CytomX Therapeutics, Inc. Morgan Stanley 24th Annual Global Healthcare Conference

Yeah. Hi, everyone, and thank you, Matthew, and the Morgan Stanley team for inviting us this year. I'm Chris Ogden, Chief Financial Officer of CytomX. Just before starting, I will be making forward-looking statements, so I'll refer you to our SEC filings for those disclosures. Just to start, CytomX is an oncology-focused company, and really, we refer to CytomX as the original masking company. We really invented the field of masked biologics. What we mean by masking is we essentially have a technology where we can limit binding. We designed to limit binding of target biologic formats in healthy tissue, but activate those therapeutics preferentially in tumor cells. What that allows us to do from a design perspective is to really go after targets that other companies can't drug.

From our perspective, that's led to clinical programs that are highly differentiated and are really enabled by our technology. We'll talk more about those, but our two clinical programs, one is an ADC for colorectal cancer, the principal indication, and the other is a cytokine program focused in melanoma. I think we'll talk much more about those, but that's really the focus of the company.

Yeah. First and foremost, for the target, EpCAM, epithelial cell adhesion molecule, it was really discovered as a CRC cancer antigen quite some time ago. The reason it was discovered a couple of decades ago is it is just so highly abundant in tumor cells that it really pops out as potentially an ideal target for a colorectal cancer therapy. To your point, it has been attempted to be drugged before in monoclonal antibodies. There have been T-cell engager formats, and they have all run into toxicity due to expression, presumably in non-tumor tissues. The toxicities that have really limited therapies before are pancreatitis, so all the first antibodies saw pancreatitis quite early in dose finding, and also liver tox was a challenge. GI has also been something that has confronted, and we will talk more about, but I believe we have a therapeutic window in that context as well.

In terms of our design, I would say it really starts with the end in mind. First, we thought this target, if you can create a therapeutic window, could make a big difference in colorectal cancer. From that perspective, we went about designing the other components of the drug, including the payload, which was developed and licensed from ImmunoGen, but we did have a former program with a maytansine payload that actually we could have advanced on a faster timeline. But we made the choice to switch out that payload with a Topo I payload because that mechanism is known to be active in colorectal cancer. Irinotecan, which is a Topo I inhibitor, is a key part of standard of care in CRC.

The design, including EpCAM, is a great target that we can unlock through masking, paired with a Topo I payload for CRC, has really been the focus of this program, and we think all the components really lined up for us to make a difference here in CRC with our technology and this target.

Yeah. I would say when we did the work, going back today with ImmunoGen, it is a DAR8 ADC, and we benchmarked the payload, DXd, the payload on ENHERTU. In terms of the design and the pre-clinical work, we thought about this as really ENHERTU for EpCAM. That was the design principles, and so when you think about the payload potency and those types of things, potential bystander effect, those were all benchmarked to ENHERTU, which was emerging at that time as a best-in-class ADC and has proven to be.

Yeah. No, it's an important question. Before doing that, I do want to just zoom out. I think most investors and people in the audience will appreciate this, but when we think about the context of colorectal cancer, the way we think about it at the company is it's one of the, if not the most urgent health crisis in oncology. It's the second leading cause of death in the U.S. It's the leading cause of death in patients under 50, and as you've seen in the news, growing at an alarming rate. When we think about our place in the industry and the chance to make a difference there, I think that perspective will be highlighted in how we're thinking about the initial development and how much unmet need there is for these patients.

To your question, in the context of third line plus, first of all, I would just say it's unfortunately a big market. We think in the U.S., there's about 40,000 patients that progress to third line or later colorectal cancer. If you look at the benchmarks in the latest line, which are single-agent TKIs for the most part, response rates are 1% to 2% progression-free survival. The amount of time a patient stays on therapy without the tumor growing is only a few months, and unfortunately, their overall survival is 6 to 7 months. In the context of that pretty poor set of outcomes, we've been very pleased with what we've seen with Varseta-M and the chance to make a difference and improve upon those benchmarks. Our patient population has been really fourth line or later.

This is a clinical study population, so we're getting very sick patients. What we've observed over the course of phase I or the last couple of years is response rates in the 20%-30% range. Again, that compares to 1%-2% for benchmarks and our estimated progression-free survival of 6-7 months, again, comparing to just a few months in standard of care. We've not reported overall survival, but that is something now that we've been in the clinic for a couple of years, we do expect to have initial reads on later this year. Just getting back to how important this category and unmet need is, I think the data we have really underscore how much urgency we have to progress this to late-phase development.