CytomX Therapeutics, Inc.

Good day, ladies and gentlemen, and welcome to the CytoMix Therapeutics Fourth Quarter 2019 and Full Year Financials Conference Call. At this time, all participants are in a listen-only mode. As a reminder, this call may be recorded. I would now like to introduce your host for today's conference, Christopher Keenan, Vice President of Investor Relations. Chris, you may begin.

Thank you, Lee. Good afternoon, and thank you for joining us. Earlier today, we issued a press release that includes a summary of our recent progress in fourth quarter 2019 and full-year financial results. This press release and a recording of this call can be found under the Investors & News section of our website at sitomx.com. With me today are Sitomx President, Chief Executive Officer and Chairman, Dr. Sean McCarthy, Sitomx Chief Development Officer, Dr. Amy Peterson, and Sitomx Vice President of Finance, Robin Nifsund. 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 that are difficult to predict, and many of which are outside of our control. Important risks and uncertainties are set forth in our most public recent filings with the SEC at SEC.gov, including our Form 10-K file today. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments, or otherwise. I would now like to turn the call over to Sean.

Great, thank you very much, Chris, and good afternoon, everyone. Thanks very much for joining us. It's a pleasure to be here to provide an update on our progress during the fourth quarter and throughout 2019. I'll begin with an overview and some recent highlights across the pipeline, and we'll then turn the call over to Amy to review our lead CX072 and CX2009 programs in more depth. Robin will then review our fourth quarter and fourth year financial update, and I'll wrap up with upcoming 2020 milestones before opening up the call for questions. At Cytomix, we see a major opportunity to more effectively target therapeutic antibodies into diseased tissue, generating new classes of anti-cancer therapies. We believe our unique pro-body therapeutic platform represents a fundamental advance and we are highly focused on the discovery and development of a broad clinical pipeline of novel drug candidates to make a meaningful difference in the treatment of cancer. Our unique science offers the potential for new and highly effective anti-cancer therapies, including potentially best-in-class molecules against validated targets, first-in-class molecules against novel undruggable targets, and new combination therapies. ProBodies are fully recombinant antibody prodrugs comprised of a therapeutic antibody and a mask designed to block the binding of the antibody to its target until the mask is removed. Mask removal is achieved specifically and selectively within cancer tissue by certain disease-associated proteins called proteases. This allows us to localize antibody activity into cancer tissue, decreasing target engagement in normal tissues and broadening or, in fact, even creating a therapeutic window. We have pioneered this new approach that we see as an important evolution of the therapeutic antibody field with broad potential to improve and optimize a range of antibody formats, including cancer immunotherapies, antibody drug conjugates, and T-cell engaging by specific antibodies. This is an exciting time for our company as our pipeline continues to mature, as our partnerships advance, and as our research engine continues to produce innovative new molecules. In total today, we have more than 20 programs at various stages of discovery and development within our proprietary pipeline and in collaboration with our partners. Since our first presentation of clinical data for our platform less than two years ago, we have now generated and presented a wealth of data to support clinical proof of concept for our technology, and our three most advanced programs have all recently progressed into focused phase two clinical studies. We expect to provide several significant data updates throughout 2020. Earlier this week, we announced an important pipeline milestone in our foundational oncology collaboration with Bristol-Myers Squibb. The leading edge of this alliance is the anti-CTLA-4 probody BMS-986249. CTLA-4, the target of ipilimumab, is the prototypical checkpoint target, and blocking this mechanism has proven highly effective both as monotherapy and in combination with PD pathway inhibitors in the broad treatment of patients with melanoma and in many other cancer types. While a very important advance, ipilimumab can cause severe immune-related toxicities, creating a clear opportunity for a probody version of this agent to improve tolerability, increase duration of treatment, and potentially improve activity. BMS and cytomics have previously presented preclinical proof of concept for CTLA-4 probodies at several major research conferences. and BMS has completed enrollment now in the Phase 1 clinical studies with BMS 986249, the results of which we expect to see presented this year. As we announced on Monday, BMS has now initiated a randomized Phase 2 expansion study evaluating the tolerability and activity of BMS 986249 plus the PD-1 inhibitor nivolumab versus nivolumab with or without ipilimumab in metastatic melanoma. The advancement of BMS-986249 into this study has triggered a milestone payment of $10 million to Cytomix from BMS. This is an important study that, if positive, has the potential to place the ipilimumab probody on a registrational path. Moreover, this work is a direct embodiment of exactly what we set out to do with our platform when it was first conceived of, and we are very excited about the potential for cancer patients. Additional recent progress within our foundational BMS alliance includes the initiation of the dose escalation phase of a Phase I-IIa clinical study for a second anti-CTLA-4 probody, BMS 986288, which is based on a modified version of ipilimumab. This second clinical probody program demonstrates BMS commitment to our technology platform as a way to potentially unlock additional value in the CTLA-4 mechanisms. As these CTLA-4 programs progress through clinical development, potential regulatory approval, and commercialization, CytomX is eligible to receive certain milestone payments and royalties. And it's important to note that we also continue to work closely with BMS to initiate new discovery programs under this broad-based alliance. In addition to this progress with BMS, 2019 was a year of many achievements for CytomX within our wholly-owned lead programs. the anti-PDL1 probody CX072 and the anti-CD166 probody drug conjugate CX2009. We also advanced a very unique program in partnership with AbbVie, the CD71 targeting probody drug conjugate CX2029. CX072 is a probody therapeutic directed against the validated immuno-oncology target PDL1. We believe that CX072 has the potential to become a differentiated foundation for combination anti-cancer therapies by increasing tolerability, achieving optimal dosing, and delivering increased anti-cancer activity to improve patient outcomes. We have shown previously that CX072 is active as a monotherapy in multiple tumor types and that the probody has the activity to be expected from a checkpoint inhibitor, providing the first clinical proof of concept for our unique platform. In the fourth quarter, we advanced CX072 into a Phase II clinical trial to further evaluate the activity and tolerability of CX072 plus ipilimumab in patients with relapsed or refractory melanoma. Building on our encouraging Phase I-II data, this trial is evaluating CX072 in combination with the full labeled monotherapy dose and schedule of IPI with a goal of driving meaningful anti-cancer activity in this difficult-to-treat patient population. We believe this combination has the potential to become a best-in-class regimen not only for melanoma but potentially other cancer types. Initial data is anticipated from Stage 1 of the Phase 2 study during 2020. Now turning to our second wholly-owned drug candidate, CX2009, a pro-body drug conjugate designed to target the previously undruggable target CD166. CD166 is a unique tumor antigen that is expressed at high levels on most solid tumors, but that's also present on most normal tissues, ruling it out as a target for a typical antibody drug conjugate. We're exploring the ability of a pro-body drug conjugate to unlock the potential of this target by focusing anti-cancer activity to tumor tissue and not normal cells. Based on encouraging phase one clinical data we reported last year, We initiated in Q4 2019 a Phase 2 expansion study of CX2009 monotherapy in patients with hormone receptor-positive HER2-negative breast cancer. This study was initiated in the fourth quarter. Amy will provide more context on this program in a few moments. Now, returning briefly to our collaborations, and specifically within our AbbVie Alliance, We continue to enroll patients in the dose escalation and refinement phase of the Proclaim CX2029 Phase 1-2 study, evaluating monotherapy CX2029, a first-in-class pro-body drug conjugate targeting CD71. And this is in patients with solid tumors. This is a very novel and ambitious program. CD71's biological role is to function as what we call a professional internalizer as it moves iron from the extracellular space to intracellular compartments CD71 is, in fact, the gold standard internalizer used to assess ADC activity in vitro. Now, while an attractive target for payload delivery to cancer cells, it has remained undruggable, and, in fact, we have shown that an ADC to CD71 is lethally toxic in preclinical models. In partnership with AbbVie, we've created a pro-body drug conjugate, CX2029, in which a masked antibody to CD71 is conjugated to the cytotoxic payload, MMAE. Dose escalation in the clinic was initiated in mid-2018 and is ongoing as we progress towards the selection of a recommended Phase II dose. We anticipate the presentation of initial data from this exploratory clinical work in 2020. Should the study progress to cohort expansions at the recommended phase 2 dose, we anticipate the presentation of proof of concept data in 2021. For this program, CytomX has responsibility to advance it through initial proof of concept whereupon, if successful, the program will transition to AbbVie for registrational studies and ultimate commercialization. CytomX retains profit split and certain co-commercialization rights for this asset. Before handing the call over to Amy for more detail on our lead programs, I'd like to spend a few moments on two earlier stage programs that are emerging as a potential second wave of IND candidates in our pipeline. Starting with our collaboration with Immunogen, from whom in Q4 we obtained exclusive worldwide development and commercial rights to an EPCAM-targeting pro-body drug conjugate. This program was developed utilizing cytomix pro-body technology and Immunogen's drug conjugate technology under rose from our previous strategic collaboration between the parties. At the 2018 European Antibody Congress and also at AACR 2019, Immunogen presented encouraging preclinical data demonstrating that an EPCAM pro-body drug conjugate has potent activity in in vivo efficacy models as well as improved tolerability and exposure compared to an unmasked EPCAM antibody drug conjugate. CytomX now has full development control and commercial rights for this promising program. Another promising preclinical program is our T-cell bispecific probody targeting EGFR and CD3. This program is partnered with Amgen with CytomX retaining development control and certain commercial rights. We're really excited about the prospects for the T-cell bispecific application of probodies to enable solid tumor targeting of this modality. Solid tumor targeting with unmasked T-cell bispecifics has been very challenging for the field due to narrow or non-existent therapeutic window. We anticipate advancing a lead clinical candidate for this program during 2020. So now let me turn the call over to Amy.