CytomX Therapeutics, Inc. 12th Annual Cantor Fitzgerald Global Healthcare Conference

You're very welcome, Olivia, and sometimes it does feel like we're joined at the hip, Chris and I, because we do spend a lot of time together.

Of course. As many may know, CytomX is, I refer to us as the original masking company. We're the company that really has pioneered a strategy of antibody and biologics masking to improve therapeutic window. We've really led this space now for quite some time, and today we have two lead clinical programs that really demonstrate the power and versatility of the technology. The first that we're highly focused on is Varseta, varsetatug masetecan, Varseta-M, our EpCAM-targeting antibody-drug conjugate that we're developing initially in colorectal cancer, and we're working towards launching potentially a first pivotal study in the first half of next year. I'm sure we'll spend plenty of time talking about that program and the progress that we've been making. The second program is a cytokine that we've used our masking technology also to improve therapeutic window. It's a masked version of interferon alfa-2b.

We call it CX-801, and we are in a phase I study in melanoma, late line post-checkpoint melanoma, and on track to have initial data from that program in the first half of next year. We continue broadly to apply the technology, including in a collaboration with Regeneron that we recently were really excited to expand. We announced a significant expansion of that collaboration resulting in a $37 million upfront payment, which helped strengthen the balance sheet and keep us in a strong financial position to execute on this really exciting pipeline.

Yeah. One of the defining features of EpCAM as a target is it is so broadly expressed in so many different cancers. It was initially identified in colorectal cancer, believe it or not, in 1979. It was, I guess, relatively easy to identify at that time because there is just so much of it on colorectal cancer cells. We really intentionally designed the drug for CRC initially. We have selected a topoisomerase I inhibitor payload, which is indicated for the treatment of colorectal, as you know, irinotecan is a core component of the standard of care for CRC. We applied the masking technology to localize the antibody in tumor tissue away from normal tissues. That has been a challenge with EpCAM-directed therapies over the years. It has been a very difficult target to drug because of its expression in normal tissues.

It is really the combination of the target, and the payload, and the masking strategy, and it just made total sense to go into CRC first. It was quite a big decision, actually, to decide to do all of our dose escalation only in colorectal.

given how challenging of a setting that's been over the years. I think it's really paid off.

Yeah. Let me just walk you through how the program has unfolded over the last year and a half or so. We presented the first look at phase I data in May of last year, the first 25 or so patients, and it became clear very quickly that this is a highly active drug in late-line colorectal. We've enrolled patients, and we continue to enroll patients who are fourth line or later. So we are treating the most difficult to treat patients, but that's also where the unmet need is greatest. So we think this is an important place to be, at least initially. So that first data set in May showed clearly this is an active drug. We showed a significant 20%+ response rate across various dose levels, and a really encouraging safety profile. I think at that time, it really caught investors' attention.

I think the key question that came out of that early update was, can that efficacy be replicated as we continue to expand?

We ran three expansion cohorts at three separate doses, 7.2, 8.6, and 10 mgs per kg given on a q three-week schedule. That is the data that we reported in March this year. I think everybody agrees that, yes, the efficacy absolutely held up. In fact, in a way, it strengthened in terms of seeing a clear dose response across those three dose levels. I think really showing that this is an active drug in this late-line population. We also learned a lot more about safety, coming to understand that first of all, things that we do not see, which is great. We see very low rates of hematologic toxicity for a TOP1-ADC. It is kind of a remarkably low rate of hem tox, actually. We see no interstitial lung disease. Crucially, we see none of the classic EpCAM toxicities like acute pancreatitis.

The one safety signal that we are focused on and learning more about is a GI signal, where we do see a certain level of grade 3 diarrhea, which we are learning more about now as we continue the current stage of the phase I, which is dose optimization. Over the last six months or so, we have been enrolling patients into two dose optimization cohorts, focused on the two highest doses from the expansion phase, 8.6 and 10 mg/kg Q3W. Also implementing upfront prophylaxis with loperamide and budesonide to try to get ahead of that grade 3 diarrhea and also using adjusted ideal body weight dosing. The goal of the AIBW being to really normalize dosing across a patient population that has quite a wide range of body weight.