CytomX Therapeutics, Inc.

listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during a session, you need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I now have to hand the conference over to your host for today, Ms. Stephanie Asher with Investor Relations. Ma'am, please go ahead.

Good afternoon, and thank you for joining us on today's call. With me today are Cytomix's President, Chief Executive Officer and Chairman, Dr. Sean McCarthy, Chief Development Officer, Amy Peterson, and Chief Financial Officer, Carlos Campoy. Earlier today, Cytomix issued a press release that includes a summary of our recent progress and third quarter 2020 financial results. We encourage everyone to read today's press release as well as associated materials which have been filed with the SEC. In addition, the press release and a recording of this call can be found under the Investors and News section of our website at sitomics.com. During today's call, we will be making forward-looking statements. Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks, including the uncertainty surrounding the COVID-19 pandemic, 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. including our Form 10-Q filed today. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. I would like to turn the call now over to Sean.

Thank you, Stephanie, and good afternoon, everyone. Thanks for joining us today. I'd like to open today's call with a brief update on our pipeline progress this past quarter. Then I'll hand the call over to Amy to provide context on clinical data we've presented to date. and where we're heading with our most advanced programs. Finally, Carlos will round out the call with our financial results for the quarter. I'd like to start with a few words about our overarching strategy at Cytomix. We are defining a new class of conditionally activated antibody therapeutics with broad potential for bringing new approaches to the treatment of cancer. We aim to leverage our differentiated platform to discover, develop, and commercialize a portfolio of new cancer therapies to make a difference in the treatment of many tumor types. Throughout 2020, and despite the ongoing pandemic, we have continued to make steady progress towards advancing our pipeline and building our company. We have five product candidates in clinical development, and together with our partners, we now have eight active Phase II evaluations in seven different tumor types, providing multiple opportunities for potential advancement towards registrational studies as we build our pipeline and company for the long term. Our pioneering work on conditional antibody activation is aimed at changing the way we think about monoclonal antibody treatments for cancer by developing what we call probodies, a novel class of therapeutic antibodies. The advantage of our probody approach is that these unique antibody therapies are designed to bind to targets in tumor tissue and minimize binding in normal tissue. Why is this important? Well, traditionally, therapeutic antibody targets have been chosen based on their selective presence in disease tissue. This selective expression is usually critical because conventional antibodies will bind to their targets wherever they are present, even on normal tissues. Unwanted normal tissue expression of targets can lead to undesired toxicities, particularly with potent antibody formats like antibody drug conjugates and T-cell engaging bispecifics. This has substantially limited the available universe of tumor targets for these increasingly important modalities. Cytomix ProBody Therapeutics are designed to reduce target binding in healthy tissue by masking the target recognition site of the antibody until it reaches tumor tissue where the mask is removed in the tumor microenvironment, allowing the antibody to bind to its target and elicit its anti-cancer effect. In normal tissue, the mask is intended to remain intact and prevent binding to the target. This unique and elegant approach has shown potential to create a therapeutic window where previously there was none, thereby opening up the therapeutic landscape to new, abundantly expressed tumor antigens, for example, CD166, CD71, and Epcam. Fundamentally, we believe our ProBody technology has the potential to unlock many previously undruggable targets, leading to new first-in-class cancer treatments. At Cytomics, we have built a robust scientific foundation for our ProBody platform and a fully integrated research and development engine. We believe we have established clinical proof of concept for our platform against multiple cancer targets. We have demonstrated single-agent anti-cancer activity in each of the three programs for which efficacy data has been presented publicly, and each of our clinical programs have shown encouraging tolerability profiles. Our translational data from tumor biopsies support mechanistic performance of the platform. We have established robust and proprietary manufacturing processes for probodies. that apply to multiple formats including drug conjugates and T-cell engaging bispecific pro-bodies. And we are well positioned to build a late stage development company around our emerging platform driven pipeline that I will now briefly review. Starting with CX2009, our wholly owned pro-body drug conjugate or PDC targeting CD166, a cell surface protein that is highly expressed in many cancer types. We've seen a lot of excitement about the antibody drug conjugate field this year with developments such as the approval of Travaldi for the treatment of breast cancer, which of course drove the acquisition of Immunomedics by Gilead. Antibody drug conjugates have now been repeatedly validated and the search is on for new targets for the next generation of ADCs. Although highly expressed in many tumors, CD166 is not a great ADC target due to its expression on many healthy cells. but it's exactly the kind of target that we have the potential to address with our platform. CX2009 has been designed to unlock CD166 targeting using the cytotoxic warhead DM4. Our previously reported Phase I clinical evaluation of CX2009 in solid tumors has shown evidence of single-agent anti-cancer activity in HER2 non-amplified breast cancer in addition to ovarian cancer, head and neck cancer, and also lung cancer. Our current clinical focus for CX2009 is on breast cancer. CD166 is highly expressed in more than 80% of hormone receptor positive HER2 non-amplified breast cancers and in approximately 50% of patients with triple negative breast cancers. During Q4, we will be initiating a phase two study of CX2009 in hormone receptor positive HER2 non-amplified breast cancer and triple negative breast cancer to further define the clinical activity of this unique agent. Amy will walk you through the design, goals, and timing of this study in a few moments. Turning now to CX2029, a pro-body drug conjugate targeting CD71 that we are developing in collaboration with our partner, AbbVie. CD71 is also known as the transferrin receptor, is involved in iron metabolism, and is overexpressed in a variety of cancers. Its biologic function involves very rapid internalization from the cell surface, And this property would, in theory, make CD71 an attractive target for an ADC. However, CD71 is also expressed in healthy tissues, especially dividing tissues where iron transport is necessary to cell division. And even low doses of an ADC to CD71 are lethal in animal studies. CD71 has therefore been a high potential but elusive target with a non-viable therapeutic index. we have explored the ability of our platform to open a therapeutic window for a CD71-targeted pro-body drug conjugate, potentially creating a novel first-in-class anti-cancer approach. Our first clinical evaluation of CX2029 presented at ASCO 2020 realized our objective of achieving therapeutic levels of a CD71-targeting drug conjugate in cancer patients and demonstrated encouraging single-agent anti-cancer activity. This morning we were pleased to announce the treatment of the first patient in the Phase II expansion stage of our evaluation of this unique agent. Amy will recap our Phase I findings for CX2029 and some additional details on the expansions in a few moments. I would like to move now to our anti-CTLA-4 program, where we have made important progress in collaboration with Bristol-Myers Squibb, working to develop potentially safer and more effective versions of ipilimumab. Having established a key role in the treatment of melanoma, anti-CTLA-4 regimens are expected to become increasingly important therapies across multiple solid tumor indications. And while the blockade of CTLA-4 has been shown to augment T-cell activation, proliferation, and anti-cancer activity, this often results in high levels of systemic immune-related toxicities that can lead to the reduction in therapeutic dosing or treatment discontinuation. Our ongoing work with BMS is aimed at decreasing the systemic side effects of anti-CTLA-4 therapy while maintaining anti-cancer activity. BMS 986249 is a pro-body version of ipilimumab that we have developed together in our alliance and which has shown an attractive tolerability profile as both monotherapy and in combination with nivolumab in phase one studies in patients with advanced cancers. And these data were presented by BMS at ASCO earlier this year. BMS is now conducting a randomized controlled study evaluating the tolerability and activity of BMS 986249 in combination with NEVO compared to NEVO plus IPI in patients with previously untreated metastatic melanoma. This study holds the potential to demonstrate the ability of our pro-body masking technology to improve tolerability, increase duration of treatment, and enhance patient outcomes with this important immunotherapy. BMS 986288 is also being advanced in this partnership, and this is a probody of a non-fucosylated version of ipilimumab. This program is designed to broaden the therapeutic window for a more potent version of IPI. BMS is continuing to enroll patients in Phase I dose escalation of BMS 986288 in patients with select advanced solid tumors. We look forward to seeing additional progress from BMS on these important anti-CTLA-4 probody programs in 2021 and beyond. In terms of our preclinical pipeline, we continued during Q3 to advance CX904, our T-cell engaging bispecific probody, targeting EGFR and CD3, and partnered with Amgen towards IND-enabling studies with a filing expected in 2021. In addition to our work with Amgen, we also continue bispecific probody drug discovery activities as part of our strategic collaboration with Astellas, our second pharma partner in this exciting area. The overarching goal of our work on bispecific T-cell engagers is to use masking and conditional activation to broaden the therapeutic window for solid tumor treatment with this emerging class of antibody therapeutics. Finally, I would like to highlight our ongoing preclinical work on another undruggable ADC target, EPCAM, and our EPCAM targeting pro-body drug conjugate CX2043. EPCAM, or epithelial cell adhesion molecule, also known as TROP1, is expressed in multiple cancers. However, it has proven to be very challenging to drug since, as the name suggests, the target is present on the majority of normal epithelial tissues. Previous attempts to drug EPCAM with systemic therapies have resulted, not surprisingly, in significant dose-limiting toxicities. It's encouraging, however, that at least one locally delivered therapy, recombinant toxin fusion, has demonstrated clinical activity in bladder cancer suggesting that targeting EPCAM could have even broader potential if we use our conditional activation approach to enable systemic administration. We're advancing CX2043, utilizing our pro-body technology and immunogens drug conjugate technology, and specifically the next-generation metanzine warhead, DM21, which is more potent than earlier generations of this payload chemistry. At the recent EORTC triple meeting, we presented updated preclinical data showing potent anti-cancer activity for CX2043 and significantly improved preclinical tolerability of the probody relative to the underlying ADC. We're now advancing this PDC candidate towards IND enabling studies and a potential IND filing in 2021, continuing the theme of using our platform to drug the undruggable. Now I'd like to hand the call over to Amy.