CytomX Therapeutics, Inc.

Today's call is being recorded. I want to hand the call over to your host for today, Chris Ogden, Citomex's Chief Financial Officer. Please go ahead.

Thank you. Good afternoon, and thank you for joining us. Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements. Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and 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 obligations to update any forward-looking statements, 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 second quarter 2024 financial results and highlights recent progress at Cytomix. 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 and 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 the company's progress and pipeline before I cover the financials for the quarter and we open up the call for Q&A. With that, I'll turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. We're delighted today to provide an update on our recent progress, which includes the continued development of CX904 and Phase I dose escalation, and clinical study initiation for our newest polio programs, CX2051 and CX801. Cytomics ProBody therapeutic platform encompasses more than a decade of innovation in antibody masking and conditional activation, and it's designed to enable the clinical development of anti-cancer modalities directed against targets that would otherwise be undruggable or significantly limited by therapeutic window. Cytomix currently has 15 active programs across our internal and partnered research and development activities, including three clinical stage probody therapeutics designed to address large patient populations. Based on our continued strong execution, Cytomix is currently very well positioned to build value and make a meaningful difference for cancer patients. Let me dive right in and start with CX904, our masked probody T-cell engager targeting EGFR. Last quarter, we announced positive initial phase 1A clinical data for CX904, which was an important first step in the clinical development of this program. EGFR is a very attractive target given its broad expression across multiple tumor types and also its high level of clinical and commercial validation with multiple approved small molecule and antibody therapies. CX904 constitutes a novel therapeutic strategy that leverages EGFR as an address to direct T-cell mediated killing to tumor cells via CD3 binding. EGFR-CD3 has previously been considered an attractive but undruggable target combination because of the widespread expression of EGFR in normal tissues. In the absence of masking, we would expect an EGFR CD3 bispecific to be severely toxic and undevelopable, likely with high rates of severe skin rash and cytokine release syndrome. By using the Cytomix ProBody platform to mask both EGFR and CD3 binding domains, however, we are opening a therapeutic window for this target combination, and we've been very encouraged by our clinical findings reported to date. In May, we were delighted to release positive initial Phase Ia dose escalation results for CX904, achieving our early Phase I goals. In this first stage of release for CX904, based on an April 16, 2024 data cutoff, we reported on 35 heavily pretreated patients with a median of four prior lines of therapy. The initial safety profile of CX904 looks very encouraging, specifically in step dosing cohorts up to a target dose of 10 milligrams, we did not see any cytokine release syndrome. And across all 35 patients treated with non-step and step dosing schedules, we saw only one grade three rash. In common with certain other T-cell engagers, we observed some musculoskeletal events that were manageable, in part with totalizumab prophylaxis. These early findings show that masking is effectively blunting CRS and other toxicities that would be expected for the corresponding unmasked EGFR CD3 T-cell engager. In the context of this emerging favorable safety profile, we also reported encouraging early signs of single agent anti-cancer activity for CX904. In 26 efficacy-evaluable patients treated at doses above 750 micrograms, we observed eight measurable tumor reductions, including confirmed partial responses in two of six efficacy-evaluable patients with pancreatic ductal adenocarcinoma. These initial findings are particularly encouraging because pancreatic cancer has not been shown historically to respond to immunotherapy or to EGFR antibodies. However, EGFR is expressed in more than 90% of pancreatic cancer patients, and our data suggests that CD3-mediated T cell killing via EGFR binding can be effective in this cancer type. Moreover, there's also increasing evidence from others in the field that pancreatic cancer can be immune-competent and mount a T cell response. This is both based on progress with neoantigen vaccines and recent data from ASCO 2024 for a Claudine 18 CD3 T-cell engager. In our view, our early CX904 results in pancreatic cancer highlight exactly why CX904 was designed, and they illustrate the power of antibody masking, opening a therapeutic window for an undruggable T-cell engager target and bringing a unique pharmacology to a cancer type of high incidence and significant unmet medical need. Indeed, pancreatic ductal adenocarcinoma is currently the third leading cause of cancer death in the US, and second-line treatments have response rates of less than 10% and only two to three months of progression pre-survival, leaving a major need for new therapies. We are now accelerating enrollment in pancreatic cancer to further explore this signal, and in parallel, We're prioritizing enrollment in head and neck and non-small cell lung cancers where we had not previously enrolled a meaningful number of patients in the initial dose escalation. We continue to enroll in multiple dose levels to further inform the selection of a recommended phase 1B dose or potentially doses. Our principal goal for the second half of the year is to generate data to enable strategic dialogue with our global development partner, Amgen, regarding potential initiation of CX904 Phase 1B expansions in select EGFR-expressing tumor types. And we expect to provide a CX904 program update by the end of 2024. Turning now to CX2051, our wholly-owned, first-in-class, EPCAM-directed ProBody ADC. Epcam or epithelial cell adhesion molecule is a high potential oncology target with high cell surface expression in many solid tumor types, and that has been implicated in many aspects of cancer biology. Anti-Epcam therapeutic strategies have previously been translated into clinical activity, but to date, clinical success has been limited to local administration because Epcam is present in most normal epithelial tissues. Efforts to generate systemically administered antiepcam therapies have not been successful to date due to toxicities in epithelial tissues, including in the gastrointestinal tract. Our innovative drug candidate, CX2051, is a masked ADC tailored to optimize the therapeutic window for epcam-expressing epithelial cancers by masking the antibody to reduce binding in normal tissues but allowing activation in tumor tissue. We have armed the antibody with a cytotoxic payload based on cancer thesin, a topoisomerase I inhibitor, which is a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets, leading in recent years to dramatic advances for patients. CX2051 has demonstrated a wide predicted therapeutic index in multiple preclinical models, including colorectal cancer. And like EGFR discussed previously in the context of CX904, CX2051 could also potentially address large patient populations because EPCAM is highly expressed across many indications, including colorectal, lung, gastric, endometrial, pancreatic, and ovarian cancers. In April of this year, we treated our first patient in our phase one dose escalation study of CX2051. and we're now already enrolling into our third patient cohort. At this stage, enrollment is principally focused in colorectal cancer, where EPCAM expression is particularly high, and we're really looking forward to seeing what CX2051 could do for patients. And based on this progress, we remain on track to share initial data for CX2051 in the first half of 2025. Now turning to our third clinical program, CX801, which is our dually masked interferon alpha 2B pro-body cytokines. We're excited about CX801 as a foundational immuno-oncology agent with potential for activity across multiple tumor types, including those that are insensitive to current immuno-oncology therapies. Interferon is a compelling and differentiated opportunity for a masked cytokine for two key reasons. First, the biology of interferon is unique in that it has been shown to directly kill tumor cells, and interferon also increases adjutant presentation to activate T cells, making it an ideal mechanism for combination with checkpoint inhibition. Secondly, as a previously approved cancer therapy, interferon has a high level of prior clinical validation, including as both a localized therapy and systemically when combined with PD-1. The use of interferon at its broader development as a systemic therapy has been limited, however, due to systemic toxicities. Our preclinical data for CX801, most recently presented at CITSE 2023, demonstrates synergy for our masked interferon alpha with PD-1 inhibition, both in terms of anti-tumor activity and activation of the tumor inflammatory microenvironment. Moreover, we've also shown that systemic activity of our masked interferon is significantly reduced And overall tolerability is markedly improved compared to the unmasked cytokine in animal models. Our phase one dose escalation study is now open and our first clinical site has been activated. This study will evaluate safety and signs of clinical activity for CX801 as a monotherapy and in combination with Keytruda under a collaboration and supply agreement that we recently executed with Merck. We anticipate initial data for CS801 in the second half of 2025. On the collaboration front, we continue to have more than 10 ongoing research programs with our partners, which include Amgen, Astellas, BMS, Moderna, and Regeneron, with the majority of our partnered research currently focused in masked T cell engagers. To date in 2024, we've already achieved $10 million in preclinical milestones, through our collaboration with Astellas. And across our collaborations, we have the potential to earn additional milestones over the next 12 to 18 months and beyond. Cytomix also retains significant U.S. commercial rights in certain partnerships, including with Astellas for a select number of programs and with Amgen as part of our global development alliance on CX904. And partnering continues to be a cornerstone of our business strategy. Before handing over to Chris to cover financials, let me first congratulate him on his promotion to Chief Financial Officer. We're really excited to have Chris's cross-functional leadership and strategic finance experience in this key role. My colleagues and I look forward to continuing to partner with Chris as we build value in Citomics over the near and long term. With that, let me hand over to Chris to provide an update on our finances.