CytomX Therapeutics, Inc.

Thank you for standing by. Welcome to the Cytomics Therapeutics Fourth Quarter 2024 Financial Results Call. Please be advised that today's call is being recorded. I would now like to hand the call over to your host for today, Chris Ogden, Cytomics' Chief Financial Officer. Please go ahead.

Thank you. Good afternoon, and thank you for joining us. Before we begin, I'd like to remind everyone that during this call, we'll be making forward-looking statements. Because forward-looking statements relate to the future, they're subject to inherent uncertainties and risks that are difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. We undertake no obligation to update any forward-looking statement whether as a result of new information, future developments, or otherwise. Earlier this afternoon, we issued a press release that includes a summary of our 2024 full-year financial results and highlights recent progress at Citomix. We encourage everyone to read today's press release and the associated materials, which have been filed with the SEC. Additionally, the press release, recording of this call, and our SEC filings can be found under the Investors in News section of our website. With me on the call today is Dr. Sean McCarthy, Cytomix's Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I walk through the financials for 2024. We will then conclude with a Q&A session. With that, I'll now turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. We're very pleased to be here with you today to provide updates on our continued progress at Cytomix towards our mission of urgently advancing our pro-body therapeutic pipeline for the maximum benefit of cancer patients. As a pioneer in the field of antibody masking and conditional activation, we continue to direct our powerful technology platform towards major unmet needs in oncology. We're seeing broad strategic interest in antibody masking, and Cytomix is uniquely positioned with expertise and capabilities to deliver novel mask therapeutics across multiple treatment modalities, including antibody drug conjugates, T-cell engagers, and cytokines. Our current clinical programs have been built on over a decade of scientific and clinical expertise and follow clear design principles aimed at optimally selecting the cancer type of interest, the tumor target, and the relevant effector function in order to deliver differentiated cancer therapies. 2024 was a very productive year for us, including the advancement of two new programs into the clinic, CX2051 and CX801. In January 2025, we announced the prioritization of these programs and the streamlining of our organization, extending our cash runway to Q2 of 2026. supporting our ability to deliver upon key clinical milestones. We see our lead program, CX2051, as a highly differentiated first-in-class ADC that is designed to address a large unmet need in colorectal cancer and build significant value for cytomics. CX801 is a mass version of interferon alpha with, we believe, broad potential as a next-generation targeted immunotherapy. 2025 promises to be an exciting year for Cytomics, where we expect to generate initial clinical data for both CX2051 and CX801 that we believe could drive significant near-term value creation. I'd like to cover recent progress in our pipeline before handing over to Chris, who will review our financials. I'll start with our lead program, CX2051, our first in class masked ADC targeting epithelial cell adhesion molecule. We are the only organization to our knowledge addressing this target in this unique way. EPCAM has been viewed as a high potential opportunity for many years due to its pan-tumor expression and its particularly high expression in colorectal cancer. However, EPCAM is also expressed at moderate to high levels in normal tissues, which has prohibited the successful development of systemic therapeutics against this target. There's strong evidence, though, that EPCAM targeting with locally delivered approaches can achieve clinical anti-cancer activity, including the multi-specific antibody, Corjuni, that is currently being relaunched in the EU for the localized treatment of intraperitoneal malignant ascites. Despite success with localized therapies, however, prior systemic EPCAM targeting strategies have not been able to reach therapeutically active drug levels in patients. And these include the T-cell engager, solitimab, and other antibody approaches, which showed early promise but were unable to deliver a viable therapeutic window due to dose-limiting toxicities in the pancreas, liver, and gastrointestinal tract. CX2051 is a pro-body ADC comprising a high-affinity Epcam antibody with a peptide mask and a protease cleavable mask linker that has been validated in prior clinical work by Cytomix. In designing CX2051, our goal is to mitigate potential on-target Epcam toxicities and to localize CX2051 preferentially to tumor tissue. Preclinically, CX2051 has shown a wide potential therapeutic index and potent anti-cancer activity in multiple EPCAM-expressing indications. The payload on CX2051-CAMP59 is a topoisomerase-1 inhibitor selected specifically to treat topo-1 sensitive tumors, and in particular, colorectal cancer. The topo-1 inhibitor, Irinotecan, is of course a key component in the treatment of metastatic CRC in the first and second line settings. And so it's well established that this cancer can respond well to this class of drug. The global unmet need in colorectal cancer is one of the most significant in oncology with more than 1.9 million new cases annually and limited new treatments emerging for patients over the last two decades. Unfortunately, there's also an increasing percentage of new CRC cases diagnosed as metastatic and a concerning trend of growing incidence in younger patient populations. First and second line treatments for metastatic CRC are still primarily based on systemic chemotherapy regimens that include arenatecan or axalaplatin. In the later line setting, patient options remain highly inadequate. In patients that have generally had three or more prior lines of therapy, Current standard of care only achieves low to mid-single digit objective response rates and median progression pre-survival of only two to four months. We advanced CX2051 into the clinic in Q2 last year, and we have been pleased with the execution and enrollment in the study to date. We are currently focused in late-line CRC with enrolled patients generally having received at least three prior systemic therapies. Given the consistently high levels of EPCAM expression in CRC, we are not pre-selecting patients for EPCAM expression in our Phase 1 study or for disease characteristics such as KRAS mutational status or liver metastases. In dose escalation thus far, we've been encouraged by the CX2051 safety profile, having successfully dose escalated to levels that we predict, based on preclinical modeling, to be biologically active, and that we're confident could not be achieved with an unmasked ADC. As we continue in dose escalation, our expectation is that the maximum tolerated dose of 2051 will be largely driven by the cytotoxic payload. Specifically, we will be fully characterizing the anticipated GI toxicities and cytopenias, such as neutropenia and anemia, that are commonly associated with TOPO1 inhibitors. We're currently evaluating the seventh dose level in our dose escalation, and we have also begun to selectively backfill at certain dose levels to gain additional experience with the drug. Overall, we believe our early clinical experience with CX2051 is showing that this first-in-class ADC is performing as designed, underpinning its prioritization as the lead program for cytomics, and our focus on bringing this therapy to patients as quickly as possible. We remain on track to provide initial Phase Ia data in CRC in the first half of 2025, and we expect to be in a position to define next steps for the program in the second half of the year. Now, moving to CX801, our masked ProBody Interferon Alpha 2B, which is also making good early progress in Phase I. Interferon Alpha is a well-validated therapeutic and was one of the first immunotherapies to be approved for cancer treatment. Interferon has established single-agent anti-cancer activity in multiple tumor types, including renal cancer, bladder cancer, and melanoma. Over time, systemic interferon has fallen out of clinical use in oncology, primarily due to its poor tolerability arising from systemic toxicities. However, interferon alpha is a powerful driver of T-cell activation and antigen presentation, making it an ideal combination agent with checkpoint inhibitors. Similarly to EPCAM, it's been shown recently that localized interferon-alpha-2b can be very effective as an anticancer therapy. Specifically, the recently approved gene therapy, adstiladrin, encoding interferon-alpha-2b, achieved a 51% complete response rate in patients with bladder cancer, reaffirming that this potent cytokine can indeed achieve robust antitumor responses in patients. It's also been shown that interferon can potentiate the clinical effects of PD-1 inhibition, including a Merck-sponsored study demonstrating a 60% response rate with Keytruda in combination with interferon alpha-2b in advanced PD-1-naive melanoma. This combination was not further developed, however, due to grade 3 or higher adverse events occurring in approximately 50% of patients. CX801 is designed to harness the proven power of interferon alpha-2b by reducing systemic activity and localizing therapeutic activity to the tumor microenvironment. We initiated our phase one dose escalation study of CX801 in the third quarter of 2024, focused in the advanced metastatic melanoma setting. We've made very good progress to date in the study, and we're currently enrolling the fourth monotherapy dose escalation cohort. Importantly, as of the third dose level, we had already achieved doses that surpass the approved dose of unmasked interferon alpha 2B, styletron. Our translational science program for CS801 is multifaceted and includes systemic and intratumoral analysis of PD biomarkers that will give us insight into molecular performance of the drug candidate, and, we hope, the induction of an inflammatory tumor microenvironment conducive to PD-1 combination therapy. Our goal is to present initial Phase Ia translational data for 801 in the second half of this year. Based on our progress to date, we also anticipate initiation of combination therapy with Keytruda in 2025 under the collaboration and supply agreement we secured with Merck last year. Overall, we believe CX801 is well positioned to demonstrate clinical proof of concept in advanced melanoma where the unmet need remains very high. Longer term, we see CX801 as a foundational combination agent which could potentially address the large population of cancer patients who do not respond to checkpoint inhibitors or who are refractory to immunotherapy. Turning now to our research collaborations, Our partnerships continue to be very important to us in 2024 and remain so in 2025. I'm very pleased to say that in February of this year, we achieved another $5 million milestone payment in our Astellas T-cell engager collaboration as a result of Astellas selecting a collaboration clinical candidate to advance into GLP toxicology studies. We look forward to continued progress with Astellas, as well as strong execution in our discovery programs with Bristol-Myers Squibb, Amgen, Moderna, and Regeneron. Right now, the majority of our partner discovery programs are masked T-cell engagers, an area in which cytomics and our partners continue to see significant potential. Regarding our first partner T-cell engager program entered into the clinic, CX904, we communicated earlier this year a reduction in capital allocation to this program given our overall pipeline priorities, and pending ongoing dialogue with our partner, Amgen, regarding potential next steps. Based on CX904 clinical observations to date and our respective priorities, Cytomix and Amgen have jointly decided not to continue CX904 development. We continue T cell engager discovery work with Amgen. We remain optimistic about the potential of future mass T cell engagers and really look forward to making additional progress on this modality within our partnerships. With that, let me turn the call over to Chris for updates on our finesses.