On January 6, 2025 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, reported updated pipeline priorities and anticipated milestones for 2025 (Press release, CytomX Therapeutics, JAN 6, 2025, View Source [SID1234649427]).
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"Our top strategic objective for 2025 is the development of CX-2051, a wholly-owned, first-in-class PROBODY ADC being developed initially in advanced metastatic colorectal cancer (CRC). CX-2051 targets the previously undruggable highly expressed CRC antigen, EpCAM, and carries a topoisomerase-1 inhibitor payload. This novel ADC has the potential to make a meaningful difference in the treatment of heavily pretreated CRC patients, for whom the current standard of care remains inadequate and new treatment options are urgently needed. We are encouraged by our early clinical progress and remain on track to deliver initial Phase 1a dose escalation data in the first half of 2025," said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX.
Dr. McCarthy continued, "As we look ahead to 2025, we are taking steps to focus our strategy and capital allocation, further concentrating efforts on wholly-owned clinical stage programs that we believe have the greatest potential for near-term value inflection. We also continue the important work we are doing with our collaboration partners, including ongoing clinical evaluation of CX-904 with Amgen. As we enter 2025, we have taken the difficult decision to streamline our organization and resources towards top priorities and we look forward to sharing progress from our pipeline throughout the year."
Pipeline Priorities and Organizational Changes
Clinical Pipeline:
CX-2051 (EpCAM PROBODY ADC) has been prioritized as the Company’s lead program with an initial focus in advanced metastatic CRC.
CX-904 (EGFR-CD3 PROBODY TCE) continues in Phase 1a with escalation to higher dose levels prioritized based upon the safety and anti-tumor activity profile observed to-date.
CX-801 (PROBODY Interferon-alpha 2b) Phase 1 dose escalation continues with a focused early development strategy in metastatic melanoma.
Research collaborations: Drug discovery programs with Amgen, Astellas, Bristol Myers Squibb, Moderna, and Regeneron are ongoing. These collaborations remain a strategic priority given their long-term value creation potential and the increasing relevance of masked, conditionally active therapeutics in the field of oncology research and development.
Organization: In order to direct capital resources to its clinical programs and create additional flexibility in its cost structure, CytomX will reduce organizational headcount by approximately 40 percent. Headcount reductions are expected to primarily impact areas supporting non-partnered early research, and general and administrative functions. These changes are expected to be complete by the end of the first quarter of 2025.
Financial: Cost reductions realized from the restructuring combined with focused clinical development priorities are expected to extend cash runway into the second quarter of 2026. CytomX ended Q3 2024 with $117.6 million of cash, cash equivalents and investments.
Clinical Program Updates and 2025 Milestones
CX-2051 (EpCAM PROBODY ADC)
EpCAM (Epithelial Cell Adhesion Molecule) is a highly expressed but previously undruggable tumor antigen due to expression on normal tissues. CX-2051 is designed to open a therapeutic window for this high potential target and deliver meaningful anti-cancer activity in solid tumors, including CRC.
The Phase 1 study of CX-2051 was initiated in April of 2024 and is focused in advanced metastatic CRC, one of many tumor types in which high expression of EpCAM has been documented. The CX-2051 payload (CAMP59) is a next generation topoisomerase-1 inhibitor licensed from AbbVie (formerly Immunogen), selected for specific EpCAM-expressing indications, including colorectal cancer. CX-2051 includes a cleavable payload-antibody linker designed to drive bystander effect, contributing to anti-tumor activity.
The CX-2051 study is currently in the sixth dose escalation cohort with patient enrollment to-date focused in advanced CRC patients who have generally received three or more prior lines of systemic therapy in the metastatic setting. The unmet medical need in this late-line setting is high and treatment outcomes from currently approved standard of care are poor, with objective response rates in the low-single digit percentages and approximately two to four months of progression free survival1.
In Phase 1 dose escalation to date, CX-2051 has demonstrated a favorable tolerability profile at dose levels predicted to be biologically active based on preclinical data.
Initial Phase 1a data are expected in the first half 2025.
CX-904 (PROBODY T-cell-engager (TCE) Targeting EGFRxCD3)
The Phase 1 study of CX-904 has enrolled over 70 patients to date. The 15 mg target step-dose level has been cleared and the maximum tolerated dose has not been reached.
Based on ongoing clinical observations, including evaluation of safety and anti-tumor activity across multiple EGFR positive tumor types, enrollment in 2025 will prioritize escalation to higher dose levels.
Plans for Phase 1a completion and potential advancement to Phase 1b are pending ongoing consideration of 2025 program resourcing given CytomX current capital constraints and discussions with our partner Amgen.
CX-801 (PROBODY Interferon-alpha 2b)
Phase 1 dose escalation is progressing with a focus in metastatic melanoma. The study commenced in the third quarter of 2024 and has reached monotherapy dose levels that exceed the currently approved dose of unmasked interferon-alpha.
The study will evaluate safety and initial clinical activity for CX-801 monotherapy and for CX-801 in combination with KEYTRUDA.
Initial Phase 1a data are expected in the second half of 2025.