Compugen Ltd.

Ladies and gentlemen, thank you for standing by. Welcome to Compugin's fourth quarter and full year 2020 results conference call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available in the investor section of Compugin's website, www.cgen.com. As a reminder, today's call is being recorded. I would now like to introduce Ilana Holtzman, Compugin's Director of Investor Relations and Corporate Communications. Please go ahead.

Thank you, operator, and thank you for joining us today. With me from Compugen are Dr. Anat Cohen-Dayag, President and CEO, Dr. Henry Attaway, Chief Medical Officer, Ali Krashen, CFO and COO, and Dr. Eran Ophir, VP Research and Drug Discovery. Anat will provide corporate highlights, after which Henry will review the data we disclosed earlier today, and Ali will review our financial statement and position. Anat, Henry, Ari and Eran will be available for the Q&A session. Before we begin, I would like to read the following regarding forward-looking statements. During the course of this conference call, the company may make projections or other forward-looking statements regarding future events or future business outlook, our development efforts and their outcome, anticipated progress and the timeline 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 expectations and that actual events or results may differ materially. You are kindly referred to the risk factors and cautionary language contained in the documents the company files with the Securities and Exchange Commission, including the company's most recent annual report filed on Form 20-F with the Securities and Exchange Commission. The company undertakes no obligation to update projections or forward-looking statements in the future. I will now turn the call over to Anat.

Thank you Ilana. Good morning and good afternoon everyone and welcome to our fourth quarter and full year 2020 corporate and financial update. 2020 was another important year of execution and progress at CompiGen. in which we strengthened our positioning in the cancer immunotherapy space and solidified our standing as the leader in targeting denim axis signaling pathways. Based on our years of research of this axis, we're executing a strategic and comprehensive clinical development program to evaluate our internally discovered and wholly owned anti-PVRIG and TIGIT assets across settings and combination regimens to elucidate the role of the denim axis members PVRIG and TIGIT as potentially foundational immunotherapy checkpoint targets. Our work has identified PVRIG and TIGIT as key parallel and complementary inhibitory pathways in the denim axis, which also intersects with the PD-1 pathway. Importantly, our data suggests that these three inhibitory pathways have different dominance in different tumor types and patient populations, which means certain patient populations may require the blockade of different combinations of the three pathways in order to induce effective anti-tumor immune responses. This is the underlying rationale for our comprehensive clinical program designed to develop new treatment solutions. Earlier today, we shared data from the combination arm of the Phase I dose escalation study of COM701 in combination with Bristol-Mell Squibb's Nivolumab, as well as follow-up on our monotherapy dose escalation study and data from the COM701 monotherapy cohort expansion. While Henry will provide a more detailed review of the data later in the call, I would like to present a high-level overview of our data and highlight certain results which we view as particularly encouraging. We plan to present updated data along with initial correlative data from patient samples at ASCO 2021 to which an abstract was submitted. Starting with the combination arm dose escalation data. The updated data disclosed today now include complete data from all five dose levels in the study, which we believe are highly encouraging. Overall, we see a disease control rate of approximately 67%, which given the highly refractory nature of this population, is a meaningful accomplishment. We observed durable responses, including the partial response we reported at ASAR last year, with two patients still remaining on the study since our last data presentation in April 2020 for approximately 10 additional months. In addition, and most excitingly, one of these two patients who progressed on an immune checkpoint inhibitor Prior to enrolling to our study has converted to a confirmed complete response. Based on this data, we're excited to expand our collaboration with BMS to include a Phase 1b cohort expansion combination study evaluating COM701 with nivolumab in parallel to our ongoing triplet study. This dual combination expansion study will continue our clinical momentum and will add an additional layer to our clinical strategy, expanding this potentially promising combination regimen as a possible unique and effective treatment opportunity. It will also provide additional insights to the contribution of the different components of the denim axis across our ongoing and future COM7-1 studies and specifically our ongoing triplet study. We're also happy that the amendment of our agreement with BMS was revised to include a specific date for the expiration of the exclusivity period so that it ends at the earlier of six months after the study's completion or on December 31st, 2023. This will ensure termination of exclusivity period in the event that the ongoing dual and triple studies continue beyond their currently expected timeframe. This doublet expansion study is expected to begin in the second quarter of 2021 and will enroll patients with ovarian, breast, endometrial, and microsatellite-stable colorectal cancers. Our recent results, including the complete response in a patient who relapsed on PD-1 therapy increase our confidence that there are certain patient subpopulations which are likely to respond to a PVRIG PD-1 dual blockade in a clinical setting, including those progressed on immune checkpoint blockers. We also shared initial data from our COM701 monotherapy cohort expansion. While this study was designed as a safety and tolerability study, we used a biomarker-informed strategy to select tumor types likely to respond to treatment alone or in combination based on preclinical expression data and clinical results from the dose escalation arm. These indications are endometrial, breast, ovarian, colorectal, and non-small cell cancer. In this study of 20 patients for which enrollment was completed in Q4 2020, we had six patients with the best response of stable disease across endometrial, non-small cell lung, and ovarian cancer. We also had durable anti-tumor activity in two patients on treatment as of the data cut. The combined data of this cohort expansion study with data from previously reported monotherapy dose escalation study that includes a patient with a durable confirmed partial response still on study treatment for more than a year, demonstrate signals of anti-tumor activity of COM-701 treatment in patients with highly refractory disease and in tumor types typically unresponsive to immune checkpoint inhibitors as previously suggested by us. While information from a small monotherapy study may be limited, this data supports the potential role of PVRIG inhibition in patients who have exhausted all available standard therapies and sets the basis for our next combination studies. We are now performing correlative assessments based on data from patient samples. to gain insights relating to COM701 and the PVRIG-PVRL2 pathway biology, particularly in indications that are typically not responsive to PD-1. This will allow us to further learn about COM701 activity as well as to inform our COM701 and COM902 clinical program development path in indications with preliminary encouraging signals of anti-tumor activity. Our initial assessments of patients' peripheral blood samples suggest that COM701 may enhance immune activation in cancer patients alone or in combination with nivolumab. These initial findings assessing for the first time PVRIG-blockade effect In summary, the data derived from our various studies is an important milestone in our overall clinical strategy, which demonstrates that COM701 and thus PVRIG blockade is presenting signals of antitumor activity in a clinical setting that can serve as a basis for our next studies. The patients enrolled in these studies had diverse tumor types and were treated with various doses of COM701 with or without nivolumab. But the indications in which we observed the responses as well as the number of highly durable stable diseases are indications which are typically PD-L1 low or negative and generally have low response rates to available immune checkpoint inhibitors. Since immunotherapy has been most transformative in PD-L1 positive patients, to see these first signals in indications with such high unmet need that generally do not respond to immune checkpoint inhibitors is encouraging and strengthens our conviction in our approach. Moving to the next stage of executing our broad clinical strategy, our studies now include our ongoing triplet study of COM701 with nivolumab and BMS TGT inhibitor and the planned initiation of both the doublet expansion study of COM701 with nivolumab and a doublet study of COM701 and COM902 later this year. In addition, the comprehensive biomarker assessment from the various cohort expansion studies will provide us insights into the PVRIG-PVRL2 pathway biology and shed light on specific contributors to anti-tumor activity, which may guide us to specific expanded tumor indications. This next phase of our comprehensive clinical program will allow us to quickly generate multiple data readouts and maintain our competitive edge in developing denim axis-based new cancer immunotherapy treatments. With our initial supportive clinical data for PVRIG and clinical validation of TVID by others, we're excited to witness what we believe is a growing interest in the biopharma industry in both PVRIG and TIGIT, which we discovered independently as new immunotherapy targets. We believe that our leadership position in the denim axis, our clinical programs, our initial clinical data, and perhaps most importantly, our ability to execute on this broad combination clinical strategy, testing the synergy of these two pathways and in combination with PD-1, places us in a differentiated position in the crowded space of immune oncology. Specifically, we're the only company with wholly owned clinical stage assets targeting both PVRIG and TIGIT, and thus, we're the only company capable of evaluating PVRIG monotherapy, dual blockade of PVRIG with PD-1 or TIGIT, and triple blockade of PVRIG with PD-1 and TIGIT. With our expanded collaboration with BMS, we are rapidly advancing our clinical programs and we believe that we will be the first to generate data which will maintain our position in developing denim axis-based new cancer immunotherapy treatments. Moving next to a brief overview of the status of our ongoing clinical trials and our expected clinical milestones in 2021. Starting with our COM701 monotherapy cohort expansion, additional clinical data and initial correlative assessments based on data from patient samples collected in our clinical studies are planned to be presented at ASCO 2021. Our recently announced Phase 1b cohort expansion combination study evaluating COM701 with nivolumab is planned to begin during the second quarter of 2021. Our Phase 1-2 triple combination study evaluating the safety, tolerability, and preliminary anti-tumor activity of COM701 in combination with BMS TIGIT antibody and nivolumab is currently enrolling patients and we expect to share initial data from the study in the fourth quarter of 2021. This study rapidly propels forward The evaluation of our triple blockade hypothesis, which we believe is an ultimate way to test our hypothesis that blocking the three intersecting pathways has the potential to synergistically enhance anti-tumor immune responses in selected patient populations not responsive or refractory to PD-1 blockers alone. And finally, touching upon our COM902 monotherapy dose escalation study. While there are currently other clinical programs evaluating TGT inhibitors, we have always believed it is important to pursue the development of our own candidate to maintain our control of what we believe are two key arms of the denim axis and our ability to independently evaluate multiple combination approaches which include TGIT in the clinic. COM902 enables us to advance this strategy and our study is currently on track with enrollment. We expect to provide initial data from the study in the fourth quarter of 2021. Importantly, as we disclosed on our last call, we also intend to begin studies evaluating COM701 in combination with COM902 in the second half of 2021. This study will further expand the breadth of our combination programs, allowing us to evaluate the dual blockade of PVRIG and TIGIT, which we believe may enhance anti-tumor immune responses in a subset of patients. We look forward to providing additional details on this study in the coming months. Before we move on, I'd like to briefly touch upon the characteristics and biology that underlies our two clinical assets. As I mentioned earlier, it is our clinical programs combined with our deep scientific expertise and preclinical data that position us as leaders in the genome access immunotherapy space. As a reminder, Both COM701 and COM902 were discovered and developed in-house, giving us the unique opportunity to rationally design these candidates in ways we believe will position them to be successful in the clinic. There has been a fair amount of scientific debate regarding the role of the isotypes of therapeutic checkpoint antibodies and the function of their respective FC portions. Our position has been, and remains, that an antibody with effector function carries the risk to deplete CD8 plus T cells, which we know are crucial for driving immune responses in the tumor setting. Because of this, both COM701 and COM902 were developed as IgG4 antibodies which have reduced FCA effector function. So starting with COM701, We know that PVRIG is highly expressed in CD8 plus T cells and NK cells, and thus, we believe moving forward with IgG4 was important to avoid the potential risk of depleting the target cell population which we want to reactivate. Our initial clinical data, even in patients with highly refractory disease who are not expected to respond to checkpoint inhibitors, suggests that PVRIG antibody with an IgG4 isotype is active in the clinic. However, it is yet to be demonstrated in the clinic where the potential additional modulatory effects of effector function active antibodies will outweigh possible depletion of CD8 plus T cells required for activity. It is important to highlight that the underlying clinical strategy of choosing IgG1 antibodies is largely driven by preclinical data in mice, where we know the biology of FC receptors differs significantly from humans. In fact, we have seen multiple examples where this preclinical activity did not translate to the clinic, specifically in the case of both CTLA-4 and PD-L1 antibodies, for which preclinical activity of antibodies with effect of function did not translate clinically. The story with TGIT becomes a bit more complicated as opposed to PVRIG. TGIT and PVRIG are expressed on different cell populations, specifically with TGIT on Tregs, which may be a target for anti-TGIT depleting antibodies. While there is activity in the clinic with IgG1 antibodies that do have effect of function, Our hypothesis is that enhancing CD8 plus T cell activity not depleting Tregs will ultimately be responsible for driving activity of anti-TGIT antibodies. Based on our strong conviction that enhancing CD8 plus T cell activity is critical in driving anti-tumor immune responses, we have advanced ADG4 candidates for both PVRIG and TGIT. We believe This will enable the reactivation of CD8 plus thesis function in the tumor setting. However, it is yet to be demonstrated whether such antibodies will present superior activity in the clinic. Next, I'd like to highlight some corporate accomplishments outside of our scientific and clinical progress. In 2020, We continue to invest in our early stage pipeline which serves as our growth engine. Our early stage pipeline consists of multiple programs targeting the immunosuppressive tumor microenvironment via various mechanisms of action including myeloid biology. These are early stage programs, but as they progress, some may serve as the future of our preclinical and clinical programs. This past year, We were also granted multiple patents to protect our pipeline candidates, and we now have composition of matter and use patents protecting COM902 and COM701 in the US, Europe, and other jurisdictions such as COM902 in China, as well as a patent covering the use of anti-PVRIG antibody that activates T cells and or NK cells for using treatment of cancer in Europe and other jurisdictions. We're pleased to announce the first preclinical milestone through our ongoing license agreement with AstraZeneca for the development of bispecific and multispecific antibodies. As a reminder, We provided an exclusive license to AstraZeneca for the development of bispecific and multispecific antibody products based on one of our pipeline programs and with AstraZeneca responsible for all research, development and commercial activities. In connection with this first milestone, we received a $2 million payment from AstraZeneca. Last quarter, We also updated that Bayer decided to focus on treating IO-naive first-line head and neck squamous cell carcinoma patients with a combination of Bay-1-90-52-54 and Keytruda in the Phase I study. This antibody against IL-DR2 was licensed by us to Bayer and is targeting the third novel immunotherapy target we discovered computationally. We're proud to partner with three global pharmaceutical companies and believe that the agreements we have in place serve as a validation of the power of our internal discovery and development capabilities. These agreements reflect our strategy of collaborating with biopharma to monetize pipeline candidates while also advancing drug candidates internally to develop novel cancer immunotherapies. Finally, before turning the call over to Henry, I would like to very briefly touch upon the ongoing COVID-19 pandemic. As in previous quarters, we're incredibly unfortunate to have avoided significant impacts on our activities in 2020, with prior guidance for enrollment and data across our studies unchanged. I remain proud of the commitment and dedication showed by our team at CompiGen, who together have enabled our continued steady progress throughout this notable year. In addition, we're grateful to our partners, investigators, and shareholders, and look forward to continued progress. And with that, I'll turn the call over to Henry to provide additional details on our recently presented data.