CytomX Therapeutics, Inc.

Good afternoon, everyone. Thank you for standing by. Welcome to the Cytomics Therapeutics Third Quarter 2025 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 are 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 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 third quarter 2025 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, Citomix's Chief Executive Officer and Chairman. Sean will provide an update on our pipeline and company progress before I cover the financials for the quarter. We will then conclude with a Q&A session. With that, I'll turn the call over to Sean.

Thanks, Chris, and good afternoon, everyone. We're very pleased to be here today to provide an update on our third quarter developments and our strong continued company momentum at Citomix. I'd like to start by welcoming Rachel Lester to the team as Chief Business Officer. Rachel's broad strategic planning and business development experience will be highly valuable as we shape our pipeline and corporate development strategy towards realizing our ambition of building Cytomix to commercial stage. Rachel's a terrific addition to a wonderful team that I'm privileged to work with every day. Our goal at Cytomix is to make innovative medicines for people with cancer that are substantially more effective than currently available treatments. Our most advanced drug candidate, CX2051, is currently focused in colorectal cancer, one of the biggest unmet needs in oncology today, with more than 1.9 million new cases annually worldwide, expected to exceed 3 million by 2040. I'll refer to colorectal cancer as CRC from here on. CRC is also increasing in younger patients and is the second leading cause of cancer death. Five years survival for metastatic CRC is only 13%. At Cytomix, we have used our proprietary ProBody therapeutic platform to attack this problem in a new and different way. The ProBody approach is a masking technology that allows us to hit cancer cells hard and with stealth, sparing normal tissues, opening up therapeutic strategies that were previously impossible. Specifically with CX2051, we have deployed our platform to bring the power of an antibody drug conjugate to the treatment of CRC. ADCs are transforming the treatment of many cancers. There are currently more than a dozen approved in the United States, but thus far ADCs have not broken through in CRC, a notoriously difficult cancer to treat. There's an enormous opportunity here to meaningfully impact patient lives, and access a global multi-billion dollar market. And our ambition at Cytomix is to build an integrated commercial stage organization around this exciting opportunity. CX2051 is a masked ProBody ADC targeting Epcam. This drug candidate has been intentionally designed by selecting the optimal target, tumor type, and cell killing mechanism to deliver potent anti-cancer activity. CX2051 is, we believe, a truly differentiated molecule being the first and only EPCAM directed ADC in development. EPCAM is a very highly and consistently expressed target in CRC. While certain locally administered EPCAM strategies have shown promise in cancer treatment, systemic approaches have consistently failed due to toxicities in normal tissues where EPCAM is also expressed. To solve this problem and realize the potential of EPCAM, CX2051 leverages our masking strategy to reduce normal tissue binding and maximize activity within tumor tissue. The CX2051 payload is a topoisomerase 1 inhibitor, known as CAP59, selected because of the well-established responsiveness of CRC to this mechanism of cell killing, underscored by the widespread use of arenatecan in CRC therapy. Our CX2051 product design strategy was quickly validated with our positive interim phase one data reported in May this year from a highly focused dose escalation study in late stage unselected metastatic CRC. This first look at data from our phase one study demonstrated robust clinical activity and the potential, we believe, for CX2051 to become a new standard of care in this setting. To briefly recap the data, CX2051 demonstrated meaningful tumor reductions, including confirmed objective responses or disease control in nearly every patient, as well as preliminary median progression-free survival of 5.8 months, a potentially substantial improvement over currently available treatments for late-stage CRC that provide only two to three months of benefit. Patients included in this initial data set had a median of four prior lines of therapy, with all patients previously having been treated with Irinotecan. Encouragingly, anti-cancer activity was observed across a wide range of clinical characteristics, including in patients with liver metastases and KRAS mutations. The activity we've seen across this broad late-stage patient population, together with the fact that we don't need to select for EPCAM expression in CRC, suggests that CX2051 could become a pan-CRC drug. CX2051 was generally well tolerated, including a notable absence of safety events such as pancreatitis and liver toxicity that have limited prior EPCAM therapies, strongly suggesting that our masking technology is working as designed. We were encouraged with the hematologic safety profile of CX2051, which could be favorable for future chemotherapy combinations. The most common adverse event in early phase one was diarrhea, a known side effect of TOPL1-based therapies such as Orinotica. We're currently focused on better characterizing and managing gastrointestinal adverse events as part of our ongoing development program. Based on these very promising initial results, we're now well into the expansion phase of the Phase 1 study with our next data update planned for Q1 2026. With that, let's review our progress with CX2051 this quarter as well as next steps. In August, we announced that the CX2051 dose expansion cohorts at the 7.2, 8.6, and 10 mg per gig doses had reached our enrollment goal of approximately 20 patients each. Since August, we've continued enrollment in the dose expansion cohorts, and we now expect total enrollment in the CX2051 phase 1 study to be about 100 patients by our planned data update in the first quarter next year. As we work towards our goal of initiating a potential registrational study for CX2051 monotherapy in late-line CRC, we expect this expanded Phase I patient enrollment will further inform dose selection, including FDA dialogue regarding Project Optimus. Additionally, given the momentum within the program, we expect to initiate a Phase Ib study with the anti-VEGF antibody Bevacizumab in the first quarter of 2026. Bevacizumab is a core component of CRC therapy across multiple lines of treatment, and we anticipate this combination data will unlock broad additional potential. Beyond CRC, we continue to see potential for CX2051 across many other cancers where APCAM is also expressed. Given our compelling initial results in CRC, we're currently assessing additional indications for future development, and we expect to provide an update on non-CRC indications in 2026. Now turning to CX801, our masked interferon alpha 2B program currently being developed in combination with Keytruda in advanced melanoma. The metastatic melanoma landscape continues to evolve rapidly as checkpoint inhibition moves to earlier stage treatment, leaving considerable unmet need in later stage settings. Advances are being made, for example, with cell therapy and oncolytic virus strategies, but new approaches are urgently needed. We're very excited about the potential for CX801 in melanoma as illustrated by the positive initial biomarker data we will present at CITSE this weekend. In designing CX801, we have applied a similarly focused set of design principles as we did with CX2051 by selecting a validated pathway, a potent effector mechanism, and a focused initial clinical development path centered on clear unmet medical need. Interferon Alpha 2B is a well-validated, powerful immune system modulator that has previously been approved for cancer therapy, but that has been limited in use due to poor tolerability. Our masking strategy for CX801 is highly novel and includes masks on both the cytokine domain and an FC masking domain to really minimize activity in the periphery while directing activity towards the tumor microenvironment. Conceptually, what we're aiming for here is to harness the potent ability of interferon-alpha to selectively activate the tumor-immune microenvironment, allowing for synergistic anti-tumor activity in combination with checkpoint inhibition. We treated our first patient in the CX801 Phase I study in September last year, and we've made excellent progress thus far in the clinic. Monotherapy dose escalation has reached the fourth dose level, including multiple dose levels that exceed the approved clinical dose of unmasked interferon alpha 2B. Now, this is important since it already suggests that masking is working as designed. Our CISI presentation this weekend encompasses biomarker data from five melanoma patients treated with monotherapy. CSH01 has been generally well tolerated through the first three dose levels and is inducing robust interferon signaling within the tumor microenvironment. Specifically, our initial data includes gene expression analysis of pre- and post-treatment patient tumor biopsies, demonstrating consistently increased expression of interferon-stimulated genes, evidence of T cell activation, and upregulation of immune checkpoint inhibitors such as checkpoint genes, including PD-1 and PD-L1. We also observed evidence of sustained chemokine elevation in the tumor microenvironment with stable chemokine levels in the blood, suggesting preferential 801 activation in the tumor. Furthermore, CX801 is activating cell populations of both the innate and adaptive immune systems as anticipated and consistent with interferon-alpha's broad mechanism of action. This initial progress with CX801 is exactly what we aimed for in assessing the initial monotherapy performance, and it lays a strong foundation for the potential of the combination with Keytruda, which we initiated in May of this year. We currently expect initial data for the CX801 Keytrude accommodation by the end of 2026, and we look forward to sharing those results. Before handing over to Chris for financials, I'd like to also briefly highlight a second poster presentation we have at CITSE this weekend, introducing a new program at Cytomix, CX908, a masked T-cell engager targeting CDH3, also known as P. cadherin. In addition to our work on masked ADCs and cytokines, we continue to be active in the T-cell engager space, and this preclinical data highlights the power of masking to substantially widen therapeutic window for this modality. We also continue to be active in T-cell engagers and bispecifics in our collaborations, including with Astellas and with Regeneron. With that, let me hand over to Chris.