CytomX Therapeutics : 2024 Annual report (d82a2d)

Published: 2025-05-20 23:14:05 ET CTMX

Published on 05/20/2025 at 23:14

2024

Annual Report

Dear Fellow CytomX Shareholder,

Over the last year, CytomX made important progress towards our mission of urgently advancing our PROBODY® therapeutic pipeline for the maximum benefit of cancer patients. As a pioneer in the field of antibody masking and conditional activation, we continue to direct our powerful technology platform towards major unmet needs in oncology across multiple treatment modalities, including in antibody drug conjugates (ADCs), T-cell engagers and cytokines.

Our current clinical programs are built on over a decade of scientific and clinical expertise and follow clear design principles aimed at optimally matching the cancer type of interest with the tumor target and relevant cell-killing mechanism, to deliver differentiated cancer therapies for patients.

2024 was a very productive year for us, including the advancement of two new programs into the clinic, CX-2051 and CX-801. In early 2025, we announced the prioritization of these programs and the streamlining of our organization. These steps were taken to strengthen our financial position and support our ability to deliver upon key clinical milestones. 2025 promises to be an exciting year for CytomX where we expect to generate initial clinical data for both programs that we believe could drive significant near-term value creation.

CX-2051 is our lead program and is currently in a Phase 1 clinical trial in patients with advanced colorectal cancer (CRC). The global unmet need in colorectal cancer is one of the most significant in oncology with more than 1.9 million new cases annually and limited new treatments emerging for patients over the last two decades. First and second line treatments for metastatic CRC are still primarily based on chemotherapy regimens, and treatments in later line settings are highly inadequate with very low response and survival rates. Furthermore, an increasing percentage of new CRC cases are already metastatic at first diagnosis, and there is a concerning trend of growing incidence in younger patient populations.

CX-2051 is designed to target epithelial cell adhesion molecule (EpCAM), which has been viewed as a high potential opportunity for many years due to its pan-tumor expression and particularly high expression in CRC. However, EpCAM is also present in normal tissues, which has limited the successful development of therapeutics against this target. CX-2051 is designed to reduce potential on-target EpCAM toxicities and to localize CX-2051 preferentially to tumor tissue. Our goal is to open a therapeutic window for this high potential target and deliver meaningful anti-cancer activity in solid tumors. The cell-killing payload on CX-2051 is a topoisomerase-1 inhibitor, selected specifically to treat tumors like CRC. We are the only organization, to our knowledge, addressing EpCAM in this unique way.

We advanced CX-2051 into the clinic in the second quarter of 2024 and our Phase 1 study is currently focused on patients with advanced CRC. We are pleased with our clinical progress to date, marked by an encouraging initial safety profile and the ability to successfully reach dose levels that we predict, based on preclinical modeling, to be in the biologically active range. We're confident these dose levels could not be achieved with a conventional, unmasked ADC to EpCAM, highlighting the power of our technology platform. We believe our early clinical experience with CX-2051 is showing that this unique ADC is performing as designed, underpinning its prioritization as the lead program for CytomX and our focus on bringing this therapy to patients as quickly as possible. We expect to provide initial Phase 1a data in CRC in the first half of 2025 and to define next steps for the program in the second half of the year. We believe CX-2051 is a highly differentiated, first-in-class ADC that is designed to address a large unmet need in CRC and build significant value for CytomX shareholders.

Interferon-alpha is a well validated therapeutic and was one of the first immunotherapies to be approved for cancer treatment. It is a powerful driver of T-cell activation and antigen presentation, making it an ideal combination agent with immunotherapies such as checkpoint inhibitors. Interferon-alpha has established single agent anti-cancer activity in multiple tumor types including in renal cancer, bladder cancer, and melanoma. However, over time its clinical use has become limited due to poor tolerability arising from systemic toxicities. CX-801 is designed to harness the proven power of IFN alpha-2b by reducing systemic activity and localizing the therapy to the tumor microenvironment.

CX-801 is currently progressing through a Phase 1 clinical trial in patients with advanced, metastatic melanoma. We initiated the study in the third quarter of 2024 and have made very good progress to date, quickly reaching doses that surpass the approved clinical doses of unmasked IFN alfa-2b therapeutic. Our translational science program for CX-801 is multi-faceted and includes systemic and intra-tumoral analysis of pharmacodynamic biomarkers that will

give us insight into the molecular performance of the drug candidate and its potential to stimulate an inflammatory microenvironment conducive to PD-1 combination therapy. We look forward to presenting initial Phase 1a translational data in the second half of 2025 and initiating combination therapy with KEYTRUDA® in 2025 under the collaboration and supply agreement we secured with Merck in 2024. Overall, we believe CX-801 is well positioned to demonstrate clinical proof of concept in advanced melanoma, where the unmet need remains high. Longer-term we see CX-801 as a foundational next-generation combination agent with potential to substantially extend the reach of cancer immunotherapy to the many patients who do not currently benefit from treatment.

Our partnerships continued to be very important to us in 2024 and remain so in 2025. The majority of our alliance discovery programs are masked T-cell engagers, an area in which CytomX and our partners continue to see significant promise. Over the last 12 months CytomX has achieved $15M in milestone payments related to progress in advancing development candidates under our Astellas T-cell engager collaboration. We look forward to continued progress with Astellas as well as strong execution in our discovery programs with Bristol Myers Squibb, Amgen, Moderna, and Regeneron. Regarding CX-904, our first partnered T-cell engager program to enter the clinic, in early 2025 we reduced the capital allocation to this program given our overall pipeline priorities. Subsequently, CytomX and Amgen jointly decided not to continue its development. While we were disappointed to have to make this decision, we learned a lot from the CX-904 clinical study. We remain optimistic about the potential of future masked T-cell engagers and look forward to making additional progress on this modality within our partnerships.

2024 brought challenges for the biotech industry related to the broader macro environment, and new challenges have arisen in 2025, but we remain steadfast and highly focused. We continue to make data-driven decisions and exert discipline in our capital allocation and resource management. In 2025, we believe we are well positioned to advance our promising pipeline, deliver value to shareholders, and ultimately bring important new treatment options to cancer patients.

I want to express our gratitude to the patients who join our studies, their families and our clinical investigators. I also want to thank our board of directors, advisors and investors for their unwavering support. I remain incredibly proud of the CytomX team for their dedication and perseverance in advancing potential new medicines that offer hope to cancer patients. We have never been more committed to our vision, mission and values at CytomX and we look forward to an exciting year ahead.

Sincerely,

Sean A. McCarthy, D.Phil.

Chief Executive Officer and Chairman

WASHINGTON, D.C. 20549

(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, 2024 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

(Exact Name of Registrant as Specified in Its Charter)

Delaware 27-3521219

(State or other jurisdiction of incorporation or organization)

151 Oyster Point Boulevard, Suite 400

(I.R.S. Employer Identification No.)

South San Francisco, California 94080

(Address of principal executive offices) (Zip Code)

(650) 515-3185

(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 28, 2024, 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 $94.4 million, based on the closing price of the registrant's common stock on the Nasdaq Global Select Market on June 28, 2024 of $1.22 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 28, 2025, 80,099,889 shares of the registrant's common stock, $0.00001 par value per share, were outstanding. This number does not include 6,923,077 shares of common stock issuable upon the exercise of pre-funded warrants outstanding as of February 28, 2025 (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 2025 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.

Disclaimer

CytomX Therapeutics Inc. published this content on May 21, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 21, 2025 at 03:13 UTC.