers, including third-party manufacturers, and their subcontractorsother entities involved in the manufacture and distribution of approved biologics are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP which impose certain procedural and documentation requirements upon us and our third-party manufacturers. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements upon us and any third-party manufacturers that we may decide to use.other laws. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain compliance with cGMP compliance. Future inspections by the FDA and other aspectsregulatory agencies may identify compliance issues at the facilities of our contract manufacturing organizations, or CMOs, that may disrupt production or distribution or require substantial resources to correct. In addition, the discovery of conditions that violate these rules, including failure to conform to cGMP regulations, could result in enforcement actions, and the discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or sponsor of an approved NDA or BLA, including, among other things, voluntary recall and regulatory compliance.sanctions as described below.

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, could result in adverse consequences to the Company. Examples of these consequences include, without limitation, the following: may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, amongprogram; complete withdrawal of the product from the market or other things:limits on marketing or manufacture of the product; imposition of civil or criminal penalties.

The FDA closely regulates the marketing, labeling, advertising and promotion of biologics.biopharmaceutical products. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.

Pediatric exclusivity

Pediatric exclusivity is a type of non-patent marketing exclusivity available in the United States and, if granted, it provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity or listed patents. This six-month exclusivity may be granted if a sponsor submits pediatric data that fairly responds to a Written Request from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection cover the product are extended by six months. The issuance of a Written Request does not require the sponsor to undertake the described studies.

Biosimilars and Reference Product Exclusivity

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively, the ACA, signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-approvedFDA-licensed reference biological product. To date, a number of biosimilars have been licensed under the BPCIA, and numerous biosimilars have been approved in Europe. The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.

Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. Complexities associated withbiologic without such alteration or switch. Upon licensure by the larger, and often more complex, structures of biological products, as well asFDA, an interchangeable biosimilar may be substituted for the processes by which such products are manufactured, pose significant hurdles to implementationreference product without the intervention of the abbreviated approval pathwayhealth care provider who prescribed the reference product.

The biosimilar applicant must demonstrate that are still being worked out by the FDA.product is biosimilar based on data from (1) analytical studies showing that the biosimilar product is highly similar to the reference product; (2) animal studies (including toxicity); and (3) one or more clinical studies to demonstrate safety, purity and potency in one or more appropriate conditions of use for which the reference product is approved. In addition, the applicant must show that the biosimilar and reference products have the same mechanism of action for the conditions of use on the label, route of administration, dosage and strength, and the production facility must meet standards designed to assure product safety, purity and potency. 

UnderA reference biological product is granted 12 years of data exclusivity from the BPCIA,time of first licensure of the product, and the first approved interchangeable biologic product will be granted an exclusivity period of up to one year after it is first commercially marketed. In addition, the FDA will not accept an application for a biosimilar or interchangeable product may not be submitted tobased on the FDAreference biological product until four years followingafter the date thatof first licensure of the reference product was first licensed byproduct.

Hatch-Waxman exclusivity

Market exclusivity provisions under the FDA. In addition,FDCA can delay the submission or the approval of certain marketing applications. The FDCA provides a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed. During this 12-yearfive-year period of non-patent data exclusivity another company may still marketwithin the United States to the first applicant to obtain approval of an NDA for a competing version of the reference productnew chemical entity. A drug is a new chemical entity if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law.

A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs fromhas not

previously approved any other new drug containing the endsame active moiety, which is the molecule or ion responsible for the action of otherthe drug substance. During the exclusivity protectionperiod, the FDA may not accept for review an abbreviated new drug application, or patent term, may be grantedANDA, or an NDA submitted under Section 505(b)(2) (505(b)(2) NDA) submitted by another company for another drug based on the voluntary completionsame active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

 The FDCA alternatively provides three years of non-patent exclusivity for an NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active agent for the original indication or condition of use. Five-year and three-year exclusivity will not delay the submission or approval of a pediatricfull NDA. However, an applicant submitting a full NDA would be required to conduct, or obtain a right of reference to, all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

FDA Regulation of Companion Diagnostics

We believe that certain of our product candidates may require an in vitro diagnostic to identify appropriate patient populations for investigation and/or use of our product candidates. These diagnostics, often referred to as companion diagnostics, are regulated as medical devices. In the United States, the FDCA and its implementing regulations, and other federal and state statutes and regulations govern, among other things, medical device design and development, preclinical and clinical testing, premarket clearance or approval, registration and listing, manufacturing, labeling, storage, advertising and promotion, sales and distribution, export and import, and post-market surveillance. Unless an exemption applies, diagnostic tests require marketing clearance or approval from the FDA prior to commercial distribution. The two primary types of FDA marketing authorization applicable to a medical device are premarket notification, also called 510(k) clearance, and premarket approval, or PMA. Most companion diagnostics for oncology product candidates utilize the PMA pathway.

If use of companion diagnostic is deemed essential to the safe and effective use of a drug product, then the FDA generally will require approval or clearance of the diagnostic contemporaneously with the approval of the therapeutic product. On August 6, 2014, the FDA issued a final guidance document addressing the development and approval process for “In Vitro Companion Diagnostic Devices.” According to the guidance, for novel product candidates, a companion diagnostic device and its corresponding drug candidate should be approved or cleared contemporaneously by FDA for the use indicated in the therapeutic product labeling. The guidance also explains that a companion diagnostic device used to make treatment decisions in clinical trials of a drug generally will be considered an investigational device, unless it is employed for an intended use for which the device is already approved or cleared. If used to make critical treatment decisions, such as patient selection, the diagnostic device may be considered a significant risk device under the FDA's Investigational Device Exemption, or IDE, regulations. In which case, the sponsor of the diagnostic device will be required to submit and obtain approval of an IDE application, and subsequently comply with the IDE regulations. However, according to the guidance, if a diagnostic device and a drug are to be studied together to support their respective approvals, both products can be studied in the same investigational study, in accordance withif the study meets both the requirements of applicable IDE regulations and the IND regulations. The guidance provides that, depending on the details of the study plan and degree of risk posed to subjects, a sponsor may seek to submit an FDA-issued “Written Request” for such a study.IND alone, or both an IND and an IDE. 

The BPCIAFDA has generally required companion diagnostics intended to select the patients who will respond to cancer treatment to obtain approval of a PMA for that diagnostic simultaneously with approval of the therapeutic. The PMA process, including the gathering of clinical and preclinical data and the submission to and review by the FDA, can take several years or longer. It involves a rigorous premarket review during which the applicant must prepare and provide the FDA with reasonable assurance of the device's safety and effectiveness and information about the device and its

components regarding, among other things, device design, manufacturing and labeling. In addition, PMAs for certain devices must generally include the results from extensive preclinical and adequate and well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is complexsought. In particular, for a diagnostic, the applicant must demonstrate that the diagnostic produces reproducible results when the same sample is tested multiple times by multiple users at multiple laboratories. As part of the PMA review, the FDA will typically inspect the manufacturer's facilities for compliance with the Quality System Regulation, or QSR, which imposes elaborate testing, control, documentation and continuesother quality assurance requirements.

 If the FDA's evaluation of the PMA application is favorable, the FDA may issue an approvable letter requiring the applicant's agreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to secure final approval of the PMA. If the FDA's evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter. A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is necessary to make the PMA approvable. The FDA may also determine that additional clinical trials are necessary, in which case the PMA approval may be interpreteddelayed for several months or years while the trials are conducted and implementedthen the data submitted in an amendment to the PMA. If and when the FDA concludes that the applicable criteria have been met, the FDA will issue a PMA for the approved indications, which can be more limited than those originally sought by the applicant. The PMA can include post-approval conditions that the FDA believes necessary to ensure the safety and effectiveness of the device, including, among other things, restrictions on labeling, promotion, sale and distribution. Once granted, PMA approval may be withdrawn by the FDA if compliance with post approval requirements, conditions of approval or other regulatory standards are not maintained or problems are identified following initial marketing.

 After a device is commercialized, it remains subject to significant regulatory requirements. Medical devices may be marketed only for the uses and indications for which they are cleared or approved. Device manufacturers must also establish registration and device listings with the FDA. A medical device manufacturer's manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices. Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA. In addition, recent government proposals have soughtThe FDA also may inspect foreign facilities that export products to reduce the 12-year reference product exclusivity period. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. As a result, the ultimate impact, implementation, and impact of the BPCIA is subject to significant uncertainty.United States.

Other U.S. HealthcareHealth Care Laws and Compliance Requirements

InAlthough we currently do not have any products on the United States,market, our business operations and current and future arrangements with investigators, healthcarehealth care professionals, consultants, third-party payors and customers may be subject to regulation and enforcement by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare and Medicaid Services, or CMS, other divisions of the U.S. Department of Health and Human Services, or HHS, (such as the Office of Inspector General and the Health Resources and Service Administration), the Department of Justice, or the DOJ, and individual U.S. Attorney offices within the DOJ, and state and local governments. For example, sales, marketing and scientific/educational grant programs may have to comply with the anti-fraud and abuse provisions of the Social Security Act, the false claims laws, the privacy and security provisions of the Health Insurance Portability and Accountability Act, or HIPAA, and similar state laws, each as amended, as applicable.

The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any item or service reimbursable, in whole or in part, under Medicare, Medicaid or other federal healthcarehealth care programs. The term remuneration has been interpreted broadly to include anything of value. Further, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. The federal Anti-Kickback Statute has been interpreted to apply to arrangements between therapeutic product manufacturers on one hand and prescribers and purchasers on the other. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution. The exceptions and safe harbors are drawn narrowly and practices that involve remuneration that may be alleged to be intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor. Further, courts have found that if “one purpose”

of remuneration is to induce referrals, the federal Anti-Kickback statute is violated. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the federal Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Our practices, including our arrangements with physicians, may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor.

Additionally, the intent standard under the federal Anti-Kickback Statute was amended by the ACA to a stricter standard such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Further, courts have found that if “one purpose” of remuneration is to induce referrals, the federal Anti-Kickback statute is violated. In addition, the ACA codified case law that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act, or FCA.

The federal false claims and civil monetary penalty laws, including the False Claims Act, or FCA, which can be enforced by private citizens through civil qui tam actions, prohibit any person or entity from, among other things, knowingly presenting, or causing to be presented, a false or fraudulent claim for payment to, or approval by, the federal healthcarehealth care programs, including Medicare and Medicaid, or knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government. A claim includes “any request or demand” for money or property presented to the U.S. government. For instance, historically, pharmaceutical and other healthcarehealth care companies have been, and continue to be, prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. A violation of the Anti-Kickback Statute makes any claim submitted as a result of the violation of the Anti-Kickback Statute a false claim under the FCA. Other companies have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, off-label, and thus generally non-reimbursable, uses.

such individuals or entities, and to report annually certain ownership and investment interests held by physicians and their immediate family members. Beginning in 2022, applicable manufacturers also will be required to report such information regarding payments and transfers of value provided, as well as ownership and investment interests held, during the previous year to certain other healthcare professionals, including physician assistants and nurse practitioners. In addition, many states also govern the reporting of payments or other transfers of value, many of which differ from each other in significant ways, are often not pre-empted, and may have a more prohibitive effect than the Sunshine Act, thus further complicating compliance efforts.

In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of drug and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state. Some states also impose requirements on manufacturers and distributors to establish the

more limited than the purposes for which the product is approved by the FDA or comparable foreign regulatory

and additional legislative changes in the United States has increased, and we expect will continue to increase, the pressure on healthcarehealth care pricing. The downward pressure on the rise in healthcarehealth care costs has become very intense. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Some of the provisions of the ACA have yet to be implemented, and there have been legal and political challenges to certain aspects of the ACA. Since January 2017, President Trump has signed two executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the ACA. Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the ACA. While Congress has not passed comprehensive repeal legislation, two bills affecting the implementation of certain taxes under the ACA have been signed into law. In December 2017, the Tax Cuts and Jobs Act of 2017 was enacted which repeals, effective January 1, 2019, the tax penalty for an individual’s failure to maintain ACA-mandated health insurance, commonly referred to as the “individual mandate.” On December 20, 2019, President Trump signed into law the Further Consolidated Appropriations Act, which repealed effective January 1, 2020, the Cadillac tax, and the medical device excise tax and, effective January 1, 2021, also eliminates the health insurer tax. Further, the BBA among other things, amends the ACA, effective January 1, 2019, to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” More recently, in July 2018, CMS published a final rule permitting further collections and payments to and from certain ACA qualified health plans and health insurance issuers under the ACA risk adjustment program in response to the outcome of federal district court litigation regarding the method CMS uses to determine this risk adjustment. Since then, the ACA risk adjustment program payment parameters have been updated annually. In addition, CMS published a final rule that would give states greater flexibility, starting in 2020, in setting benchmarks for insurers in the individual and small group marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces.

Otherother legislative changes have been proposed and adopted in the United States since the ACA was enacted. In August 2011, President Obama signed into lawthat affect health care expenditures. These changes include aggregate reductions to Medicare payments to providers pursuant to the Budget Control Act of 2011, which among other things, included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect beginning on April 1,began in 2013 and, due to subsequent legislative amendments, to the statute will stayremain in effect through 20302032, unless additional Congressional action is taken. However, pursuant to the Coronavirus Aid, Relief and Economic Security Act, or CARES Act, the 2% Medicare sequester reductions have been suspended from May 1, 2020 through December 31, 2020 due to the COVID-19 pandemic. In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, reduced Medicare payments to several providers, including hospitals, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Further,Moreover, there has been increasing legislative and enforcement interestheightened governmental scrutiny over the manner in the United States with respect to specialty drug pricing practices. Specifically, there have beenwhich manufacturers set prices for their marketed products, which has resulted in several recent U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drugproduct pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs. Atdrug products. 

In addition, the IRA has multiple provisions that may impact the prices of drug products that are both sold into the Medicare program and throughout the United States. Starting in 2023, a manufacturer of a drug or biological product covered by Medicare Parts B or D must pay a rebate to the federal level,government if the Trump administration’s budget proposaldrug product’s price increases faster than the rate of inflation. This calculation is made on a drug product by drug product basis and the amount of the rebate owed to the federal government is directly dependent on the volume of a drug product that is paid for by Medicare Parts B or D. Additionally, starting in payment year 2026, CMS will negotiate drug prices annually for a select number of single source Part D drugs without generic or biosimilar competition. On August 29, 2023, the list of the first ten drugs that will be subject to price negotiations was published, although the Medicare drug price negotiation program is currently subject to legal challenges. CMS will also negotiate drug prices for a select number of Part B drugs starting for payment year 2028. If a drug product is selected by CMS for negotiation, it is expected that the revenue generated from such drug will decrease. The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has and will continue to issue and update guidance as these programs as implemented. These provisions take effect progressively starting in fiscal year includes2023. It is unclear how the IRA will be implemented but is likely to have a $135 billion allowance to support legislative proposals seeking to reduce drug prices, increase competition, lower out-of-pocket drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs. On March 10, 2020,significant impact on the Trump administration sent “principles” for drug pricing to Congress, calling for legislation that would, among other things, cap Medicare Part D beneficiary out-of-pocket pharmacy expenses, provide an option to cap Medicare Part D beneficiary monthly out-of-pocket expenses, and place limitspharmaceutical industry. Further, on pharmaceutical price increases. Additionally, the Trump administration previouslyFebruary 14, 2023, HHS released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer competition, increasereport outlining three new models for testing by the negotiating power of certain federal healthcare programs, incentivize manufacturersCenters for Medicare & Medicaid Services Innovation Center which will be evaluated on their ability to lower the listcost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Additionally, on December 7, 2023, the Biden administration announced an initiative to control the price of their productsprescription drugs through the use of march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and reduceTechnology published for comment a Draft Interagency Guidance Framework for Considering the outExercise of pocket costsMarch-In Rights which for the first time includes the price of drug products paid by consumers. HHS has solicited feedback on some of these measures and implemented others under its existing authority. For example, in September 2018, CMS issued a final ruleproduct as one factor an agency can use when deciding to allow Medicare Advantage Plans the option to use step therapy for Part B drugs beginning January 1, 2019. This final rule codified CMS’s policy changeexercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that was effective January 1, 2019. On July 24, 2020, President Trump signed four Executive Orders aimed at lowering drug prices. The Executive Orders direct the Secretary of HHS to: (1) eliminate protection under an Anti-Kickback Statute safe harbor for certain retrospective price reductions provided by drug manufacturers to sponsors of Medicare Part D plans or pharmacy benefit

Additional Regulation

In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business. These and other laws govern our use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated by, our operations. If our operations result in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages and governmental fines. We believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations.

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.

Employees and Human Capital Resources

As of December 31, 2020,2023, we had 2355 full-time employees, including 1238 who hold advanced degrees. Of these 55 employees, 1926 were engaged in research and development activities and 429 were engaged in general and administrative activities. 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.

Item 1A. Risk Factors

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As noted throughout this Annual Report, we are subject toan investment in shares of our common stock involves a numberhigh degree of risks and uncertainties.risk. You should carefully consider and read carefully all of the risks and uncertainties described below,following risk factors, as well as other information included in this Annual Report includingas well as our financial statements and related notes appearing atother public filings with the end of this Annual Report andSEC before deciding whether to invest in our “Management’s Discussion and Analysis of Financial Conditions and Results of Operations.” The risks described below are not the only ones facing us.common stock. The occurrence of any of the following risksevents or additional risks and uncertainties not presently known to us or that we currently believe to be immaterialdevelopments described below could materially and adversely affectharm our business, financial condition, or results of operations.operations and/or prospects or cause our actual results to differ materially from those contained in forward-looking statements we have made in this Annual Report and those we may make from time to time. In such case,an event, the tradingmarket price of our common stock could decline and you may lose all or part of your investment. This Annual Report also contains forward-looking statements and estimates that involve risks and uncertainties. Our actual results could differ materially from those anticipated inYou should consider all of the forward-looking statements as a result of specificrisk factors including the risks and uncertainties described below.when evaluating our business.

Risks Related to Our Business

We are a preclinical stage biopharmaceutical company with a history of losses. We expect to continue to incur significant losses for the foreseeable future and may never achieve or maintain profitability.

We are a preclinical stage biopharmaceuticalbiotechnology company with a history of losses. Since our inception, we have devoted substantially all of our resources to research and development, raising capital, pursuing strategic transactions, building our management team and building our intellectual property portfolio, and we have incurred significant operating losses. As of December 31, 2020,2023, we had an accumulated deficit of $54.4$222.8 million. Our net loss was $17.8$106.8 million and $10.4$36.9 million for the years ended December 31, 20202023 and 2019,2022, respectively. Substantially all of our losses have resulted from expenses incurred in connection with our research and development programs and from general and administrative costs associated with our operations. In 2023, the net loss included $80.8 million of in-process research and development (IPR&D) expense in relation to our acquisition of Morphimmune, which occurred in October 2023. To date, we have not generated any revenue from product sales, and we have not identified or sought or obtained regulatory approval for the marketing or sale of any product candidate.product. Furthermore, we domay not expect to generate any revenue from product sales for the foreseeable future, and we expect to continue to incur significant operating losses for the foreseeable future due to the cost of research and development preclinical studies and clinical trialsactivities and the regulatory approval process for our potential future productdevelopment candidates.

We expect our net losses to increase substantially as we identify product candidates and enter into IND-enabling and other preclinical studies and clinical development related tocontinue our IMM-BCP-01 program or our IMM-ONC-01 program. However,operations; however, the amount of our future losses is uncertain. Our ability to achieve or sustain profitability, if ever, will depend on, among other things, successfully identifying and developing productour development candidates, obtaining regulatory approvals to marketfor marketing and commercialize product candidates,commercialization, manufacturing any approved products on commercially reasonable terms, performance as anticipated by our vendors, entering into additional potential future strategic partnerships and performing and meeting milestones on strategic partnerships, establishing a sales and marketing organization or suitable third-party

 Our limited operating history may make it difficult to evaluate our drug candidates and predict our future performance. Our short history as an operating company makes any assessment of our future success or viability subject to significant uncertainty. We will encounter risks and difficulties frequently experienced by early clinical-stage companies in evolving fields. If we do not address these risks successfully, our business will suffer. Similarly, we expect that our financial condition and operating results will fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. As a result, our stockholders should not rely upon the results of any quarterly or annual period as an indicator of future operating performance.

 In addition, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown circumstances. As we advance our drug candidates, including AL102, we will need to transition from a company with a research focus to a company capable of supporting clinical development and if successful, commercial activities. We may not be successful in such a transition.

We have not yet demonstrated successful completion of clinical development, submitted a New Drug Application, obtained FDA approval for marketing, or successfully commercialized a drug product, and we may be unable to do so. Furthermore, AL102, which we recently acquired, is currently in Phase 3 development, but such acquisition and prior clinical success is not indicative of our ability to obtain new drug application, or NDA, approval or successfully commercialize AL102.

As an organization, we have not yet demonstrated an ability to successfully complete clinical development, obtain regulatory approvals, manufacture a commercial-scale product, conduct sales and marketing activities necessary for successful commercialization, or arrange for a third party to do any of the foregoing on our behalf. Prior to obtaining approval to commercialize a product candidate in the United States or elsewhere, we or our collaborators must demonstrate with substantial evidence from well-controlled clinical trials, and to the satisfaction of the FDA or comparable foreign regulatory authorities, that such product candidates are safe and effective for their intended uses. In 2022, we advanced IMM-BCP-01 into Phase 1 clinical trials for the treatment of SARS-CoV-2, but we since decided to cease further development of IMM-BCP-01 until we identify a partner to continue trials and further development. As such, AL102 is currently our only clinical trial candidate. We acquired this asset and have not yet conducted or completed any clinical trials for our current development candidates previously. We also have limited experience as accurate as they coulda company in preparing and submitting marketing applications and have not previously submitted an NDA or other comparable foreign regulatory submission for any product candidate. In addition, we have had limited interactions with the FDA or other comparable foreign regulatory authorities and cannot be certain how many additional clinical trials of our development candidates will be required or how such additional trials should be designed. Consequently, we may be unable to successfully and efficiently execute and complete necessary clinical trials in a way that leads to submission of an application for and obtaining regulatory approval of any of our development candidates. Notably, AL102's prior development was not conducted by us. As a result, our assumptions about AL102's development potential are based in large part on the data generated from clinical trials conducted by Ayala and we may observe materially and adversely different results in ongoing or future clinical trials. In addition, results from nonclinical studies and clinical trials can be interpreted in different ways. Even if we hadbelieve the nonclinical or clinical data for AL102 is promising, compliance or data integrity issues may later arise and even if not, the data may not be sufficient to support approval by the FDA or comparable foreign regulatory authorities. Marketing approval of AL102 or any other applications that we may submit may be delayed by several years or may require us to expend significantly more resources than we have available. 

In addition, even if we were to obtain marketing approval, regulatory authorities may approve any of our product candidates for fewer or more limited indications than we request, may impose significant limitations in the form of narrow indications, warnings, or a historypost-marketing risk management strategy such as a Risk Evaluation and Mitigation Strategy, or REMS, or the equivalent in another jurisdiction. Regulatory authorities may grant approval contingent on the performance of successfully developing and commercializing pharmaceutical products.costly post-marketing clinical trials or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could materially harm the commercial prospects for AL102 or our earlier-stage product candidates.

We will need to raise substantial additional funds to advance development of potential productour development candidates and our discovery platform,and ADC platforms, and we cannot guarantee that we will have sufficient funds available in the future to develop and commercialize any of our potential future productdevelopment candidates.

The research and development of biopharmaceutical product candidatesbiotechnology products is capital-intensive. If our potential future productdevelopment candidates enter andcontinue to advance through preclinical studies and clinical trials, we will need substantial additional funds to expand our development, regulatory, manufacturing, marketing and sales capabilities. We have used substantial funds to develop and acquire our discovery enginedevelopment candidates and will require significant funds to continue to developadvance our discovery platformand ADC platforms and conduct further research and development, including preclinical studies and clinical trials, of our potential future product candidates, to seek regulatory approvals for our potential future product candidates and to manufacture and market products, if any, that are approved for commercial sale. In addition, we incur additional costs associated with operating as a public company.

As of December 31, 2020, we had $39.9 million in cash. Based on our current operating plan, we believeexpect that our existing cash, as ofcash equivalents and marketable securities at December 31, 20202023, in combination with the proceeds from the 2024 Financing, will be sufficientenable us to fund our operations throughcurrent and planned operating expenses and capital expenditures for at least 12 months from the second fiscal quarterfiling date of 2022.this Annual Report on Form 10-K. Our future capital requirements and the period for which we expect our existing resources to support our operations may vary significantly from what we expect. Our monthly spending levels vary based on new and ongoing research and development and other corporate activities. Because the length of time and activities associated with successful research and development of product candidatesbiotechnology products is highly uncertain, we are unable to estimate the actual funds we will require for development and any approved marketing and commercialization activities.

Any additional capital-raising efforts may divert our management from their day-to-day activities, which may adversely affect our ability to develop and, if approved, commercialize our current and any future development candidates. Additional funding may not be available on acceptable terms, or at all. As a result of actual or anticipated changes in interest rates and economic inflation and the impact of the Russia/Ukraine conflict and Israel-Hamas conflict, the global credit and financial markets have experienced and may in the future experience extreme volatility and disruptions, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, and uncertainty about economic stability. If the equity and credit markets deteriorate, including as a result of recent or future bank failures, it may make any necessary debt or equity financing more difficult to obtain in a timely manner on favorable terms or at all.

The timing and amount of our operating expenditures will depend largely on:on factors outside of our control, some of which are discussed in this section, including the following:

To date, we have primarily financed our operations through the sale of equity securities and convertible debt, and through our other transaction authority contract with the DoD.collaborations. We may seek to raise any necessary additional capital through a combination of public or private equity offerings, debt financings, additional collaborations, strategic alliances, licensing arrangements, government contracts and other marketing arrangements. We cannot assure you that we will be successful in acquiring additional funding at levels sufficient to fund our operations or on terms favorable to us or that the DoD will not exercise its termination right under the contract.at all. If we are unable to obtain adequate financing when needed, we may have to delay, reduce the scope of or suspend one or more of our preclinical studies, clinical trials, research and

to demonstrate thetheir safety and efficacy of our product candidates in humans. We cannot be certain of the timely completion or outcome of our research and development activities or our planned preclinicalclinical studies and cannot predict if the FDA or other regulatory authorities will accept our proposed clinical programs or if the outcome of our preclinical studies will ultimately support the further developmentadvancement of our future productdevelopment candidates. We have not yet met with or discussedMost of our product development plans with FDA or any other regulatory authorities. As a result, we cannot be sure that we will be able to submit INDs or similar applications for our current discovery programs on the timelines we expect, if at all, and we cannot be sure that submission of INDs or similar applications will result in the FDA or other regulatory authorities allowing clinical trials to begin.

Our IMM-BCP-01 and IMM-ONC-01 programscandidates are in the research stage,early stages of development, other than AL102, which is a Phase 3 clinical asset, and we are subject to the risks of failure inherent in the identification of potential product candidates and the research and development of those product candidates based on novel approaches, targets and mechanisms of action. We expect to prepare and submit

In November 2021, we submitted an IND for the product candidate related to our IMM-BCP-01 program prior to initiatingthe FDA. In March 2022, the FDA communicated that the clinical study can be initiated for our antibody cocktail for the treatment of SARS-CoV-2 following a brief clinical hold, and we initiated the Phase 1b study of IMM-BCP-01 in patients infected with SARS-CoV-2 in June 2022. On January 6, 2023, we announced that we successfully completed dosing of the first cohort of patients in a Phase 1 clinical1b trial with no significant treatment-related adverse events. We decided to seek a partner in order to continue the trial and for any further development activities. No assurance can be given that we will be able to find a suitable partner for IMM-BCP-01, that any potential partner will offer us satisfactory partnering terms or that any such partner will have success in its development and commercialization efforts. 

We anticipate submitting INDs for IM-3050 and IM-1021 in the later part of the second quarter or in the early part of the thirdfirst quarter of 2021. We expect to prepare2025 and submit to the FDA an IND for the product candidate related to our IMM-ONC-01 program and to initiateIM-4320 at a Phase 1 clinical trial for this product candidate in the second half of 2021.later date. However, there can be no guaranteeassurance that we will be able to do so as anticipated or that we will not face regulatory or other hurdles, including the requirement to provide additional data. 

If we do not advance IM-4320, IM-1021 or IM-3050 to IND as a result of that filing,anticipated, we may incur significant delays and with respect specifically to IMM-BCP-01, particularlyexpense identifying another development candidate, if any. Accordingly, you should consider our prospects in light of the lack of certainty around the regulatory framework.costs, uncertainties, delays, and difficulties frequently encountered by biotechnology companies such as ours.

We may not have the financial resources to continue development of, or to enter into new collaborations for, the product candidates that may result from our IMM-BCP-01 and IMM-ONC-01 programs or any potential future product

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Further, we and any existing or potential future partners may never receive approval to marketnecessary marketing and commercialize any product candidate.commercialization approvals from regulatory authorities. Even if we or a potential future partner obtains regulatory approval, the approval may be delayed, or may be for targets, disease indications or patient populations that are not as broad as we intended or desired or may require labeling that includes significant use or distribution restrictions or safety warnings. We or a potential future partner may be subject to post-marketing testing requirements to maintain regulatory approval.

We may not be successful in our efforts to use and expand our discovery engine to build a pipeline of product candidates.

A key element of our strategy is to use and expand our discovery engine to build a pipeline of productpursue particular programs or development candidates and progress these product candidates through preclinical and clinical development for the treatment of various diseases. Although our research efforts to date suggests that blocking the IL-38 function using an inhibitory antibody restores the

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The ongoing COVID-19 pandemic continues to evolve. The extent to which the COVID-19 pandemic may impact​

There is no guarantee that our business and contemplated clinical trialscollaboration with AbbVie Global Enterprises Ltd., or AbbVie, will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the ultimate geographic spread of the disease, the duration of the pandemic, travel restrictions and social distancingresult in the United States and other countries, business closures or business disruptions and the effectiveness of actions taken in the United States and other countries to contain and treat the disease.

If any of our future product candidates, including those that may result from our IMM-BCP-01 and IMM-ONC-01 programs, are ever tested in human subjects, they may not demonstrate the combination of safety and efficacy necessary to become approvable or commercially viable.

We have not conducted testing in human subjects of any product candidate resulting from our IMM-BCP-01 and IMM-ONC-01 programs or any other product candidate. We may ultimately discover that any product candidates we develop do not possess certain properties that we believe will be helpful for therapeutic effectiveness and safety. For example, although our IL-38 targeting program has exhibited encouraging results in preclinical research, it may not demonstrate similar results in further research or exhibit the same properties in humans and may interact with human biological systems in unforeseen, ineffective or harmful ways. As a result, we may never succeed in developing a marketable product based on our IMM-ONC-01 and IMM-BCP-01 programs or based on our discovery engine. If the product candidates resulting from our IMM-BCP-01 and IMM-ONC-01 programs or any of our potential future product candidates prove to be ineffective, unsafe or commercially unviable, our entire pipeline could have little, if any, value, which could require us to change our focus and approach tosuccessful discovery and development, which would have a material and adverse effect on our business, financial condition, resultsvalidation of operations and prospects.

Our pursuit of an antibody cocktail product candidate is at a very early stage. We may be unable to identify or produce a product that successfully treats COVID-19 or prevents infection from the SARS-CoV-2 virus in a timely manner, if at all, and preliminary data may not be indicative of future success.

Our work in our IMM-BCP-01 program is in early stages, and we may be unable to produce an antibody cocktail product candidate that successfully treats COVID-19 or prevents infection from the SARS-CoV-2 virus in a timely manner, if at all. Despite the proven applicability of a B-cell discovery platform in infectious diseases such as polio, we do not have extensive expertise in the development of therapeutics in infectious disease applications. We are also committing resources and personnel to the development of a potential antibody cocktail product candidate, which may cause delays in or otherwise negatively impact our other development programs. Our business could be negatively impacted by our allocation of significant resources to a global health threat that is unpredictable or against which our antibody cocktail, if developed, may not be partially or fully effective. Furthermore, even though we may report preliminary preclinical or other data that could appear to be positive, no assurance can be given that any product candidate we identify will be safe in humans or prove to be effective once trials commence. We will not be able to commercialize or market any antibody cocktail product candidate unless and until we are able to demonstrate that our antibody cocktail candidate is safe and effective in humans.

In July 2020, we were awarded up to $13.3 million in funding from the U.S. Department of Defense, or DoD, to develop an antibody cocktail as a potential approach to combat the ongoing COVID-19 pandemic. Various government entities, including the U.S. government, are offering incentives, grants and contracts to encourage additional investment by commercial organizations into preventative and therapeutic agents against coronavirus, and this may have the effect of increasing the number of competitors and/or providing advantages to known competitors. As well, our COVID-19 program is being funded by DoD, and they can terminate our contract with them at-will. We do not know how recent changes in the U.S. government may impact the likelihood that our contract with DoD would be terminated before

Preliminary results from our preclinical studies and clinical trials that we announce or publish from time to time may change as more data become available and as the data undergo audit and verification procedures. Furthermore, clinical development includes a lengthy and expensive process withhas an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.

Our potential future product candidates relatedFrom time to time, we may publish preliminary results from our IMM-BCP-01preclinical studies and IMM-ONC-01 programsclinical trials. Interim results from clinical trials are in preclinical development, andsubject to the risk that one or more of failure relatedthe clinical outcomes may materially change as enrollment continues and more data becomes available. Preliminary or top-line results also remain subject to these potential product candidatesaudit and verification procedures that may result in the final data being materially different from the data we previously published or publish. As a result, preliminary and interim data should be viewed with caution until the final data is high. available. Differences between preliminary or interim data and final data could significantly affect our business prospects. 

It is impossible to predict when or if any potential future productof our programs or development candidates will prove effective and safe in humans or will receive regulatory approval. Before obtaining marketing approval from regulatory authorities, for the sale of any product candidate, we must, as applicable, complete preclinical studies and then conduct extensive clinical trials to demonstrate the safety and efficacy of that product candidate in humans. Particularly with respect to our IMM-BCP-01 program, we may be unable to complete clinical development and testing while COVID-19 remains a global health threat. Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any time during the development process. The results of preclinical studies and early clinical trials of any of our potential future productdevelopment candidates may not be predictive of the results of later-stage clinical trials. ProductIn addition, development candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. A number of companies in the pharmaceutical industrycompanies have suffered significant setbacks in advanced clinical trials due to lack of efficacy or safety profiles, notwithstanding promising results in earlier trials.

We expect to prepare In addition, AL102's prior development was not conducted by us, and submit an INDwe did not conduct any of the preclinical studies for the product candidate related toROR1 ADC that we in-licensed from Zentalis. As a result, our IMM-BCP-01 program prior to initiating a Phase 1 clinical trial inassumptions about the later part of the second quarter or in the early part of the third quarter of 2021. We expect to prepare and submit to the FDA an IND for the product candidate related to our IMM-ONC-01 program and to initiate a Phase 1 clinical trial for this product candidate in the second half of 2021. Commencing any clinical trial is subject to finalizing the trial design and filing an IND with the FDA. Even after we file an IND related to eitherpotential of these programs are based in large part on the FDA could disagree that we have satisfied their requirements to commence ourdata generated in preclinical studies and clinical trials conducted by these third parties. Results from nonclinical studies and clinical trials can be interpreted in different ways. We may observe materially and adversely different results in any ongoing or future preclinical studies or clinical trials, or disagreelater discover errors or other issues with our study design, which may require us to complete additional preclinical studies or amend our protocols or impose stricter conditions on the commencement of clinical trials.data generated by these third parties. 

We may experience delays in completing our preclinical studies and initiating or completing clinical trials of our potential future product candidates. We do not know whether planned preclinical studies and clinical trials will be completed on schedule or at all, or whether planned clinical trials will begin on time, need to be redesigned, enroll patientsparticipants on time or be completed on schedule, if at all. Our development programs may be delayed for a variety of reasons, including delays related to:

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Furthermore, we expect to rely on CROs, and clinical trial sites and other vendors to ensure the proper and timely conduct of our clinical trials and, while we expect to enter into agreements governing their committed activities, we have limited influence over their actual performance.

We could encounter delays if prescribing physicians encounter unresolved ethical issues associated with enrolling patients in clinicalClinical trials of our potential future product candidates in lieu of prescribing existing treatments that have established safety and efficacy profiles. Further, a clinical trial may be suspended or terminated by us, our partners, the IRBs of the institutions in which such trials are being conducted, the Data Safety Monitoring Board for such trialtrials or by the FDA or other regulatory authorities due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, inability to recruit appropriate subjects or an adequate number of subjects, failure to demonstrate a benefit from using a drug or therapeutic biologic, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. If we experience delays in the completion of, or termination of, any clinical trial of any of our potential future product candidates,programs, the commercial prospects of such product candidate will be harmed, and our ability to generate product revenue from such product candidates will be delayed. In addition, any delays in completing our clinical trials will increase our costs, slow our product development and approval process and jeopardize our ability to commence product sales and generate revenue. Any of these occurrences may materially and adversely affect our business, financial condition, results of operations and prospects. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our potential future product candidates.approval.

If we encounter difficulties enrolling patientsparticipants in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.

We may not be able to initiate or continue clinical trials for our potential future productprograms or development candidates if we are unable to locate and enroll a sufficient number of eligible patientsparticipants to participate in these trials as required by the FDA or other regulatory authorities. In particular, we are preparing to advance a product candidate related to our IMM-BCP-01

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In addition, our future clinical trials will compete with other clinical trials for productdevelopment candidates that are in the same therapeutic areas as our product candidates,those being pursued by us, and this competition will reduce the number and types of patientsparticipants available to us, because some patientsparticipants who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patientsparticipants who are available for our clinical trials at such clinical trial sites. Additionally, because we anticipate that some of our oncology clinical trials will be in patients with advanced solid tumors, the patients are typically in the late stages of the disease and may experience disease progression or adverse events independent from our productdevelopment candidates, making them unevaluable for purposes of the trial and requiring additional enrollment. Delays in patient enrollment may result in increased costs or may affect the timing or outcome of the planned clinical trials, which could prevent completion of these trials and adversely affect our ability to advance the development of our product candidates.pipeline.

We have not yet tested anyface substantial competition, which may result in others discovering, developing or commercializing products more quickly or marketing them more successfully than us. If their product candidates are shown to be safer or more effective than ours, then our commercial opportunity will be reduced or eliminated.

The development and commercialization of new product candidates is highly competitive. We compete in clinical trials. Success in preclinical studiesthe segments of the pharmaceutical, biotechnology and other related markets that develop therapies for the treatment of cancer, which is highly competitive with rapidly changing standards of care. As such, our commercial opportunity could be reduced or earlier clinical trials may not be indicative of results in future clinical trials.

Success in preclinical testingeliminated if our competitors develop and early clinical trials does not ensurecommercialize products that later clinical trials will generate the same resultsare safer, more effective, have fewer or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate. Preclinical tests and Phase 1 and Phase 2 clinical trials are primarily designed to test safety, to study pharmacokinetics and

there can be no assurance that such application will be accepted or that approval will be granted on a timely basis, or at all. Particularly as it relatesrequire systemic treatment. Desmoid tumors treatments also include surgery, hormonal therapy, targeted therapy and chemotherapy. 

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There are several other companies developing FAP-targeted radioligand therapies which may represent the most direct competition to our IMM-BCP-01IM-3050 program. Novartis is advancing a FAP-targeted radioligand therapy (177Lu-FAP-2286) that was acquired from Clovis Oncology and is currently in Phase 1/2. In December 2023, Eli Lilly and Company acquired POINT Biopharma, which is developing a FAP-targeted radioligand therapy (PNT2004) that is currently in Phase 1. Yantai LNC Biotechnology has also initiated a Phase 1 trial for another FAP-targeted radioligand therapy (LNC1004.) Additionally, our IM-3050 program faces competition from competitors who may have superior access to a consistent supply of radioactive isotopes. 

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In January 2023, we exclusively licensed a preclinical ROR1 ADC program from Zentalis with the existencepotential to address hematologic and solid tumor indications. There are several other companies developing antibodies, ADCs, and CAR-T therapies targeting ROR1, and they may represent the most direct competition to our ROR1 ADC program. Merck has an ADC program (Zilovertamab vedotin) in a Phase 2/3 clinical trial for B-cell lymphoma. CStone Pharmaceuticals, Inc. has an ADC program in a Phase I trial. Companies advancing clinical ROR1-CAR T therapy programs include Octernal Therapeutics (ONCT-808) in a Phase 1/2 in B-cell malignancies, and Lyell Immunopharma (LYL797) in a Phase 1 trial. 

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Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, performing preclinical studies, conducting clinical studies, integrating assets into their portfolio, obtaining regulatory approvals and marketing approved vaccines,products than we have. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical study sites and patient registration for clinical studies, as well as in acquiring technologies complementary to, or ones available under Emergency Use Authorizations,necessary for, our programs. In addition, these larger companies may cause the FDA to limit the number of additional accelerated approvals granted. The FDA also could require us to conduct further studies or trials prior to considering our application or granting approval of any type. We might not be able to fulfill the FDA’s requirements in a timely manner, which would cause delays, or approval might not be granted because our submission is deemed incomplete by the FDA.

Even if we receive accelerated approval from the FDA, we will be subject to rigorous post-marketing requirements, including the completion of confirmatory post-market clinical trials to verify the clinical benefit of the product, and submission to the FDA of all promotional materials prior touse their dissemination. The FDA could seek to withdraw accelerated approval for multiple reasons, including if we fail to conduct any required post-market study with due diligence; a post-market study does not confirm the predicted clinical benefit; other evidence shows that the product is not safe or effective under the conditions of use; or we disseminate promotional materials that are found by the FDA to be false and misleading.

A failuregreater market power to obtain accelerated approval or any other formmore favorable supply, manufacturing, distribution and sales-related agreements with third parties, which could give them a competitive advantage over us. 

Further, as more product candidates within a particular class of expediteddrugs proceed through clinical development review or approval for a product candidate that we may choose to develop would result in a longer time period prior to commercializing such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in the marketplace.

We may not elect or be able to take advantage of any expedited development or regulatory review and approval, processes available tothe amount and type of clinical data that may be required by regulatory authorities may increase or change. Consequently, the results of our clinical trials for product candidates granted breakthrough therapyin that class will likely need to show a risk benefit profile that is competitive with or fast track designation bymore favorable than those products and product candidates in order to obtain marketing approval or, if approved, a product label that is favorable for commercialization. If the FDA.

We intendrisk benefit profile is not competitive with those products or product candidates, or if the approval of other agents for an indication or patient population significantly alters the standard of care with which we tested our product candidates, we may have developed a product that is not commercially viable, that we are not able to evaluate and engage in discussions with the FDA on regulatory strategiessell profitably or that could enable usis unable to take advantage of expedited development pathways for certain ofachieve favorable pricing or reimbursement. In such circumstances, our future product candidates, although we cannotrevenue and financial condition would be certain that our future product candidates will qualify for any expedited development pathways or that regulatory authorities will grant, or allow us to maintain,materially and adversely affected.

Mergers and acquisitions in the relevant qualifying designations. Potential expedited development pathways that we could pursue include breakthrough therapypharmaceutical and fast track designation.

Breakthrough therapy designation is intended to expedite the development and review of product candidates that are designed to treat serious or life-threatening diseases when preliminary clinical evidence indicates that the drugbiotechnology industries may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The designation of a product candidate as a breakthrough therapy provides potential benefits that include more frequent meetings with FDA to discuss the development plan for the product candidate and ensure collection of appropriate data needed to support approval; more frequent written correspondence from FDA about such things as the design of the proposed clinical trials and use of biomarkers; intensive guidance on an efficient drug development program, beginning as early as Phase 1; organizational commitment involving senior managers; and eligibility for rolling review and priority review.

Fast track designation is designed for product candidates intended for the treatment of a serious or life-threatening disease or condition, where nonclinical or clinical data demonstrate the potential to address an unmet medical need for this disease or condition.

Accordingly, even if we believe a particular future product candidate is eligible for breakthrough therapy or fast track designation, we cannot assure you that the FDA would decide to grant it. Breakthrough therapy designation and fast track designation do not change the standards for product approval, and there is no assurance that such designation or eligibility will result in expedited revieweven more resources being concentrated among a smaller number of our competitors. Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical study sites and subject enrollment for clinical studies, as well as in acquiring technologies complementary to, or approvalnecessary for, our current or that the approved indication will not be narrower than the indication covered by the breakthrough therapy designationfuture products or fast track designation. Thus, even if we do receive breakthrough therapy or fast track designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may withdraw breakthrough therapy or fast track designation if it believes that the product no longer meets the qualifying criteria. Our business may be harmed if we are unable to avail ourselves of these or any other expedited development and regulatory pathways.programs.