Compugen Ltd.

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's fourth quarter and full year 2021 results conference call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available in the Investors section of Compugen's website, www.cgen.com. As a reminder, today's call is being recorded. I would now like to introduce Yvonne Naughton, Head of Investor Relations, and corporate communications. Yvonne, please go ahead.

Thank you, Operator, and thank you all for joining us on the call today. Joining me to present a prepared remarks are Dr. Nat Cohen-Diag, President and CEO, and Ari Krashen, Chief Financial and Operating Officer. For the Q&A session, we will also be joined by Dr. Henry Adewoye, Chief Medical Officer, and Dr. Eran Ofer, Vice President, Research and Drug Discovery. Before we begin, we'd like to remind you that during this call, the company may make projections or forward-looking statements regarding future events, business outlook, development efforts and their outcome, the company's discovery platform, anticipated progress, results and timelines of our programs, financial and accounting-related matters, as well as statements regarding our cash position. We wish to caution you that such statements reflect only the company's current beliefs, expectations, and assumptions. but actual results, performance, or achievements of the company may differ materially. These statements are subject to known and unknown risks and uncertainties, and we refer you to the SEC filings for more details on these risks, including the company's most recent annual report on file form 20F filed with the SEC on February 25th, 2021. The company undertakes no obligation to update projections and forward-looking statements in the future. With that, I now turn the call over to Anat.

Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to our fourth quarter and full year 2021 update. I'm proud to say that Compugn made excellent progress in 2021. Our fundamentals have improved and we're delivering on our promises. COMPIGEN has done groundbreaking work on the biology of the key targets of the DENAM axis, PVRIG, and TIGIT. This is evidenced by our numerous publications and patent filings. We are pioneers in an uncharted territory. We're the first to test in the clinic two agents never combined before, primarily focused on PD-1 non-responsive patients. Our differentiated clinical strategy with our potential first-in-class anti-PVRIG antibody COM701 is to lead the next wave of innovation by executing a unique combination approach to realize the full potential of TIGIT and PVRIG. Immune checkpoint inhibitors have become multibillion-dollar drugs and are having a major impact on cancer care. However, As most patients do not respond to immunotherapies, there is a need for new drugs for these cancer patients. At Compugen, we believe that immune checkpoint inhibitors that target the denim axis have the potential to be a game changer in the treatment of cancer. As we continue as leaders in the denim axis by unlocking the potential of both PVRIG and TGIT pathways, with a vision to deliver the next transformational drugs. We're excited to see the growing interest in the space by major pharma companies, providing further validation of our hypothesis and the possibility of opening additional opportunities for us in the future. Data from our clinical studies presented in 2021 with COM701 and COM902 support our hypothesis that treatments that target the denim axis could be effective in inflamed or even more exciting, less inflamed tumors. Our studies show early signals of anti-tumor activity with immune activation across studies and a good safety profile in mono, dual, and triple therapy settings. Today, we would like to update you on our clinical program, upcoming anticipated milestones, and report on our financial results for the fourth quarter and full year 2021. I'll start by updating you on our key 2021 accomplishments and 2022 anticipated milestones. Then I will review the clinical program with you. Ari will summarize our financial results, and then I will come back to make a few closing remarks. 2021 has been a year of progress for Compugen with a strong execution across our differentiated clinical strategy. I want to highlight three of our important accomplishments in 2021. First, in keeping with our goal to develop first-in-class or best-in-class immune therapies for cancer patients who are not responding to currently available therapies, we delivered on our clinical milestones to complete dose escalation studies and begin expansion cohorts across all our programs. These encouraging results from our initial clinical studies reported at major medical and scientific meetings throughout the year paved the way for a comprehensive evaluation of Compugen's Dynamaxis hypothesis in our ongoing expansion cohort studies. Second, In keeping with our goal of maximizing value for patients, we expanded our collaboration with Bristol-Mell Squibb and are happy to see AstraZeneca progressing their TGPD-1 bispecific derived from our COM902 into the clinic. In addition, we expanded our research collaboration with Johns Hopkins University. These partnerships support our focus on expediting our early and clinical stage programs and bringing them to the market. Third, in keeping with our leadership position in the field and our goal to advance immune oncology research, throughout 2021, we presented new research and translational data at scientific conferences to support the unique biology of PVRIG, and the potential of its blockade to target less inflamed tumor types. In addition, along with one of our trusted advisors and long-term collaborators, Professor Drew Pardol, we co-authored a review on the biology and potential therapeutic relevance of the DENAM assays in cancer immunotherapy in the prestigious high-impact journal, Cancer Discovery. Looking ahead to 2022, we're conducting three very important phase 1-2 combination studies. As you know, our clinical strategy has been designed to allow us to systematically evaluate our hypothesis that simultaneously blocking three pathways, PVRIG, TGIT, and PD-1 in selected biomarker-informed tumor types may produce game-changing results for cancer patients with inflamed, or less inflamed tumors. PVRIG, which is differentiated from TG10PD1, may be the missing piece when current immunotherapies have failed by potentially generating new waves of T cells to infiltrate the tumor microenvironment, turning it to a more inflamed environment. Our ongoing combination studies are signal-seeking studies evaluating preliminary antitumor activity of COM701 in addition to safety and tolerability in multiple indications. These studies also include a parallel comprehensive translational analysis assessing immune activation to further evaluate our unique drug mechanism of action and potential biomarker identification that may be of relevance for future patient selections. Based on establishing proof of concept in specific indications, we will share our path forward in such indications, targeting the fastest path for registration to maintain our first mover advantage. Our studies have been designed to efficiently identify the optimal inhibitor combinations and tumor types. Although these are signal-seeking studies, this approach which includes some overlapping indications across studies, is intended to help us understand the contribution of each study drug. Enrollment is underway in our ongoing clinical studies. The first study, initiated at the end of June 2021, is designed to evaluate an anti-PVRIG PD-1 combination with COM701-Evalumab in patients with ovarian, endometrial, breast, and microsatellite-stable colorectal cancer. The second study, initiated in July 2021, is designed to evaluate the anti-TGIT-PVRIG-PD1 triple combination with COM701, nivolumab, and bristomersquibs anti-TGIT in patients with ovarian, endometrial, and head and neck squamous cell carcinoma, plus a cohort of subjects who have high expression of PVRL2, which we will start enrolling following the assessment of correlation between PVRL2 level of expression and response. The third study, most recently initiated in November 2021, is evaluating an anti-tigit PVRLG combination with our wholly-owned COM902, COM701 drug candidates, in patients with head and neck squamous cell carcinoma, non-small cell cancer, and microsatellite stable colorectal cancer. Our intention is to report data from fully enrolled cohorts of each of these studies, taking into consideration that certain cohort indications enroll faster than others and use the results to define our regulatory strategy on a cohort-by-cohort basis. Based on the current enrollment rate, first data from combination studies are expected to be reported in Q4 2022, starting with a microsatellite-stable colorectal cancer cohort from the COM701 Nivolumab study. And we expect to complete enrollment in all cohorts by end of 2023. As enrollment progresses, we plan to share further guidance with respect to the other cohorts. Microsatellite-stable colorectal cancer is a tumor type that has so far been immunologically unresponsive. There is no approved therapy specifically for these MSS CRC patients, and immune checkpoint inhibitors have demonstrated limited or no activity in this patient population. Treatment in this setting is typically regorafenib or LUNSERV, which show ORR of 1%, median PFS of 2 months, and median OS of 6 to 7 months. As of today, we have presented data from 12 patients using various doses of COM701 with or without nivolumab across studies and have shown encouraging preliminary antitumor activity with a disease control rate of 58%, including one partial response of 44 weeks. Our current COM701 Evolumab study consists of additional 20 MSS CRC patients, which will help us further assess the potential of this drug combination in this setting. Looking back over 2021, I've been very pleased with the encouraging data in our Phase I studies across mono, dual, and triple therapy in multiple tumor types, as presented at ASCO and CITI, as well as the expansion of our collaboration with Bristol-Mass Quibb based on the data we've presented to date. Three observations from our overall translational data set stand out to me. First, Our most recently presented translational data demonstrating immune activation across our COM701 studies with the most potent immune activation in triple blockade of PVRIG, TGIT, and PD-1 supports our suggested drug mechanism of action as well as the differentiation of PVRIG from that of TGIT and PD-1. Second, I'm pleased that our approach to develop our anti-TG antibody using an IgG4 backbone, similar to the leading anti-PD-1 antibodies with less effects of function than IgG1, appears to be an appropriate strategy. Indeed, in our COM902 dose escalation study, which represented at 60, we showed that there is no depletion of the CD8 plus T cells, the most effective anti-tumor immune subsets. We were the first to present clinical data with an IgG4 antitigit antibody with low FC effector function, and we believe this may also come with additional benefits on the safety side to be confirmed in the clinic. Third, our initial data suggests that COM701 may have potential to address less inflamed tumor types where other immune checkpoint inhibitors have not been successful in line with supportive data from our PVRIG research. In addition, we achieved encouraging signals of antitumor activity in our studies with several notable durable responses in heavily pretreated patients who had exhausted all available therapies with a good safety profile. To summarize, our translational observations coupled with our encouraging data to date, suggest a differentiated profile for COM701 and COM902 with the potential to unlock the value of denim axis as a game changer in the treatment of cancer. I'm enthusiastic about our program and look forward to sharing the results of our ongoing studies with you. Before I turn the call over to Ari, I would like to thank the patients and their families caregivers, investigators, and study sites.