CytomX Therapeutics Conference: CFO Highlights Varseta-M CRC Response Data, Next Catalysts

CytomX Therapeutics (NASDAQ:CTMX) Chief Financial Officer Chris Ogden outlined the company’s current priorities and upcoming catalysts during a fireside chat moderated by Guggenheim senior biotech analyst Michael Schmidt. Ogden said CytomX has spent more than 15 years developing its “masked biologics” technology, which is designed to keep an antibody or other biologic therapeutics inactive in circulation and healthy tissue, but allow activation within tumors due to a dysregulated protease microenvironment that can “clip” the mask.

Masked biologics focus narrowed to two clinical programs

Ogden said CytomX has pioneered multiple masked formats that can be applied to antibody-drug conjugates (ADCs), T-cell engagers, and cytokines, but the company’s focus today is concentrated on two clinical-stage programs. He characterized both programs as the “most focused application” of CytomX’s technology to date, reflecting lessons learned about masking strategy and therapeutic format selection.

The lead program discussed was Varseta-M, a masked EpCAM-targeting ADC. The second clinical program, CX-801, is a masked interferon alpha-2b (IFNα-2b) candidate.

Why CytomX chose EpCAM—and why it is using an ADC format

Ogden described EpCAM (epithelial cell adhesion molecule) as one of the broadest solid-tumor targets, with high expression across many solid tumors and historically recognized as a colorectal cancer (CRC) antigen. However, he said prior attempts to drug EpCAM systemically have been constrained by toxicity, including pancreatitis and liver toxicity seen with high-affinity EpCAM antibodies at relatively low doses.

He said CytomX believes masking can help create a therapeutic window for EpCAM-directed therapy. The company selected an ADC approach in part because ADCs are a “highly validated” modality, and it paired the EpCAM antibody with a topoisomerase-1 (topo-1) payload. Ogden noted that irinotecan, a topo-1 inhibitor, is standard of care in multiple lines of CRC, which he framed as supportive of topo-1 as a de-risked effector mechanism in this tumor type.

Asked about additional tumor types beyond CRC, Ogden said EpCAM is expressed in most solid tumors and cited gastric, pancreatic, prostate, triple-negative breast, and lung cancers as examples. He said the near-term priority is advancing the ADC in CRC, while the company expects to begin focusing work in additional indications in the second half of the year to broaden Varseta-M’s pan-tumor strategy.

Early phase I CRC data: responses, disease control, and safety observations

Ogden highlighted unmet need in metastatic CRC, citing 1.9 million global cases and a five-year survival rate of 13% in the metastatic setting. He also referenced a recent announcement that colorectal cancer is the leading cause of cancer death in U.S. patients under 50. He argued that therapeutic innovation in CRC has lagged compared with cancers such as lung and breast, with treatment still largely reliant on chemotherapy and older monoclonal antibodies.

In the company’s initial phase I dataset in last-line metastatic CRC, Ogden said patients had a median of four prior therapies (characterized as roughly a fifth-line population). He emphasized that the study did not select patients based on EpCAM expression or other clinical factors such as liver metastases or KRAS mutation status. Against what he described as a backdrop of 1%–2% response rates and only a few months of progression-free survival (PFS) for standard options in this setting, Ogden said the initial data showed:

• 28% objective response rate
• 94% disease control (17 of 18 evaluable patients in key dose ranges)
• Early PFS estimate of 5.8 months

On safety, Ogden said the company did not observe the “classic EpCAM toxicities” that have limited other therapies, specifically citing no pancreatitis and no liver toxicity signals in the initial look. He said hematologic toxicity appeared “reasonable” and manageable for an ADC. The main toxicity discussed was diarrhea, with about 21% Grade 3 diarrhea, which he said is consistent with topo-1 payloads and with irinotecan experience.

Dose expansion and what CytomX plans to evaluate next

Ogden said the company expanded enrollment at three dose levels where activity had been observed—7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg—initially aiming for about 20 patients per dose. He added that CytomX later expanded the target to approximately 100 patients for a first-quarter data update. The intent, he said, is to better understand efficacy and safety across the dose range to inform dose selection for later-stage development.

Ogden said the company will assess response rate by dose and is increasingly focused on PFS by dose, noting that PFS can integrate both efficacy and tolerability and will be important for planning later-phase studies. He also said CytomX implemented prophylactic measures—prophylactic loperamide—at the time of expansion in the second quarter of 2025 to help manage diarrhea, and the company expects to learn more about the effectiveness of this approach in the larger dataset.

On the cause of diarrhea, Ogden said the company does not yet know whether it is primarily payload-related or potentially related to low-level EpCAM binding in healthy gastrointestinal tissue, noting EpCAM’s expression in the GI tract and describing masking as shifting the binding curve by “about a hundredfold.” He also noted the ADC uses a novel linker-payload licensed from ImmunoGen.

Regulatory and development strategy, plus updates on CX-801

Looking ahead, Ogden said the company’s first goal is to see the initial profile hold up in a larger sample size, and then to use follow-up to support discussions with the U.S. Food and Drug Administration around mid-year on what a next study could look like. He said CytomX hopes that next study could be registrational and that the company aims to start it no later than the first half of 2027.

On a potential path to market, Ogden said CytomX is prioritizing speed in late-line CRC and discussed the possibility of a study versus a single-agent tyrosine kinase inhibitor such as fruquintinib, citing a 1%–2% response rate and 3.7 months PFS for that comparator. He also said the company is not ruling out a head-to-head study versus LONSURF plus bevacizumab, which he described as the most common regimen in third line, with PFS of about 5.6 months.

Ogden said the longer-term vision is to replace chemotherapy, particularly irinotecan, and that CytomX plans to begin combination experience starting with bevacizumab in the first quarter. He also said the company expects to ultimately evaluate chemotherapy combinations as part of a strategy to move earlier in treatment lines, including a “FOLFIRI replacement” approach.

Briefly addressing competition, Ogden said he views ADC data as “by far the most compelling” among emerging CRC approaches, and he cited other ADCs in development, including a cMet-targeting ADC from AbbVie (which he estimated is relevant to about a third of CRC patients due to target expression) and a CEACAM5 ADC from Merck KGaA, which he described as encouraging and “de-risking” for CytomX.

Ogden closed by discussing CX-801, describing interferon alpha-2b as a highly validated immune stimulator historically limited by toxicity. CytomX’s thesis, he said, is to help turn “cold tumors hot.” The company is starting CX-801 in late-line, PD-1–refractory melanoma, initially in combination with KEYTRUDA, and is currently in dose escalation. Ogden said CytomX is working toward an initial clinical update in the second half of the year.

About CytomX Therapeutics (NASDAQ:CTMX)

CytomX Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on the discovery and development of next-generation therapeutics based on its proprietary Probody® platform. The company engineers masked antibody prodrugs that remain inactive in healthy tissue but are selectively activated in the tumor microenvironment. This approach is designed to enhance the safety and tolerability of antibody-based therapies, particularly those targeting immuno-oncology pathways.

At the core of CytomX’s pipeline is Pacmilimab (CX-072), an anti–PD-L1 Probody therapeutic currently undergoing clinical evaluation for multiple solid tumor indications.