CytomX Q3 2025: Contradictions Emerge in Earlier Lines of Therapy, Accelerated Approval, and Diarrhea Management Strategies

Date of Call: November 6, 2025

Financials Results

• Revenue: $6.0M, compared to $33.4M in Q3 2024

Guidance:

• Cash runway expected to fund operations to at least Q2 2027.
• CX-2051: Phase I expansion to ~100 patients; data update planned Q1 2026 to inform dose selection and FDA (Project Optimus) dialogue.
• CX-2051: Initiate Phase Ib combo study with bevacizumab in Q1 2026; aim to support movement into earlier lines (eventual second-line).
• CX-801: KEYTRUDA combination initial data expected by end of 2026.
• Additional non-CRC indications for CX-2051 being evaluated with updates in 2026.

Business Commentary:

* Clinical Progress and Patient Enrollment: - CytomX's Phase I study for CX-2051 is expected to enroll approximately 100 patients by Q1 2026. - This is due to strong interest from investigators and patients, reflecting the high potential and promising interim data, including an integrated confirmed response rate of 28% and a preliminary median progression-free survival of 5.8 months.

• Cash Position and Financial Guidance:
• CytomX ended Q3 2025 with $143.6 million in cash, cash equivalents, and investments, with projections to fund operations until at least the second quarter of 2027.
• The decrease from the previous quarter's $158.1 million is primarily due to the completion of performance obligations under the Bristol Myers Squibb collaboration and a reduction in R&D expenses, particularly for CX-904.

• Pipeline and Development Strategy:
• CytomX plans to initiate a Phase Ib study with bevacizumab in Q1 2026, exploring combinations to expand CX-2051's potential into earlier lines of therapy.

• This is part of a strategic focus on broadening CX-2051's development to increase its market competitiveness and realizes its pan-CRC potential.

• Interactions with FDA and Regulatory Strategy:

• CytomX anticipates regulatory discussions with the FDA next year as part of planning for potential registrational studies in CRC.
• The company is considering various regulatory strategies, including the possibility of a fourth-line monotherapy trial, based on the potential of CX-2051 to comprehensively beat standard of care in this setting.

Sentiment Analysis:

Overall Tone: Positive

• Management highlighted 'positive interim Phase I data' and 'robust clinical activity' for CX-2051, called CX-2051 'generally well tolerated', and reiterated near-term milestones: CX-2051 data update in Q1 2026 and CX-801/KEYTRUDA combo data by end of 2026. CFO stated cash of $143.6M 'will be able to fund CytomX operations to at least the second quarter of 2027.'

Q&A:

• Question from Edward Tenthoff (Piper Sandler & Co.): What should we expect for ORR and PFS in the ~100-patient 2051 readout; any chance for deepening?
  Response: May interim data showed a 28% confirmed response rate across the 7.2/8.6/10 mg/kg doses and preliminary PFS of 5.8 months versus 2–3 months SOC; expect a more mature Q1 2026 update.

• Question from Edward Tenthoff (Piper Sandler & Co.): Will you break out efficacy by dose and have enough data to select dose(s)?
  Response: Yes — the next update will break out data by dose to inform efficacy/safety and support dose selection.

• Question from Nabeel Nissar (Jefferies LLC): What drove enrollment pickup, any feedback from trial partners, prophylaxis progress, and thoughts on ESMO competitor data?
  Response: Rapid enrollment reflects strong investigator/patient demand post-disclosure; loperamide prophylaxis has been instituted to manage diarrhea and will be refined; no ESMO findings changed belief that 2051 is differentiated.

• Question from Olivia Brayer (Cantor Fitzgerald & Co.): Strategy for bevacizumab combination — which lines and will monotherapy data inform combo dose escalation?
  Response: Plan to start the bevacizumab combo in Q1 2026 exploring multiple 2051 doses concurrently with ongoing monotherapy dose evaluation, aiming to support advancement into earlier lines (ultimately second-line).

• Question from Olivia Brayer (Cantor Fitzgerald & Co.): What percent of patients will receive loperamide prophylaxis, any restrictions, and can it be used proactively and reactively?
  Response: Loperamide is used both prophylactically and reactively; prophylaxis was added in the expansion with investigator discretion and the AE management plan will evolve as data accumulate.

• Question from Matthew Biegler (Oppenheimer & Co. Inc.): Regulatory strategy — can monotherapy go head-to-head vs bev-Lonsurf in third line or is fourth-line more likely?
  Response: All options remain on the table; early data indicate potential to outperform SOC in fourth-line; third-line competitiveness is TBD pending mature, dose-specific PFS data expected by Q1 2026.

• Question from Joyce (JPMorgan): Which non-CRC tumor types for 2051 are most exciting, timing/cadence for PoC studies next year, and balance with CRC plans?
  Response: EpCAM expression gives pan-tumor potential (gastric, pancreatic, endometrial/uterine, lung, etc.); additional cohorts/indication initiations are expected in 2026 while prioritizing CRC development.

• Question from Etzer Darout (Barclays Bank PLC): Is additional enrollment skewed to any of the three doses and will you break out less-pretreated vs heavily pretreated patients in the ~100?
  Response: New enrollment is within the same expansion dose ranges (not specifying exact doses yet); the ongoing patient mix remains largely late-line and consistent with the initial cohort (median ~4 prior lines).

• Question from Mitchell Kapoor (H.C. Wainwright & Co, LLC): What interactions have you had with the FDA about registrational expectations and when will you meet next?
  Response: Regulatory discussions are planned and will be a focus in 2026; no specific FDA efficacy benchmarks were disclosed to date.

• Question from Mitchell Kapoor (H.C. Wainwright & Co, LLC): Thoughts on BioAtla's EpCAM bispecific and differentiation/strategy implications?
  Response: BioAtla's EpCAM CD3 approach is interesting, but CytomX believes its PROBODY ADC strategy offers meaningful differentiation for EpCAM-targeted therapy.

Contradiction Point 1

Progression into Earlier Lines of Therapy

It involves the company's strategic direction concerning the progression of CX-2051 into earlier lines of therapy, which could impact clinical trial designs and patient populations.

What is the expected ORR for CX-2051, and could it improve further? - Edward Tenthoff(Piper Sandler)

2025Q3: The focus remains on the late-line opportunity, but there's intent to progress into earlier lines. Combination studies will evaluate CX-2051 with bevacizumab to explore earlier lines. - Sean McCarthy(CEO)

What factors are driving the decision to move into earlier lines of colorectal therapy? - Edward Tenthoff(Piper Sandler)

2025Q2: Combination studies will evaluate CX-2051 with bevacizumab to explore earlier lines to evaluate CX-2051 in earlier lines of colorectal therapy. - Sean McCarthy(CEO)

Contradiction Point 2

Accelerated Approval Strategy and Endpoints

It involves the company's approach to accelerated approval, with differing emphasis on the relevance of ORR versus PFS/OS, which are critical for regulatory strategies and market expectations.

What is the regulatory strategy for monotherapy? - Matthew Biegler(Oppenheimer)

2025Q3: Encouraging activity of CX-2051 in Phase I, and we believe that to be meaningful in late-line CRC, we believe it to be quite differentiated in this setting. - Sean McCarthy(CEO)

What is the threshold for accelerated approval in CRC? - Matthew Biegler(Opco)

2025Q2: Accelerated approval discussions with FDA would consider the encouraging activity of CX-2051. ORR, PFS, and OS are all relevant, and the current regulatory uncertainty must be considered. - Sean McCarthy(CEO)

Contradiction Point 3

Diarrhea Management Strategy

It involves the company's approach to managing diarrhea, a common side effect of CX-2051, which could impact patient safety and trial enrollment.

What factors contributed to the enrollment increase, and what feedback do you have on prophylaxis and diarrhea management? - Nabeel Nissar(Jefferies)

2025Q3: Diarrhea is being actively managed. Loperamide prophylaxis was implemented early in the expansion phase. - Sean McCarthy(CEO)

Will alternative strategies be explored for managing Grade 3 diarrhea in trials? - Jeff B. Riley(B. Riley)

2025Q2: As Sean said, we're on track to meet our overall objective with the first cohort. Loperamide is the primary strategy, but other methods could be explored. - Sean McCarthy(CEO)

Contradiction Point 4

ORR and Dose Selection

This contradiction centers around the expectations for the objective response rate (ORR) and the process of dose selection for CX-2051, which are crucial for the development and approval of the drug.

What is the expected ORR for CX-2051 and potential for improvement? What is CytomX's PFS success metric? - Edward Tenthoff (Piper Sandler & Co., Research Division)

2025Q3: Integrated confirmed response rate was 28% across the 7.2, 8.6, and 10 mg/kg doses. This substantially beats current standards in late-line settings. - Sean McCarthy(CEO)

What are the baseline characteristic differences between stable disease patients and responders? How likely is antitumor activity to deepen over time with 10 of 18 patients still on treatment? - Jiale Song (Jefferies)

2025Q1: We've seen an impressive disease control rate and response rate across various dose levels in this hard-to-treat tumor type. - Sean McCarthy(CEO)

Contradiction Point 5

Regulatory Strategy and FDA Interactions

It involves the company's strategy for regulatory approval and interactions with the FDA, which are crucial for the drug's approval pathway and market access.

Could you clarify the regulatory approach for monotherapy, especially regarding bev-Lonsurf in the third-line setting? - Matthew Biegler (Oppenheimer & Co. Inc., Research Division)

2025Q3: Early data shows potential to beat standard of care in the fourth line. We await more data to assess third-line potential. - Sean McCarthy(CEO)

What are the success criteria for CX-2051, and is it targeting third- or fourth-line CRC? - Peter Lawson (Barclays)

2024Q4: We're optimistic about seeing RECIST responses in this late-line CRC population. - Sean McCarthy(CEO)