CytomX Therapeutics at H.C. Wainwright: Strategic Pipeline Developments

On Tuesday, 09 September 2025, CytomX Therapeutics (NASDAQ:CTMX) presented at the H.C. Wainwright 27th Annual Global Investment Conference, outlining its robust pipeline and financial position. The company emphasized advancements in its Probody therapeutic pipeline, notably CX2051 and CX801, while highlighting a strong cash position extending into 2027. However, challenges remain as CytomX navigates the competitive oncology landscape.

Key Takeaways

• CytomX has secured a $100 million financing, ensuring a cash runway into Q2 2027.
• Promising interim Phase 1 data for CX2051 in metastatic colorectal cancer, with a 28% overall response rate.
• Expansion of the CX2051 study from 25 to 73 patients, with a data update expected in Q1 2026.
• CX801 is being evaluated in combination with Keytruda, with initial biomarker data anticipated by the end of 2025.
• Partnerships with Bristol Myers Squibb and Moderna bolster growth in the T-cell engager space.

Financial Results

• CytomX raised $100 million in Q2 2025, supporting operations into Q2 2027.
• The company maintains approximately 70 employees with integrated R&D capabilities.
• Financial stability excludes potential milestones or new business development deals.

Operational Updates

• CX2051 (EpCAM ADC) has shown a 28% overall response rate and 5.8 months progression-free survival in metastatic colorectal cancer.
• The study expanded significantly, with patient enrollment increasing from 25 in May to 73 in August 2025.
• CX801 is in a clinical study for melanoma, with combination trials with Keytruda starting in Q2 2025.

Future Outlook

• CytomX plans to initiate a potentially registrational late-line study for CX2051 in 2026.
• The company aims to explore combination therapies and expand into other tumor types.
• CX801 combination results with Keytruda are expected in 2026, offering insights into its efficacy in melanoma.

Q&A Highlights

• CEO Sean McCarthy expressed optimism about CX2051’s potential as a new standard of care in late-line colorectal cancer.
• The company is on track for a data update in Q1 2026, with hopes to achieve multi-billion dollar annual sales for CX2051.
• CytomX’s strategy focuses on leveraging its Probody platform to enhance the therapeutic window of biologics in oncology.

CytomX’s presentation at the conference underscores its commitment to advancing its pipeline and achieving significant milestones. For detailed insights, refer to the full transcript below.

Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:

Jade Montgomery, Associate Biotech Research Analyst, HC Wainwright: Good afternoon, everyone, and thank you for joining the 2025 HC Wainwright 27th Annual Global Investment Conference. I’m Dr. Jade Montgomery, an Associate Biotech Research Analyst at the firm, and I’d like you to please join me in welcoming Dr. Sean McCarthy, CEO of CytomX Therapeutics. Sean?

Sean McCarthy, CEO, CytomX Therapeutics: Thank you, Jade, and thanks to the HC Wainwright team for the invitation to present and participate in the conference. I’m very pleased to be here today to talk to you about our multimodality Probody therapeutic pipeline addressing major unmet needs in oncology. I will be making certain forward-looking statements. I refer you to our SEC filings. CytomX Therapeutics is a South San Francisco, California-based biotech company. We are focused on developing and advancing a pipeline based on our Probody therapeutic platform. This is a unique masking strategy for biologics, which is aimed at improving or enhancing the therapeutic window for oncology products. We currently have two clinical programs: CX2051, which is our EpCAM targeting Probody Topoisomerase 1 ADC, and CX801, which is our Probody version of Interferon Alpha 2B.

We have a long history of partnering at CytomX and currently are fortunate to work with Bristol Myers Squibb and Moderna. The majority of work being done in these partnerships is actually in the T-cell engager space, which is one of the several modalities that we believe our technology can uniquely enable. We’re in a strong cash position. We were able to raise a $100 million financing in Q2 of this year on the heels of positive initial phase one data for our EpCAM Probody ADC. This provides cash runway into Q2 2027, and that excludes any milestones or new business development. We currently have about 70 employees and integrated R&D capabilities. This slide shows our core technology. We are a pioneer in this field of antibody masking.

We are, in fact, the first company to show clinical responses with masked antibodies, the first to show molecular activation and unmasking in patient biopsies, the first to show significant reductions in T-cell engager cytokine release syndrome in the context of clinical responses. We’ve really led this space. Antibody masking is now something that multiple other organizations are engaged in, and the way the technology works, as shown on the schematics here, is the basic idea is we take an antibody and we engineer it so that it has a peptide mask that blocks the ability of the antibody to bind to its target until the mask is removed. The masks are removed specifically and selectively in the tumor microenvironment by tumor-associated proteases. Proteases are dysregulated in tumors.

We’ve known this for many decades, and it’s this difference in protease activity in tumor versus normal tissue that gives us the therapeutic window with masked antibodies. CytomX has really pioneered this field. In terms of our two clinical programs with the CX2051 EpCAM ADC, we presented initial phase one data in the first half of this year, and we’re working towards phase one expansion data, which we are on track to share in Q1 of 2026. We are planning towards initiating our next clinical study next year in 2026, and also to begin combination work with this drug. This is a wholly owned asset with a payload licensed from Immunogen. CX801, our Interferon Alpha 2B masked cytokine, is in a clinical study in melanoma. We initiated a combination study with Keytruda and dosed our first patient in Q2 this year.

We’re on track for initial phase one monotherapy biomarker data towards the end of this year and clinical results for the Keytruda combination in 2026. Let me focus on the EpCAM ADC. We are highly focused in colorectal cancer with this drug candidate at the moment. CRC remains one of the biggest unmet needs in oncology, as I’m sure you all know. It’s a leading cause of cancer death worldwide, and we have a lot of work to do to improve outcomes for patients with CRC. The scale of the problem, particularly in the late line setting, is highlighted on this slide, where you can see that the current standard of care in the third line or later metastatic CRC setting is highly inadequate. We have overall response rates in the low single digits. We have PFS of just a few months.

By the time patients come onto third or fourth line therapy, they’re really in desperate need of new approaches. CX2051 aims to bring the concept of antibody-drug conjugates to colorectal cancer. ADCs are transforming oncology care. There’s been very little progress in ADCs in CRC to date. We think this is a field that is ripe for evaluation of ADCs, and we see enormous opportunities for value creation here with 2051, just highlighting, of course, several major value creation events in the ADC field with a number of M&A transactions over the last few years that you’ll all be, I would think, quite familiar with. In May this year, we announced positive interim phase one clinical data for CX2051.

In terms of the clinical activity, we saw very robust activity in metastatic CRC with a 28% confirmed overall response rate, 94% disease control, and a preliminary assessment of progression-free survival of 5.8 months, positioning CX2051 from this early dataset as potentially a new standard of care in late line colorectal cancer. We demonstrated a favorable safety profile, no dose-limiting toxicities during dose escalation, and having observed a favorable safety profile, good evidence that EpCAM masking is working as designed. I’ll say more about EpCAM masking in a moment as I talk about the design of CX2051. Furthermore, we have demonstrated that EpCAM, given its high expression in CRC, we think it’s a pan-CRC target. We think we can treat every patient with colorectal cancer regardless of clinical characteristics, and I’ll say more about that in just a moment. Let’s talk about the target.

EpCAM is an epithelial cell adhesion molecule. It’s a target that we’ve known about in oncology for a long time, several decades, in fact. This slide just shows IHC staining actually for one of the patients in our phase one study. You can see the high, intense, uniform expression of EpCAM across pretty much every cancer cell in this metastatic CRC biopsy. We have high and uniform expression of EpCAM, so it’s really a terrific CRC target. What has limited EpCAM in the past is its presence on normal tissues. Some of the early approaches to drug EpCAM with systemic antibody therapies hit tox roadblocks quite early in development, notably pancreatitis, liver toxicity, and certain GI toxicities. Masking is designed to minimize those toxicities in normal tissues by limiting binding in normal tissue, maximizing binding in tumor tissue. We designed CX2051 very intentionally to address CRC. The target is EpCAM.

The antibody is masked using our protease-dependent masking. The masking domains you can see here highlighted in the circles. The payload has been carefully selected for colorectal cancer. This is a topoisomerase 1 inhibitor. We know that CRC can respond to TOPO1 inhibition. In fact, irinotecan, which is a TOPO1 inhibitor, is embedded in the standard of care in first and/or second line CRC. We know that this tumor type can respond. We really believe that we’ve chosen the right target for this tumor type and the right payload and deploying our masking strategy to try to open a therapeutic window for a systemic anti-EpCAM ADC for the first time. I should also say that we have had clues in the past that if you can get an anti-EpCAM drug to tumor tissue, it can be effective in shrinking tumors.

This has been shown with locally administered drug candidates, for example, in bladder cancer, where if you can get the antibody to the tumor, it can be quite effective. No one’s achieved that with a systemic therapy before. We’re really breaking new ground here with this very intentionally designed drug, CX2051. The phase one study for this drug commenced in April 2024. By early this year, or by our May disclosure this year, we had progressed through multiple dose levels in our dose escalation. We began at a dose of 2.4 milligrams per kilogram, escalated through seven dose levels, and the data that we reported was up to and including the fifth dose level of 10 milligrams per kilogram, given every three weeks.

The data that I’ll show you encompasses 25 safety evaluable patients as of the data cutoff of April 7, 2024, and 18 efficacy evaluable patients across those three dose levels of 7.2, 8.6, and 10. The reason I highlight those dose levels in particular is that they are dose levels that we had already decided to expand at the time of the data presentation in May 2024. I’ll come back to the expansions in a moment. The patient population is a late-stage patient population with a median number of priors of four, essentially a fifth line CRC patient population. Admittedly, a tough place to start with a study like this, but certainly a patient population that really reflects the unmet medical need. All patients enrolled into the study had been treated with prior irinotecan.

About half had liver metastases, about half had KRAS mutations, and all patients, with the exception of one who was not evaluable, were microsatellite stable. We saw impressive anti-tumor activity in the first 18 efficacy evaluable patients, a confirmed overall response rate of 28%, 5 of 18 patients with confirmed PRs. At the top dose of 10 milligrams per kilogram, we saw 3 out of 7 confirmed PRs for an ORR of 43%. I just want to track you back to the table I showed earlier on, which is that in this line of therapy, the current standard of care response rate is in the low single digits. This is impressive clinical activity, the likes of which you really don’t see in this kind of patient population.

Also, importantly, if you look at the table at the bottom, the activity, the tumor shrinkage that we’ve seen so far with CX2051, is independent of clinical characteristics that are often used to segment and select patients. We saw activity regardless of whether patients have KRAS mutations, regardless of whether they have liver mets, and all patients that were evaluable had high EpCAM expression. We have not needed to select patients for target, which could be a huge advantage as we move towards commercialization. In terms of duration of benefit, we saw 94% disease control, and you can see deep and durable responses here across all three of our expansion doses. This is very exciting in terms not just of the initial tumor shrinkage that we see, but also the ability to maintain patients on drug and keep them stable for significant periods of time.

That is reflected in our preliminary assessment of progression-free survival of 5.8 months, which again compares very favorably to just two to three months for the current standard of care. This is a very strong start for CX2051 in terms of its efficacy profile in this very difficult-to-treat tumor type. Moving now to safety and the most frequently observed treatment-related adverse events, CX2051 was well tolerated in this patient population, beginning with hematologic toxicities, low rates of grade 3 anemia and neutropenia. In terms of non-hematologic toxicities, low rates of nausea and vomiting, which is sometimes a hallmark of Topo1 inhibitors, and about a 21% grade 3 diarrhea rate. This is an adverse event that we’re watching and monitoring carefully as we move forward with further expansions of the drug.

Overall, a manageable and reversible set of AEs and a very encouraging adverse event profile with no grade 4s or grade 5s as of this data cutoff. Just to again put our data in context of the current standard of care, I think you can all agree that this supports very competitive positioning of CX2051 in the CRC landscape, and we’re very excited to move this drug forward aggressively. What are we doing next? We are expanding these three dose levels to 20 patients per cohort. We actually announced a couple of weeks ago that these expansion cohorts have already been enrolled, and we’ve currently increased the number of patients enrolled into the study from 25 as of May 12th to 73 patients as of August 13th. The expansions are enrolled, and that means we’re right on track to have the next data update in Q1 of 2026.

Thinking about our next steps with the drug, our principal objective will be to move CX2051 into a late line study that could be potentially registrational beginning in 2026, and we’ll start in the third line or later. This is where the unmet need is particularly high. This is where we’ve started our clinical study. It’s where we have extremely competitive efficacy results so far in terms of overall response rate, disease control, and PFS. You’ll hear more about that study design as we move into Q1 of next year. In the longer term, we see enormous potential to bring CX2051 earlier in the treatment paradigm into potentially the second line. Because the payload on CX2051 is a TOPO1 inhibitor, we see a tremendous opportunity to potentially replace irinotecan in the second line.

That will require some exploratory combination work in 2026, but this drug has transformational potential, we believe, in colorectal cancer. Beyond colorectal cancer, one of the other really attractive aspects of EpCAM is this target is present on most solid tumors at high levels. In addition to potentially being a pan-CRC drug, this drug could also have pan-tumor potential across multiple other tumor types. We are right now remaining highly focused in CRC. We have a lot of work to do in colorectal cancer, but we’re very excited about expanding out into other tumor types over time. We have, in fact, presented previously some preliminary preclinical results that show that CX2051 is effective in several of these cancers. To summarize on CX2051, we’ve demonstrated early clinical proof of concept after just one year in the clinic for this EpCAM TOPO1 ADC in colorectal cancer.

This is a potentially first-in-class ADC with multi-billion dollar annual sales potential in third and fourth line alone. As we move to earlier lines, this drug has enormous potential on a global basis. Our top priority right now is to advance towards a potential first approval in late line metastatic CRC, open combination studies in 2026, and begin to explore other tumor opportunities. CX2051 really does have what we call pipeline-in-a-product potential, and I hope you can see tremendous value-creating potential for our company and the ability to impact many, many patients around the world. I want to finish up in the last few minutes by talking about our other clinical program, which is our Probody Interferon Alpha 2B. Switching gears into the field of cancer immunotherapy, Interferon Alpha is an old friend to many of us in the oncology space.

It actually was the first immunotherapy to be approved some decades ago. It’s a very powerful immune modulator, and it has shown clinical activity in multiple tumor types, including melanoma and bladder cancer. It’s been a challenging drug over the years, though, because it has significant systemic side effects. Interferon is quite difficult to use in the clinic, and in fact, it’s fallen out of use because of the difficulty of managing its systemic side effects. Interferon does many things within the tumor microenvironment, and as we seem to have, in a way, with all of the progress made with checkpoint inhibitors over the last couple of decades, we seem to have peaked in IO. We need new mechanisms to unlock new strategies for treatment of patients, particularly in the post-checkpoint setting.

Interferon does a lot in the tumor microenvironment to modulate multiple immune cell types and regulate multiple immune responsive genes and activate the inflammatory microenvironment in the tumor. It’s a great drug if we can find ways to harness its powerful tumor microenvironment activation properties. We reason that by taking Interferon Alpha and masking it, we could turn it into a locally activated immune modulator. We’ve actually engineered CX801 as a dually masked Interferon. We’ve masked both the Interferon domain, shown here in yellow, and also we have a steric mask, both of which are protease cleavable. In the tumor, the idea is that the mask removal unleashes the power of Interferon as an immune modulating agent within the tumor microenvironment. We have been in the clinic for a little less than a year. We’re dose escalating in melanoma.

There remains a very high unmet need in late-stage melanoma, particularly in the post-checkpoint inhibitor setting. You can see an ideal opportunity for Interferon to reactivate the immune system in patients who have progressed on immune therapy such as Ipi/Nivo or Opduro/Lag. Dose escalation began last year. We quickly and successfully moved through several monotherapy dose levels, allowing us to open our combination cohort earlier this year. We treated our first patient in combination with Keytruda in Q2. The real concept here, the drug concept, is to demonstrate proof of concept with Keytruda, with anti-PD-1, in combination with Interferon, because we believe that Interferon will upregulate Interferon responsive genes, which actually include the checkpoint inhibitors PD-1 and PD-L1. It’s an ideal setting in which to reactivate the tumor microenvironment to become checkpoint responsive again by using this locally administered Interferon in melanoma. We’re really excited about this program.

We will have, as I mentioned, initial translational biomarker data from paired on-treatment biopsies later this year, with clinical results from the combination in melanoma coming in 2026. We have a supply agreement in place with Merck for access to Keytruda. Just to summarize then, for CX2051, initial, we think, impressive proof of concept demonstrated this year with our May disclosure. Really excited about this program. On track for phase one expansion data in 2026 in Q1. Planning our next study, which we believe could potentially be registrational to initiate in the first half of 2026, whilst we also initiate combination work and potentially move into other tumor types. Our conditional masked Interferon Alpha 2B, we have initiated our Keytruda combination and on track for initial data this year and combination data next year. It’s a terrific program across the company.

Thank you for your time and happy to answer any questions. Thank you very much.

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