Compugen Ltd.

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's fourth quarter and full year 2022 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 from Compogen for the prepared remarks are Dr. Anatko Ndiag, President and Chief Executive Officer, and Alberto Sessa, Chief Financial Officer. Dr. Henry Adewoy, Chief Medical Officer, and Dr. Iran Ofer, Senior Vice President, Research and Drug Discovery, will join us for the Q&A. Before we begin, we would 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 potential outcome, the company's discovery platform, anticipated progress and plans, results and timelines for its programs, financial and accounting-related matters, as well as statements regarding the company's future 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 Form 20F filed with the SEC on February 28, 2022. The company undertakes no obligation to update projections and forward-looking statements in the future. And now I turn the call over to Anar.

Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to our fourth quarter and full year 2022 update. Immunotherapies have been a revolution for the treatment of many patients with cancer. 2022 annual cells of PD-1 pathway inhibitors alone were greater than $35 billion. But still, as we all know, there remains an urgent unmet medical need for the majority of the cancer patients who are resistant to anti-PD-1. To address the needs of these patients, many drug combinations are being evaluated, including IO-IO combinations. is the leader in the triple IO-IO combinations blocking PDR-IG, TGIT, and PD-1. While TGIT-blocking antibodies in combination with PD-1 inhibitors may function in PD-L1 high-expressing patients, our data consistently show that the addition of an anti-PDR-IG may sensitize tumors to respond to PD-1 and TGID blockade even in PD-L1 low-expressing patients. As leaders in the DENAM-AXIS space, we believe that evaluating the triple combination of our potential first-in-class anti-PVRIG COM701 with our potential best-in-class anti-TGID COM902 and the PD-1 inhibitor has the potential to maximize clinical benefit for patients. On this front, we have made significant progress, and I would like to share our top highlights for 2022, which we believe set us up for success in realizing our vision to transform the lives of patients by extending the reach of cancer immunotherapies to those who are resistant to anti-PD-1 therapies. First, in 2022, we took a strategic decision to narrow down our broad signal-seeking study to focus on two indications with high unmet medical need and less competitive landscape, microsatellite-stable colorectal cancer and platinum-resistant ovarian cancer. We believe that this focus provides us with the highest probability of success for several reasons. One, these are indications where we have shown encouraging clinical benefit supported by immune activation that aligns with the COM701 mechanism of action backed with a biological rationale and which we believe provides the fastest route to additional meaningful data to inform on the next steps in building a path to registration. Two, as a result of our decision to prioritize two indications, we concluded our collaboration with Bristol Mills Squibb, thereby enabling us to focus our time and cash on two indications, as well as switch to evaluate our own potential best-in-class anti-tigit COM902 as part of our triple combination going forward. And now that COM701 is no longer restricted, we also have the opportunity to advance and partner both our potential first-in-class anti-PVRIG COM701 in addition to COM 902. And lastly, the decision has enabled us to extend our cash runway through at least the end of 2024, which is sufficient time to complete our small proof-of-concept studies aimed at strengthening the evidence and de-risk our lead assets in these two indications. Moving now to the second highlight of 2022, which was the encouraging clinical data we presented in the fourth quarter of 2022 in two indications. The first set of data we presented was in patients with microsatellite-stable colorectal cancer at CITSE Conference in November 2022. And the second set of data was in patients with platinum-resistant ovarian cancer, which we presented at ESMO Immuno-Oncology Conference in December 2022. As far as we are aware, we are the only company reporting clinical benefit with an immune checkpoint inhibitor supported by an underlying biological rationale in this patient population with microsatellite-stable colorectal cancer and liver metastasis, which makes up approximately 70% of the MSS CRC patients in this metastatic setting. This is encouraging, as this is an indication with a high unmet medical need, and these patients have no approved treatment options after failure of standard of care therapies. In these patients with platinum-resistant ovarian cancer, there was a lot of excitement from investigators reporting durable shrinking or stabilization of tumors in some of their patients who had previously progressed on all available treatment options. The totality of the clinical benefit in these patients including a 20% overall response rate, with several patients responding over nine months, with responses also achieved in a hard-to-treat high-grade serous adenocarcinoma patient, along with a favorable safety profile, is encouraging compared to current standard of care. The translational work with samples taken from these patients is in progress and we expect to share the data in one of the upcoming medical conferences during 2023. In both indications, the clinical benefit is supported by biological rationale and points to a COM701-mediated mechanism of action, increasing T cell numbers and mediating anti-tumor immunity. in tumor types and in patient populations that could not be addressed otherwise. And the third highlight is AstraZeneca rapid progress and continued expansion of their PD-1-treated bispecific, rilvagustinib, which is derived from our COM902. This progress and continued investment by global leader in oncology in our opinion, exemplifies belief in the TGIT mechanism of action, and more specifically, in our differentiated anti-TGIT COM902. Like COM902, which is a high-affinity, reduced FC effector function anti-TGIT antibody, rilvegastamib was engineered to reduce the FC-effects of functionality with the potential to enhance anti-tumor activity. With Argus-Gilead randomized Phase II data with an FC-silent TIGIT antibody and AstraZeneca's antibody design strategy, we believe our choice of a reduced FC-effects of function anti-TIGIT is well-reinforced. Last year, AstraZeneca progressed rivagostimib into Phase II development in metastatic non-small cell cancer, and since then, AstraZeneca has extended development for the treatment of naive non-small cell cancer and gastric cancer patients. AstraZeneca announced that it also plans to initiate a Phase III study this year and has suggested that this could be one of its 10 programs with a blockbuster potential. This is great news for us, as we may be entitled to receive up to an aggregate of $200 million in milestones for these products, as well as tiered royalties on future product sales. We look forward to the success of Real Velgost in it. During our call today, I will provide an overview of the opportunity and path forward in our prioritized indication, microsatellite-stable colorectal cancer and platinum-resistant ovarian cancer. I will go on to describe our next pipeline asset, COM503, which is the lead asset in our early pipeline and why we're excited about its potential. Alberto will take you through the financials. I will summarize our upcoming milestones and then we will open the call up for questions. Starting with the opportunity and path forward with our prioritized indications. We're initiating two proof of concept studies in platinum resistant ovarian cancer and in microsatellite stable colorectal cancer. The goal of these proof-of-concept studies is to strengthen the evidence, help us better understand the contribution of components, and build on the extensive biomarker work we're doing to try and understand the patients most likely to respond with the purpose of building a path to registration in these indications. Colorectal cancer is the third most common cancer in the US. It is estimated that in 2023, approximately 153,000 new cases will be diagnosed in the US, and about 52,000 patients will die from this cancer in the US. Microsatellite-stable colorectal cancer represents about 95% of the colorectal cancer patients with limited treatment options. Around 70% of the patients with metastatic colorectal cancer have metastasis to the liver, and as far as we're aware, we're the only company who has reported clinical benefit in this patient population with a checkpoint inhibitor. I am delighted to report that we have multiple sites opened which are actively screening patients to enroll in our MSS CRC triple combination proof-of-concept study. Patients will be eligible if they are PD-1 naive and have received up to three prior lines of therapy, and we will be including patients with liver metastasis. With the enthusiasm of our study investigators and the lack of good treatment options for these patients, we anticipate completing enrollment of up to 20 patients and plan to share initial findings this year with full data disclosure expected in the first half of 2024. In terms of what success looks like, we believe that even if we repeat the 12% overall response rate in patients with liver metastasis, and also take into consideration other clinically relevant endpoints, such as progression-free survival, durability of antitumor activity, deaths of response, safety, presence of coexisting adverse prognostic features, such as KRAS mutation, we would be informed are next steps for a potential path to registration, ideally with the right partner. Moving to platinum-resistant ovarian cancer, where there is also an urgent medical need, as these patients have very limited treatment options. Platinum-resistant ovarian cancer is a hard-to-treat tumor type with limited T-cell infiltration, which are required for immune checkpoint inhibitors to be effective. Historically, most immune checkpoint inhibitors have demonstrated limited activity in such tumors. It is estimated that in 2023, in the U.S. alone, approximately 20,000 new cases will be diagnosed and 13,000 patients will die of this cancer. We believe that PVRIG's unique biology, different than other checkpoints, has the potential to generate different outcomes in these patients. I'm delighted to say that we're on track to dose the first platinum-resistant ovarian cancer patient in our triple combination proof-of-concept study in the second quarter of this year. Immune checkpoint inhibitor-naive patients will be eligible if they have received up to three prior lines of therapy and we will include patients of all histologies. We plan to employ a staged approach. We will enroll up to 40 patients in total in the triplet with the first 20 patients until the end of the year and the full cohort in the first half of 2024. Once we complete enrollment of the first 20 patients on triplet, we intend to evaluate the inclusion of an additional doublet arm of up to 20 patients, which is a combination of COM-701 and pembrolizumab without COM-902, to help us better understand the contribution of the components. We plan to report initial findings by the end of this year. Together with the data we have in hand, this triplet study is expected to bring us to an overall assessment of up to 60 platinum resistant ovarian cancer patients on triplet treatment, which we expect will inform us on next steps in building a potential path to registration, which again, ideally, would be done with the right partner. In terms of what success looks like, we believe that if we see at least 20% overall response rate in these additional patients, along with a safety profile reported to date, and taking into consideration tumor histology and other clinically relevant endpoints, like durability of anti-tumor activity deaths of response, and progression-free survival, we would be informed on the next steps towards a potential path to registration. Of course, in both indications, the identification of a biomarker would greatly contribute to further defining a study population to most likely derive clinical benefits. While identifying biomarkers in the field of checkpoint inhibition is not a given, with our years of expertise in understanding the underlying biology of the genome axis, evident by the quality of the translational data we have generated from patient biopsies using cutting-edge technologies and our computational capabilities, we believe were well-suited to identify biomarkers which can help define the patients who may benefit from our COM701 combination and will therefore allow us to better design and execute targeted, well-defined, randomized studies. Moving next to our leading early pipeline asset, COM503. We're very excited about the progress we have made with our early stage programs originating from our computational discovery engine. While PVRIG and TIGIT were totally new targets and pathways upon discovery, our next program is different. Here, we're targeting a known pathway in a completely unique way with a potential first-in-class therapeutic candidate. we identified a potential dominant immunosuppressive mechanism which is used by macrophages in tumors to escape the immune system. This is the interleukin-18 binding protein and interleukin-18 complex. The inflammasome-induced pro-inflammatory cytokine, interleukin-18, is present at high levels in the tumor microenvironment where it is expected to naturally activate anti-tumor effector cells such as T and NK cells. But IL-18 is one of the rare cytokines that is naturally blocked by an endogenous high affinity inhibitor called interleukin-18 binding protein. Cytokines are powerful tools and are used therapeutically. However, there is a challenge of giving them systemically at levels high enough to reach and modulate the tumor microenvironment without causing systemic side effects. As a result of their narrow therapeutic window, conventional recombinant cytokines are limited in terms of efficacy. Some recent clinical failures exemplify this challenge. Specifically, IL-18 has been administered to cancer patients in the past but failed, most probably because of general limitations of recombinant cytokines just mentioned and potentially because IL-18 is inactivated by its natural blocker IL-18 binding protein. With that in mind, We have developed a potential first-in-class, fully human, high-affinity monoclonal antibody, COM503, which targets IL-18 binding protein to release endogenous, naturally occurring IL-18 to activate T and NK cells in the tumor macroenvironment. In our preclinical models, we have shown that blocking IL-18 binding protein can displace IL-18 from IL-18 binding protein in the tumor microenvironment, enabling the physiological IL-18 to have immune-stimulating activity and, in turn, mediate potent anti-tumor efficacy. We believe that one major advantage of using an IL-18 binding protein antibody over administration of IL-18 cytokine is a better therapeutic window due to IL-18 pathway upregulation confined to the tumor microenvironment. We have shown that an antibody against IL-18 binding protein modulates the tumor microenvironment for potent antitumor immunity without affecting peripheral immunity. We believe that our COM543 program represents a new and differentiated approach to harness cytokine biology for cancer therapeutics. The program is now advancing in IMD-enabling studies with a goal to file IMD in 2024. We plan to present this new approach at a scientific conference in 2023. With that, I'll turn the call over to Alberto.