Compugen Ltd.

Ladies and gentlemen, thank you for joining us today. Welcome to CompuGen's third quarter 2023 results conference call. At this time, all participants are in a listen-only mode. As a reminder, today's call is being recorded. An audio webcast of this call will be made available on the investor section of CompuGen's website, www.cgen.com. Please note that if the sirens go off during this call, we will need to end the call to take shelter. I would now like to introduce Yvonne Naughton, Head of Investor Relations and Corporate Communications. Yvonne, please go ahead.

Thank you, Yanni, and thank you all for joining us on the call today. Joining me from Compogen for the prepared remarks are Dr. Nat Cohen-Diag, President and Chief Executive Officer, and Alberta Sessa, Chief Financial Officer. Dr. Henry Adewoye, Chief Medical Officer, will join us for the Q&A session. 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, research and development efforts, and their potential outcome, anticipated progress and plans, results and timelines for its programs, financial and accounting-related matters, including projected financial information, as well as statements regarding the company's future cash position and other results, and the company's future initiatives. We wish to caution you that such statements reflect only the company's current beliefs, expectations and assumptions, and that actual results, performance or achievements of the company may differ materially. These statements are subject to known and unknown risks and uncertainties, which could cause the company's actual results to differ materially from those projected in such forward-looking statements. 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, 2023, as later amended. The company undertakes no obligation to update projections and forward-looking statements in the future. And now I turn the call over to Anat.

Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to our third quarter 2023 update. I will start by saying a few words on the heartbreaking situation in Israel a humanitarian disaster. We're traumatized and devastated by the inhuman slaughtering and kidnapping of civilians by the terrorist group Hamas. This brutal attack shook us to our core. I'm deeply thankful for all the kind words of support I've received from so many friends, colleagues, partners, investors, analysts, and the medical associations from across the world. Your solidarity means so much to me and provides comfort amidst all the anguish and unbearable pain. Thank you. We recognize the emotional toll this is taking on our employees in Israel, and we're taking care to manage the employee needs with a lot of sensitivity and care. Despite what our team members are going through, this is a time when we see teamwork at its best. Everyone supporting each other and stepping in to ensure we have no gaps. The teams are working hard together to ensure we continue to execute and meet our goals. Some are giving 150% when others are not able to. I'm seeing it every day and it makes me proud. The infrastructure for remote working was established during the COVID pandemic. And although we allow certain teams to work remotely, we are encouraging our employees to come to the office. As a global company with headquarters in Israel and presence in the US, Europe and Singapore, some management members and teams responsible for some of our key functions, including clinical development, preclinical development, and IT systems, are based outside of Israel. Our clinical trials are run in the US and operating in the ordinary course of business, including with respect to CMC and drug supply. Most of our preclinical activities related to COM543 are performed outside of Israel. We continue to work with no material impact on our operations, and if this changes, we will communicate it to the market. At Compugen, our goal is to transform the treatment of cancer patients who have no effective treatment options by using our pioneering computational platform to discover novel drug targets and develop potential first-in-class drugs. On this front, we're executing on our differentiated clinical approach to evaluate the blockade of the three pathways, PVRIG, TGIC, and PD-1. We're also advancing IND-enabling studies with our lead preclinical potential first-in-class anti-IL-18BP antibody COM543, offering a novel approach to harness cytokine biology to address resistance to cancer immunotherapy. And we're advancing our earlier stage pipeline with additional new potential first-in-class programs. At CT conference, which just took place, we presented additional data reinforcing a COM701-mediated anti-tumor activity in tumors typically not responding to immunotherapy. This data, which we continue to collect and share from our prior signal-seeking studies, adds to the breadth of tumor types typically not responding to anti-PD-1, but responding to COM701 combinations. Also, the biopsies taken from patients treated in these studies allows us to advance our biomarker insights as well as further confirm the COM701-mediated mechanism of action. And in parallel, we're conducting our ongoing studies focusing on MSS-CRC and platinum-resistant ovarian cancer. Building on data we presented at ESMO-IO last year, At CICI, we reported clinically meaningful durable partial responses in platinum-resistant ovarian cancer patients treated with COM71 triple combination with no new safety signals. Three patients are continuing study treatment for more than 16 months. While the numbers are small, typical median duration of response for this population is 3 to 4 months with standard chemotherapy, while 6.9 months reported in patients treated with a recently approved antibody drug conjugate. In addition to these durable responses, our triple combination has the potential added benefit of a favorable safety and tolerability profile, which, as we reported previously, investigators believe is important for patients' quality of life. We also reported that clinical benefit defined as partial response or stable disease of at least 180 days was independent of basal inflammatory status and was associated with an increase in CD8 plus T cells infiltration into the tumor, suggesting again, and consistent with what we've previously reported, a COM701-mediated mechanism of action. Excitingly, at CICI, we showed, for the first time, in tumor biopsies, an association between the expression of the PVRIG ligand PVRL2 and clinical benefit, which may suggest the potential of patients' baseline PVRL2 levels as a biomarker to help enrich for patients who may gain clinical benefit from COM701 combination. This is consistent with the basic computational-driven hypothesis we shared for this pathway in the past. This initial association finding suggests a COM701-mediated mechanism of action and has the potential for informing our studies, and I will come back to it later. At CITI, we also reported data in heavily pretreated metastatic breast cancer patients. COM701, when combined with nivolumab, resulted in preliminary antitumor activity with an overall response rate of 12%, including one complete response for over 21 months in a patient with HER2-negative metastatic breast cancer, a tumor that that is considered immune called, and a partial response for 10 months in a patient with a triple negative breast cancer, which is the fastest growing and most aggressive kind of breast cancer. The disease control rate was 29%, and the three patients with stable disease were PD-L1 low and with low tumor mutation burden at baseline. suggesting a COM701-mediated mechanism of action. And again, we reported good safety and tolerability with this dual combination. These findings are important because this is yet another indication in which patients are deriving durable benefits from COM701 combinations despite typically not responding to immunotherapy. Additionally, like the initial biomarker work in platinum-resistant ovarian cancer, in these metastatic breast cancer patients, we showed that baseline PVRL2 expression levels are higher in patients with clinical benefit, further supporting our biomarker hypothesis. And finally, at CITSEE, As part of an oral and poster presentation, we shared new data on our preclinical potential first-in-class anti-IL-18 binding protein antibody COM543, further supporting our exciting novel approach to harnessed cytokine biology to tackle resistance to cancer immunotherapy. As a reminder, there is a huge excitement in this space as cytokines have the potential to be powerful therapeutics, but have been plagued with challenges of giving them systemically at levels high enough to reach and modulate the tumor microenvironment without causing systemic side effects. We have found a way to address this for the IL-18 pathway. COM543 blocks the interaction between IL-18 binding protein and IL-18 thereby freeing natural IL-18 to inhibit cancer growth in the tumor microenvironment. The data we presented at CICI addressed two pertinent questions. One, are IL-18 levels in the tumor sufficient to provoke an anti-tumor response following antibody blockade of IL-18 BP? And two, is an IL-18 BP antibody safer than an engineered IL-18 cytokine that is given systemically. With respect to the first question, relating to IL-18 levels in the tumor, we showed that, one, antibody inhibition of IL-18 BP freeing natural IL-18 prevents tumor growth in multiple mouse tumor models, and two, COM543 has the potential to release local production of IL-18 in human tumors above the minimum range needed to stimulate the immune system. We also showed that antibody inhibition of IL-18 BP induced a significant increase in functional immune cells, such as the effector T cells, and induced a T cell clonal expansion in the tumor as well as immune memory response. So, our data suggests that the answer to the first question is yes. Iolating levels in the tumor are sufficient to provoke an anti-tumor immune response following antibody blockade of Iolating BP. In addressing the second question, relating to whether an IL-18BP antibody is safer than an engineered IL-18 cytokine given systemically, we showed that an engineered cytokine generated peripheral inflammatory responses, evidenced by increased serum cytokines and lymphocytes. This contrasts with our IL-18BP antibody approach, which modulates the tumor microenvironment without affecting the periphery. The overall data for our COM543 program suggests that our anti-ILATIN-BP antibody approach has a leading edge in inhibiting tumor growth while avoiding peripheral toxicity associated with administration of a recombinant ILATIN cytokine. Along with a successful CT, I would like to refer to additional progress we have made in the quarter. We're delighted to report that we have completed enrollment in the MSS CRC proof of concept study, which is a testament to the substantial unmet medical need in these patients and lack of alternative options. We continue to monitor patients on study treatments And we believe it will be more prudent to provide an update when we have longer follow-up from this cohort in the first half of 2024. And our preference is to do this at a medical conference. In the platinum-resistant ovarian cancer study, enrollment is increasing since we last reported with the activation of two additional sites. Nevertheless, Completion of enrollment of up to 20 patients will move into 2024. The platinum-resistant ovarian cancer landscape is continually evolving and becoming more competitive. Although we did not expect an impact of mirotoximab on our enrollment, which as per label is restricted to about 40% of folate alpha high patients, Ovarian cancer investigators are indicating that as the clinical community gain more confidence in the use of Mivetoxamab, this is having an impact on our enrollment. Following comprehensive discussions with our investigators, we're optimistic that we can address this gap and are working closely with our investigators on patient enrollment. our investigators remain enthusiastic to further enroll to our study based on the durability of responses with our triple combination reported at CITSE, as well as favorable safety profiles. In addition to our progress, I'm delighted to see the progress of our partner AstraZeneca is making with Revalgostomy. Their PD-1-tigit bispecific derives from our COM902 which has progressed into phase three as adjuvant therapy for biliary tract cancer after resection in combination with chemotherapy. In addition, AstraZeneca continues to progress their resveratamic phase one and two programs in additional indications. I believe that the progress of the resveratamic clinical program demonstrate the commitment to explore the potential of TGIT and our differentiated anti-TGIT COM902. Like COM902, a reduced ST-effector function anti-TGIT antibody, rilvagastamig was engineered to reduce ST-effector functionality with the potential to enhance anti-tumor activity. Now, moving on to what you should expect to see from us next. First, we plan to report data from our ongoing proof of concept study in MSS CRC in the first half of 2024. Second, we plan to enroll up to 20 patients in our ongoing proof of concept study in platinum resistant ovarian cancer and report data in 2024. More specific guidance will be shared during our end-of-year conference call. Third, identification of a predictive biomarker to enrich for responders for COM-701 combinations was always important for us. To this extent, We're excited about the progress we have made on generating initial biomarker data, which I alluded to earlier, showing for the first time an association between the expression of PVRIG ligand PVRL2 and clinical benefit that is consistent with our computational prediction. We will continue to build on these preliminary findings as part of our ongoing platinum-resistant ovarian cancer study, in which biopsies are mandatory. In parallel, we're also optimizing our PGRS2 assay to fit a potential patient selection study. Having the potential to enrich for responders in the platinum-resistant ovarian cancer patient population, Together with the durability of response and the safety profile of our triplet combination may allow us to build a unique development path for our triplet regimen. We will communicate early next year on how we will use this data to inform future direction. And finally, we're on track for IMD filing for COM 503 in 2024. Before handing over to Alberto, I will touch briefly on our finances and then Alberto will go into the details. We have an expected cash runway through at least the end of 2024, which we believe is sufficient to support all planned operations. This does not include any potential cash inflows, including potential milestone payments which we may become eligible for through our partnership with AstraZeneca. Also, as we indicated, obtaining non-dilutive cash from partnering is a priority and we are focusing our efforts on that front. With that, I will hand over to Alberto for the financial update.