CytomX Therapeutics, Inc. Q4 FY2025 earnings call

Shawn McCarthy introduced the focus on Phase 1 data for EPCAM - targeting antibody drug conjugate Varsetta. Colorectal cancer is a major unmet need. Varsetta - M targets EPCAM, designed with ProBody platform. Phase one study enrollment updated to 93 patients. Safety data shared with progress in managing diarrhea. Wayne Chiu walked through baseline characteristics, efficacy data showing 32% confirmed overall response rate at 10 mg per kg and 20% at 8.6 mg per kg, PFS improvements. Safety observations and learnings from dose escalation and expansion, with dose optimization cohorts implementing adjusted ideal body weight dosing and dual prophylaxis. Shawn discussed value creation layers: first approval in late - line CRC, expansion into early - aligned CRC, and other EPCAM - positive tumors. Upcoming milestones include rapid advancement to registrational studies in first half of 2027, sharing more data in second half of 2026.

Top priority is to move Varsetta forward aggressively into its first registration study starting in first half of 2027. Intend to share additional data from phase one study including dose optimization cohorts and registration study design in second half of 2026. Strength of data brings focus to conducting first registration study in third line, continuing to assess as data matures. Already initiated phase one assessment of Varsetta in combination with Bevacizumab and plan to start combination work with bevacizumab plus chemo by end of year, and start first clinical study outside of CRC later this year.

Q: Regarding the pivotal trial, how large is it anticipated and potential other indications outside of CRC?

A: Still work in progress on pivotal study size, but think it could be manageable and executed quickly. For other indications, EPCAM is expressed in many solid tumors like gastric, pancreatic, lung, ovarian, certain breast cancers, and will move into other tumor types by end of year.

Q: On initial dose expansion diarrhea prophylactic protocol implementation and PFS as primary endpoint?

A: Prophylactic protocol implementation had challenges due to rapid enrollment and patient choices, but feel it will be adhered to as refined. Planning for OS to be primary endpoint, not guiding to PFS as primary in late - line CRC setting.

Q: Positioning relative to other ADCs in development?

A: Varsetta is first - in - class anti - EPCAM ADC, may be best - in - class for CRC based on data, with competitive data set and potential for earlier line treatment due to safety profile.

Q: Looked at data in third line only patients and diarrhea duration?

A: Data in late - line patient population showing good activity, duration of diarrhea median time to onset is about five weeks, and PFS from expansion phase without optimized prophylaxis can improve with optimization.

Q: Confirmed partial responses in 8.6 and 10 mg per kg cohorts, pivotal comparator, and prophylaxis in combination approach?

A: In study, it's unselected patient population with activity across lines. Pivotal comparator in third line may be Bevacizumab plus Lonsurf. Prophylactic strategy with loperamide and budesonide should be manageable in combination setting as both are oral and similar to standard anti - GI motility agents.

Q: Dose selection for BEV combination studies and KRAS activity?

A: Work in progress on dose selection for BEV combo, and Varsetta is active in unselected patient population regardless of KRAS status.

Q: Difference in 8.6 and 10 mg doses in dose optimization, focus indications for broadening study?

A: Dose optimization cohorts data is early, but PK exposure efficacy model is predictive. Non - CRC has many opportunities, but details on cohorts size to be provided later.

Q: Frequency of grade 3 diarrhea events, attribution of grade 3 diarrhea improvement, median time on therapy for optimized safety cohort patients?

A: Focus in optimization cohorts is on prevention, adjusted ideal body weight dosing and prophylaxis working well, details on grade 3 diarrhea recurrence and median time on therapy to be learned over time with more data