CytomX Therapeutics, Inc. Wells Fargo 21st Annual Healthcare Conference

Thank you, Jessica, and thanks to the Wells Fargo team for their kind introduction to be here today. It's a pleasure to be here to share our latest progress at CytomX Therapeutics. I will be making certain forward-looking statements in the course of my presentation today, and I refer you to our SEC filings. I'll talk to you today about how we're unmasking advances in oncology using our proprietary Probody therapeutic technology platform. This is a platform we've been working on for a number of years. We have pioneered the space of antibody masking now for more than a decade and applied it to a number of target strategies. With the two programs that we're currently advancing, we have, I believe, really pinned down the combination of going after the right target, the right tumor type, and the right effector mechanism.

We really believe it's the combination of all three of these that are leading to our current success applying our unique technology. We currently have two programs in the clinic, varsetatug masetecan, otherwise known as Varseta-M, formerly known as CX-2051. This is an EpCAM-targeting masked antibody-drug conjugate that we're developing initially in late-line colorectal cancer. We're also developing a Probody masked version of Interferon alfa-2b in melanoma. We are in a robust financial position. We reported recently more than $350 million of cash, including a significant influx of cash from an expansion of our longstanding collaboration with Regeneron. We are based in the San Francisco Bay Area, an integrated R&D company with about 90 employees. Speaking specifically, and initially about Varseta-M, this is a drug we're very excited about. As I mentioned, it's a masked antibody drug conjugate targeting EpCAM.

This is the only EpCAM-targeting ADC that we are aware of. This is a first-in-class antibody drug conjugate. We believe with our technology, we're the first to unlock EpCAM as a drug target. The program thus far has been focused in late-line colorectal cancer, and I'm delighted to report that just a week or so ago, we announced Fast Track designation awarded by FDA in relapsed refractory metastatic CRC. We have shared very encouraging anti-tumor activity in late-line colorectal cancer, most recently in an update in mid-March this year, reporting a very significant overall response rate, highly encouraging progression-free survival in an all-comer patient population in late-line colorectal. We've also reported an encouraging safety profile. EpCAM has been a very difficult target to drug over the years. We've really broken through on this target, which is highly abundant in colorectal cancer.

We have an attractive safety profile with low rates of hematologic toxicity, no measurable interstitial lung disease, no classic EpCAM toxicities that have been a challenge with this target in the past. The one adverse event of note we are learning more about all the time, which is a certain rate of high-grade diarrhea that we are learning about and learning to manage as we move through dose optimization. We are currently in the dose optimization stage of phase I, with the goal of initiating our first pivotal study in the first half of next year. I know I do not need to tell you that the colorectal cancer market is absolutely enormous.

This is a huge unmet need on a global basis, and this is a highly strategic opportunity for us to move this drug forward in initially late-line colorectal and then subsequently bring the drug into earlier lines and further into additional tumor types beyond that. It is a very exciting time for our company as we advance this drug candidate. In terms of the program itself, it is both broadening and deepening in real time. As I mentioned, we are on track to initiate our first registrational study in the first half of next year. We are also expanding into combination studies. We have a phase I combination with bevacizumab underway, with initial data anticipated in the first half of next year. We are also working towards initiating combination studies with chemotherapy in late-line colorectal also later this year.

We have also recently announced expansion into three additional tumor types, gastroesophageal junction cancers, pancreatic cancer, and also biliary tract cancer. As I said, the program is advancing and broadening very, very quickly. In addition to that, the 801 program is also moving forward. Let me take a deep dive on Varseta-M, and show you the context for this program, where we are, and where we are headed. As you all know, colorectal cancer has seen a real dearth of innovation, really for more than a decade. It is a very difficult disease to treat, particularly in the late line setting. With Varseta-M, we can say today that the promise of antibody drug conjugates is coming to colorectal cancer.

ADCs, of course, have broken through in a number of solid tumor types following on from initial approval in multiple hematologic indications, and we are very thrilled to be at the leading edge of bringing ADCs to colorectal with Varseta-M. Again, this is the only EpCAM-targeting ADC in development that we are aware of. Colorectal cancer remains one of the biggest unmet needs in oncology. The numbers are very large. The number of patients on a global basis is in the millions. It is the second leading cause of cancer death worldwide. Five-year survival is a dismal 13%. Rather alarmingly, colorectal cancer is growing in incidence in younger patients. This indeed could be considered an emerging global health crisis. New solutions are needed. From the commercial point of view, it is an absolutely enormous market on a global basis.

In the late line alone, this is a multi-billion-dollar opportunity. As we march earlier into third line, and ultimately our goal is to bring this drug into the front line in colorectal, the numbers get very large very quickly. From a value creation standpoint, certainly from where we stand today, this represents a huge opportunity for value build in CytomX, in the near, medium, and longer term. The design of Varseta-M has been highly intentional. EpCAM is a protein. It is a target that we have known about since 1979. It is such an abundant antigen. It was one of the first colorectal cancer antigens to ever be described. Ever since that time, many institutions and companies have tried to target EpCAM, given its high level of expression.

The challenge has been that EpCAM, as the name suggests, epithelial cell adhesion molecule, is also present on many normal epithelial tissues. That has led to systemic toxicities for a wide range of different approaches that have been taken to try to target EpCAM previously. It has previously been impossible to open a therapeutic window for this target, whether with an antibody, whether with a T-cell engager, certain conjugate structures. No one has been able to achieve therapeutically active levels of a systemically administered drug targeting EpCAM. We do know, however, that if you can locally target EpCAM, you actually can induce antitumor responses. This has been shown by two agents, one of which was recently reapproved in Europe. It is called Corjuni. It is an anti-EpCAM targeting tri-specific antibody, which is effective in the treatment of malignant ascites, but the drug has to be administered intraperitoneally because it has too many systemic side effects.

That is an important clue. It shows that if we get an empowered antibody actually to the target to EpCAM, it is possible to induce antitumor responses. How have we approached and how have we solved this problem at CytomX? We have brought our masking technology to bear, our Probody therapeutic masking strategy. First of all, we made an antibody to EpCAM, a high-affinity antibody. We then used our protease-dependent masking to engineer what we call a Probody version of that antibody, so that the Probody has limited ability to bind to target until the mask is removed, and the mask is removed specifically and selectively within cancer tissue by tumor-associated proteases.

This is the core of our platform. Tumor-associated proteases, which are switched on in cancer, clip off the mask, allowing the antibody to recognize and bind its target and elicit its therapeutic effect. The therapeutic effect of Varseta-M is mediated by the cytotoxic payload that we have conjugated to this ADC. This payload is called CAP-059. It is a novel topoisomerase I inhibitor. It now has a new generic name called masetecan, and it is linked to the antibody through a trialanine cleavable peptide linker. This is a novel masked EpCAM-directed antibody drug conjugate. Right target, right tumor type, right payload. We chose to first study Varseta-M solely in colorectal cancer to really see what this drug candidate can do. One of the main reasons for that is, first of all, the target is so highly expressed in CRC. That is what this drug was designed to do.

This slide shows the current standard of care in late-line colorectal, and you can see that the numbers are really pretty dismal in terms of response rates, progression-free survival, and overall survival. Once patients have progressed in CRC through conventional chemotherapy in the first and the second-line settings, their opportunities for treatment in the later line are really poor, and it's this problem that we're looking to solve with Varseta-M. In terms of development strategy, we have a multi-tiered strategy to walk through multiple lines of development over time. First of all, to generate proof of concept in late-line metastatic CRC and move towards our first registration in this setting. We're on our way to do that, potentially launching our first study in the first half of next year, building on the 113-patient phase I study, for which I'll show you an update in a moment.

We then plan to bring the drug into earlier line settings, into second-line, and then ultimately into first-line through combination strategies. Then over time, and we've started already, we plan to expand into additional tumor types. EpCAM is expressed not only in CRC, but actually on most other solid tumors as well. So in the long run, we think that Varseta-M has the potential to even reach a tumor-agnostic pan-tumor label across multiple cancer types. One step at a time. Let's talk about where we are with the monotherapy in the late-line setting. Just to recap here, we do see a broad development opportunity in metastatic CRC.