CytomX Therapeutics, Inc.

Good morning, everyone, and thank you for standing by. Welcome to the CitumX Therapeutics CX2051 Phase 1 Interim Clinical Data 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, CitumX's Chief Financial Officer. Please go ahead.

Thank you. Good morning, and thank you for joining us. Before we begin, I would like to remind everyone that during this call we were 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 filing 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 today, we issued a press release that includes a summary of our first quarter 2025 financial results and highlights recent progress at Cytomix. Additionally, this morning, we are excited to announce both positive interim phase one data for CX2051 and advanced colorectal cancer, as well as a $100 million financing with a leading group of healthcare investors. The focus of our call today will be the phase one data for CX2051. For details on the company's financial results and pipeline updates, we encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC. Additionally, the press releases A 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 are Dr. Sean McCarthy, Sytomix's Chief Executive Officer and Chairman, and Dr. Wayne Chu, Sytomix's Chief Medical Officer. Sean will provide introductory remarks regarding CX2051 design and clinical strategy. Wayne will then walk through the CX2051 phase one interim clinical results and next steps for the program. We will then wrap up with concluding remarks before we move to Q&A. With that, I'll turn the call over to Sean for opening remarks.

Thanks, Chris. It's a real pleasure to be here today to share our exciting update on CX2051. This is a transformational moment for cytomics. We believe we've really broken new ground in colorectal cancer with this novel antibody drug conjugate that has been uniquely enabled by the Cytomix ProBody therapeutic platform. The results we're sharing today represent the integration of years of learning about our technology and importantly, how to best direct it to the maximum benefit for cancer patients. Before getting to CX2051, we're of course delighted to have also announced today As Chris just mentioned, $100 billion financing with a top tier syndicate of healthcare specialist investors. Their belief in cytomics truly underscores the importance of what we have achieved with 2051 and the potential of this product. This financing positions us extremely well to continue our determined and focused execution towards bringing transformational cancer therapies to patients. Turning now to CX2051. Colorectal cancer remains one of the biggest unmet needs in oncology today with approximately 1.9 million patients diagnosed each year on a global basis. And this disease burden is expected to increase considerably over the next couple of decades to more than 3 million and is currently the second leading cause of cancer death worldwide. This is a significant global health problem and despite many advances across many other cancer types in recent years, colorectal cancer has not seen very much impact at all from innovation over that period of time, resulting in a current five-year survival rate in metastatic colorectal cancer of only 13%. This dire situation is unfortunately really underscored by just how inadequate options are for the treatment of late stage CRC in the third and fourth line settings or later. Current standard of care therapies have poor response rates and limited survival benefit. There is enormous room for improvement. At Phytomics, we've taken this challenge head-on by designing a colorectal cancer-targeting antibody drug conjugate, CX2051. Antibody drug conjugates are transforming cancer care, making a really big impact in the treatment of many solid tumors, accruing benefit for many, many thousands of patients around the world. This class of differentiated targeted oncology therapeutics continues to build very substantial value. ATCs have yet to break through, however, in colorectal cancer. Our goal is to transform colorectal cancer care with CX2051, a first-in-class antibody drug conjugate that we have carefully designed to target a protein called EPCAM that is present at high levels in CRC. We've been highly focused on running a phase one clinical trial over the past year, entirely focused in CRC. This is a very tough cancer to treat, but we really wanted to do the killer experiment to see what CX2051 can do for these patients. Today, we are very excited to share positive phase one clinical data for CX2051. In our first 12 months in the clinic, we have demonstrated robust anti-cancer activity for CX2051 in metastatic CRC with a 28% confirmed overall response rate, a 94% disease control rate, and 5.8 months of preliminary progression-free survival. This strong anti-cancer activity offers the potential to position CX2051 as a new standard of care in late-line colorectal cancer. Regarding safety, CX2051 has shown a favorable safety profile to date, including no dose-limiting toxicities during dose escalation. We believe the safety profile we have seen to date in late-line CRC is strongly supportive of developing 2051 in earlier lines of therapy, including in combinations. Furthermore, our masking strategy has succeeded in avoiding classic EPCAM toxicities that have impeded the successful development of drugs against this target before. Additionally, we can say with some confidence that EPCAM has the potential to be a pan-CRC target since we have validated that the target is indeed present at high levels in all patients we have tested. Taken together, we see this as a very strong start to the CX2051 development program. Before I hand over to Wayne to walk through our exciting results, I'd like to make a few comments on the molecular design of CX2051 and our phase one clinical strategy. First of all, a few words on the target. EPCAM or epithelial cell adhesion molecule, we really believe is an ideal CRC target enabled by the Cytomix ProBody platform. EPCAM has high and uniform expression across colorectal cancer. And you can see here an immunohistochemistry image of a patient actually in our phase one clinical trial showing just how high EPCAM expression is in this cancer type. In fact, this patient has a maximum score, a score of 300 by this assay. Now, the challenge with EPCAM in the past has been its expression in normal tissues. And this is limited drug development due to toxicities that have emerged, including acute pancreatitis. So we have developed and designed CX2051 as a first-in-class EPCAM-targeting antibody drug conjugate. we really believe with this molecule we have the right target the right payload and the right tumor type and it's really how these three design elements come together that underscore the progress that we are sharing today with this really exciting program so 2051 is based on a high affinity anti-epcam monoclonal antibody that we have masked using our proprietary probody therapeutic platform, and the masking is designed to reduce epcam binding in normal tissues. The masks, however, are removed specifically and selectively within tumor tissue by tumor-associated proteases, resulting in anti-cancer activity within the tumor. We have empowered this mask antibody with the topoisomerase 1 inhibitor, CAMP59. which is a cytotoxic payload designed to kill cancer cells. The payload is linked to the antibody through a cleavable peptide linker optimized for what we call bystander effect, which is the ability of the drug to kill neighboring cancer cells. The drug antibody ratio for CX2051 is eight. Moving now to our clinical strategy, we commenced this phase one study just about one year ago, And we really have made terrific progress. We began dose escalation at the dose of 2.4 milligrams per kilogram administered every three weeks. And we have escalated through seven dose levels to date. The focus of today's update will be the first five dose levels where we have 25 safety-evaluable patients across the doses of 2.4 to 10 milligrams per kilogram. We have 23 safety-evaluable patients at the doses of 7.2, 8.6, and 10 milligrams per kilogram. And these three doses, we have already started to expand based on the exciting results we have already seen with 2051. We have 18 efficacy-evaluable patients across these three dose levels. And we do anticipate once these expansions are completed towards the end of this year, that our recommended phase two doses will come from among this broad dose range. I should also say that in this clinical study, every patient enrolled was a metastatic CRC patient. We didn't enroll any patients with any other tumor types. So this has been a highly focused study. And we did not select for EPCAM expression because of our expectation that the target would be highly expressed in all patients enrolled. And Wayne will update you on that in just a moment. So it's been a really strong year of execution, and I'll now hand over to Wayne to talk through our findings so far. Thanks, Sean.