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

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

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

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

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

As of November ~~11, 2021,~~2, 2022, there were ~~49,392,123~~60,223,498 shares of the registrant’s Common Stock, par value $0.0001 per share, outstanding.

This Quarterly Report on Form 10-Q contains forward-looking statements and information within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act, which are subject to the “safe harbor” created by those sections. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “could,” “expect,” “would,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “intend,” “project” or “continue,” or the negative or plural of these terms or other comparable terminology.

These statements are only current predictions and are subject to known and unknown risks, uncertainties and other factors that may cause our or our industry’s actual results, levels of activity, performance, or achievements to be materially different from those anticipated by the forward-looking statements. We discuss many of these risks in this report in greater detail in the section titled “Risk Factors” and elsewhere in this report. You should not rely upon forward-looking statements as predictions of future events.

Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we are under no duty to update or revise any of the forward-looking statements, whether as a result of new information, future events or otherwise.

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

1. Nature of Business

Syndax Pharmaceuticals, Inc. (“we,” “us,” “our” or the “Company”) is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. We were incorporated in Delaware in 2005. We base our operations in Waltham, Massachusetts and we operate in 1one segment.

2. Basis of Presentation

The Company has prepared the accompanying condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States of America (“U.S. GAAP”). Certain information and footnote disclosures normally included in the ~~Company��s~~Company’s annual financial statements have been condensed or omitted. The interim unaudited condensed financial statements have been prepared on the same basis as the annual audited financial statements and in the opinion of management, reflect all adjustments, which include only normal recurring adjustments, necessary for the fair statement of the Company’s financial position as of September 30, ~~2021,~~2022, and the results of operations and comprehensive loss for the three and nine months ended September 30, ~~2021~~2022 and ~~2020,~~2021, and cash flows for the nine months ended September 30, ~~2021~~2022 and ~~2020.~~2021. The results for the three and nine months ended September 30, ~~2021~~2022 are not necessarily indicative of the results to be expected for the year ending December 31, ~~2021,~~2022, any other interim periods, or any future year or period. These interim financial statements should be read in conjunction with the audited financial statements as of and for the year ended December 31, ~~2020,~~2021, and the notes thereto, which are included in the Company’s Annual Report on Form 10-K as filed with the Securities and Exchange Commission (“SEC”) on March ~~12, 2021.~~1, 2022.

In 2011, the Company established a wholly owned subsidiary in the United ~~Kingdom. There have been no activities for this entity to date. In~~Kingdom, in 2014 the Company established a wholly owned U.S. subsidiary, ~~Syndax Securities Corporation. In~~and in 2021, the Company established a wholly owned subsidiary in the Netherlands. There have been no material activities for ~~this entity~~these entities to date. ~~The condensed consolidated financial statements include the accounts of the Company and its wholly owned subsidiaries.~~ All intercompany balances and transactions have been eliminated in consolidation.

3. Summary of Significant Accounting Policies

Significant Accounting Policies

The Company’s significant accounting policies, which are disclosed in the audited consolidated financial statements for the year ended December 31, ~~2020~~2021, and the notes thereto are included in the Company’s Annual Report on Form 10-K that was filed with the SEC on March ~~12, 2021.~~1, 2022. Since the date of ~~that~~ filing, there have been no material changes to the Company’s significant accounting policies except as noted below.

Use of Estimates

The preparation of condensed consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the condensed consolidated financial statements and the reported amounts of costs and expenses during the reporting period. The Company bases estimates and assumptions on historical experience when available and on various factors that it believes to be reasonable under the circumstances. The Company evaluates its estimates and assumptions on an ongoing basis.

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

Significant Risks and Uncertainties

We have implemented business continuity plans designed to address and mitigate the impact of the ongoing COVID-19 pandemic on our business. We anticipate that the COVID-19 pandemic could have an impact on the clinical development timelines for one or more of our clinical programs. The extent to which the COVID-19 pandemic impacts our business, our clinical development, manufacturing of clinical and commercial drug substance and drug product, and regulatory efforts, our corporate development objectives and the value of and market for our common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the ~~United States,~~U.S., Europe and other countries, ~~the slow rollout of mass vaccinations for COVID-19 and any limitations to the efficacy of such vaccines~~ and the effectiveness of ~~other~~ actions taken globally to contain and treat the disease. The global economic slowdown, the overall disruption of global healthcare

systems and the other risks and uncertainties associated with the pandemic could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

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

~~Use of Estimates~~New Accounting Pronouncements

~~The preparation of condensed consolidated financial statements in conformity with U.S. GAAP requires management~~From time to ~~make estimates and assumptions~~time, new accounting pronouncements are issued by the Financial Accounting Standards Board (“FASB”) or other accounting standard setting bodies that ~~affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date~~we adopt as of the condensed consolidated financial statements and the reported amounts of costs and expenses during the reporting period. The Company bases estimates and assumptions on historical experience when available and on various factors that it believes to be reasonable under the circumstances. The Company evaluates its estimates and assumptions on an ongoing basis. The Company’s actual results may differ from these estimates under different assumptions or conditions.

~~We anticipate~~specified effective date. Unless otherwise discussed below, we do not believe that the ~~COVID-19 pandemic will~~adoption of recently issued standards have anor may have a material impact on ~~the clinical~~our consolidated statements or disclosures.

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

Basic net loss per share attributable to common stockholders is computed by dividing the net loss attributable to common stockholders by the weighted-average number of common shares outstanding for the period. Because the Company has reported a net loss for all periods presented, diluted net loss per common share is the same as basic net loss per common share for those periods. The following table summarizes the computation of basic and diluted net loss per share attributable to common stockholders of the Company:

Three Months Ended September 30,

Nine Months Ended September 30,

2021

2020

2021

2020

(In thousands, except share and per
share data)

(In thousands, except share and per
share data)

Numerator—basic and diluted:

Net loss
$
(20,639
)

$
(20,437
)

$
(71,272
)

$
(52,735
)
Deemed dividend due to warrant reset

—

—

—

(3,906
)
Net loss attributable to common
   stockholders—basic and diluted
$
(20,639
)

$
(20,437
)

$
(71,272
)

$
(56,641
)
Net loss per share attributable to common
   stockholders—basic and diluted
$
(0.40
)

$
(0.46
)

$
(1.38
)

$
(1.43
)
Denominator—basic and diluted:

Weighted-average number of common shares
   used to compute net loss per share attributable
   to common stockholders—basic and diluted

51,962,320

44,156,808

51,690,173

39,714,490


	Three Months Ended September 30,						Nine Months Ended September 30,
	2022			2021			2022			2021
	(In thousands, except share and per share data)						(In thousands, except share and per share data)
Numerator—basic and diluted:
Net loss	$	(35,403	)	$	(20,639	)	$	(110,144	)	$	(71,272	)
Net loss attributable to common stockholders—basic and diluted	$	(35,403	)	$	(20,639	)	$	(110,144	)	$	(71,272	)
Net loss per share attributable to common stockholders—basic and diluted	$	(0.58	)	$	(0.40	)	$	(1.84	)	$	(1.38	)
Denominator—basic and diluted:
Weighted-average number of common shares used to compute net loss per share attributable to common stockholders—basic and diluted		60,670,294			51,962,320			59,941,384			51,690,173

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


	September 30,				September 30,
	2021		2020		2022		2021
Options to purchase common stock		7,340,654		6,770,660		7,386,063		7,340,654
Warrants to purchase common stock		—		689,242
Employee Stock Purchase Plan		21,063		18,838		17,135		21,063
Non-vested restricted stock units (RSUs)		132,333		18,500		226,038		132,333

In June 2018, the Company signed an exchange agreement with an investor under which the investor exchanged 2,000,000 shares of common stock for 2,000,000 warrants. Further, as discussed in Note 12, in March 2019, the Company sold 2,095,039 shares of common stock as well as 2,500,000 pre-funded warrants and 4,595,039 Series 1 and Series 2 warrants. The pre-funded warrants are exercisable into shares of common stock for $0.0001 per share.In January 2020, the Company sold 3,036,719 shares of common stock ~~as well as 1,338,287~~at $8.00 per share and pre-funded ~~warrants. The~~ warrants ~~are exercisable into~~to purchase 1,338,287 shares of common stock for $0.0001 per share. The shares of common stock into which the pre-funded warrants may be exercised are considered outstanding for the purposes of computing earnings per share. All Series 1 and Series 2 warrants were exercised in 2020.

~~During the first quarter of~~stock. In February 2021, 250,000 pre-funded warrants were exchanged for shares of common stock in a cash exercise and in November 2021, 475,784 pre-funded warrants were exchanged for shares of common stock in a cashless exercise. In September 2022, 2,832,165 pre-funded warrants were exchanged for 2,832,151 shares of common stock in a cashless exercise. As of September 30, ~~2021, 3,307,952~~2022, 1,142,856 pre-funded warrants were ~~outstanding.~~issued and outstanding.

8. Prepaid Expenses and Other Current Assets

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


	September 30, 2022		December 31, 2021
Prepaid insurance	$	1,157	$	642
Interest receivable on investments		410		429
Prepaid subscription		298		230
Prepaid conference, meeting costs		252		-
Other		152		150
Total prepaid expenses and other current assets	$	2,269	$	1,451

September 30, 2021

December 31, 2020

(In thousands)

Short-term deposits

$
6,499

$
4,683

Prepaid insurance

1,259

427

Interest receivable on investments

182

175

Prepaid subscriptions

242

203

Prepaid clinical supplies

—

58

Reimbursable costs

3

24

Other

238

114

Total prepaid expenses and other current assets

$
8,423

$
5,684

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


	September 30, 2022		December 31, 2021
Accrued clinical costs	$	5,297	$	7,760
Accrued compensation and related costs		3,998		4,342
Accrued professional fees		732		662
Other		3,186		1,701
Total accrued expenses and other current liabilities	$	13,213	$	14,465

In January ~~2021,~~2022, the number of shares of common stock available for issuance under the 2015 Omnibus Incentive Plan (“2015 Plan”) was increased by ~~1,915,248~~2,198,134 shares due to the automatic annual provision to increase shares available under the 2015 Plan. As of September 30, ~~2021,~~2022, the total number of shares of common stock available for issuance under the 2015 Plan was ~~1,001,470.~~ 1,460,079. The Company recognized stock-based compensation expense related to the issuance of stock option awards to employees and non-employees and related to the 2015 Employee Stock Purchase Plan (“ESPP”) in the condensed consolidated statements of comprehensive loss as follows:

Compensation expense by type of award in the three and nine months ended September 30, ~~2021~~2022 and ~~2020~~2021 was as follows:

During the nine months ended September 30, ~~2021,~~2022, the Company granted ~~1,537,400~~2,282,050 stock options to certain executives, consultants and employees having service-based vesting conditions. The grant date fair value of the options granted in the nine months ended September 30, ~~2021,~~2022, was ~~$22.7~~$25.8 million, or ~~$14.74~~$11.31 per share on a weighted-average basis and will be recognized as compensation expense over the requisite service period of ~~three~~two to four years.

In 2019, the Company granted to certain employees583,000 performance-based stock options (“2019 Performance Awards”), primarily related to the achievement of certain clinical and regulatory development milestones related to product candidates. Additionally, in 2022, the Company granted to certain employees 140,000 performance-based stock options (“2022 Performance Awards”), primarily related to the achievement of certain regulatory development milestones related to product candidates. Recognition of stock-based compensation expense associated with these performance-based stock options commences when the performance condition is probable of achievement, using management’s best estimates, which consider the inherent risk and uncertainty regarding the future outcomes of the milestones.

In the fourth quarter of 2020 one of the performance milestones of the 2019 Performance Awards was achieved and of the associated 194,331 stock options, 64,777 stock options vested, and 388,669 options were cancelled. In 2021, 64,780 stock options vested. As of September 30, 2022, 56,999 options (net of cancellations) remain to vest. For the remaining milestones, the performance conditions were not met as of September 30, 2022. Therefore, no expense has been recognized related to these awards for the nine months ended September 30, 2022, and 7,778 options were canceled in 2022.

In the first quarter of 2022, management estimated one of the milestones, for the 2022 Performance Awards, was probable of achievement and, as such, the Company recorded approximately $346,000 of stock compensation expense for these awards for the nine months ended September 30, 2022. As of September 30, 2022, 140,000 stock options outstanding were unvested, and no options had been cancelled.

During the nine months ended September 30, 2022, 1,167,295 options were exercised for cash proceeds of $10.1 million. During the nine months ended September 30, 2021, 414,809 options were exercised for cash proceeds of ~~$3.3~~$3.3 million. ~~During~~

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


	Number of Shares			Weighted Average Grant Date Fair Value
Unvested—December 31, 2021		132,333		$	20.11
Granted (1)		131,205		$	15.79
Vested		(37,500	)	$	17.49
Unvested—September 30, 2022 (2)		226,038		$	18.04

(1) RSU’s granted in 2022 and 2021 had a weighted average grant date fair value of $15.79 and $21.19, respectively. The fair values of RSU’s vested in 2022 and 2021 totaled $656,000 and $60,000, respectively.

(2) Unvested as of September 30, ~~2020, 311,871 options~~2022, include 93,333 RSU's which were ~~exercised for cash proceeds~~granted to members of ~~$3.1 million.~~the Board of Directors, which will not be considered issued and outstanding until either the separation from service, death, disability or a change in control.

As of September 30, ~~2021,~~2022, there was ~~$28.7~~$35.4 million of unrecognized compensation ~~cost~~costs related to employee and non-employee unvested stock options and RSUs granted under the 2015 and 2007 Plans, which is expected to be recognized over a weighted-average remaining service period of ~~3.0~~2.8 years. ~~Stock-based~~Stock compensation costs have not been capitalized by the Company.

12. Stockholders’ Equity

The following table presents the changes in stockholders’ equity for the three and nine months ended September 30, ~~2021, the Company’s maturities of principal obligations under its long-term debt are as follows:~~2022:


(In thousands, except share data)	Common Stock $0.0001 Par Value				Additional Paid-In Capital		Accumulated Other Comprehensive (Loss) / Income			Accumulated Deficit			Total Stockholders’ Equity
	Shares		Amount
Balance as of December 31, 2021		54,983,105	$	6	$	952,019	$	45		$	(543,702	)	$	408,368
Stock purchase under ESPP		18,946		—		—		—			—			—
Stock-based compensation expense		—		—		3,478		—			—			3,478
Unrealized gains on short-term investments		—		—		—		(685	)		—			(685	)
Employee withholdings ESPP		—		—		92		—			—			92
Proceeds from exercise of stock options		28,839		—		465		—			—			465
Net loss		—		—		—		—			(37,169	)		(37,169	)
Balance as of March 31, 2022		55,030,890	$	6	$	956,054	$	(640	)	$	(580,871	)	$	374,549
Proceeds from ATM sales		1,111,111		—		19,427		—			—			19,427
Stock-based compensation expense		—		—		3,938		—			—			3,938
Unrealized gains on short-term investments		—		—		—		(695	)		—			(695	)
Employee withholdings ESPP		—		—		58		—			—			58
Proceeds from exercise of stock options		257,733		—		2,235		—			—			2,235
Net loss		—		—		—		—			(37,572	)		(37,572	)
Balance as of June 30, 2022		56,399,734	$	6	$	981,712	$	(1,335	)	$	(618,443	)	$	361,940
Stock purchase under ESPP		10,053		—		—		—			—			—
Stock-based compensation expense		—		—		4,362		—			—			4,362
Unrealized gains on short-term investments		—		—		—		(270	)		—			(270	)
Exercise of prefunded warrants		2,832,151		—		—		—			—			—
Employee withholdings ESPP		—		—		110		—			—			110
Proceeds from exercise of stock options		880,723		—		7,363		—			—			7,363
Net loss		—		—		—		—			(35,403	)		(35,403	)
Balance as of September 30, 2022		60,122,661	$	6	$	993,547	$	(1,605	)	$	(653,846	)	$	338,102

Amount

Remainder of 2021
$
2,285

2022

9,727

2023

7,988

Total principal outstanding

20,000

Amortized final fee

589

Unamortized debt issuance costs

(111
)
Total

20,478

Term loan, current portion

9,489

Term loan, less current portion
$
10,989

~~12. Stockholders’ Equity~~

The following table presents the changes in stockholders’ equity for the three and nine months ended September 30, 2021:


(In thousands, except share data)	Common Stock $0.0001 Par Value				Additional Paid-In Capital		Accumulated Other Comprehensive Income / (Loss)			Accumulated Deficit			Total Stockholders’ Equity			Common Stock $0.0001 Par Value				Additional Paid-In Capital		Accumulated Other Comprehensive Income / (Loss)			Accumulated Deficit			Total Stockholders’ Equity
	Shares		Amount													Shares		Amount
Balance as of December 31, 2020		47,881,223	$	5	$	820,815	$	(4	)	$	(568,628	)	$	252,188			47,881,223	$	5	$	820,815	$	(4	)	$	(568,628	)	$	252,188
Stock purchase under ESPP		16,382		—		—		—			—			—			16,382		—		—		—			—			—
Stock-based compensation expense		—		—		2,767		—			—			2,767			—		—		2,767		—			—			2,767
Unrealized gains on short-term investments		—		—		—		13			—			13									13						13
Pre-funded warrant exchange		250,000		—		—		—			—			—
Prefunded warrant exchange																	250,000		—		—					—			—
Employee withholdings ESPP		—		—		79		—			—			79			—		—		79		—			—			79
Proceeds from exercise stock options		100,954		—		881		—			—			881
Proceeds from exercise of stock options																	100,954		—		881		—			—			881
Net loss		—		—		—		—			(27,723	)		(27,723	)		—		—		—		—			(27,723	)		(27,723	)
Balance as of March 31, 2021		48,248,559	$	5	$	824,542	$	9		$	(596,351	)	$	228,205			48,248,559	$	5	$	824,542	$	9		$	(596,351	)	$	228,205
Stock-based compensation expense		—		—		3,240		—			—			3,240			—		—		3,240		—			—			3,240
Unrealized gains on short-term investments		—		—		—		8			—			8			—		—		—		8			—			8
Employee withholdings ESPP		—		—		64		—			—			64			—		—		64		—			—			64
Proceeds from ATM offering, net of $200 offering expenses		277,629		—		5,131		—			—			5,131
Proceeds from exercise stock options		90,440		—		825		—			—			825
Proceeds from ATM Offering, net $200 offering expense																	277,629		—		5,131		—			—			5,131
Proceeds from exercise of stock options																	90,440		—		825					—			825
Net loss		—		—		—		—			(22,910	)		(22,910	)		—		—		—		—			(22,910	)		(22,910	)
Balance as of June 30, 2021		48,616,628	$	5	$	833,802	$	17		$	(619,261	)	$	214,563			48,616,628	$	5	$	833,802	$	17		$	(619,261	)	$	214,563
Stock-based compensation expense		—		—		3,381		—			—			3,381			—		—		3,381		—			—			3,381
Unrealized loss on short-term investments		—		—		—		(6	)		—			(6	)
Unrealized gains on short-term investments																	—		—		—		(6	)		—			(6	)
Employee withholdings ESPP		—		—		99		—			—			99			—		—		99		—			—			99
Stock purchase under ESPP		10,496		—		—		—			—			—			10,496		—		—		—			—			—
Proceeds from exercise stock options		223,415		—		1,606		—			—			1,606
Proceeds from exercise of stock options																	223,415		—		1,606		—			—			1,606
Net loss		—		—		—		—			(20,639	)		(20,639	)		—		—		—		—			(20,639	)		(20,639	)
Balance as of September 30, 2021		48,850,539	$	5	$	838,888	$	11		$	(639,900	)	$	199,004			48,850,539	$	5	$	838,888	$	11		$	(639,900	)	$	199,004

~~The following table presents the changes in stockholders’ equity for the three and nine months ended September 30, 2020:~~

(In thousands, except share data)

Common Stock
$0.0001
Par Value

Additional
Paid-In
Capital

Accumulated
Other
Comprehensive
Income / (Loss)

Accumulated
Deficit

Total
Stockholders’
Equity

Shares

Amount

Balance as of December 31, 2019

27,140,484

$
3

$
527,067

$
—

$
(495,470
)

$
31,600

Stock purchase under ESPP

12,601

—

—

—

—

—

Stock-based compensation expense

—

—

1,829

—

—

1,829

Proceeds from direct offering, net of $93
    offering expenses

3,036,719

—

24,201

—

—

24,201

Proceeds from pre-funded common stock
    warrant from direct offering, net of $41
    offering expenses

—

—

10,665

—

—

10,665

Deemed dividend from repricing Series 1
   and 2 warrants

—

—

3,906

—

—

3,906

Repricing Series 1 and 2 warrants

—

—

(3,906
)

—

—

(3,906
)
Proceeds from exercise of stock options

51,034

—

338

—

—

338

Unrealized gains on short-term investments

—

—

—

48

—

48

Employee withholdings ESPP

—

—

64

—

—

64

Net loss

—

—

—

—

(15,236
)

(15,236
)
Balance as of March 31, 2020

30,240,838

$
3

$
564,164

$
48

$
(510,706
)

$
53,509

Stock-based compensation expense

—

—

2,130

—

—

2,130

Issuance of common stock in exchange
    for pre-funded warrants

280,332

—

—

—

—

—

Exercise Series 1 and Series 2 warrants

1,512,229

—

—

—

—

—

Proceeds from direct offering, net of $7,099
    of offering expenses

6,388,889

1

107,900

—

—

107,901

Proceeds from exercise of stock options

90,456

—

1,015

—

—

1,015

Unrealized gains on short-term investments

—

—

—

69

—

69

Employee withholdings ESPP

—

—

85

—

—

85

Net loss

—

—

—

—

(17,062
)

(17,062
)
Balance as of June 30, 2020

38,512,744

$
4

$
675,294

$
117

$
(527,768
)

$
147,647

Stock-based compensation expense

—

—

3,063

—

—

3,063

Stock purchase under ESPP

21,105

—

—

—

—

—

Exercise Series 1 and Series 2 warrants

130,151

—

—

—

—

—

Offering expenses associated with direct
   offering

—

—

(33
)

—

—

(33
)
Proceeds from exercise of stock options

170,381

—

1,707

—

—

1,707

Unrealized loss on short-term investments

—

—

—

(64
)

—

(64
)
Employee withholdings ESPP

—

—

94

—

—

94

Net loss

—

—

—

—

(20,437
)

(20,437
)
Balance as of September 30, 2020

38,834,381

$
4

$
680,125

$
53

$
(548,205
)

$
131,977

In March 2021, the Company entered into a new sales agreement with Cowen and Company, LLC (“Cowen”) under which the Company may issue and sell shares of its common stock having aggregate sales proceeds of up to ~~$75.0~~$75.0 million from time to time through Cowen, acting as agent, in a series of one or more ATM equity offerings (the “2021 ATM Program”). Cowen is not required to sell any specific amount but acts as the Company’s sales agent using commercially reasonable efforts consistent with its normal trading and sales practices. Shares sold pursuant to the sales agreement will be sold pursuant to a shelf registration statement on Form S-3ASR (Registration No. 333-254661), which became automatically effective upon filing on March 24, 2021. The Company’s common stock will be sold at prevailing market prices at the time of the sale; and as a result, prices may vary. InFor the ~~nine months~~period ended September 30, ~~2021,~~2022, the Company sold ~~277,629~~no additional shares of common stock under the 2021 ATM ~~Program,~~Program.

In December 2021, in connection with the Incyte License and the Incyte Share Purchase Agreement, the Company issued 1,421,523 shares of common stock, with net proceeds of approximately ~~$5.1~~$35.0 million.

~~In March 2019,~~ The Company recorded the Company issued 2,095,039 shares of its common stock and pre-funded warrants to purchase 2,500,000 shares of common stock to certain investors in a registered direct offering. The pre-funded warrants are exercisable immediately upon

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

The Series Warrants were immediately exercisable. Each Series 1 Warrant had an initial exercise price of $12.00 per share of common stock and each Series 2 Warrant had an initial exercise price of $18.00 per share of common stock, in each case subject to certain adjustments. All Series 1 and Series 2 warrants were exercised in 2020.

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

The Series Warrants were classified as a component of permanent equity and were recorded at the issuance date using a relative fair value allocation method. The Series Warrants are equity classified because they are freestanding financial instruments that are legally detachable and separately exercisable from the equity instruments, are immediately exercisable, do not embody an obligation for the Company to repurchase its shares, and permit the holders to receive a fixed number of shares of common stock upon exercise. In addition, such warrants do not provide any guarantee of value or return. ~~The Company valued the Series Warrants at issuance in March 2019 using the Black Scholes option pricing model and determined the~~ fair value of $24.8 million based on the ~~4,595,039 Series Warrants at $3.4 million. The key inputs to the valuation model included the weighted average volatility of 89.1% and the weighted-average expected term of 1.4 years.~~

In January 2020, the Company sold 3,036,719 shares of common stock and pre-funded warrants to purchase 1,338,287 shares of common stock. The offering price for the securities was $8.00 per share of common stock or $7.9999 for each pre-funded warrant. As a result of this offering, the exercisemarket price of Series 1 Warrants and Series 2 Warrants outstanding reset from $12.00 per share to $10.00 per share and from $18.00 per share to $13.00, respectively. The Company recorded $3.9 million as a deemed dividend which represents the ~~value transferred to~~stock on the warrant holders due to the Series Warrant adjustment mechanism being triggered. The deemed dividend was recorded as both an increase and a decrease in Additional Paid-in-Capital and reduced net income available to common stockholders by the same amount. The key inputs to the valuation model included the weighted average volatilitydate of ~~96.74% and the weighted average expected term of 0.4 years.~~issuance.

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


	September 30, ~~2021~~2022
Common stock issuable under pre-funded warrants		~~3,307,952~~1,142,856
Options to purchase common stock		~~1,001,470~~9,072,180
Employee Stock Purchase Plan		~~1,275,347~~1,517,411

13. Commitments and Contingencies

From time to time, the Company may be subject to various claims and proceedings in the ordinary course of business. If the potential loss from any claim, asserted or unasserted, or proceeding is considered probable and the amount is reasonably estimable, the Company will accrue a liability for the estimated loss. There were no contingent liabilities recorded as of September 30, 2022.

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations

~~Item 2.~~

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

The following information should be read in conjunction with the unaudited financial information and the notes thereto included in this Quarterly Report on Form 10-Q and the audited financial information and the notes thereto included in our Annual Report on Form 10-K that was filed with the Securities and Exchange Commission, or SEC, on March ~~12, 2021.~~1, 2022.

Company Overview

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

We have no products approved for commercial sale and have not generated any product revenues from product sales to date. We continue to incur significant research and development and other expenses related to our ongoing operations. ~~As a result,~~We have generated minimal license revenue, except for in 2021. Other than in 2021, we are not and have never been profitable and have incurred losses in each period since our inception in 2005. For the nine months ended September 30, ~~2021~~2022 and ~~2020,~~2021, we reported a net loss of ~~$71.3~~$110.1 million and ~~$52.7 million, respectively. We reported a net loss attributable to stockholders of~~ $71.3 million, ~~and $56.6 million for the nine months ended September 30, 2021 and 2020,~~ respectively. As of September 30, ~~2021,~~2022, we had an accumulated deficit of ~~$639.9~~$653.8 million, which included non-cash charges for stock-based compensation, preferred stock accretion and extinguishment charges. As of September 30, ~~2021,~~2022, we had cash, cash equivalents and short-term investments of ~~$229.7~~$337.8 million.

Clinical Developments

Revumenib

•

On November 3, 2022, we announced updated positive data from the Phase 1 portion of the ongoing AUGMENT-101 trial of revumenib in patients with R/R NPM1 mutant or MLLr (also referred to as KMT2Ar) acute leukemia which highlighted an improved 30% (18/60) CR/CRh rate and a median duration of CR/CRh response of 9.1 months. Additionally, of the 12 patients who achieved a complete response on revumenib treatment and then went on to receive a stem cell transplant, nine (75%) remained in remission as of the data cutoff date, with a median follow-up of 12.3 months. Three patients were treated with revumenib maintenance in the compassionate use setting following stem cell transplant or non-myeloablative stem cell boost, two of whom (67%) remained in remission for over one year. To date, there have been no discontinuations due to treatment-related adverse events. Data reported on November 3, 2022, will be featured in two oral sessions at the ASH Annual Meeting on Saturday, December 10, 2022.

•

In the data that we reported on November 3, 2022, revumenib was well-tolerated and no new safety signals were identified in the trial, including in patients who proceeded to stem cell transplant. The only dose limiting toxicity observed was asymptomatic Grade 3 QT prolongation. No ventricular arrythmias or other clinical sequelae related to QTc prolongation were reported. All cases of differentiation syndrome were Grade 2, and readily managed with standard therapies.

•

The pivotal Phase 2 portion of AUGMENT-101 is ongoing, enrolling patients across each of three distinct trial populations: patients with NPM1 mutant acute myeloid leukemia (AML), patients with MLLr AML, and patients with MLLr acute lymphocytic leukemia (ALL). Based on discussions with the U.S. Food and Drug Administration, AUGMENT-101 may serve as the basis for regulatory filings in each of the three distinct populations. We expect completion of enrollment in the first trial to extend into the first quarter of 2023 and to report topline data from at least one of the trials starting in the third quarter of 2023. We continue to ~~monitor~~expect to submit our ~~daily operations~~first NDA filing for revumenib by the end of 2023.

•

Two trials, BEAT-AML and ~~program timelines during~~AUGMENT-102, are ongoing and will assess the ~~evolving coronavirus 2019 (COVID-19) pandemic.~~safety, tolerability, and preliminary anti-leukemic efficacy of revumenib, and establish an appropriate Phase 2 dose when used in combination with other approved agents. BEAT-AML is a front-line combination trial of revumenib with venetoclax and azacitidine being conducted as part of the Leukemia & Lymphoma Society’s Beat AML® Master Clinical Trial. AUGMENT-102 is a trial assessing revumenib in combination with chemotherapy in patients with R/R mNPM1 or MLLr acute leukemias.

•

We expect the Australasian Leukaemia and Lymphoma Group (ALLG) to initiate the INTERCEPT trial of revumenib as monotherapy in patients with AML who are minimal residual disease-positive following initial treatment, in the fourth quarter of 2022. The ~~health~~trial is a part of the INTERCEPT AML Master Clinical Trial, a collaborative clinical trial investigating novel therapies to target early relapse and ~~safety~~clonal evolution as pre-emptive therapy in AML. Revumenib is the first menin inhibitor to be included in the INTERCEPT AML Master Clinical Trial.

•

We remain on track to initiate a proof-of-concept clinical trial of ~~our employees as well as~~revumenib in patients with unresectable metastatic microsatellite stable colorectal cancer in the ~~patients and people participating in and operating our clinical trials are~~fourth quarter of ~~paramount importance. COVID-19, including its variants, has not impacted our financial guidance or changed our timelines for clinical data in 2021, to date.~~

~~Clinical Developments~~

~~SNDX-5613~~

2022.
•

The Phase 2 portion of AUGMENT-101 is currently enrolling patients with NPM1c mutant and MLLr relapsed/refractory acute leukemias. A total of 64 adult and up to 10 pediatric patients will be enrolled across each of the following three distinct trial populations: patients with NPM1 mutant acute myeloid leukemia (AML), patients with MLLr AML, and patients with MLLr acute lymphocytic leukemia. Discussions with the FDA have confirmed that AUGMENT-101 may potentially serve as the basis for regulatory filings in each of the three distinct trials. The primary endpoint for each of the three trials will be efficacy as measured by complete remission rate (complete response [CR] + CR with partial hematologic recovery rate [CRh]), with key secondary endpoints including duration of response and overall survival.

•

In November 2021, we announced that updated data from the Phase 1 portion of the ongoing AUGMENT-101 trial will be featured during an oral session at the 63rd ASH Annual Meeting being held December 11-14, 2021. Data included in the abstract demonstrated robust clinical activity with durable responses and no discontinuations due to treatment-related adverse events. The oral presentation will include updated Phase 1 data from additional patients as of a more recent cutoff date, as well as further details on durability and CR/CRh rate by mutational status.

•

In November 2021, we also announced plans to initiate a new trial to assess the anti-leukemic efficacy of SNDX-5613 in NPM1 or MLLr patients with measurable residual disease (MRD) progression following initial treatment. The trial will be conducted as part of the Australian Leukemia and Lymphoma Group (ALLG) INTERCEPT Master Clinical Trial, a collaborative clinical trial investigating novel therapies to target early relapse and clonal evolution as pre-emptive therapy in AML. SNDX-5613 is the first menin inhibitor to be included in the INTERCEPT AML Master Clinical Trial. We expect ALLG to initiate the trial in the first half of 2022.

•

In August 2021, we announced plans to initiate two additional trials to assess the safety, tolerability, and preliminary anti-leukemic efficacy of SNDX-5613 in combination with venetoclax and azacitidine as part of the Leukemia & Lymphoma Society’s Beat® AML Master Clinical Trial, and in combination with chemotherapy in patients with R/R NPM1 or MLLr acute leukemias in the AUGMENT-102 trial. We expect both trials to initiate in the first half of 2022.

Axatilimab

•

In November 2021, we announced that updated data from its Phase 1/2 trial of axatilimab in patients with cGVHD will be featured during an oral session at the 63rd ASH Annual Meeting. Data included in the abstract demonstrated broad efficacy and tolerability for axatilimab in patients with relapsed or refractory cGVHD. The oral presentation will include additional follow up on all patients enrolled.

~~Enrollment is ongoing~~•

On November 3, 2022, we and our partner, Incyte, announced completion of enrollment in ~~our global~~the pivotal ~~Phase 2~~ AGAVE-201 trial ofevaluating axatilimab in patients with cGVHD ~~with topline data expected in 2023.~~following two or more prior lines of therapy. The trial ~~will evaluate~~is evaluating the safety and efficacy of three ~~doses and schedules~~dosing regimens of axatilimab. The primary endpoint will assess objective response rate based on the 2014 NIH consensus criteria for cGVHD, with key secondary endpoints including duration of response and improvement in modified Lee Symptom Scale score.

We expect to report topline data in mid-2023, with the expectation for a BLA filing later in 2023.

•

In September 2021, together with Incyte we announced that we entered into an exclusive worldwide collaboration and license agreement to develop and commercialize axatilimab. The companies are seeking to develop axatilimab as a backbone therapy for patients with cGVHD as well as in additional immune-mediated diseases where CSF-1R-dependent monocytes and macrophages are believed to contribute to organ fibrosis. In addition to the ongoing global pivotal Phase 2 AGAVE-201 trial of axatilimab monotherapy in patients with cGVHD, the companies also plan to initiate additional trials of axatilimab in patients with cGVHD in 2022, including a Phase 2 trial in combination with a JAK inhibitor in patients with steroid-refractory cGVHD. Beyond cGVHD, we plan to commence a Phase 2 proof of concept trial of axatilimab mid next year in patients with IPF, a serious, life-limiting orphan disease for which axatilimab may represent a much-needed treatment option with a novel mechanism of action.

•

We plan to initiate a Phase 2b trial to assess the efficacy, safety and tolerability of axatilimab in patients with idiopathic pulmonary fibrosis (IPF) in the fourth quarter of 2022. This 52-week, randomized, double-blind and placebo-controlled trial is expected to enroll approximately 170 patients. The primary endpoint will assess the change from baseline in forced vital capacity, which is the current registrational endpoint in IPF.

•

We are working with our partner, Incyte, to initiate a trial testing axatilimab in combination with ruxolitinib in steroid naive cGVHD. The Phase 1 trial is in preparation and is expected to begin in the first quarter of 2023.

COVID-19 ~~Business Update~~and Other Trend Updates

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

~~Supply Chain~~

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

~~Clinical Development~~

~~With respect~~We continue to ~~clinical development, we have taken~~take measures to implement remote and virtual approaches, including remote patient monitoring where possible, to maintain patient safety and trial continuity and to preserve study integrity. We have, and may continue to experience, disruptions and/or delays in our ability to initiate trial sites and enroll and assess patients. As the COVID-19 pandemic continues, we anticipate an ongoing, ~~slight~~though minimal, impact on our ability to maintain patient enrollment in ~~the AUGMENT-101 and AGAVE~~our clinical trials. We could also see an impact on the ability to supply study drug, report trial results, or interact with regulators, ethics committees or other important agencies due to limitations in regulatory authority employee resources or otherwise. In addition, we rely on contract research organizations or other third parties to assist us with clinical trials, and we cannot guarantee that they will continue to perform their contractual duties in a timely and satisfactory manner as a result of the COVID-19 pandemic. If the COVID-19 pandemic continues, ~~and persists for an extended period of time,~~ we could experience ~~significant~~ongoing disruptions to our clinical development timelines, which would adversely affect our business, financial condition, results of operations and growth prospects.

~~Corporate Development~~

With our strong cash balance, we anticipate having sufficient liquidity to make planned investments in our business this year in support of our long-term growth strategy. We believe that our cash, cash equivalents and marketable securities as of September 30, 2021 will fund our current operating plans through at least the next 12 months. However, our operating plan may change as a result of many factors currently unknown to us, and we may need to seek additional funds sooner than planned, through public or private equity

or debt financings, third-party funding, marketing and distribution arrangements, as well as other collaborations, strategic alliances and licensing arrangements, or any combination of these approaches. However, the COVID-19 pandemic continues to rapidly evolve and has already resulted in a significant disruption of global financial markets. If the disruption persists and deepens, we could experience an inability to access additional capital, which could in the future negatively affect our operations.

~~Other Financial and Corporate Impacts~~

~~While we continue to evaluate whether~~Additionally, the ~~COVID-19 pandemic will~~recent trends towards rising inflation may also materially adversely affect our business ~~operations~~ and corresponding financial ~~results,~~position and cash flows. Inflationary factors, such as increases in the cost of our clinical trial materials and supplies, interest rates and overhead costs may adversely affect our operating results. Rising interest and inflation rates also present a recent challenge impacting the U.S. economy and could make it more difficult for us to obtain traditional financing on acceptable terms, if at all, in the future. Although we do not believe that inflation has a material impact on our financial position or results of operations to date, we may experience increases in the near future (especially if inflation rates continue to rise) on our operating costs, including our labor costs and research and development ~~and regulatory efforts, our corporate development objectives~~costs, due to supply chain constraints, consequences associated with COVID-19 and the ~~value of~~ongoing conflict between Russia and ~~market for our common stock, will depend~~Ukraine, and employee availability and wage increases, which may result in additional stress on ~~future developments that are highly uncertain and cannot be predicted with confidence at this time, such as~~ the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the United States, Europe and other countries, and the effectiveness of actions taken globally to contain and treat the disease. For example, if remote work policies for certain portions of our business, or that of our business partners, are extended longer than we currently expect, we may need to reassess our priorities and our corporate objectives for the year.Company's working capital resources.

Financial Overview

Revenue

To date, we have not generated any product revenues. Our ability to generate revenue and become profitable depends upon our ability to obtain marketing approval of and successfully commercialize our product candidates. Our ~~revenues~~revenue for the three and nine months ended September 30, 2021, ~~and 2020 have~~had been solely derived from our license, development and commercialization agreement with Kyowa Kirin Co., Ltd., or KKC, under which we granted KKC an exclusive license to develop and commercialize entinostat in Japan and Korea, or the KKC license agreement. In 2015, we received a $25.0 million upfront payment from KKC, inclusive of an equity investment. We allocated $17.3 million of the upfront payment to the license fee, and such fee is being recognized as revenue ratably over our expected performance period (currently expected to be through 2029). The balance of the upfront payment of $7.7 million was allocated to KKC’s purchase of shares of our convertible preferred stock.

In October 2017, KKC enrolled the first Japanese patient into a local pivotal study of entinostat for the treatment of hormone receptor positive, human epidermal growth factor 2 negative breast cancer. In accordance with the terms of the KKC License Agreement, in December 2017 we received a $5.0 million milestone payment from KKC for achievement of the development milestone.

KKC. In September 2021, KKC informed us that they ~~have~~ discontinued the entinostat program and ~~have~~ cancelled the license to develop and commercialize entinostat. ~~As a result,~~

In September 2021, the Company entered into the Incyte License Agreements covering the worldwide development and commercialization of SNDX-6352 (axatilimab). We granted Incyte an exclusive license to develop and commercialize axatilimab in the United States and the rest of the world. In 2021, we ~~recognized $12.4~~received $152.0 million in total consideration, of which $126.6 million was allocated to the license and recognized as license revenue ~~which was previously deferred.~~as of December 31, 2021. For the three and nine months ended September 30, 2022, no additional revenue has been recognized under the Incyte Agreements.

Research and Development

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

•

expenses incurred under agreements related to our clinical trials, including the costs for investigative sites and contract research organizations, or CROs, that conduct our clinical trials;

•

employee-related expenses associated with our research and development activities, including salaries, benefits, travel and non-cash stock-based compensation expenses;

•

manufacturing process-development, clinical supplies and technology-transfer expenses;

•

license fees and milestone payments under our license agreements;

•

consulting fees paid to third parties;

•

allocated facilities and overhead expenses; and

•

costs associated with regulatory operations and regulatory compliance requirements.

•

~~expenses incurred under agreements related to our clinical trials, including the costs for investigative sites and contract research organizations, or CROs, that conduct our clinical trials;~~

•

~~employee-related expenses associated with our research and development activities, including salaries, benefits, travel and non-cash stock-based compensation expenses;~~

•

~~manufacturing process-development, clinical supplies and technology-transfer expenses;~~

•

~~license fees and milestone payments under our license agreements;~~

•

~~consulting fees paid to third parties;~~

•

~~allocated facilities and overhead expenses; and~~

•

~~costs associated with regulatory operations and regulatory compliance requirements.~~

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

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

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

•

per patient costs;

•

the number of patients that participate;

•

the number of sites;

•

the countries in which the studies and trials are conducted;

•

the length of time required to enroll eligible patients;

•

the potential additional safety monitoring or other studies requested by regulatory agencies;

•

the duration of patient monitoring;

•

the efficacy and safety profile of the product candidates; and

•

timing and receipt of any regulatory approvals.

•

~~per patient costs;~~

•

~~the number of patients that participate;~~

•

~~the number of sites;~~

•

~~the countries in which the studies and trials are conducted;~~

•

~~the length of time required to enroll eligible patients;~~

•

~~the potential additional safety monitoring or other studies requested by regulatory agencies;~~

•

~~the duration of patient monitoring;~~

•

~~the efficacy and safety profile of the product candidates; and~~

•

~~timing and receipt of any regulatory approvals.~~

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

General and Administrative

General and administrative expenses consist primarily of employee-related expenses, including salaries, benefits, non-cash stock-based compensation and travel expenses, for our employees in executive, finance, business development and support functions. Other general and administrative expenses include facility-related costs not otherwise allocated to research and development expenses and accounting, tax, legal and consulting services. We anticipate that our general and administrative expenses will increase in the future as we increase our headcount to support our continued research and development and potential commercialization of our product candidates. Additionally, if and when we believe a regulatory approval of the first product candidate appears likely, we anticipate an increase in payroll and related expenses as a result of our preparation for commercial operations, especially as it relates to the sales and marketing of our product candidates.

Interest ~~expense~~Expense

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

Interest Income

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

Other (Expense) Income

Other (expense) income includes income recorded for the change in fair value of derivative liability established based on the terms of the Incyte License and Collaboration Agreement and Share Repurchase Agreement, or the Incyte Agreement.

New Accounting Standards

For a discussion of new accounting standards please read Note 3 Summary of Significant Accounting Policies, to our condensed consolidated financial statements included in this report.

Critical Accounting ~~Policies and Use of~~ Estimates

Our management’s discussion and analysis of financial condition and results of operations are based on our financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States of America. The preparation of these financial statements requires us to make estimates and judgments that affect the reported amounts of assets,

liabilities and expenses and the disclosure of contingent assets and liabilities in our financial statements. We base our estimates on historical experience, known trends and events and various other factors that are believed to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. In making estimates and judgments, management employs critical accounting policies.

There have been no material changes to our critical accounting ~~policies~~estimates described in the “Management’s Discussion and Analysis of Financial Condition and Results of Operations” contained in our Annual ~~Report.~~Report on Form 10-K.

Results of Operations

Comparison of the three months ended September 30, ~~2021~~2022 and ~~2020:~~2021:


	Three Months Ended September 30,						Increase (Decrease)						Three Months Ended September 30,						Increase (Decrease)
	2021			2020			$			%			2022			2021			$			%
	(In thousands)												(In thousands)
Revenue:
License fees	$	12,375		$	379		$	11,996			3165	%	$	—		$	12,375		$	(12,375	)		-100	%
Total revenues		12,375			379			11,996			3165	%		—			12,375			(12,375	)		-100	%
Operating expenses:
Research and development		25,606			14,408			11,198			78	%		26,901			25,606			1,295			5	%
General and administrative		6,801			5,824			977			17	%		8,240			6,801			1,439			21	%
Total operating expenses		32,407			20,232			12,175			60	%		35,141			32,407			2,734			8	%
Loss from operations		(20,032	)		(19,853	)		179			1	%		(35,141	)		(20,032	)		15,109			75	%
Other (expense) income:
Other (expense) income, net:
Interest expense		(649	)		(635	)		(14	)		2	%		(1,748	)		(649	)		(1,099	)		169	%
Interest income		83			177			(94	)		-53	%		1,781			83			1,698			2046	%
Other (expense) income, net		(41	)		(126	)		85			-67	%		(295	)		(41	)		(254	)		620	%
Total other (expense) income		(607	)		(584	)		(23	)		4	%		(262	)		(607	)		345			-57	%
Net loss	$	(20,639	)	$	(20,437	)	$	202			1	%	$	(35,403	)	$	(20,639	)	$	14,764			72	%

License Fees

For the three months ended September 30, 2022, we recognized no revenue under our current agreements, which are not revenue generating. For the three months ended September 30, 2021, ~~and 2020,~~ we recognized ~~license fees~~revenue of $12.4 million, ~~and $0.4 million respectively,~~ derived from the KKC license ~~agreement.~~agreement which was terminated during the period.

Research and Development

For the three months ended September 30, ~~2021,~~2022, our total research and development expenses increased approximately ~~$11.2~~$1.3 million, or ~~78%~~5%, to ~~$25.6~~$26.9 million from ~~$14.4~~$25.6 million for the comparable quarter in the prior year. The increase in research and development expenses was primarily due to ~~increases in~~increased employee related expenses of $2.8 million and increased professional fees of $0.5 million, partially offset by decreased clinical and manufacturing activities of ~~$9.5 million, employee related expenses of $1.0 million and professional fees of $0.2 million and stock-based comp expense of $0.5~~$2.0 million. ~~Increases in~~Decreased clinical and manufacturing expenses were primarily due to decreased manufacturing activities ~~related to menin research~~for revumenib of ~~$4.2~~$1.6 million, decreased milestones expenses of $2.3 million, decreased clinical activities for entinostat of $0.3 million and ~~CMC drug production costs~~increased collaboration cost reimbursement of ~~$2.1~~$4.6 million, partially offset by increasedclinical activities for revumenib of $0.9 million, increased clinical activities for axatilimab of $3.9 million, and increased manufacturing activities for axatilimab of $2.0 million. ~~We also recognized a $2.0 million expense upon the achievement of a certain milestone in connection with the SNDX-6352 program.~~ Employee related ~~expenses and stock-based compensation primarily~~activities increased due to ~~an increase in~~increased headcount expenses of $2.1 million and ~~new hire grants.~~increased stock compensation of $0.7 million. We expect research and development expenses to fluctuate from quarter to quarter depending on the timing of clinical trial activities, clinical manufacturing and other development activities.

Research and development expenses consisted of the following:

Three Months Ended September 30,

Increase (Decrease)

2021

2020

$

%

(In thousands)

External research and development expenses

$
20,658

$
10,968

$
9,690

88
%
Internal research and development expenses

4,948

3,440

1,508

44
%
Total research and development expenses

$
25,606

$
14,408

$
11,198

78
%


	Three Months Ended September 30,				Increase (Decrease)
	2022		2021		$			%
	(In thousands)
External research and development expenses	$	18,898	$	20,658	$	(1,760	)		-9	%
Internal research and development expenses		8,003		4,948		3,055			62	%
Total research and development expenses	$	26,901	$	25,606	$	1,295			5	%

General and Administrative

For the three months ended September 30, ~~2021,~~2022, our total general and administrative expenses increased $1$1.4 million, or ~~17%~~21%, to ~~$6.8~~$8.2 million from ~~$5.8~~$6.8 million for the comparable period in the prior year. The increase in general and administrative expenses was primarily due to ~~an increase in professional service fees~~increased employee related expenses of ~~$0.9 million,~~$1.4 million.

Interest Income and ~~insurance expense of $0.1 million.~~Interest Expense

~~Interest expense~~

For the three months ended September 30, ~~2021,~~2022, interest income increased $1.7 million to $1.8 million from $0.1 million for the comparable period in the prior year primarily due to increased interest rates and increased average balance on cash equivalents and short-term investments.

For the three months ended September 30, 2022, interest expense increased $1.1 million to $1.7 million from $0.6 million for the comparable period in the prior year primarily due to the interest expense ~~on the loan payable.~~

~~Interest income~~

~~For the three months ended September 30, 2021, interest income decreased from the comparable period in the prior year primarily due to a decrease on interest income~~ related to the ~~average balance of cash equivalents and short-term investments.~~Amended Loan Agreement.

Comparison of the nine months ended September 30, ~~2021~~2022 and ~~2020:~~2021:


	Nine Months Ended September 30,						Increase (Decrease)						Nine Months Ended September 30,						Increase (Decrease)
	2021			2020			$			%			2022			2021			$			%
	(In thousands)												(In thousands)
Revenue:
License fees	$	13,133		$	1,138		$	11,995			1054	%	$	—		$	13,133		$	(13,133	)		-100	%
Total revenues		13,133			1,138			11,995			1054	%		—			13,133			(13,133	)		-100	%
Operating expenses:
Research and development		64,348			34,913			29,435			84	%		86,658			64,348			22,310			35	%
General and administrative		18,314			17,787			527			3	%		23,066			18,314			4,752			26	%
Total operating expenses		82,662			52,700			29,962			57	%		109,724			82,662			27,062			33	%
Loss from operations		(69,529	)		(51,562	)		17,967			35	%		(109,724	)		(69,529	)		40,195			58	%
Other income (expense):
Other (expense) income, net:
Interest expense		(1,906	)		(1,722	)		(184	)		11	%		(3,094	)		(1,906	)		(1,188	)		62	%
Interest income		312			735			(423	)		-58	%		2,884			312			2,572			824	%
Other expense (income), net		(149	)		(186	)		37			-20	%
Total other income		(1,743	)		(1,173	)		(570	)		49	%
Other income (expense), net														(210	)		(149	)		(61	)		41	%
Total other (expense), net														(420	)		(1,743	)		1,323			-76	%
Net loss	$	(71,272	)	$	(52,735	)	$	18,537			35	%	$	(110,144	)	$	(71,272	)	$	38,872			55	%

License Fees

For the nine months ended September 30, 2022, we recognized no revenue under our current agreements, which are not revenue generating. For the nine months ended September 30, 2021, ~~and 2020,~~ we recognized ~~license fees~~revenue of $13.1 million, ~~and $1.1 million respectively,~~ derived from the KKC license ~~agreement.~~agreement which was terminated during the period.

Research and Development

For the nine months ended September 30, ~~2021,~~2022, our total research and development expenses increased ~~$29.4~~$22.3 million, or ~~84%~~35%, to ~~$64.3~~$86.7 million from ~~$34.9~~$64.3 million for the comparable period in the prior ~~year~~year. The increase in research and development expenses was primarily due to ~~increases in~~increased clinical and manufacturing activities of ~~$25.3~~$14.3 million, increased employee related expenses of ~~$2.2~~$6.5 million, ~~stock-based compensation of $1.4 million~~ and increased professional fees of ~~$0.5~~$1.5 million. ~~Increases in~~Increased clinical and manufacturing activities were primarily due to increased clinical activities for revumenib of $8.5 million, for axatilimab of $10.5 million, for manufacturing activities related to ~~menin and~~ axatilimab of ~~$6.7~~$10.7 million, and ~~$5.7~~increased milestone expense in connection with the axatilimab program of $3.5 million, ~~respectively, and increases in~~partially offset by decreased clinical activities for ~~menin and axatilimab~~entinostat of ~~$3.4~~$0.9 million and ~~$4.5 million, respectively.~~by collaboration cost reimbursement of $18.0 million. Employee related expenses ~~and stock-based compensation~~ primarily increased due to increased headcount and ~~related new hire grants.~~stock compensation. We expect research and development expenses to fluctuate from period to period depending on the timing of clinical trial activities, clinical manufacturing, and other development activities.

Research and development expenses consisted of the following:


	Nine Months Ended September 30,				Increase (Decrease)					Nine Months Ended September 30,				Increase (Decrease)
	2021		2020		$		%			2022		2021		$		%
	(In thousands)									(In thousands)
External research and development expenses	$	50,327	$	24,564	$	25,763		105	%	$	66,344	$	50,327	$	16,017		32	%
Internal research and development expenses		14,021		10,349		3,672		35	%		20,314		14,021		6,293		45	%
Total research and development expenses	$	64,348	$	34,913	$	29,435		84	%	$	86,658	$	64,348	$	22,310		35	%

General and Administrative

For the nine months ended September 30, ~~2021,~~2022, our total general and administrative expenses increased ~~$0.5~~$4.8 million, or 3%26%, to ~~$18.3~~$23.1 million from ~~$17.8~~$18.3 million for the comparable period in the prior year. The ~~increases~~increase in general and administrative expenses ~~were~~ was

primarily due to ~~increases in stock-based compensation $0.9~~increased employee related expenses of $4.0 million, ~~associated with increase related to Board RSU grants, $0.3 million related to employee bonuses and $0.2 million related to insurance expense, partially offset by decrease in~~increased professional ~~services~~ fees of ~~$0.9~~$0.5 million, and increased insurance related ~~to the termination~~expense of ~~E2112 commercialization.~~$0.3 million.

Interest Income and Interest Expense

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

~~Interest Income~~

For the nine months ended September 30, ~~2021,~~2022, interest income ~~decreased~~increased $2.6 million to $2.9 million from $0.3 million the comparable period in the prior year primarily due to ~~lower~~ interest ~~rates.~~rates and increased average balance on cash equivalents and short-term investments.

For the nine months ended September 30, 2022, interest expense increased $1.2 million to $3.1 million from $1.9 million the comparable period in the prior year primarily due to the interest expense related to the payoff of the Amended Loan Agreement.

Liquidity and Capital Resources

Overview

As of September 30, ~~2021,~~2022, we had cash, cash equivalents and short-term investments totaling ~~$229.7 million, which includes $5.1 million in net proceeds from the sale of 277,629 shares of common stock under our 2021 ATM Program (as described below).~~$337.8 million. Our operations have been primarily financed by net proceeds from ~~our initial~~ public ~~offering, our follow-on~~ stock offerings, and ~~proceeds~~revenue from our license agreements. We believe that our present cash, cash equivalents and short-term investments as of September 30, 2022, will fund our projected operating expenses and capital expenditure requirements for at least the next 12 months. In addition to our existing cash, cash equivalents and short-term investments, we are eligible to receive research and development funding and to earn milestone and other contingent payments for the achievement of defined collaboration objectives and certain development, regulatory and commercial milestones and royalty payments under our collaboration agreements. Our ability to earn these milestone and contingent payments and the timing of achieving these milestones is primarily dependent upon the outcome of our collaborators’ research and development activities and is uncertain at this time.

The COVID-19 pandemic continues to rapidly evolve and has already resulted in a significant disruption of global financial markets. If the disruption persists and deepens, we could experience an inability to access additional capital, which could in the future negatively affect our operations.

Loan and Security Agreement

~~On February 7, 2020, we~~In December 2021, the Company entered into aAmendment No. 1 to the Company’s loan and security agreement or(the “First Amendment” and the Loan Agreement, as amended, the “Amended Loan Agreement”) with several banks and financial institutions or entities from time-to-time party thereto (collectively, the “Lender”) and Hercules Capital, ~~Inc., or Hercules, which provides~~Inc, in its capacity as administrative agent for itself and the Lender (in such capacity, the “Agent”).

The Amended Loan Agreement provided for an aggregate maximum ~~borrowings~~borrowing of up to ~~$30.0~~$80.0 million, consisting of (i) a term loan of up to ~~$20.0~~$20 million (the “Initial Advance”), (ii) second tranche of up to $30.0 million with $15.0 million being available at the Company’s option through April 30, 2022 and the remaining $15.0 million being available at the Company’s option through November 30, 2022, which availability period would be extended to April 30, 2023 if the first $15.0 million was drawn prior to April 30, 2022, and (iii) third tranche of up to $30.0 million which was ~~funded on February 7, 2020, and (ii)~~available, subject to ~~Hercules’~~the Agent’s investment committee approval, ~~an additional term loan~~through the Interest-Only Period (as defined in the Amended Loan Agreement).

On September 23, 2022, the Company made a prepayment of up$21.5 million to $10.0 million, available for borrowing from February 7, 2020 to December 15, 2020, which we refer to as the Tranche 2 Advance. We did not request the available additional borrowings by the due date. Borrowings under the Loan Agreement are repayablesatisfy in monthly interest-only payments through October 1, 2021. After the interest-only payment period, borrowings under the Loan Agreement are repayable in equal monthly payments of principal and accrued interest until the maturity date of the loan, which is September 1, 2023. Borrowings under the Loan Agreement bear interest at an annual rate equal to the greater of (i) 9.85% or (ii) 5.10% plus the Wall Street Journal~~prime rate. The Wall Street Journal prime rate as of September 30, 2021, was 3.25%. At our option, we may prepay all, but not less than~~full all of the ~~outstanding borrowings, subject to a prepayment premium. Borrowings~~Company's principal and interest obligations and related fees under the Amended Loan ~~Agreement are collateralized by substantially all of our and our subsidiaries personal property and other assets, other than our intellectual property.~~Agreement. For additional information, ~~regarding the~~see Note 11 Loan ~~Agreement with Hercules, see Note 11~~Payable to our condensed consolidated financial statements ~~located~~included elsewhere in this report.

At-the-Market Offering Program

In March 2021, we entered into a new sales agreement with ~~Cowen and Company, LLC, or~~ Cowen, under which we may issue and sell shares of our common stock having aggregate sales proceeds of up to $75.0 million from time to time through Cowen, acting as agent, in a series of one or more ATM equity offerings ~~or the~~(the “2021 ATM Program”). Cowen is not required to sell any specific amount but acts as our sales agent using commercially reasonable efforts consistent with its normal trading and sales practices. Shares sold pursuant to the sales agreement will be sold pursuant to a shelf registration statement on Form S-3ASR (Registration No. 333-254661), which became automatically effective upon filing on March 24, 2021. Our common stock will be sold at prevailing market prices at the time of the sale; and as a result, prices may vary. ~~As of~~For the three months ended September 30, ~~2021,~~2022, we ~~sold 277,629~~did not sell any shares of common stock under the 2021 ATM ~~Program for net proceeds~~Program. As of ~~approximately $5.1 million.~~November 2, 2022, the Company had $49.7 million available under the 2021 ATM Program.

Future Funding Requirements

We believe that our available cash, cash equivalents and short-term investments and continued access to our term loan are sufficient to fund existing and planned cash requirements for the next 12 months. Our primary uses of capital are, and we expect will continue to be, compensation and related expenses, third-party clinical research and development services, clinical costs, legal and other regulatory expenses and general overhead costs. We have based our estimates on assumptions that may prove to be incorrect, and we could use our capital resources sooner than we currently expect.

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

•

the initiation, progress, timing, costs and results of clinical trials for our product candidates;

•

the outcome, timing and cost of seeking and obtaining regulatory approvals from the FDA and comparable foreign regulatory authorities, including the potential for such authorities to require that we perform more trials than we currently expect;

•

the cost to establish, maintain, expand and defend the scope of our intellectual property portfolio, including the amount and timing of any payments we may be required to make, or that we may receive, in connection with licensing, preparing, filing, prosecuting, defending and enforcing any patents or other intellectual property rights;

•

market acceptance of our product candidates;

•

the cost and timing of selecting, auditing and developing manufacturing capabilities, and potentially validating manufacturing sites for commercial-scale manufacturing;

•

the cost and timing for obtaining pricing and reimbursement, which may require additional trials to address pharmacoeconomic benefit;

•

the cost of establishing sales, marketing and distribution capabilities for our drug candidates if either candidate receives regulatory approval and we determine to commercialize it ourselves;

•

the costs of acquiring, licensing or investing in additional businesses, products, product candidates and technologies;

•

the diversion of healthcare resources away from the conduct of clinical trials as a result of the ongoing COVID-19 pandemic, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials;

•

the interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel, quarantines or social distancing protocols imposed or recommended by federal or state governments, employers and others in connection with the ongoing COVID-19 pandemic;

•

the cost of disruptions to our supply chain and operations, and associated delays in the manufacturing and supply of our products, which would adversely impact our ability to continue our clinical trial operations.

•

the effect of competing technological and market developments; and

•

our need to implement additional internal systems and infrastructure, including financial and reporting systems, to meet our requirements as a public company.

•

~~the initiation, progress, timing, costs and results of clinical trials for our drug candidates;~~

•

~~market acceptance of our drug candidates;~~

•

~~the cost and timing of selecting, auditing and developing manufacturing capabilities, and potentially validating manufacturing sites for commercial-scale manufacturing;~~

•

~~the cost and timing for obtaining pricing and reimbursement, which may require additional trials to address pharmacoeconomic benefit;~~

•

~~the cost of establishing sales, marketing and distribution capabilities for our drug candidates if either candidate receives regulatory approval and we determine to commercialize it ourselves;~~

•

~~the costs of acquiring, licensing or investing in additional businesses, products, product candidates and technologies;~~

•

the cost of disruptions to our supply chain and operations, and associated delays in the manufacturing and supply of our products, which would adversely impact our ability to generate sales of and revenues from entinostat, if approved, and to continue our clinical trial operations;

•

~~the effect of competing technological and market developments; and~~

•

~~our need to implement additional internal systems and infrastructure, including financial and reporting systems, to meet our requirements as a public company.~~

We have no products approved for commercial sale and have not generated any product revenues from product sales to date. Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings and additional funding from license and collaboration arrangements. Except for any obligations of

our collaborators to reimburse us for research and development expenses or to make milestone payments under our agreements with them, we will not have any committed external source of liquidity.

Our material contractual obligations and commitments as of September 30, 2022, primarily relate to our maturities of operating leases for office space and equipment and capital leases for office equipment. As of September 30, 2022, we have $0.6 million payable within 12 months.

Except as disclosed above, we have no material non-cancelable purchase commitments with service providers, as we have generally contracted on a cancelable, purchase-order basis. We enter into contracts in the normal course of business with equipment and reagent vendors, CROs, CMOs and other third parties for clinical trials, preclinical research studies and testing and manufacturing services. These contracts are cancelable by us upon prior notice. Payments due upon cancellation consist only of payments for services provided or expenses incurred, including noncancelable obligations of our service providers, up to the date of cancellation. These payments are not determinable.

We have incurred losses and cumulative negative cash flows from operations since our ~~inception; and as~~inception, excluding the year ended December 31, 2021. As of September 30, ~~2021,~~2022, we had an accumulated deficit of ~~$639.9~~$653.8 million. We anticipate that we will continue to incur significant losses for at least the next several years. We expect that our research and development and general and administrative expenses will continue to increase. As a result, we will need additional capital to fund our operations, which we may raise through a combination of the sale of equity, debt financings, or other sources, including potential collaborations. The ongoing COVID-19 pandemic has resulted in a significant disruption of global financial markets. If the disruption persists and deepens, we could experience an inability to access additional capital, which could in the future negatively affect our operations. To the extent that we raise additional capital through the future sale of equity or debt, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing common stockholders. If we raise additional funds through collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or drug candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market drug candidates that we would otherwise prefer to develop and market ourselves.

Cash Flows

The following is a summary of cash flows:


	Nine Months Ended September 30,						Nine Months Ended September 30,
	2021			2020			2022			2021
	(In thousands)						(In thousands)
Net cash used in operating activities	$	(71,578	)	$	(55,629	)	$	(110,781	)	$	(71,578	)
Net cash provided by / used in investing activities		19,083			(78,390	)
Net cash (used in) provided by investing activities								(48,559	)		19,083
Net cash provided by financing activities		8,685			165,766			8,752			8,685
Net increase (decrease) in cash, cash equivalents and restricted cash	$	(43,810	)	$	31,747
Net (decrease) in cash, cash equivalents and restricted cash							$	(150,588	)	$	(43,810	)

Net Cash Used in Operating Activities

Net cash used in operating activities for nine months ended September 30, 2022, was $110.8 million and primarily consisted of our net loss of $110.1 million adjusted for non-cash items, including stock-based compensation of $11.8 million, a net decrease in operating assets and liabilities of $12.3 million, an investment accretion of $1.4 million, a non-cash operating lease expense of $0.3 millionand non-cash interest expense associated with the term loan of $1.1 million. The increase in net loss was primarily due to increased clinical trial activities and CMC expenses. The net decrease in operating assets and liabilities primarily consisted of increased accounts payable of $1.4 million, increased prepayments and deposits of $7.7 million, increased other receivables of $4.5 million, partially offset by decreased accrued expenses and other liabilities of $1.5 million.

Net cash used in operating activities for the nine months ended September 30, 2021, was $71.6 million and primarily consisted of our net loss of $71.3 million adjusted for non-cash items, including stock-based compensation of $9.4 million, a net decrease in operating assets and liabilities of $10.9 million, an investment accretion of $0.5 million, a non-cash operating lease expense of $0.3 million and non-cash interest expense associated with the term loan of $0.4 million. The increase in net loss was primarily due to increased ~~clinical~~pre-clinical trial activities and CMC expenses partially offset by decreased pre-commercialization activities. The net decrease in operating assets and liabilities primarily consisted of increased accounts payable of $1.6 million, increased prepayments and deposits of $1.5 million, ~~and~~ increased accrued expenses and other liabilities of $2.1 million and decreased deferred revenue of $13.1 million.

Net Cash (Used in) Provided by Investing Activities

Net cash used in ~~operating~~investing activities for the nine months ended September 30, ~~2020,~~2022, was ~~$55.6~~$48.6 million and primarily consisted of our net loss of $52.7 million adjusted for non-cash items, including stock-based compensation of $7.0 million, a net decrease in operating assets and liabilities of $10.4 million, an investment accretion of $0.2 million and non-cash interest expense associated with the term loan of $0.3 million. The increased net loss iswas primarily due to ~~increased clinical activities in our axatilimab program, increased clinical and CMC activities in our SNDX-5613 program, increased pre-commercialization activities~~the purchase of $244.5 million of available-for-sale securities partially offset by ~~reduced CMC expenses for axatilimab~~the $195.7 million of proceeds from the maturities of available-for-sale securities and ~~decreased activities related to our entinostat program. The net decrease in operating assets and liabilities primarily consisted~~by the $0.2 million of ~~decreased accounts payable~~proceeds from sale of ~~$2.4 million, increased prepayments and deposits of $5.8 million, and decreased accrued expenses and other liabilities of $1.1 million and deferred revenue of $1.1 million.~~equipment.

~~Net Cash Provided by / Used in Investing Activities~~

Net cash provided by investing activities for the nine months ended September 30, 2021, was $19.1 million and was primarily due to the purchase of $189.5 million of available-for-sale ~~marketable~~ securities partially offset by the $208.6 million of proceeds from the maturities of available-for-sale securities.

Net Cash Provided by Financing Activities

Net cash ~~used in investing~~provided by financing activities for the nine months ended September 30, ~~2020, was $78.4~~2022, of $8.8 million ~~and~~ was primarily due to proceeds from sales under the ~~purchase~~2021 ATM Program, net of ~~$150.4~~discounts and commissions of $19.4 million, ~~of available-for-sale marketable securities~~proceeds from the ~~proceeds~~exercise of ~~the January 2020 direct offering~~stock options of $10.1 million and employee participation in our Employee Stock Purchase Plan of $0.3 million, partially offset by ~~$72.0 million~~payment on term loan of ~~proceeds from the maturities of available-for-sale securities, which will primarily be used to fund the next period’s operating activities.~~

~~Net Cash Provided by Financing Activities~~$21.0 million.

Net cash provided by financing activities for the nine months ended September 30, 2021, of $8.7 million was primarily due to proceeds from sales under the 2021 ATM Program, net of discounts and commissions of $5.1 million, proceeds from the exercise of stock options of $3.3 million, ~~and~~ employee participation in our Employee Stock Purchase Plan of $0.2 million.

Net cash provided by financing activities for the nine months ended September 30, 2020, of $165.8 million was primarily due to the proceeds from our direct placement and follow-on offering, net of fess, of $142.7 million, net proceeds from our term loan of $19.7 million, proceeds from stock option exercises of $3.1 million and employee participation in our Employee Stock Purchase Plan of $0.2 million.

~~Off-Balance Sheet Arrangements~~

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

~~Emerging Growth Company and Smaller Reporting Company Status~~

We are an “emerging growth company,” or EGC, as defined in the Jumpstart Our Business Startups Act of 2012, or JOBS Act. Section 107 of the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. Thus, an emerging growth company can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. We have irrevocably elected not to avail ourselves of this extended transition period and, as a result, we will adopt new or revised accounting standards on the relevant dates on which adoption of such standards is required for other public companies. We will cease to be an “emerging growth company” on December 31, 2021.

As of June 30, 2021, we no longer qualify as a smaller reporting company as defined in the Securities Exchange Act of 1934, as amended. We have historically taken and may continue through the filing of our Annual Report on Form 10-K for the year ending December 31, 2021 to take, advantage of certain scaled disclosures available to smaller reporting companies.

Item 3. Quantitative and Qualitative Disclosures about Market Risk

~~Item 3.~~

~~Quantitative and Qualitative Disclosures about Market Risk~~

The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates. As of September 30, ~~2021,~~2022 we had cash and cash equivalents of $71.4 million, consisting of overnight investments, interest-bearing money market funds, commercial papers and short-term corporate bonds, and short-term investments of ~~$158.3~~$266.5 million, consisting of commercial paper, and highly rated corporate bonds. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates. The primary objectives of our investment activities are to ensure liquidity and to preserve principal while at the same time maximizing the income we receive from our marketable securities without significantly increasing risk. We have established guidelines regarding approved investments and maturities of investments, which are designed to maintain safety and liquidity. Due to the short-term maturities of our cash equivalents and the low risk profile of our short-term investments, an immediate 100 basis point change in interest rates would not have a material effect on the fair market value of our cash equivalents and short-term investments.

~~We also have exposure~~

On September 23, 2022, the Company made a prepayment to ~~market risk on our~~satisfy in full all of the Company's principal and interest obligations and related fees under that certain Loan and Security Agreement, ~~with Hercules. Our Loan Agreement accrues interest from its date of issue at a variable interest rate equal to greater of (i) 9.85% and (ii) 5.10% plus~~dated February 7, 2020, as amended (as amended, the Wall Street Journal prime rate. As of September 30, 2021, $20.0 million in loan principal was outstanding under the Loan Agreement. The effect of a 100 basis points adverse change in market interest rates on our 2020"Loan Agreement"). For additional information, see Note 11 Loan Payable to our condensed consolidated financial statements elsewhere in ~~excess of applicable minimum floors, on our interest expense would be approximately $0.4 million.~~this report.

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

Item 4. Controls and Procedures

~~Item 4.~~

~~Controls and Procedures~~

~~Management’s Evaluation of Our~~ Disclosure Controls and Procedures and Internal Control over Financial Reporting

Controls and Procedures

We ~~maintain disclosure controls and procedures that are designed to ensure that information required to be disclosed in the reports that we file or submit~~have carried out an evaluation, under the ~~Securities~~supervision and ~~Exchange Act~~with the participation of ~~1934 is (1) recorded, processed, summarized, and reported within the time periods specified in the SEC’s rules and forms and (2) accumulated and communicated to~~ our management, including our principal executive officer and principal financial officer, ~~to allow timely decisions regarding required disclosure.~~

As of ~~September 30, 2021, our management, with the participation of our principal executive officer and principal financial officer, evaluated~~ the effectiveness of the design and operation of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities ~~and~~ Exchange Act of ~~1934). Our~~1934, as amended), as of September 30, 2022. Based upon that evaluation, our principal executive officer and principal financial officer concluded that, as of the end of the period covered by this report, our disclosure controls and procedures are effective in ensuring that:

(a)

the information required to be disclosed by us in the reports we file or submit under the Securities Exchange Act is recorded, processed, summarized and reported within the time periods specified in the U.S. Securities and Exchange Commission’s rules and forms; and

(b)

the information is accumulated and communicated to our management, ~~recognizes~~including our principal executive officer and principal financial officer as appropriate to allow timely decisions regarding required disclosure.

In designing and evaluating our disclosure controls and procedures, our management recognized that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving ~~their~~the desired control objectives, and our management necessarily ~~applies~~was required to apply its ~~judgment~~judgement in evaluating the ~~cost-benefit~~cost- benefit relationship of possible controls and procedures. Our principal executive officer and principal financial officer have concluded based upon the evaluation described above that, as of September 30, 2021, our disclosure controls and procedures were effective at the reasonable assurance level.

Changes in Internal Control over Financial Reporting

There was no change in our internal control over financial reporting during the quarter ended September 30, 2022, that ~~occurred during our most recent fiscal quarter that~~have materially affected, or isare reasonably likely to materially affect, our internal control over financial reporting. We have not experienced any material impact to our internal controls over financial reporting despite the fact that our employees are working remotely due to the COVID-19 pandemic. We are continually monitoring and assessing the COVID-19 situation on our internal controls to minimize the impact on their design and operating effectiveness.

PART II. OTHER INFORMATION

Item 1. Legal Proceedings

~~Item 1.~~

~~Legal Proceedings~~

In the ordinary course of business, we are from time to time involved in lawsuits, claims, investigations, proceedings, and threats of litigation relating to intellectual property, commercial arrangements and other matters. While the outcome of these proceedings and claims cannot be predicted with certainty, as of September 30, ~~2021,~~2022, we were not party to any material legal or arbitration proceedings. No governmental proceedings are pending or, to our knowledge, contemplated against us.

Item 1A. Risk Factors

~~Item 1A.~~

~~Risk Factors~~

An investment in shares of our common stock involves a high degree of risk. You should carefully consider the following information about these risks, together with the other information appearing elsewhere in this Quarterly Report on Form 10-Q, including our condensed consolidated financial statements and related notes hereto, before deciding to invest in our common stock. The occurrence of any of the following risks could have a material adverse effect on our business, financial condition, results of operations and future growth prospects or cause our actual results to differ materially from those contained in forward-looking statements we have made in this report and those we may make from time to time. In these circumstances, the market price of our common stock could decline; and you may lose all or part of your investment. We cannot assure you that any of the events discussed below will not occur.

Summary of Selected Risks

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

•

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

•

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

•

Public health threats could have an adverse effect on our clinical trials, operations and financial results.

•

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

•

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

•

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

•

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

•

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

•

Incyte may fail to perform its obligations as expected under the collaboration or may deprioritize its investment to further develop and commercialize axatilimab.

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Risks Related to Our Business and Industry

Public health threats could have an adverse effect on our clinical trials, operations and financial results.

We face various risks related to epidemics, pandemics, and other outbreaks, including the ongoing COVID-19 pandemic, including newly discovered strains of the virus, which could adversely affect our ongoing or planned business operations. In particular, the ongoing COVID-19 pandemic has resulted in quarantines, restrictions on travel and other business and economic disruptions. We cannot presently predict the scope and severity of any future business shutdowns or disruptions, but if we or any of the third parties with whom we engage, including the partners and other third parties with whom we conduct business, were to experience shutdowns or other business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and adversely impacted.

The ongoing COVID-19 pandemic could continue to disrupt supply chain and operations, including associated delays in the manufacturing and supply of our products, which may affect our operations, including the conduct of clinical studies, or the ability of regulatory bodies to grant approvals or supervise our candidates and products, may further divert the attention and efforts of the medical community to coping with the COVID-19 and disrupt the marketplace in which we operate and may have a material adverse effects on our operations. COVID-19 may also affect our employees and employees and operations at suppliers that may result in delays or disruptions in supply. Even after the COVID-19 pandemic has subsided, we may continue to experience an adverse impact to our business as a result of COVID-19’s global economic impact, including any recession that has occurred or may occur in the future and the uncertainty of the timing of the broader economic recovery to pre-pandemic levels.

•

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

•

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

•

~~Our dependency upon our pending collaboration with Incyte to further develop and commercialize axatilimab.~~

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

~~Risks Related to Our Business and Industry~~

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

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

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

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

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

COVID-19 continues to evolve rapidly, and multiple variants of the virus that cause COVID-19 are circulating globally. The extent to which the COVID-19 pandemic impacts our business, our clinical development and regulatory efforts will depend on future developments that are highly uncertain and cannot be predicted with confidence, such as the duration of the outbreak, travel restrictions, quarantines, social distancing requirements, business closures in the United States and other countries, the rollout of mass vaccinations for COVID-19 and any limitations to the efficacy of such vaccines and the effectiveness of other actions taken in the United States and other countries to contain and treat the disease. Accordingly, we do not yet know the full extent of potential delays or impacts on our business, our clinical and regulatory activities, healthcare systems or the global economy as a whole. However, these impacts could adversely affect our business, financial condition, results of operations and growth prospects.

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

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

•

direct and indirect effects of the ongoing COVID-19 pandemic on various aspects and stages of the clinical development process, including the impact to expected site initiation, enrollment and participation in our clinical trials;

•

significant reprioritization and diversion of healthcare resources away from the conduct of clinical trials as a result of the ongoing COVID-19 pandemic, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials;

•

timely completion of one or more of the pivotal Phase 2 cohorts of the AUGMENT-101 trial of revumenib in patients with relapsed/refractory, or r/r, acute leukemias;

•

the timing of the progress and receipt of data from the AUGMENT-102 trial of revumenib in combination with chemotherapy in patients with R/R mutant nucleophosmin, NPM1, or mixed lineage leukemia rearranged, MLLr, acute leukemias;

•

the timing of the progress and receipt of data from the combination trial of revumenib as part of the Leukemia & Lymphoma Society’s Beat® AML Master Trial® and as a monotherapy as part of the Australian Leukemia and Lymphoma Group (ALLG) INTERCEPT Master Clinical Trial, each of which is not a Company sponsored trial;

•

timely completion of the pivotal Phase 2 trial, AGAVE-201, of axatilimab in patients with chronic Graft Versus Host Disease, or cGVHD;

•

the timing of the progress and receipt of data from the Phase 2 trial of axatilimab in idiopathic pulmonary fibrosis;

•

the timing of the progress and receipt of data from the Phase 1 trial of revumenib in patients with unresectable metastatic microsatellite stable colorectal cancer;

•

timely completion of any future clinical trials of revumenib and axatilimab;

•

interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel, quarantines or social distancing protocols imposed or recommended by federal or state governments, employers and others in connection with the ongoing COVID-19 pandemic or geopolitical tensions, such as the Russia-Ukraine war;

•

whether we are required by the FDA or foreign regulatory authorities to conduct additional clinical trials prior to receiving marketing approval;

•

the prevalence and severity of adverse drug reactions in any of our clinical trials;

•

the ability to demonstrate safety and efficacy of our product candidates for their proposed indications and the timely receipt of necessary marketing approvals from the FDA and foreign regulatory authorities;

•

successfully meeting the endpoints in the clinical trials of our product candidates;

•

achieving and maintaining compliance with all applicable regulatory requirements;

•

the potential use of our product candidates to treat various cancers and fibrotic diseases;

•

the availability, perceived advantages, relative cost, relative safety and relative efficacy of alternative and competing treatments;

•

the effectiveness of our own or our potential strategic collaborators’ marketing, sales and distribution strategy and operations in the United States and abroad;

•

the ability of our collaboration partner and of third-party contract manufacturers to produce trial supplies and to develop, validate and maintain a commercially viable manufacturing process that is compliant with cGMP;

•

our ability to successfully commercialize our product candidates in the United States and abroad, whether alone or in collaboration with others; and

•

our ability to enforce our intellectual property rights with respect to our product candidates.

•

~~direct~~ and indirect effects of the ongoing COVID-19 pandemic on various aspects and stages of the clinical development process, including the impact to expected site initiation, enrollment and participation in our clinical trials;

•

~~timely completion of the Phase 1/2 clinical trial, AUGMENT-101, of SNDX-5613 in patients with relapsed/refractory MLLr and NPM1c acute leukemia;~~

•

~~timely completion of the pivotal Phase 2 clinical trial, AGAVE-201, of axatilimab in patients with chronic Graft Versus Host Disease, or cGVHD;~~

•

~~timely completion of any future clinical trials of SNDX-5613 and axatilimab;~~

•

~~whether we are required by the FDA or foreign regulatory authorities to conduct additional clinical trials;~~

•

~~the prevalence and severity of adverse drug reactions in any of our clinical trials;~~

•

~~successfully meeting the endpoints in the clinical trials of our product candidates;~~

•

~~achieving and maintaining compliance with all applicable regulatory requirements;~~

•

~~the potential use of our product candidates to treat various cancer indications and fibrotic diseases;~~

•

~~the availability, perceived advantages, relative cost, relative safety and relative efficacy of alternative and competing treatments;~~

•

~~the effectiveness of our own or our potential strategic collaborators’ marketing, sales and distribution strategy and operations in the United States and abroad;~~

•

~~the ability of our third-party contract manufacturers to produce trial supplies and to develop, validate and maintain a commercially viable manufacturing process that is compliant with cGMP;~~

•

~~our ability to successfully commercialize our product candidates in the United States and abroad, whether alone or in collaboration with others; and~~

•

~~our ability to enforce our intellectual property rights in and to our product candidates.~~

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

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

Research suggests that certain acute leukemias, such as mixed lineage leukemia-rearranged, or MLLr, leukemias and nucleophosmin 1, or NPM1, mutant acute myeloid leukemia, or AML, are driven by the interaction of menin, a nuclear protein involved in transcription, with the N-terminus of MLL1 protein, a histone methyl transferase. In NPM1 mutant AML the interaction with menin occurs via the wild type MLL1 protein, and in MLLr acute leukemias, the interaction occurs via a mutant form of MLL1, a fusion protein known as MLLr. MLLr results from a rare, spontaneous fusion between the N-terminus of the mixed lineage leukemia protein-1, or MLL1, and a host of signaling molecules and nuclear transcription factors. This fusion produces an aberrant transcription program that drives leukemic transformation. In pre-clinical animal models, small molecule inhibitors of the menin-MLLr interaction, such as ~~SNDX-5613,~~revumenib, which bind to, and block the interaction of menin with either MLLr or MLL1, have demonstrated deep and durable single agent treatment effects in multiple leukemic xenograft models harboring MLL fusions or NPM1 mutations. Our strategy for developing ~~SNDX-5613~~revumenib is to conduct a Phase 1/2 clinical trial in ~~relapsed/refractory~~r/r patients with MLLr and NPM1

mutant acute leukemias and determine if the observed clinical efficacy supports further development. The Phase 1 portion of the trial is assessing the safety, tolerability and pharmacokinetics of ~~SNDX-5613,~~revumenib, and seeks to establish a recommended Phase 2 dose. It is open label, and we have released and may in the future release results from time to time that reflect small numbers of patients which may not be accurately predictive of safety or efficacy results later in the trial or in subsequent trials. The Phase 2 portion ~~will evaluate~~is evaluating the efficacy of ~~SNDX-5613~~revumenib across three expansion cohorts enrolling pediatric and adult patients with r/r MLLr acute lymphoblastic leukemia, or ALL,

r/r MLLr acute myeloid leukemia, or AML, and r/r NPM1 mutant AML. While we believe that we have established sufficient efficacy to warrant continued development in these indications, we have not yet sufficiently demonstrated a favorable risk-benefit of ~~SNDX-5613~~revumenib in patients.

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

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

From time to time, we may publish interim top-line or preliminary data from our clinical trials. For example, in April and December 2021 and in November 2022, we announced interim data from our Phase 1/2 clinical trial of ~~SNDX-5613.~~revumenib. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Preliminary or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. Preliminary or top-line data may include, for example, data regarding a small percentage of the patients enrolled in a clinical trial, and such preliminary data should not be viewed as an indication, belief or guarantee that other patients enrolled in such clinical trial will achieve similar results or that the preliminary results from such patients will be maintained. As a result, interim and preliminary data should be viewed with caution until the final data are available. Differences between preliminary or interim data and final data could significantly harm our business prospects and may cause the trading price of our common stock to fluctuate significantly.

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

Before obtaining marketing approval from regulatory authorities for the sale of any of our product candidates, we or our collaborators must conduct extensive trials to demonstrate the safety and efficacy of the product candidates in humans. Clinical testing is expensive and difficult to design and implement, can take many years to complete and is inherently uncertain as to the outcome. A failure of one or more trials can occur at any stage of testing. The outcome of preclinical studies and early clinical trials may not accurately predict the success of later trials, and interim results of a trial do not necessarily predict final results. For example, in May 2020, we announced that ECOG-ACRIN advised us that the E2112 trial did not achieve the primary endpoint of demonstrating a statistically significant overall survival benefit over hormone therapy alone in the Phase 3 clinical trial and we decided to deprioritize the entinostat program to focus resources on advancing the remainder of our pipeline. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials.

We are dependent upon our collaboration with Incyte to further develop and commercialize axatilimab. If we or Incyte fail to perform as expected the potential for us to generate future revenues under the collaboration could be significantly reduced, the development and/or commercialization of axatilimab may be terminated or substantially delayed, and our business could be adversely affected.

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

For example, there is no assurance that the parties will achieve any of the regulatory development or sales milestones, that we will receive any future milestone or royalty payments under the collaboration agreement. Incyte’s activities may be influenced by, among other things, the efforts and allocation of resources by Incyte, which we cannot control. If Incyte does not perform in the manner we expect or fulfill its responsibilities in a timely manner, or at all, the clinical development, manufacturing, regulatory approval, and commercialization efforts related to axatilimab could be delayed or terminated. In addition, our license with Incyte may be unsuccessful due to other factors, including, without limitation, the following:

•

Incyte may terminate the agreement for convenience upon 90 or 180 days’ notice depending on whether or not the parties have commercialized axatilimab in an indication in the respective territory;

•

Incyte may change the focus of its development and commercialization efforts or prioritize other programs more highly and, accordingly, reduce the efforts and resources allocated to axatilimab

•

Incyte may, within its commercially reasonable discretion, choose not to develop and commercialize axatilimab in all relevant markets or for one or more indications, if at all; and

•

if Incyte is acquired during the term of our collaboration, the acquirer may have competing programs or different strategic priorities that could cause it to reduce its commitment to our collaboration or to terminate the collaboration.

We cannot ensure that the potential strategic benefits and opportunities expected from this collaboration with be realized on our anticipated timeline or at all.

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

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

•

the impact of public health epidemics, such as the COVID-19 pandemic, or geopolitical tensions, such as the Russia- Ukraine war;

•

perception about the relative efficacy of our product candidates versus other compounds in clinical development or commercially available;

•

evolving standard of care in treating cancer patients;

•

the size and nature of the patient population, especially in the case of any orphan indications, we are pursuing;

•

the number and location of clinical trial sites enrolled;

•

competition with other organizations or our own clinical trials for clinical trial sites or patients;

•

the eligibility and exclusion criteria for the trial;

•

the design of the trial;

•

ability to obtain and maintain patient consent; and

•

risk that enrolled subjects will drop out before completion.

•

~~direct and indirect effects of the ongoing COVID-19 pandemic;~~

•

~~perception about the relative efficacy of our product candidates versus other compounds in clinical development or commercially available;~~

•

~~evolving standard of care in treating cancer patients;~~

•

~~the size and nature of the patient population, especially in the case of an orphan indication such as MLLr acute leukemia;~~

•

~~the number and location of clinical trial sites enrolled;~~

•

~~competition with other organizations or our own clinical trials for clinical trial sites or patients;~~

•

~~the eligibility and exclusion criteria for the trial;~~

•

~~the design of the trial;~~

•

~~ability to obtain and maintain patient consent; and~~

•

~~risk that enrolled subjects will drop out before completion.~~

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

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

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

•

we may be required to undertake the expenditure of substantial operational, financial and management resources;

•

we may be required to issue equity securities that would dilute our existing stockholders’ percentage of ownership;

•

we may be required to assume substantial actual or contingent liabilities;

•

we may not be able to control the amount and timing of resources that our strategic collaborators devote to the development or commercialization of our product candidates;

•

strategic collaborators may delay clinical trials, provide insufficient funding, terminate a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new version of a product candidate for clinical testing;

•

strategic collaborators may not pursue further development and commercialization of products resulting from the strategic collaboration arrangement or may elect to discontinue research and development programs;

•

strategic collaborators may not commit adequate resources to the marketing, sales and distribution of our product candidates, limiting our potential revenues from these products;

•

disputes may arise between us and our strategic collaborators that result in the delay or termination of the research, development or commercialization of our product candidates or that result in costly litigation or arbitration that diverts management’s attention and consumes resources;

•

strategic collaborators may experience financial difficulties;

•

strategic collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in a manner that could jeopardize or invalidate our proprietary information or expose us to potential litigation;

•

business combinations or significant changes in a strategic collaborator’s business strategy may also adversely affect a strategic collaborator’s willingness or ability to complete its obligations under any arrangement;

•

strategic collaborators could decide to move forward with a competing product candidate developed either independently or in collaboration with others, including our competitors; and

•

strategic collaborators could terminate the arrangement or allow it to expire, which would delay the development and may increase the cost of developing, our product candidates.

•

~~we may be required to undertake the expenditure of substantial operational, financial and management resources;~~

•

~~we may be required to issue equity securities that would dilute our existing stockholders’ percentage of ownership;~~

•

~~we may be required to assume substantial actual or contingent liabilities;~~

•

~~we may not be able to control the amount and timing of resources that our strategic collaborators devote to the development or commercialization of our product candidates;~~

•

~~strategic collaborators may not commit adequate resources to the marketing and distribution of our product candidates, limiting our potential revenues from these products;~~

•

~~strategic collaborators may experience financial difficulties;~~

•

~~strategic collaborators could decide to move forward with a competing product candidate developed either independently or in collaboration with others, including our competitors; and~~

•

~~strategic collaborators could terminate the arrangement or allow it to expire, which would delay the development and may increase the cost of developing, our product candidates.~~

We may explore strategic collaborations that may never materialize or may fail.

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

The FDA and comparable foreign regulatory authorities extensively and rigorously regulate and evaluate the manufacture, testing, distribution, advertising and marketing of drug products prior to granting marketing approvals with respect to such products. This approval process generally requires, at minimum, testing of any product candidate in preclinical studies and clinical trials to establish its safety and effectiveness, and confirmation by the FDA and comparable foreign regulatory authorities that any such product candidate, and any parties involved in its manufacturing, testing and development, complied with current Good Manufacturing Practices, or GMP, current Good Laboratory Practices, or GLP, and current Good Clinical Practices, or GCP, regulations, standards and guidelines during such manufacturing, testing and development. The time required to obtain approval by the FDA and foreign regulatory authorities is unpredictable, but typically takes many years following the commencement of preclinical studies and clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions. We have not obtained regulatory approval for any of our product candidates and it is possible that we will never obtain regulatory approval for our existing product candidates or any future product candidates.

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

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failure to demonstrate that our product candidates are effective for their proposed indication and have an acceptable safety profile;

•

failure of clinical trials to meet the primary endpoints or level of statistical significance required for approval;

•

failure to demonstrate that the clinical and other benefits of a product candidate outweigh any of its safety risks;

•

disagreement with our interpretation of data from preclinical studies or clinical trials;

•

disagreement with the design, size, conduct or implementation of our or our collaborators’ trials;

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the insufficiency of data collected from trials of our product candidates to support the submission and filing of an NDA, BLA or other submission or to obtain regulatory approval;

•

failure to obtain approval of the manufacturing and testing processes or facilities of third-party manufacturers with whom we contract for clinical and commercial product supplies or preclinical or clinical testing;

•

receipt of a negative opinion from an advisory committee due to a change in the standard of care regardless of the outcome of the clinical trials; or

•

changes in the approval policies or regulations that render our preclinical and clinical data insufficient for approval.

•

~~failure to demonstrate that our product candidates are safe and effective;~~

•

~~failure of clinical trials to meet the primary endpoints or level of statistical significance required for approval;~~

•

~~failure to demonstrate that the clinical and other benefits of a product candidate outweigh any of its safety risks;~~

•

~~disagreement with our interpretation of data from preclinical studies or clinical trials;~~

•

~~disagreement with the design or implementation of our or our collaborators’ trials;~~

•

~~the insufficiency of data collected from trials of our product candidates to support the submission and filing of an NDA or other submission or to obtain regulatory approval;~~

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~~failure to obtain approval of the manufacturing and testing processes or facilities of third-party manufacturers with whom we contract for clinical and commercial supplies;~~

•

~~receipt of a negative opinion from an advisory committee due to a change in the standard of care regardless of the outcome of the clinical trials; or~~

•

~~changes in the approval policies or regulations that render our preclinical and clinical data insufficient for approval.~~

The FDA or foreign regulatory authorities may require more information, including additional preclinical or clinical data, to support approval, which may delay or prevent approval and our commercialization plans, or may cause us to decide to abandon our development program. Even if we were to obtain approval, regulatory authorities may approve one or more of our product candidates for a more limited patient population than we request, may grant approval contingent on the performance of costly post-marketing trials, may impose a risk evaluation and mitigation strategy, or REMS, or foreign regulatory authorities may require the establishment or modification of a similar strategy that may, for instance, restrict distribution of one or more of our product candidates and impose burdensome implementation requirements on us, or may approve it with a label that does not include the labeling claims necessary or desirable for the successful commercialization of one or more of our product candidates, all of which could limit our ability to successfully commercialize our product candidates.

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

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

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the efficacy and safety profile as demonstrated in trials;

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the timing of market introduction as well as competitive products;

•

the clinical indications for which the product candidate is approved;

•

acceptance of the product candidate as a safe and effective treatment by physicians, clinics and patients;

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the potential and perceived advantages of our product candidates over alternative treatments;

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the cost of treatment in relation to alternative treatments;

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pricing and the availability of coverage and adequate reimbursement by third-party payors, including government authorities;

•

our willingness or ability to pay adequate rebates to payors or pharmacy benefit managers;

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relative convenience and ease of administration;

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the frequency and severity of adverse events;

•

the effectiveness of sales and marketing; and

•

unfavorable publicity relating to our product candidates.

•

~~the efficacy and safety profile as demonstrated in trials;~~

•

~~the timing of market introduction as well as competitive products;~~

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~~the clinical indications for which the product candidate is approved;~~

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~~acceptance of the product candidate as a safe and effective treatment by physicians, clinics and patients;~~

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~~the potential and perceived advantages of our product candidates over alternative treatments;~~

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~~the cost of treatment in relation to alternative treatments;~~

•

~~pricing and the availability of coverage and adequate reimbursement by third-party payors, including government authorities;~~

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~~relative convenience and ease of administration;~~

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~~the frequency and severity of adverse events;~~

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~~the effectiveness of sales and marketing; and~~

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~~unfavorable publicity relating to our product candidates.~~

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

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

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

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

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

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

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

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issue warning letters or untitled letters;

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mandate modifications to promotional materials or require us to provide corrective information to healthcare practitioners;

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require us to enter into a consent decree, which can include imposition of various fines, reimbursements for inspection costs, required due dates for specific actions and penalties for noncompliance;

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seek an injunction or impose civil or criminal penalties or monetary fines;

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suspend or withdraw regulatory approval;

•

suspend any ongoing clinical trials;

•

refuse to approve pending applications or supplements to applications filed by us;

•

suspend or impose restrictions on operations, including costly new manufacturing requirements; or

•

seize or detain products or refuse to permit the import or export of products.

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~~issue warning letters or untitled letters;~~

•

~~mandate modifications to promotional materials or require us to provide corrective information to healthcare practitioners;~~

•

~~require us to enter into a consent decree, which can include imposition of various fines, reimbursements for inspection costs, required due dates for specific actions and penalties for noncompliance;~~

•

~~seek an injunction or impose civil or criminal penalties or monetary fines;~~

•

~~suspend or withdraw regulatory approval;~~

•

~~suspend any ongoing clinical trials;~~

•

~~refuse to approve pending applications or supplements to applications filed by us;~~

•

~~suspend or impose restrictions on operations, including costly new manufacturing requirements; or~~

•

~~seize or detain products, or refuse to permit the import or export of products.~~

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

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

In the United States, engaging in the impermissible promotion of our products for off-label uses can also subject us to false claims litigation under federal and state statutes, which can lead to administrative, civil and criminal penalties, damages, monetary

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

Undesirable side effects caused by our product candidates could cause the interruption, delay or halting of the trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other foreign regulatory authorities. Results of the clinical trials may reveal a high and unacceptable severity and prevalence of side effects or other unexpected characteristics. In such event, the trials could be suspended or terminated, or the FDA or foreign regulatory authorities could deny approval of our product candidates for any or all targeted indications. Drug-related side effects could affect patient recruitment or the ability of enrolled subjects to complete the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects.

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

•

we may suspend marketing of, or withdraw or recall, the product;

•

regulatory authorities may withdraw approvals;

•

regulatory authorities may require additional warnings on the product labels;

•

the FDA or other regulatory authorities may issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings about the product;

•

the FDA may require the establishment or modification of a REMS or foreign regulatory authorities may require the establishment or modification of a similar strategy that may, for instance, restrict distribution of the product and impose burdensome implementation requirements on us;

•

regulatory authorities may require that we conduct post-marketing studies;

•

we could be sued and held liable for harm caused to subjects or patients; and

•

our reputation may suffer.

•

~~we may suspend marketing of, or withdraw or recall, the product;~~

•

~~regulatory authorities may withdraw approvals;~~

•

~~regulatory authorities may require additional warnings on the product labels;~~

•

~~the FDA or other regulatory authorities may issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings about the product;~~

•

~~regulatory authorities may require that we conduct post-marketing studies;~~

•

~~we could be sued and held liable for harm caused to subjects or patients; and~~

•

~~our reputation may suffer.~~

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

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

In order to market and sell our product candidates in other jurisdictions, we must obtain separate marketing approvals for those jurisdictions and comply with their numerous and varying regulatory requirements. We may not obtain foreign regulatory approvals on a timely basis, or at all. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, product reimbursement approvals must be secured before regulatory authorities will approve the product for sale in that country. Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our product candidates in certain countries. Further, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries and regulatory approval in one country does not ensure approval in any other country, while a failure or delay in obtaining regulatory approval in one country may

have a negative effect on the regulatory approval process in others. Our failure to obtain approval of our product candidates by foreign regulatory authorities may negatively impact the commercial prospects of such product candidates and our business prospects could decline. Also, if regulatory approval for our product candidates is granted, it may be later withdrawn. If we fail to comply with the regulatory requirements in international jurisdictions and receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential for our product candidates will be harmed and our business may be adversely affected.

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

Even if any of our product candidates received regulatory approval, such product candidates would face competition from other therapies in the relevant indication. For example, chronic graft versus host disease has historically been managed by off-label treatments. However, in the past five years, the FDA has approved three drugs, ibrutinib (~~Imbruvica®~~Imbruvica®), belomosidil (Rezurock®) and ~~Ruxolitinib~~ruxolitinib (Jakafi®), for use in patients with cGVHD after failure of one or more lines of systemic therapy. All three of these drugs may compete with axatilimab in patients diagnosed with cGVHD.

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

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

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

•

the efficacy and safety profile of our product candidates relative to marketed products and product candidates in development by third parties;

•

the time it takes for our product candidates to complete clinical development and receive marketing approval;

•

our ability to commercialize our product candidates if they receive regulatory approval;

•

the price of our product candidates, including in comparison to branded or generic competitors;

•

whether coverage and adequate levels of reimbursement are available under private and governmental health insurance plans, including Medicare;

•

our ability to manufacture commercial quantities of our product candidates if they receive regulatory approval; and

•

our ability to negotiate preferential formulary status for our product candidates.

•

~~the efficacy and safety profile of our product candidates relative to marketed products and product candidates in development by third parties;~~

•

~~the time it takes for our product candidates to complete clinical development and receive marketing approval;~~

•

~~our ability to commercialize our product candidates if they receive regulatory approval;~~

•

~~the price of our product candidates, including in comparison to branded or generic competitors;~~

•

~~whether coverage and adequate levels of reimbursement are available under private and governmental health insurance plans, including Medicare; and~~

•

~~our ability to manufacture commercial quantities of our product candidates if they receive regulatory approval.~~

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

We are dependent upon our pending collaboration with Incyte to further develop and commercialize axatilimab. If we or Incyte fail to perform as expected, the potential for us to generate future revenues under the collaboration could be significantly reduced, the development and/or commercialization of axatilmab may be terminated or substantially delayed, and our business could be adversely affected.

In September 2021, we entered into a collaboration and license agreement (the “Incyte Agreement”) with Incyte to collaborate on the development and commercialization of axatilimab. Pursuant to the Incyte Agreement, Incyte has agreed to pay an upfront, non-refundable payment of $117 million, in addition to a $35 million equity investment. We are eligible to receive up to $450 million in aggregate regulatory, development and commercial milestone payments plus the tiered royalties. The parties have agreed to co-develop axatilimab and to share development costs associated with global and U.S.-specific clinical trials, with Incyte responsible for 55% of such costs and we are responsible for 45% of such costs. Incyte is responsible for 100% of future development costs for trials that are specific to ex-U.S. countries. If the Incyte Agreement becomes effective, there can be no assurance that the parties will achieve any of the regulatory, development or sales milestones, or that we will receive any future milestone or royalty payments under the collaboration agreement. Incyte’s activities may be influenced by, among other things, the efforts and allocation of resources by Incyte, which we cannot control. If Incyte does not perform in the manner we expect or fulfill its responsibilities in a timely manner, or at all, the clinical development, manufacturing, regulatory approval, and commercialization efforts related to axatilimab could be delayed or terminated.

~~In addition, our license with Incyte may be unsuccessful due to other factors, including, without limitation, the following:~~

•

~~Incyte may terminate the agreement for convenience upon 90 or 180 days’ notice depending on whether or not the parties have commercialized axatilimab in an indication in the respective territory;~~

•

~~Incyte may change the focus of its development and commercialization efforts or prioritize other programs more highly and, accordingly, reduce the efforts and resources allocated to axatilimab;~~

•

~~Incyte may, within its commercially reasonable discretion, choose not to develop and commercialize axatilimab in all relevant markets or for one or more indications, if at all; and~~

•

If Incyte is acquired during the term of our collaboration, the acquirer may have competing programs or different strategic priorities that could cause it to reduce its commitment to our collaboration or to terminate the collaboration.

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

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

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

Our commercial success also depends upon our ability to develop, manufacture, market and sell axatilimab. ~~In July 2016, we entered into the UCB license agreement pursuant to which we obtained~~We have a worldwide, sublicenseable, exclusive license to axatilimab ~~an IND-ready anti-CSF-1R monoclonal antibody.~~pursuant to a license agreement with UCB. Certain of the rights licensed to us under the UCB license agreement are in-licensed by UCB from third parties. We are dependent on UCB maintaining the applicable third-party license agreements in full force and effect, which may include activities and performance obligations that are not within our control. If any of these third-party license agreements terminate, certain of our rights to develop, manufacture, commercialize or sell axatilimab may be terminated as well. The occurrence of any of these events could adversely affect the development and commercialization of axatilimab, and materially harm our business.

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

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

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

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

Many of the other pharmaceutical companies that we compete against for qualified personnel have greater financial and other resources, different risk profiles and a longer history in the industry than we do. They also may provide more diverse opportunities and better chances for career advancement. Some of these characteristics may be more appealing to high-quality candidates than what we have to offer. If we are unable to continue to attract and retain high-quality personnel, the rate and success at which we can discover and develop product candidates and our business will be limited.

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

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

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

There may be significant delays in obtaining adequate coverage and reimbursement for newly approved drugs, and coverage may be more limited than the indications for which the drug is approved by the FDA or foreign regulatory authorities. Moreover, eligibility for coverage and reimbursement does not imply that a drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, marketing, sale and distribution expenses. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may only be temporary. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates

required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States.

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

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

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

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

The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to profitably sell any product candidate for which we obtain marketing approval. For example, then President Obama signed into law the Affordable Care Act. Among other cost containment measures, the Affordable Care Act established an annual, nondeductible fee on any entity that manufactures or imports branded prescription drugs and biologic agents, a Medicare Part D coverage gap discount program, and a formula that increased the rebates a manufacturer must pay under the Medicaid Drug Rebate Program. There have been executive, judicial and Congressional challenges to certain aspects of the Affordable Care Act. While Congress has not passed comprehensive repeal legislation, several bills affecting the implementation of certain taxes under the Affordable Care Act have been signed into law. The Tax Cuts and Jobs Act of 2017 includes a provision that repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the Affordable Care Act on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” On June 17, 2021, the U.S. Supreme Court dismissed a challenge on procedural grounds that argued the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress. ~~Thus, the Affordable Care Act will remain in effect in its current form.~~ Moreover, prior to the U.S. Supreme Court ruling, January 28, 2021, President Biden issued an executive order that initiated a special enrollment period for purposes of obtaining health insurance coverage through the Affordable Care Act ~~marketplace, which began on February 15, 2021 and will remain open through August 15, 2021.~~marketplace. The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Affordable Care Act. On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (the "IRA") into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in PPACA marketplaces through plan year 2025. The IRA also eliminates the "donut hole" under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum

out-of-pocket costs through a newly established manufacturer discount program. It is possible that the Affordable Care Act will be subject to judicial or Congressional challenges in the future. It is unclear how any such challenges and the healthcare reform measures of the Biden administration will impact the Affordable Care Act and our business.

Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. For example, in August 2011, then President Obama signed into law the Budget Control Act of 2011, which, among other things, created the Joint Select Committee on Deficit Reduction to recommend to Congress proposals in spending reductions. The Joint Select Committee on Deficit Reduction did not agree upon a targeted deficit reduction of at least $1.2 trillion for fiscal years 2012 through 2021, triggering the legislation’s automatic reduction to several government programs. This included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, effective as of 2013. Further legislation ~~including the BBA,~~ has extended the 2% reduction ~~to 2030~~until 2031 with the exception of a temporary suspension from May 1, 2020 through ~~December~~March 31, ~~2021~~2022 due to the COVID-19 pandemic, unless additional congressional action is taken. Under current legislation, the actual reduction in Medicare payments will vary from 1% in 2022 to up to 4% in the final fiscal year of this sequester. In January 2013, then President Obama signed into law the American Taxpayer Relief

Act of 2012, which, among other things, reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Further, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries, Presidential executive orders, and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs. At the federal level, the Trump administration used several means to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives. For example, on July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related to prescription drug pricing that sought to implement several of the administration’s proposals. As a result, the FDA released a final rule onand guidance in September ~~24, 2020, effective November 30,~~ 2020, providing ~~guidance~~pathways for states to build and submit importation plans for drugs from Canada. Further, on November 20, 2020, the U.S. Department of Health & Human Services, ~~or HHS,~~("HHS"), finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Medicare Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law. The implementation of the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which have also been delayed by the Biden administration until January 1, 2023. On November 20, 2020, the ~~Centers for Medicare & Medicaid Services, or~~ CMS issued an interim final rule implementing the Trump administration’s Most Favored Nation, or MFN, executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries. ~~The MFN regulations mandate participation by identified~~On December 27, 2021, CMS issued a final rule that rescinded the interim final rule implementing the Trump administration’s Most Favored Nation executive order. In July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to President Biden’s executive order, on September 9, 2021, HHS, released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles. Further, the IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics covered under Medicare and (2) imposes rebates under Medicare Part B ~~providers~~ and Medicare Part D to penalize price increases that outpace inflation. These provisions will ~~apply~~take effect progressively starting in ~~all U.S. states and territories for~~fiscal year 2023, although they may be subject to legal challenges. It is currently unclear how the IRA will be implemented but is likely to have a seven-year period beginning January 1, 2021 and ending December 31, 2027. On December 28, 2020, the U.S. District Court for the Northern District of California issued a nationwide preliminary injunction against implementation of the interim final rule. On January 13, 2021, in a separate lawsuit brought by industry groups in the U.S. District Court of Maryland, the government defendants entered a joint motion to stay litigationsignificant impact on the condition that the government would not appeal the preliminary injunction granted in the U.S. District Court for the Northern District of California and that performance for any final regulation stemming from the MFN model interim final rule shall not commence earlier than sixty (60) days after publication of that regulation in the Federal Register. Additionally, based on a recent executive order, the Biden administration expressed its intent to pursue certain policy initiatives to reduce drug prices.pharmaceutical industry. Congress is also considering additional health reform measures. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

~~It is also possible that additional governmental action is taken in response to the COVID-19 pandemic.~~ We cannot predict the likelihood, nature or extent of government regulations that may arise from future legislation, administrative or executive action. We expect that the Affordable Care Act, the IRA, as well as other current or future healthcare reform measures may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any approved product. This could seriously harm our future revenues. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our products.

We ~~do not currently have any~~are in the process of building our sales, marketing orand distribution ~~experience or~~ infrastructure.

In order to market any approved product candidate in the future, we must build our sales, marketing, distribution, managerial and other non-technical capabilities or make arrangements with third parties to perform these services, as we do not presently have all of these capabilities. To develop our internal sales, distribution and marketing capabilities, we ~~would have to~~must invest significant amounts of

financial and management resources in the future. For drugs where we decide to perform sales, marketing and distribution functions ourselves, we could face a number of challenges, including that:

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~~we may not be able to attract and build an effective marketing or sales force;~~

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we may not be able to attract and build an effective marketing or sales organization;

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~~the cost of establishing, training and providing regulatory oversight for a marketing or sales force may not be justifiable in light of the revenues generated by any particular product;~~

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the cost of establishing, training and providing regulatory oversight for a marketing or sales force may not be justifiable in light of the revenues generated by any particular product;

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~~our direct or indirect sales and marketing efforts may not be successful; and~~

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our direct or indirect sales and marketing efforts may not be successful; and

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there are significant legal and regulatory risks in drug marketing and sales that we have never faced, and any failure to comply with all legal and regulatory requirements for sales, marketing and distribution could result in enforcement action by the FDA or other authorities that could jeopardize our ability to market the product or could subject us to substantial liabilities.

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

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

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

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decreased demand for our product candidates;

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termination of clinical trial sites or entire trial programs;

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injury to our reputation and significant negative media attention;

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withdrawal of trial participants;

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significant costs to defend the related litigation;

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substantial monetary awards to trial subjects or patients;

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diversion of management and scientific resources from our business operations; and

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the inability to commercialize any products that we may develop.

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~~decreased demand for our product candidates;~~

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~~termination of clinical trial sites or entire trial programs;~~

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~~injury to our reputation and significant negative media attention;~~

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~~withdrawal of trial participants;~~

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~~significant costs to defend the related litigation;~~

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~~substantial monetary awards to trial subjects or patients;~~

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~~diversion of management and scientific resources from our business operations; and~~

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~~the inability to commercialize any products that we may develop.~~

While we currently hold trial liability insurance coverage consistent with industry standards, this may not adequately cover all liabilities that we may incur. We also may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise in the future. We intend to expand our insurance coverage for products to include the sale of commercial products if we obtain marketing approval for our product candidates, but we may be unable to obtain commercially reasonable product liability insurance. A successful product liability claim or series of claims brought against us, particularly if judgments exceed our insurance coverage, could decrease our cash and adversely affect our business and financial condition.

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

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

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the federal Anti-Kickback Statute prohibits persons from, among other things, knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, the referral of an individual for the furnishing or arranging for the furnishing, or the purchase, lease or order, or arranging for or recommending purchase, lease or order, or any good or service for which payment may be made under a federal healthcare program such as Medicare and Medicaid;

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the federal false claims, including the federal civil False Claims Act, impose criminal and civil penalties, including through civil whistleblower or qui tam actions, and civil monetary penalties laws, which prohibit knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

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the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which prohibits, among other things, knowingly and willfully executing, or attempting to execute, a scheme or artifice to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private), willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false, fictitious or fraudulent statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters;

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, also imposes obligations on covered entities, including certain health care providers, health plans and health care clearinghouses as well as their business associates that perform certain services involving the use or disclosure of individually identifiable health information for or on behalf of such covered entities, and their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

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the federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to CMS information related to “payments or other transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians (as defined above) and their immediate family members; and

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analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; state laws that require manufacturers to report pricing information regarding certain drugs; state and local laws that require the registration of pharmaceutical sales representatives; state and foreign laws that govern the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts; and federal, state, and foreign laws that govern the privacy and security of other personal information, including federal and state consumer protection laws, state data security laws, and data breach notification laws (a data breach affecting sensitive personal information, including health information, could result in significant legal and financial exposure and reputational damages).

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owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private), willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false, fictitious or fraudulent statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters;

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the federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to CMS information related to “payments or other transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians (as defined above) and their immediate family members. Beginning in 2022, applicable manufacturers also will be required to report information regarding payments and transfers of value provided during the previous year to physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified nurse-midwives; and

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

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

We are increasingly dependent on information technology systems and infrastructure, including mobile technologies, to operate our business. In the ordinary course of our business, we collect, store, process and transmit large amounts of sensitive information, including intellectual property, proprietary business information, personal information and other confidential information. It is critical that we do so in a secure manner to maintain the confidentiality, integrity and availability of such sensitive information. We have also outsourced elements of our operations (including elements of our information technology infrastructure) to third parties, and as a result, we manage a number of third-party vendors who may or could have access to our computer networks, our confidential information or the confidential information of third parties that is in our possession. In addition, those third-party vendors may in turn

subcontract or outsource some of their responsibilities to other parties. While all information technology operations are inherently vulnerable to inadvertent or intentional security breaches, incidents, attacks and exposures, the accessibility and distributed nature of our information technology systems, and the sensitive information stored on those systems, make such systems potentially vulnerable to unintentional or malicious, internal and external attacks on our technology environment. In addition, due to the ongoing COVID-19 pandemic, we have enabled substantially all of our employees to work remotely, which may make us more vulnerable to cyberattacks. Potential vulnerabilities can be exploited from inadvertent or intentional actions of our employees, third-party vendors, business partners, or by malicious third parties. Attacks of this nature are increasing in their frequency, levels of persistence, sophistication and intensity, and are being conducted by sophisticated and organized groups and individuals with a wide range of motives (including, but not limited to, industrial espionage) and expertise, including organized criminal groups, “hacktivists,” nation states and others. In addition to the extraction of sensitive information, such attacks could include the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other means to affect service reliability and threaten the confidentiality, integrity and availability of information. The prevalent use of mobile devices further increases the risk of data security incidents.

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

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

Risks Related to Our Financial Position and Capital Needs

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

Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate efficacy or an acceptable safety profile, gain regulatory approval or be commercially viable. We are a clinical stage biopharmaceutical company with limited operating

history. We have no products approved for commercial sale and have not generated any product revenues to date, and we continue to incur significant research and development and other expenses related to our ongoing operations and clinical development of our product candidates. As a result, we are not and have never been profitable and have incurred losses in each period since our inception in ~~2005.~~2005, except in 2021.

For the ~~nine months~~quarter ended September 30, ~~2021,~~2022, we reported a net loss attributable to stockholders of ~~$71.3~~$110.1 million. As of September 30, ~~2021,~~2022, we had an accumulated deficit of ~~$639.9~~$653.8 million, which included non-cash charges for stock-based compensation, preferred stock accretion and extinguishment charges. We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our pre-commercialization activities for, and our research and development of, and seek regulatory approvals for, our product candidates. We may also encounter unforeseen expenses,

difficulties, complications, delays and other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of ~~future~~ growth of our expenses and our ability to generate revenues, if any. Our prior losses and expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital.

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

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

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successfully complete the research and clinical development of, and receive regulatory approval for, our product candidates;

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launch, commercialize and achieve market acceptance of our product candidates, and if launched independently, successfully establish a sales, marketing and distribution infrastructure;

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continue to build a portfolio of product candidates through the acquisition or in-license of products, product candidates or technologies;

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initiate preclinical and clinical trials for any additional product candidates that we may pursue in the future;

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establish and maintain supplier and manufacturing relationships with third parties, and ensure adequate and legally compliant manufacturing of bulk drug substances and drug products to maintain that supply;

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obtain coverage and adequate product reimbursement from third-party payors, including government payors;

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establish, maintain, expand and protect our intellectual property rights; and

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attract, hire and retain additional qualified personnel.

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~~successfully complete the research and clinical development of, and receive regulatory approval for, our product candidates;~~

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~~launch, commercialize and achieve market acceptance of our product candidates, and if launched independently, successfully establish a sales, marketing and distribution infrastructure;~~

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~~continue to build a portfolio of product candidates through the acquisition or in-license of products, product candidates or technologies;~~

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~~initiate preclinical and clinical trials for any additional product candidates that we may pursue in the future;~~

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~~obtain coverage and adequate product reimbursement from third-party payors, including government payors;~~

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~~establish, maintain, expand and protect our intellectual property rights; and~~

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~~attract, hire and retain additional qualified personnel.~~

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

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

Our operations have consumed substantial amounts of cash since our inception, primarily due to our research and development efforts. We expect our research and development expenses to increase substantially in connection with our ongoing and planned activities. We believe that our existing cash, cash equivalents and short-term investments will fund our projected operating expenses and capital expenditure requirements for at least the next 12 months. Unexpected circumstances may cause us to consume capital more rapidly than we currently anticipate, including as a result of COVID-19’s global economic impact, including any recessions that has occurred or may occur in the ~~COVID-19 pandemic. For example,~~future. In addition, we may discover that we need to conduct additional activities that exceed our current budget to achieve appropriate rates of patient enrollment, which would increase our development costs.

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

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

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delay, scale back or discontinue the development or commercialization of our product candidates or cease operations altogether;

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seek strategic alliances for our existing product candidates on terms less favorable than might otherwise be available; or

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relinquish, or license on unfavorable terms, our rights to technologies or any future product candidates that we otherwise would seek to develop or commercialize ourselves.

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~~delay, scale back or discontinue the development or commercialization of our product candidates or cease operations altogether;~~

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~~seek strategic alliances for our existing product candidates on terms less favorable than might otherwise be available; or~~

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~~relinquish, or license on unfavorable terms, our rights to technologies or any future product candidates that we otherwise would seek to develop or commercialize ourselves.~~

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

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

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the initiation, progress, timing, costs and results of clinical trials of our product candidates;

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market acceptance of our product candidates;

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the cost and timing of selecting, auditing and developing manufacturing capabilities, and potentially validating manufacturing sites for commercial-scale manufacturing;

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the cost and timing for obtaining pricing, and coverage and reimbursement by third-party payors, which may require additional trials to address pharmacoeconomic benefit;

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the cost of establishing sales, marketing and distribution capabilities for our product candidates if any candidate receives regulatory approval and we determine to commercialize it ourselves;

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the costs of acquiring, licensing or investing in additional businesses, products, product candidates and technologies;

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the effect of competing technological and market developments;

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our need to acquire and implement additional internal systems and infrastructure, including compliance and financial and reporting systems, as we grow our company; and

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business interruptions resulting from pandemics and public health emergencies, including those related to the ongoing COVID-19 pandemic, geopolitical actions, including war and terrorism or natural disasters including earthquakes, typhoons, floods and fires.

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~~the initiation, progress, timing, costs and results of clinical trials of our product candidates;~~

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~~market acceptance of our product candidates;~~

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~~the cost and timing of selecting, auditing and developing manufacturing capabilities, and potentially validating manufacturing sites for commercial-scale manufacturing;~~

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~~the cost and timing for obtaining pricing, and coverage and reimbursement by third-party payors, which may require additional trials to address pharmacoeconomic benefit;~~

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~~the cost of establishing sales, marketing and distribution capabilities for our product candidates if any candidate receives regulatory approval and we determine to commercialize it ourselves;~~

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~~the costs of acquiring, licensing or investing in additional businesses, products, product candidates and technologies;~~

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~~the effect of competing technological and market developments;~~

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~~our need to implement additional internal systems and infrastructure, including financial and reporting systems, as we grow our company; and~~

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

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

Our loan and security agreement, or the Loan Agreement, with Hercules Capital, Inc., or Hercules, for aggregate maximum borrowings of up to $30.0 million, or the Credit Facility, is collateralized by substantially all of our and our subsidiaries personal property and other assets, other than our intellectual property. As of September 30, 2021, the outstanding principal balance under the Credit Facility was $20.0 million. The Credit Facility contains customary representations, warranties, affirmative and negative covenants and events of default applicable to us and our subsidiaries.

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

Changes in tax laws or regulations could materially adversely affect our company.

New tax laws or regulations could be enacted at any time, and existing tax laws or regulations could be interpreted, modified or applied in a manner that is adverse to us, which could adversely affect our business and financial condition. For example, legislation enacted in 2017, informally titled the Tax Cuts and Jobs Act, or the Tax Act, enacted many significant changes to the U.S. tax laws, including changes in corporate tax rates, which collectively may impact the utilization of our NOLs and other deferred tax assets, the deductibility of expenses, and the taxation of foreign earnings. Future guidance from the Internal Revenue Service and other tax authorities with respect to the Tax Act may affect us, and certain aspects of the Tax Act could be repealed or modified in future legislation. For example, the Coronavirus Aid, Relief and Economic Security Act, or the CARES Act, modified certain provisions of the Tax Act. In addition, it is uncertain if and to what extent various states will conform to the Tax Act, the CARES Act, or any newly enacted federal tax legislation. Most recently, the Inflation Reduction Act of 2022, or the IRA, included a number of significant drug pricing reforms, including the establishment of a drug price negotiation program within the U.S. Department of Health and Human Services that would require pharmaceutical manufacturers to charge a negotiated "maximum fair price" for certain selected drugs or

pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers under Medicare Parts B and D to penalize price increases that outpace inflation, and a redesign of the Part D benefit, as part of which manufacturers are required to provide discounts on Part D drugs and Part D beneficiaries' annual out-of-pocket spending will be capped at $2,000 beginning in 2025. The impact of changes under the Tax Act, the CARES Act, the IRA, or future reform legislation could increase our future U.S. tax expense and could have a material adverse impact on our business and financial condition.

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

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

Risks Related to Intellectual Property

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

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

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

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. As a result, the issuance, scope, validity, enforceability and commercial value of our and our current or future licensors’ or licensees’ patent rights are highly uncertain. Our and our licensors’ or licensees’ pending and future patent applications may not result in patents being issued which protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. The patent examination process may require us or our licensors or licensees to narrow the scope of the claims of our or our licensors’ or licensees’ pending and future patent applications, which may limit the scope of patent protection that may be obtained. It is possible that third parties with products that are very similar to ours will circumvent our or our licensors’ or licensees’ patents by means of alternate designs or processes. We cannot be certain that we are the first to invent the inventions covered by pending patent applications and, if we are not, we may be subject to priority disputes. We may be required to disclaim part or all of the term of certain patents or all of the term of certain patent applications. There may be prior art of which we are not aware that may affect the validity or enforceability of a patent claim. There also may be prior art of which we are aware, but which we do not believe affects the validity or enforceability of a claim, which may, nonetheless, ultimately be found to affect the validity or enforceability of a claim. No

assurance can be given that if challenged, our patents would be declared by a court to be valid or enforceable or that even if found valid and enforceable, a competitor’s technology or product would be found by a court to infringe our patents. We may analyze patents or patent applications of our competitors that we believe are relevant to our activities, and consider that we are free to operate in relation to our product candidate, but our competitors may achieve issued claims, including in patents we consider to be unrelated, which block our efforts or may potentially result in our product candidate or our activities infringing such claims. The possibility exists that others will develop products which have the same effect as our products on an independent basis which do not infringe our patents or other intellectual property rights, or will design around the claims of patents that we have had issued that cover our

products. Our and our licensors’ or licensees’ patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications, and then only to the extent the issued claims cover the technology.

Furthermore, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours. Entinostat composition of matter U.S. Patent RE39,754, which we licensed from Bayer, covers the chemical entity of entinostat and any crystalline or non-crystalline form of entinostat and expired in September 2017.

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

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

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

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

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

Filing, prosecuting, enforcing and defending patents on product candidates in all countries throughout the world is prohibitively expensive, and our or our licensors’ intellectual property rights in some countries outside the United States can be less extensive than

those in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we and our licensors may not be able to prevent third parties from practicing our and our licensors’ inventions in countries outside the United States, or from selling or importing products made using our and our licensors’ inventions in and into the United States or other jurisdictions. Competitors may use our and our licensors’ technologies in jurisdictions where we have not obtained patent protection to develop their own products and may export otherwise infringing products to territories where we and our licensors have patent protection, but enforcement is not as strong as that in the United States. These products may compete with our product candidates and our and our licensors’ patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

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

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

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

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

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

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

If the UCB license agreement is terminated, we would not be able to develop, manufacture, market or sell axatilimab and would need to negotiate a new or reinstated agreement, which may not be available to us on equally favorable terms, or at all. In addition, our collaboration with Incyte to further develop and commercialize axatilimab is dependent upon the effectiveness of the UCB license agreement. If the UCB license agreement is terminated, Incyte may terminate our collaboration and our business could be adversely affected.

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

Our commercial success depends upon our ability to develop, manufacture, market and sell ~~SNDX-5613.~~revumenib. Subject to the achievement of certain milestone events, we may be required to pay Vitae, which is now a subsidiary of AbbVie, up to $99 million in one-time development and regulatory milestone payments over the term of the AbbVie license agreement. In the event that we or any of our affiliates or sublicensees commercializes ~~SNDX-5613,~~revumenib, we will also be obligated to pay AbbVie low single to low double-digit royalties on sales, subject to reduction in certain circumstances, as well as up to an aggregate of $70 million in potential one-time

sales-based milestone payments based on achievement of certain annual sales thresholds. Under certain circumstances, we may be required to share a percentage of non-royalty income from sublicensees, subject to certain deductions, with AbbVie. ~~In June 2019, we achieved certain development and regulatory milestones. As a result, in June 2019, we recorded $4.0 million as research and development expense. The amount was paid in 2020.~~

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

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

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

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

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

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

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

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

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

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

selection patent claims or if we are successful in obtaining allowance of our biomarker based patient selection claims, we or our licensor may be unsuccessful in defending the validity of such claims if challenged before a competent court.

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

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

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

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

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

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

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this process. There could also be public

announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a downward effect on the price of shares of our common stock.

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

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

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

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

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

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

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

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

In addition to seeking patents for some of our technology and products, we also rely on trade secrets, including unpatented know-how, technology and other proprietary information, to maintain our competitive position. We seek to protect these trade secrets,

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

Risks Related to Ownership of Our Common Stock and Other General Matters

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

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

•

the success of competitive products or technologies;

•

regulatory actions with respect to our products or our competitors’ products;

•

actual or anticipated changes in our growth rate relative to our competitors;

•

announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments;

•

results of trials of our product candidates or those of our competitors;

•

regulatory or legal developments in the United States and other countries;

•

developments or disputes concerning patent applications, issued patents or other proprietary rights;

•

the recruitment or departure of key personnel;

•

the level of expenses related to our product candidates or clinical development programs;

•

actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts;

•

variations in our financial results or those of companies that are perceived to be similar to us;

•

fluctuations in the valuation of companies perceived by investors to be comparable to us;

•

share price and volume fluctuations attributable to inconsistent trading volume levels of our shares;

•

announcement or expectation of additional financing efforts;

•

sales of our common stock by us, our insiders or our other stockholders;

•

changes in the structure of healthcare payment systems;

•

market conditions in the pharmaceutical and biotechnology sectors; and

•

general economic, industry, political and market conditions, including, but not limited to the ongoing impact of the COVID-19 pandemic and the Russia-Ukraine war.

•

~~the success of competitive products or technologies;~~

•

~~regulatory actions with respect to our products or our competitors’ products;~~

•

~~actual or anticipated changes in our growth rate relative to our competitors;~~

•

~~announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments;~~

•

~~results of trials of our product candidates or those of our competitors;~~

•

~~regulatory or legal developments in the United States and other countries;~~

•

~~developments or disputes concerning patent applications, issued patents or other proprietary rights;~~

•

~~the recruitment or departure of key personnel;~~

•

~~the level of expenses related to our product candidates or clinical development programs;~~

•

~~actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts;~~

•

~~variations in our financial results or those of companies that are perceived to be similar to us;~~

•

~~fluctuations in the valuation of companies perceived by investors to be comparable to us;~~

•

~~share price and volume fluctuations attributable to inconsistent trading volume levels of our shares;~~

•

~~announcement or expectation of additional financing efforts;~~

•

~~sales of our common stock by us, our insiders or our other stockholders;~~

•

~~changes in the structure of healthcare payment systems;~~

•

~~market conditions in the pharmaceutical and biotechnology sectors; and~~

•

~~general economic, industry, political and market conditions, including, but not limited to the ongoing impact of the COVID-19 pandemic.~~

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

Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and share price.

The global economy, including credit and financial markets, has experienced extreme volatility and disruptions, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates, increases in inflation rates and uncertainty about economic stability. For example, the COVID-19 pandemic resulted in widespread unemployment, economic slowdown and extreme volatility in the capital markets. Similarly, the current Russia-Ukraine war has created extreme volatility in the global capital markets and is expected to have further global economic consequences, including disruptions of the global supply chain and energy markets. Any such volatility and disruptions may have adverse consequences on us or the third parties on whom we rely. If the equity and credit markets deteriorate, including as a result of political unrest or war, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive. Inflation can adversely affect us by increasing our costs, including personnel costs (wages). Any

significant increases in inflation and related increase in interest rates could have a material adverse effect on our business, results of operations and financial condition

Until we can generate a sufficient amount of ~~revenue~~profit from our products, if ever, we expect to finance future cash needs through public or private equity or debt offerings. If we raise additional funds through the issuance of additional equity or debt securities, it may result in dilution to our existing stockholders and/or increased fixed payment obligations. For example, during ~~2020,~~2021, we sold a total of ~~15,675,608~~3,802,144 shares of our common stock and pre-funded warrants to purchase ~~1,338,287~~1,142,856 shares of our common stock. The pre-funded warrants are exercisable into shares of common stock for $0.0001 per share. The shares of common stock into which the warrants may be exercised are considered outstanding for the purposes of computing earnings per share. As of September 30, ~~2021, we had 3,307,952~~2022, all of these pre-funded warrants were issued and outstanding. Additionally, in April 2022, the Company sold 1,111,111 common shares under the 2021 ATM Program, with net proceeds of approximately $19.4 million. The issuance of these shares of our common stock resulted, and any future issuance pursuant to the exercise of the outstanding pre-funded warrants or sales under the 2021 ATM Program will result, in dilution to our stockholders.

We may also seek additional funding through government or other third-party funding and other collaborations, strategic alliances and licensing arrangements. These financing activities may have an adverse impact on our stockholders’ rights as well as on our operations, and such additional funding may not be available on reasonable terms, if at all. Furthermore, these securities may have rights senior to those of our common stock and could contain covenants that would restrict our operations and potentially impair our competitiveness, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business. For example, on February 7, 2020, we entered into the Loan Agreement with Hercules, which provided for aggregate maximum borrowings of up to $30.0 million, consisting of (i) a term loan of up to $20.0 million, which was funded on February 7, 2020, and (ii) subject to Hercules’ investment committee approval, an additional term loan of up to $10.0 million, available for borrowing from February 7, 2020 to December 15, 2020. We did not request the available additional borrowing by the due date. Borrowings under the Loan Agreement are collateralized by substantially all of our and our subsidiaries personal property and other assets, other than our intellectual property. In addition, the Loan Agreement includes customary affirmative and restrictive covenants and representations and warranties, including a covenant against the occurrence of a “change in control,” financial reporting obligations, and certain limitations on indebtedness, liens (including a negative pledge on intellectual property and other assets), investments, distributions (including dividends), collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, and deposit accounts.

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

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

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

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

As of September 30, ~~2021,~~2022, our executive officers, directors, holders of 5% or more of our capital stock and their respective affiliates beneficially owned approximately ~~36.4%~~24.4% of our outstanding voting stock and options. As a result, these stockholders will continue to have a significant influence over all matters requiring stockholder approval. For example, these stockholders may be able to influence elections of directors, amendments of our organizational documents, or approval of any merger, sale of assets or other major corporate transaction. This may prevent or discourage unsolicited acquisition proposals or offers for our common stock that you may feel are in your best interest as one of our stockholders. The interests of this group of stockholders may not always coincide with your interests or the interests of other stockholders and they may act in a manner that advances their best interests and not necessarily those of other stockholders, including seeking a premium value for their common stock, and might affect the prevailing market price for our common stock.

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

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

•

the provisions of Section 404(b) of the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, requiring that our independent registered public accounting firm provide an attestation report on the effectiveness of our internal control over financial reporting;

•

the “say on pay” provisions (requiring a non-binding stockholder vote to approve compensation of certain executive officers) and the “say on golden parachute” provisions (requiring a non-binding stockholder vote to approve golden parachute arrangements for certain executive officers in connection with mergers and certain other business combinations) of the Dodd-Frank Act and some of the disclosure requirements of the Dodd-Frank Act relating to compensation of our chief executive officer;

•

the requirement to provide detailed compensation discussion and analysis in proxy statements and reports filed under the Securities Exchange Act of 1934, as amended, or the Exchange Act, and instead provide a reduced level of disclosure concerning executive compensation; and

•

~~any rules that the Public Company Accounting Oversight Board may adopt requiring mandatory audit firm rotation or a supplement to the auditor’s report on the financial statements.~~

~~We may take advantage of these exemptions until we are no longer an “emerging growth company.” We will cease to be an “emerging growth company” on December 31, 2021.~~

We currently take advantage of some, but not all, of the reduced regulatory and reporting requirements that are available to us so long as we qualify as an “emerging growth company.” For example, we have irrevocably elected not to take advantage of the extension of time to comply with new or revised financial accounting standards available under Section 102(b) of the JOBS Act. Our independent registered public accounting firm is not be required to provide an attestation report on the effectiveness of our internal control over financial reporting so long as we qualify as an “emerging growth company,” which may increase the risk that material weaknesses or significant deficiencies in our internal control over financial reporting go undetected. Likewise, so long as we qualify as an “emerging growth company,” we may elect not to provide you with certain information, including certain financial information and certain information regarding compensation of our executive officers, that we would otherwise have been required to provide in filings we make with the Securities and Exchange Commission, or SEC, which may make it more difficult for investors and securities analysts to evaluate our company. We cannot predict if investors will find our common stock less attractive because we may rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock, and our stock price may be more volatile and may decline.

As of June 30, 2021, we no qualify as a smaller reporting company as defined in the Securities Exchange Act of 1934, as amended, or the Exchange Act. We have historically taken, and may continue through the filing of our Annual Report on Form 10-K for the year ending December 31, 2021 to take, advantage of certain scaled disclosures available to smaller reporting companies.

~~Effective as of December 31, 2021, we will be a large accelerated filer, which will increase our costs and demands on management.~~

As a result of the market value of our common stock held by non-affiliates as of June 30, 2021, we will be a large accelerated filer as of December 31, 2021, and we will therefore no longer qualify as an EGC. Additionally, due to our public float as of June 30, 2021, we will no longer qualify as a smaller reporting company as defined in the Exchange Act. However, we are not required to reflect the change in our smaller reporting company status, and comply with the associated increased disclosure obligations, until our quarterly report for the three-month period ended March 31, 2022.

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

•

the requirement that our independent registered public accounting firm attest to the effectiveness of our internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act of 2002;

•

compliance with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor's report providing additional information about the audit and the financial statements;

•

~~the requirement that we provide full and more detailed disclosures regarding executive compensation; and~~

•

~~the requirement that we hold a non-binding advisory vote on executive compensation and obtain shareholder approval of any golden parachute payments not previously approved.~~

We expect that compliance with the additional requirements of being a large accelerated filer will increase our legal and financial compliance costs and may cause management and other personnel to divert attention from operational and other business matters to devote increased time to public company reporting requirements. In addition, if we are not able to comply with changing requirements in a timely manner, the market price of our common stock could decline, and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities, which would require additional financial and management resources are also a smaller reporting company as defined in the Securities Exchange Act of 1934, as amended, or the Exchange Act. We may continue to be a smaller reporting company even after we are no longer an emerging growth company. We may take advantage of certain of the scaled disclosures available to smaller reporting companies and will be able to take advantage of these scaled disclosures for so long as (i) our voting and non-voting common stock held by nonaffiliates is less than $250.0 million measured on the last business day of our second fiscal quarter or (ii) our annual revenue is less than $100.0 million during the most recently completed fiscal year and our voting and non-voting common stock held by non-affiliates is less than $700.0 million measured on the last business day of our second fiscal quarter.

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

Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock.

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

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

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

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

While we have been EGC, our independent registered public accounting firm has not been required to attest to the effectiveness of our internal controls over financial reporting pursuant to Section 404. This exemption will no longer apply to us as of December 31, 2021. Accordingly, beginningBeginning with our annual report on Form 10-K for the year ending December 31, 2021, we ~~will be~~were required to include an attestation from our independent registered public accounting firm on the effectiveness of our internal control over financial reporting. Our compliance with Section 404 requires that we incur substantial expense and expend significant management efforts. We currently do not have an internal audit group, and we ~~will~~may need to hire additional accounting and financial staff with appropriate public company experience and technical accounting knowledge and compile the system and process documentation necessary to perform the evaluation needed to comply with Section 404. We may not be able to complete our evaluation, testing and any required remediation in a timely fashion. During the evaluation and testing process, if we identify one or more material weaknesses in our internal control over financial reporting, we will be unable to assert that our internal control over financial reporting is effective. We cannot assure you that there will not be material weaknesses or significant deficiencies in our internal control over financial reporting in the future. Any failure to maintain internal control over financial reporting could severely inhibit our ability to accurately report our financial condition, results of operations or cash flows. If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting once that firm begin its Section 404 reviews, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by the Nasdaq Global Select Market, the SEC or other regulatory authorities. Failure to remedy any

material weakness in our internal control over financial reporting, or to implement or maintain other effective control systems required of public companies, could also restrict our future access to the capital markets.

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

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

Item 6. Exhibits

Exhibit

No.

~~Exhibits~~

~~Exhibit~~ ~~No.~~		Description

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

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

10.1**31.1		~~Collaboration and License Agreement by and between the Company and Incyte Corporation, dated as of September 24, 2021.~~

~~10.2~~		~~Stock Purchase Agreement by and between the Company and Incyte Corporation, dated as of September 24, 2021.~~

~~31.1~~		Certification of Principal Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) promulgated under the Securities Exchange Act of 1934, as amended.

31.2		Certification of Principal Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) promulgated under the Securities Exchange Act of 1934, as amended.

32.1*		Certifications of Chief Executive Officer and Chief Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.

101		Financial statements from the Quarterly Report on Form 10-Q of Syndax Pharmaceuticals, Inc. for the quarter ended September 30, ~~2021,~~2022, formatted in iXBRL (Inline eXtensible Business Reporting Language): (i) the Condensed Consolidated Balance Sheets; (ii) the Condensed Consolidated Statements of Comprehensive Loss; (iii) the Condensed Consolidated Statements of Cash Flows; and (iv) Notes to Condensed Consolidated Financial Statements.

104		Cover Page Interactive Data File (embedded within the Inline XBRL document).

* Furnished herewith and not deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, and shall not be deemed to be incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act (whether made before or after the date of the Form 10-Q), irrespective of any general incorporation language contained in such filing.

SIGNATURES

Furnished herewith and not deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and shall not be deemed to be incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act (whether made before or after the date of the Form 10-Q), irrespective of any general incorporation language contained in such filing.

**	Certain portions of this exhibit (indicated by asterisks) have been excluded pursuant to Item 601(b)(10) of Regulation S-K because they are both not material and are the type of information that the Registrant treats as private or confidential.

~~SIGNATURES~~

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

Date: November ~~15, 2021~~3, 2022


By:		/s/ ~~Briggs W. Morrison, M.D.~~Michael A. Metzger
		~~Briggs W. Morrison, M.D.~~Michael A. Metzger
		Chief Executive Officer
		(Principal Executive Officer)


By:		/s/ ~~Alexander Nolte~~Keith A. Goldan
		~~Alexander Nolte~~Keith A. Goldan
		Chief ~~Accounting~~Financial Officer and Treasurer
		(~~Principal Accounting Officer, Interim~~ Principal Financial Officer)



Delaware	32-0162505
(State or Other Jurisdiction of Incorporation or Organization)	(IRS Employer Identification No.)

35 Gatehouse Drive, Building D, Floor 3 Waltham, Massachusetts	02451
(Address of Principal Executive Offices)	(Zip Code)


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


Large accelerated filer	☐☒	Accelerated filer	☐
Non-accelerated filer	☒☐	Smaller reporting company	☒☐
Emerging growth company	☒☐


	September 30, 2022			December 31, 2021
ASSETS
Current assets:
Cash and cash equivalents	$	71,377		$	221,965
Restricted cash		115			115
Short-term investments		266,461			217,971
Short-term deposits		12,870			6,894
Collaboration receivable, net		4,539			—
Prepaid expenses and other current assets		2,269			1,451
Total current assets		357,631			448,396
Property and equipment, net		23			278
Right-of-use asset, net		1,152			983
Other assets		881			—
Total assets	$	359,687		$	449,657
LIABILITIES AND STOCKHOLDERS’ EQUITY
Current liabilities:
Accounts payable	$	7,115		$	5,669
Accrued expenses and other current liabilities		13,213			14,465
Current portion of right-of-use liability		471			361
Current portion of capital lease		4			1
Derivative liability		—			187
Total current liabilities		20,803			20,683
Long-term liabilities:
Right-of-use liability, less current portion		768			711
Capital lease, less current portion		14			—
Term loan, less current portion		—			19,895
Total long-term liabilities		782			20,606
Total liabilities		21,585			41,289
Commitments and contingencies (Note 13)
Stockholders’ equity:
Preferred stock, $0.001 par value, 10,000,000 shares authorized; 0 shares outstanding at September 30, 2022 and December 31, 2021		—			—
Common stock, $0.0001 par value, 100,000,000 shares authorized; 60,122,661 and 54,983,105 shares issued and outstanding at September 30, 2022 and December 31, 2021, respectively		6			6
Additional paid-in capital		993,547			952,019
Accumulated other comprehensive (loss) income		(1,605	)		45
Accumulated deficit		(653,846	)		(543,702	)
Total stockholders’ equity		338,102			408,368
Total liabilities and stockholders’ equity	$	359,687		$	449,657

	September 30, 2021			December 31, 2020
ASSETS
Current assets:
Cash and cash equivalents	$	71,433		$	115,243
Restricted cash		115			115
Short-term investments		158,281			177,822
Prepaid expenses and other current assets		8,423			5,684
Total current assets		238,252			298,864
Property and equipment, net		158			192
Right-of-use asset, net		1,093			290
Other assets		—			1,267
Total assets	$	239,503		$	300,613
LIABILITIES AND STOCKHOLDERS’ EQUITY
Current liabilities:
Accounts payable	$	5,122		$	3,508
Accrued expenses and other current liabilities		13,732			11,246
Current portion of deferred revenue		—			1,517
Current portion of right-of-use liability		369			316
Current portion of term loan		9,489			2,285
Total current liabilities		28,712			18,872
Long-term liabilities:
Deferred revenue, less current portion		—			11,617
Right-of-use liability, less current portion		798			101
Term loan, less current portion		10,989			17,834
Other long-term liabilities		—			1
Total long-term liabilities		11,787			29,553
Total liabilities		40,499			48,425
Commitments
Stockholders’ equity:
Preferred stock, $0.001 par value, 10,000,000 shares authorized; 0 shares outstanding at September 30, 2021 and December 31, 2020		—			—
Common stock, $0.0001 par value, 100,000,000 shares authorized; 48,850,539 and 47,881,223 shares issued and outstanding at September 30, 2021 and December 31, 2020, respectively		5			5
Additional paid-in capital		838,888			820,815
Accumulated other comprehensive income (loss)		11			(4	)
Accumulated deficit		(639,900	)		(568,628	)
Total stockholders’ equity		199,004			252,188
Total liabilities and stockholders’ equity	$	239,503		$	300,613


		Page

PART I. FINANCIAL INFORMATION

Item 1.	Unaudited Financial Statements:

	Condensed Consolidated Balance Sheets as of September 30, ~~2021~~2022 and December 31, ~~2020~~2021	1

	Condensed Consolidated Statements of Comprehensive Loss for the three and nine months ended September 30, ~~2021~~2022 and ~~2020~~2021	2

	Condensed Consolidated Statements of Cash Flows for the nine months ended September30, ~~2021~~2022 and ~~2020~~2021	3

	Notes to Condensed Consolidated Financial Statements	4

Item 2.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	1614

Item 3.	Quantitative and Qualitative Disclosures About Market Risk	2523

Item 4.	Controls and Procedures	2523

PART II. OTHER INFORMATION

Item 1.	Legal Proceedings	2724

Item 1A.	Risk Factors	2724


Item 6.	Exhibits	56


	Fair Value Measurements Using
			Quoted
			Prices		Significant
			(unadjusted)		Other		Significant
	Total		in Active		Observable		Unobservable
	Carrying		Markets		Inputs		Inputs
	Value		(Level 1)		(Level 2)		(Level 3)
	(In thousands)
September 30, 2022
Assets:
Cash and cash equivalents	$	71,377	$	61,380	$	9,997	$	—
Short-term investments		266,461		—		266,461		—
Total assets	$	337,838	$	61,380	$	276,458	$	—
December 31, 2021
Assets:
Cash and cash equivalents	$	221,964	$	96,816	$	125,148	$	—
Short-term investments		217,971		—		217,971		—
Total assets	$	439,935	$	96,816	$	343,119	$	—
Liabilities:
Derivative liability		187		—		—		187
Total liabilities	$	187	$	—	$	—	$	187


	Fair Value
Derivative Liability:
Beginning Balance 12/31/21	$	187
Change in fair value		(187	)
Ending Balance 9/30/22	$	—

	Amortized		Unrealized		Unrealized
	Cost		Gains		Losses			Fair Value		Amortized		Unrealized		Unrealized
	(In thousands)									Cost		Gains		Losses			Fair Value
September 30, 2021
										(In thousands)
September 30, 2022
Commercial paper										$	191,156	$	—	$	(700	)	$	190,456
US Treasury and federal bonds											86,907		—		(905	)		86,002
										$	278,063	$	—	$	(1,605	)	$	276,458
December 31, 2021
Commercial paper	$	126,895	$	13	$	—		$	126,908	$	306,715	$	70	$	(17	)	$	306,768
Corporate bonds		27,080		—		(3	)		27,077		22,147		—		(6	)		22,141
Federal bonds		14,294		1		—			14,295
US Treasury and federal bonds											14,212		—		(2	)		14,210
	$	168,269	$	14	$	(3	)	$	168,280	$	343,074	$	70	$	(25	)	$	343,119
December 31, 2020
Commercial paper	$	154,176	$	13	$	(16	)	$	154,173
Corporate bonds		22,617		2		(3	)		22,616
U.S. Treasury		6,030		—		—			6,030
	$	182,823	$	15	$	(19	)	$	182,819

	Amount
Remainder of 2021	$	2,285
2022		9,727
2023		7,988
Total principal outstanding		20,000
Amortized final fee		589
Unamortized debt issuance costs		(111	)
Total		20,478
Term loan, current portion		9,489
Term loan, less current portion	$	10,989