CytomX Therapeutics : 2023 Annual Report

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A n n u a l R e p o r t

Dear Fellow CytomX Stockholders,

Our vision at CytomX is to transform the lives of cancer patients with safer, more effective therapies. This has been our driving force for over a decade and continues to guide our work every day. New discoveries in cancer research, including new biologic treatments, provide hope for better patient outcomes. However, many of these approaches are limited in their ability to treat certain tumor types, to provide strong or durable responses and, in many cases, to show benefit without significant toxicity. Our PROBODY® therapeutic platform is designed to enable the creation of high impact therapeutics that are localized to cancer tissue, with the goal of delivering safe and effective anti-cancer activity, leveraging novel mechanisms and modalities. Our scientific depth in this field of "masked", conditionally activated therapeutics positions the Company at the forefront of potential breakthroughs with potent biologic modalities such as T-Cell engagers, antibody drug conjugates (ADCs) and cytokines. Leveraging our expertise and platform, we aim to bring forward the next wave of oncology treatments, realizing our powerful vision.

Throughout 2023, we remained highly focused on execution against a very clear plan. With our internal pipeline and with our collaborators, we are advancing more than fifteen PROBODY programs across multiple modalities, including three clinical-stage molecules, paving the way for important milestones over the next 12 to 18 months. We operated the company in a highly capital efficient manner and maintained a strong financial position through a continued balance of non-dilutive and equity-based financing. Our accomplishments underscore our leadership in conditionally activated, masked biologic therapies and support our mission to change the treatment of cancer by urgently advancing our PROBODY pipeline.

The PROBODY Platform and the Promise of Masking and Conditional Activation

CytomX leadership in this emerging field derives from more than a decade of innovation with the PROBODY therapeutic platform which uses unique antibody masking strategies to localize anti-cancer activity to tumor cells and away from healthy cells, enhancing the therapeutic window for potent biologic modalities like ADCs, T-cell engagers and cytokines. We are proud to have created this field, that now includes multiple entrants to the space, and it is both exciting and rewarding to see increasing benefit being realized for patients. CytomX's current product candidates span multiple modalities and integrate key design elements that leverage previously validated oncology targets, potent effector mechanisms and tailored masking strategies. Masked therapeutics will be an important part of the future of biologics and we believe that CytomX is well positioned to play a leading role in this exciting frontier in cancer research and development.

CX-904 and the Promise of PROBODY T-Cell Engagers

T-cell engaging bispecific antibodies (TCEs) offer profound opportunities for the treatment of solid tumors by directing T-cells to kill cancer cells. TCEs are emerging as a validated mechanism for solid tumors with tremendous promise. However, for this modality to fully break through, there are still significant challenges to overcome. The high potency of TCEs can lead to toxicities in normal tissues where the target tumor antigen may also be present, or cytokine release syndrome when activated T-cells generate an exaggerated immune response. We believe that the PROBODY platform may be ideally suited to unlock this important modality by masking TCEs, bringing the power of these new therapies to a broader set of patients.

CX-904, our lead clinical program advancing under a global co-development collaboration with Amgen, is a PROBODY TCE targeting the tumor antigen epidermal growth factor receptor (EGFR) and CD3 on T-cells. EGFR is a validated cancer target present on many cancers. CX-904 is designed to address the principal challenges of developing an EGFR-CD3 TCE by delivering anti-tumor activity at tolerable systemic doses. In 2023, we continued to advance CX-904 through a Phase 1a clinical trial with the goal of evaluating safety and identifying dosing regimens for Phase 1b. We expect to share initial Phase 1a dose escalation data in 2024 which will inform a potential decision with our partner Amgen to initiate Phase 1b of the clinical trial in 2025.

CX-2051 and the Promise of PROBODY Antibody Drug Conjugates (ADCs)

There has been tremendous progress in the field of ADCs in the past few years with meaningful clinical results demonstrating the potential to improve upon and even replace chemotherapy over time. The impact of this anti- cancer modality highlights the need to break through with novel targets that can address a broader group of patients. Epithelial cell adhesion molecule (EpCAM) is a high potential oncology target expressed in many cancer types. EpCAM has been clinically validated with locally administered therapeutic approaches. However, efforts to generate systemic anti-EpCAM therapeutics have been limited by toxicities in normal epithelial tissues, where EpCAM is also present.

CX-2051, our first-in-class PROBODY ADC targeting EpCAM, is tailored to optimize the therapeutic index for EpCAM- expressing epithelial cancers by masking the antibody to reduce binding in normal tissues, but to allow activation in tumor tissue. CX-2051 harbors a novel cytotoxic payload that inhibits topoisomerase-1, a validated strategy for killing

many tumor types, including colorectal cancer. CX-2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models. In 2023, we advanced CX-2051 successfully through Investigational New Drug (IND)-enabling studies and filed an IND which was cleared by the U.S. Food and Drug Administration (FDA) in January 2024. We recently initiated a Phase 1 dose escalation study in solid tumors generally known to have EpCAM expression, including colorectal cancer. This clinical study is designed to evaluate the safety and preliminary anti-tumor activity of CX-2051, and to provide initial clinical proof of concept to inform a potential decision to move into dose expansions in 2025. CX-2051 could potentially address a large patient population as EpCAM is highly expressed across many indications including colorectal, gastric, endometrial and ovarian cancers.

CX-801 and the Promise of PROBODY Cytokines

Interferon alpha is a powerful cytokine with the ability to potently drive tumor antigen presentation and activate anti- tumor immunity. Interferon-alpha 2b (IFNα2b) is an approved immunotherapeutic that has demonstrated clinical

activity in multiple cancer types, including in combination with checkpoint inhibitors. IFNα2b provides a potentially superior approach to activating anti-tumor immune responses than other cytokines and recent advances in this space have reaffirmed that this potent cytokine can indeed achieve robust anti-tumor responses in patients when locally

delivered. Systemic, unmasked IFNα2b, however, is not well tolerated and is therefore not widely used in cancer therapy today.

CX-801 is our dually masked, PROBODY IFNα2b which is designed to be better tolerated, allowing for the anti- cancer potential of this cytokine to be realized. We believe CX-801 has the potential to become a cornerstone of combination immunotherapy for a wide range of tumor types including those that have either stopped responding to, or have failed to respond to, prior immunotherapy. In 2023, we advanced CX-801 through IND-enabling studies and our IND filing was cleared by the FDA in January 2024, alongside the IND for CX-2051, marking a highly productive period of execution by the CytomX team. We expect to initiate Phase 1 dose escalation in solid tumors, including melanoma, renal cancer and head and neck squamous cell carcinoma in 2024.

With our ongoing Phase 1 clinical trials for CX-904 and CX-2051, and CX-801 anticipated to enter the clinic in the near future, we believe our PROBODY therapeutic programs across established anti-cancer modalities offer a broad opportunity to make a meaningful difference in the treatment of cancer and build substantial shareholder value.

The Strategic Value of PROBODY Platform Partnerships

Our scientific leadership in the field of masking and conditional activation has attracted major partnerships with leading oncology companies, including Bristol Myers Squibb, Amgen, Astellas, Regeneron and Moderna. CytomX holds significant commercial rights on a number of collaboration programs, consistent with our goal of building a long- term, commercial stage company. To date, our partnerships have generated more than $500 million of incoming cash and we see near-term opportunities for additional milestone payments in 2024 and 2025. The progress with collaborators highlights our strategy to further extend the reach of our science and create value through a broad, diversified pipeline of wholly-owned and partnered therapeutic programs.

The Future Promise of CytomX and the PROBODY Therapeutic Pipeline

CytomX enters 2024 in a strong strategic position in the field of biologics masking and more broadly in oncology R&D. We believe our leading, multi-modality PROBODY therapeutic pipeline will address major unmet medical needs in the treatment of cancer, with the ability to unlock the power of potent anti-cancer modalities, including T-Cell engagers, ADCs and cytokines, each of which represents a highly relevant and timely area of strategic interest across the industry. 2024 will be an exciting year for us and the longer-term outlook for 2025 and beyond is highly promising as we advance CX-904,CX-2051 and CX-801 towards key milestones over the next 12 to 18 months. We remain focused on execution of these milestones to achieve our goal of delivering meaningful long-term value for patients and shareholders.

I want to thank our board of directors and advisors, who have continued to guide us, and our investors, whose support advances our mission. I am grateful to our employees for their continued commitment and contributions - collectively, you are our most valuable asset. We have a strong, values-based culture that embraces innovation, diversity and inclusion. We know that our platform and pipeline have the potential to transform lives, and we are driven by this purpose. The future for CytomX has never been brighter.

Sincerely,

Sean A. McCarthy, D.Phil.

Chief Executive Officer and Chairman

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 10-K

(Mark One)

• ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2023

OR

• TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from	to
Commission File Number 001-37587

CytomX Therapeutics, Inc.

(Exact Name of Registrant as Specified in Its Charter)

Delaware					27-3521219
(State or other jurisdiction of						(I.R.S. Employer
incorporation or organization)					Identification No.)
151 Oyster Point Boulevard, Suite 400					94080
South San Francisco, California
(Address of principal executive offices)						(Zip Code)
			[phone]
		(Registrant's telephone number, including area code)
	Securities registered pursuant to Section 12(b) of the Act:
Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.00001 par value				CTMX		The Nasdaq Global Select Market
Securities registered pursuant to Section 12(g) of the Act:
				None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.		Yes ☐	No ☒
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐	No ☒

Indicate by check mark whether the issuer (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 (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ No ☐

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

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

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 financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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

☐

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☒

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant's executive officers during the relevant recovery period pursuant to §240.10D-1(b).☐

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 June 30, 2023, the last business day of the registrant's most recently completed second fiscal quarter, the aggregate market value of the registrant's common stock held by non-affiliates of the registrant was approximately $114.1 million, based on the closing price of the registrant's common stock on the Nasdaq Global Select Market on June 30, 2023 of $1.72 per share. Shares of the registrant's common stock held by each officer and director and each person known to the registrant to own 10% or more of the outstanding common stock of the registrant have been excluded in that such persons may be deemed affiliates. This determination of affiliate status is not a determination for other purposes.

As of February 29, 2024, 67,721,658 shares of the registrant's common stock, $0.00001 par value per share, were outstanding. This number does not include

14,423,077 shares of common stock issuable upon the exercise of pre-funded warrants outstanding as of February 29, 2024 (which are immediately exercisable at an exercise price of $0.00001 per share of common stock, subject to beneficial ownership limitations) sold in the registrant's private placement in July 2023. See Note 12- Common Stock to the registrant's audited financial statements.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant's definitive proxy statement to be filed for its 2024 Annual Meeting of Stockholders are incorporated by reference into Part III hereof. Such proxy statement will be filed with the Securities and Exchange Commission within 120 days of the end of the fiscal year covered by this Annual Report on Form 10-K.

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	CYTOMX THERAPEUTICS, INC.
	ANNUAL REPORT ON FORM 10-K
	TABLE OF CONTENTS
		Page
PART I
ITEM 1.	Business	4
ITEM 1A.	Risk Factors	30
ITEM 1B.	Unresolved Staff Comments	73
ITEM 1C.	Cybersecurity	73
ITEM 2.	Properties	74
ITEM 3.	Legal Proceedings	74
ITEM 4.	Mine Safety Disclosures	74
PART II
ITEM 5.	Market for Registrant's Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity
Securities	75
ITEM 6.	[Reserved]	75
ITEM 7.	Management's Discussion and Analysis of Financial Condition and Results of Operations	76
ITEM 7A.	Quantitative and Qualitative Disclosures About Market Risk	85
ITEM 8.	Financial Statements and Supplementary Data	86
ITEM 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	117
ITEM 9A.	Controls and Procedures	117
ITEM 9B.	Other Information	118
ITEM 9C.	Disclosure Regarding Foreign Jurisdictions That Prevent Inspections	118
PART III
ITEM 10.	Directors, Executive Officers and Corporate Governance	119
ITEM 11.	Executive Compensation	119
ITEM 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	119
ITEM 13.	Certain Relationships and Related Transactions, and Director Independence	119
ITEM 14.	Principal Accountant Fees and Services	119
PART IV
ITEM 15.	Exhibits and Financial Statement Schedules	120
ITEM 16.	Form 10-K Summary	124
	Signatures	125

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Forward-Looking Statements

This Annual Report on Form 10-K contains certain forward-looking statements that involve risks and uncertainties. These forward- looking statements reflect our current views with respect to, among other things, future events and our financial performance. These statements are often, but not always, made through the use of words or phrases such as "may," "might," "should," "could," "predict," "potential," "believe," "expect," "continue," "will," "anticipate," "seek," "estimate," "intend," "plan," "projection," "would," "annualized" and "outlook," or the negative version of those words or other comparable words or phrases of a future or forward- looking nature. These forward-looking statements are not historical facts, and are based on current expectations, estimates and projections about our industry, management's beliefs and certain assumptions made by management, many of which, by their nature, are inherently uncertain and beyond our control. Accordingly, we caution you that any such forward-looking statements are not guarantees of future performance and are subject to risks, assumptions, estimates and uncertainties that are difficult to predict. Although we believe that the expectations reflected in these forward-looking statements are reasonable as of the date made, actual results may prove to be materially different from the results expressed or implied by the forward-looking statements.

A number of important factors could cause our actual results to differ materially from those indicated in these forward-looking statements, including those factors identified in "Risk Factors" or "Management's Discussion and Analysis of Financial Condition and Results of Operations" or the following:

• our expectations regarding the potential benefits, activity, effectiveness and safety of our product candidates and therapeutics developed utilizing our PROBODY® conditionally activated platform technology;
• the initiation, timing, progress and results of our ongoing clinical trials, research and development programs, preclinical studies, and Investigational New Drug Application ("IND"), Clinical Trial Application, New Drug Application ("NDA"), Biologics License Application ("BLA"); and other regulatory submissions;
• the timing of the completion of our ongoing clinical trials and the timing and availability of clinical data from such clinical trials;
• our ability to identify and develop additional product candidates;
• our dependence on collaborators for developing, obtaining regulatory approval for and commercializing product candidates in the collaboration;
• our or a collaborator's ability to obtain and maintain regulatory approval of any of our product candidates;
• our receipt and timing of any milestone payments or royalties under any research collaboration and license agreements or arrangements;
• our expectations and beliefs regarding the evolution of the market for cancer therapies and development of the immuno- oncology industry;
• the rate and degree of market acceptance of any approved product candidates;
• the commercialization of any approved product candidates;
• our ability to establish and maintain collaborations and retain commercial rights for our product candidates in such collaborations;
• the implementation of our business model and strategic plans for our business, technologies and product candidates;
• our estimates of our expenses, ongoing losses, future revenue and capital requirements;
• our ability to obtain additional funds for our operations;
• our or any collaborator's ability to obtain and maintain intellectual property protection for our technologies and product candidates and our ability to operate our business without infringing the intellectual property rights of others;
• our reliance on third parties to conduct our preclinical studies or any future clinical trials;
• our reliance on third-party supply and manufacturing partners to supply the materials and components for, and manufacture, our research and development, preclinical and clinical trial product supplies;
• our ability to attract and retain qualified key management and technical personnel;

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• our ability to secure and maintain licenses of intellectual property to protect our technologies and product candidates;
• our financial performance;
• developments relating to our competitors, our industry, international conflict or uncertainties; and
• the extent to which any future pandemic and related governmental regulations and restrictions may impact our business, including our research, clinical trials, which include ongoing site initiation and patient enrollment, manufacturing and financial condition;

Any forward-looking statements in this Annual Report on Form 10-K reflect our current views with respect to future events or to our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. Factors that may cause actual results to differ materially from current expectations include, among other things, those listed under Part I, Item 1A. Risk Factors and discussed elsewhere in this Annual Report on Form 10-K. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future.

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

Except where the context otherwise requires, in this Annual Report on Form 10-K, "we," "us," "our" and the "Company" refer to CytomX Therapeutics, Inc.

Trademarks

This Annual Report on Form 10-K includes trademarks, service marks and trade names owned by us or other companies. All trademarks, service marks and trade names included in this Annual Report on Form 10-K are the property of their respective owners.

Risk Factors Summary

We are providing the following summary of risk factors contained in this Annual Report on Form 10-K to enhance the readability and accessibility of our risk factor disclosures in accordance with SEC rules. Please carefully review the full risk factors pertaining to this summary and to additional general risk factors contained in this Annual Report on Form 10-K in their entirety for additional information regarding the material factors that make an investment in our securities speculative or risky. These risks and uncertainties include, but are not limited to, the following:

• We are a clinical-stage biopharmaceutical company with a limited operating history and have not generated any revenue from product sales.
• We expect that we will need to raise substantial additional funds to advance development of our product candidates and we cannot guarantee that this additional funding will be available on acceptable terms or at all.
• Clinical development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.
• Our product candidates are in early stages of development and may fail or suffer delays that materially and adversely affect their commercial viability.
• 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.
• Our product candidates may cause undesirable side effects at any time during or after the clinical trial process that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any, including withdrawal from the market.

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