CytomX Therapeutics, Inc.

Today, ladies and gentlemen, welcome to the Sciatonic Therapeutics Second Quarter 2020 Financial Conference Call. At this time, all participants are in listen-only mode. As a reminder, this call may be recorded. I will now introduce your host for today's conference call, Christopher Keenan, Vice President of Investor Relations. Chris, please go ahead.

Thank you, Valerie. Good afternoon, and thank you for joining us. Earlier today, we issued a press release that includes a summary of our recent progress and second quarter 2020 financial results. This press release and a recording of this call can be found under the Investors in News section of our website at sitomx.com. With me today are Sitomx President, Chief Executive Officer and Chairman, Dr. Sean McCarthy, and Sitomx Chief Financial Officer, Carlos Campoy. 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 over to Sean.

Great. Thank you, Chris, and good afternoon, everyone. Thanks for joining us. It's a pleasure to be here to provide an update on our progress during the second quarter of 2020. I'll begin today's call with a brief overview of our recent achievements, including our presentations at ASCO 2020 and the next steps for our lead clinical programs. I'll also comment briefly on our preclinical discovery progress, and we'll then turn the call over to Carlos to review Our second quarter financial results. We'll then open the call up for questions. At Cytomix, we are pioneering a novel class of therapeutic antibodies designed to target cancer tissue, allowing for the development of an innovative pipeline of novel cancer therapies. Over the past decade, we have built a strong scientific foundation for our novel technology, which has the potential to change the way we think about antibody therapeutics. Our technology called the ProBody platform is designed to direct an antibody's anti-cancer activity towards tumor tissue and away from normal healthy tissue, allowing us to attack new classes of targets that have previously been considered inaccessible to conventional antibody approaches. Our primary strategy is to use our technology to make first-in-class anti-cancer drugs for the potential treatment of a wide range of cancers by targeting these previously undruggable targets. We're also utilizing our technology to discover and develop potentially best-in-class immunotherapies. We have four clinical stage programs advancing towards or already in Phase II clinical studies. These are CX2029, a pro-body drug conjugate targeting CD71 that we are advancing into Phase II studies in multiple tumor types, including head and back and non-small cell lung cancers, CX2009, a pro-body drug conjugate targeting CD166 that we are advancing into Phase II studies in breast cancer, CX072, a pro-body therapeutic targeting PD-L1 that we are advancing in combination with CX2009 in triple negative breast cancer, and BMS986249, an anti-CTLA-4 pro-body therapeutic currently in a randomized Phase II study in melanoma, which is being run by our partner, Bristol-Myers Squibb. In parallel with building and advancing our broad clinical pipeline, we have formed many strong partnerships with leading biopharmaceutical companies, including BMS, Amgen, AbbVie, and Astellas, all of whom are advancing novel product candidates utilizing our technology. We have integrated research and development capabilities, and our ambition is to ultimately commercialize our products ourselves and with our partners as we build a long-term, sustainable, values-based organization. I'd like to spend some time laying out the high-level strategy for each of our four clinical assets and how the data we presented at ASCO 2020 has pointed the way to our Phase 2 programs as we evaluate the full potential of each product candidate in further detail. Let's begin with CX2029, a pro-body drug conjugate targeting CD71. CD71 is also known as the transferrin receptor. A protein that is highly expressed on many cancer types, but due to its involvement in iron metabolism, has been traditionally thought of as undruggable. We know, in fact, that antibody drug conjugates targeting CD71 are not developable due to lethal toxicity at low doses in animal models. However, given the high potential of CD71 as a novel anti-cancer target, we have investigated whether our probody technology can allow us to achieve therapeutic levels of an anti-CD71 drug conjugate in cancer patients, potentially unlocking this first-in-class approach across a range of different cancer types. Our phase one results presented at ASCO 2020 show for the first time that by employing our technology, CD71 can indeed be targeted successfully in patients with advanced cancers. Our dose escalation study achieved therapeutic levels of CX2029, and objective confirmed single agent responses were observed in patients with squamous non-small cell lung cancer and with head and neck squamous cell cancer. The principal dose limiting toxicity seen in this phase one study was anemia, which was managed with red blood cell transfusions. These promising phase one results for CX2029 are particularly important because targeting CD71 is likely the most rigorous test we have conducted to date to assess our probody technology. and these results we believe underscore the broad potential of our platform. These phase one data also resulted in Cytomix earning a $40 million milestone payment from AbbVie, our partner for this program, which we received in the second quarter. Cytomix continues to lead clinical development in this global co-development and commercialization alliance. We expect to initiate phase two expansion cohorts of CX2029 at the dose of three milligrams per kilogram every three weeks in head and neck squamous cell carcinoma, squamous non-small cell lung cancer, squamous esophageal carcinoma, and DLBCL in the second half of 2020, with potential for the first data readouts in late 2021. Turning now to CX2009, our wholly owned drug candidate targeting the previously undruggable target CD166. CD166 is widely expressed across multiple tumor types, and we believe has broad potential as a novel anti-cancer target. However, like CD71, CD166 is present on many normal tissues, ruling it out as a target for conventional therapeutic antibody approaches. To unlock the potential in this novel pathway, we have designed CX2009, a CD166 targeting probody conjugated to the well-characterized cytotoxic payload, DM4. Similar to our experience with CX2029 that we just discussed, our phase one dose escalation study with CX2009 in patients with selected advanced solid tumors achieved therapeutic exposures of the drug candidate. And we observed evidence of single agent fatty cancer activity in several tumor types, including breast cancer and ovarian cancer. CX2009 was generally well tolerated. The principal dose limiting toxicities were ocular. Anticipated and well-documented sequela of DM4 conjugates and that we intend to manage with ocular prophylaxis in ongoing studies. With phase one now complete for this asset, our program strategy is presently focused on breast cancer. Of note, CD166 expression is high in greater than 80% of hormone receptor positive HER2 negative breast cancer patients and in approximately 50% of patients with triple negative breast cancer. In our phase one study, we observed durable clinical activity in both of these breast cancer populations, despite these patients being very heavily pretreated. Significant unmet medical need remains in breast cancer, and accordingly, we previously announced the initiation of a phase two expansion study of CX2009 in hormone receptor positive HER2 negative breast cancer. We did elect to pause this study in March 2020 due to the impact of the COVID pandemic. However, our team has used the intervening period resulting from the pandemic to further refine the study with a focus on patient enrollment criteria, including prior treatment regimens. This revised trial will continue to evaluate CX2009 monotherapy at seven milligrams per kilogram, administered every three weeks, and we aim to enroll at least 40 patients. We expect to reinitiate the study during the second half of 2020. We're also preparing to initiate phase two expansion studies of CX2009 in triple negative breast cancer, both as monotherapy and in combination with our wholly-owned anti-PD-L1 probody, CX072. We've previously reported single-agent activity for CX072 in triple-negative breast cancer and have also presented our preclinical data that provide experimental rationale for combination treatment of CX2009 with PD inhibition consistent with the well-established benefits of combining chemotherapy and checkpoint inhibition. We're excited to also get this work underway in the second half of this year. These phase two studies of CX2009 in hormone receptor positive and triple negative breast cancers are important next steps in our further evaluation of the potential of this novel first in class drug candidate. And we are working towards initial data by the end of 2021. Moving on now to our PD-L1 inhibitor CX072 in further detail. Updated data from our Phase 1-2 trial of CX072 from multiple expansion cohorts continue to show durable anti-tumor activity in patients with IO-sensitive tumors such as triple negative breast cancer, anal squamous cell carcinoma, cutaneous squamous cell carcinoma, and tumors with high mutational burden. This data was presented at ASCO 2020. I'd like to spend a few moments here highlighting the high tumor mutational burden cohort for CX072 which is illustrative of the unique and potentially differentiated clinical profile of this asset. Fourteen patients with various advanced tumor types with high TMB were treated with CX072 at 10 mg per kg. Of 10 efficacy-evaluable patients, three confirmed partial responses and one complete response were observed. The partial responses were in colorectal cutaneous squamous cell carcinoma and neuroendocrine carcinoma. And the complete response was in a patient with anal squamous cell carcinoma. CXO72 was well tolerated with only 2% grade 3 or higher immune-related adverse events. These data are particularly of note in view of Merck's approval in mid-June this year of Keytruda in solid tumors with high TMB. As we now conclude our first clinical explorations of CXO72, which is the first pro-body therapeutic to be evaluated in humans, We're very encouraged that our platform is functioning as designed and these findings provide rationale for differentiation of CX072 from other PD inhibitors and support combination strategies with CX2009 and other anti-cancer agents. Turning now to another exciting application of our technology in cancer immunotherapy and our work with our partner Bristol-Myers Squibb, who presented data during the second quarter for two anti-CTLA-4 pro-body programs, BMS 986249 and BMS 986288, which I will refer to as BMS 249 and BMS 288 respectively. At ASCO, BMS presented the first clinical data for BMS 249, a pro-body version of the anti-CTLA-4 antibody ipilimumab. This is a novel therapeutic strategy to enhance CTLA-4 exposure in the tumor microenvironment while potentially sparing systemic toxicity. The trial evaluated BMS249 as monotherapy or in combination with the anti-PD1 antibody nivolumab in patients with advanced cancers at doses ranging from 240 milligrams to 2,400 milligrams of the probody, which for reference is approximately 3 to 30 mgs per kg. Ipilimumab is typically used clinically at doses of 1 to 3 mgs per kg. Safety data from the phase 1 trial showed that BMS249 was generally well tolerated as monotherapy, and in combination with NEVO. The types of treatment-related adverse events were consistent with those seen with the parent molecule, ipilimumab, and the incidence of grade three and above adverse events were supportive of the probody mechanism of action. Based on these phase one findings, BMS has initiated a randomized cohort expansion, evaluating the tolerability and activity of BMS249 in combination with NEVO versus NEVO with or without ipilimumab in metastatic melanoma. The advancement of BMS249 into this study triggered a milestone payment of $10 million from BMS to cytomics that was received in the second quarter. This is an important study that has the potential to provide additional validation of this novel product candidate. Staying with CTLA-4 for a few moments, also in Q2 at AACR, BMS presented preclinical data for BMS249 and also BMS288, which is a probody of a non-feucosylated version of ipilimumab. BMS249 and BMS288 demonstrated equivalent intratumoral pharmacodynamic activity and comparable antitumor activity relative to their parental antibodies. These data also showed that the pro-body versions are significantly safer than each underlying antibody, demonstrating highest non-severely toxic doses in animal models that were five-fold and three-fold improved respectively. These data support the strategy of using our probody technology to expand therapeutic index for CTLA-4 therapy and are strongly consistent with the clinical experience to date that BMS has reported with BMS249. The non-pucosalated probody BMS288 is also in the clinic in a phase one dose escalation study. Before I turn over to Carlos for a review of our financials, I'd like to provide brief updates on three earlier stage programs at Cytovix that are emerging as a potential second wave of product candidates in our pipeline. Let me begin with CX904, our T-cell bispecific probody targeting EGFR and CD3 partnered with Amgen. We believe the application of our probody technology has the potential to enable solid tumor targeting of this modality. Such targeting with unmasked T-cell bispecifics has been very challenging for the field due to narrow or nonexistent therapeutic windows. We continue to advance this candidate towards IND enabling studies and expect to file in late 2021. Turning to CX2043, our wholly owned EPCAM targeting pro-body drug conjugate. CX2043 was developed utilizing cytomics pro-body technology and immunogens drug conjugate technology and arose from our previous strategic collaboration. We continue to advance this candidate towards IND enabling studies. Lastly, as part of the strategic collaboration with Astellas that we announced in the first quarter for which we received an $80 million upfront payment, we have now launched discovery activities surrounding the development and ultimate commercialization of novel T-cell engaging bispecific antibodies in masked form. This is our second alliance in this exciting area of research, and we have high hopes for this pro-body format. With that, let me hand the call over to Carlos to review our financial update.