Compugen Ltd Q3 FY2021 Earnings Call

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's Third Quarter 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 investor's 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. Today's call is being recorded, and will be available on the Investor Relations section of our website. Joining me to present our prepared remarks are Anat Cohen-Dayag, President and CEO, Henry Adewoye, Chief Medical Officer, and Ari Krashin, Chief Financial and Operating Officer. For the Q&A session, we will also be joined by Eran Ophir, Vice President Research & Drug Discovery. Leaving slide 2. 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, our business outlook, our development efforts and their outcomes, our discovery platform, anticipated progress, results and timelines for 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 Form 20-F filed 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.

Slide 3 please. Thank you, Yvonne. Good morning and good afternoon, everyone. Welcome to our Third Quarter 2021 update. Today is a notable day for Compugen with the announcement yesterday regarding the expansion of our strategic collaboration with BMS and a $20 million equity investment. We also released our presentation today, providing clinical, translational, and preclinical data that illustrate our strong performance across our unique clinical and scientific strategy, further supporting our future path. To our knowledge, this is the first-ever data presentation on the treatment blockade of PVRIG, TIGIT, and PD-1, as well as the first presentation of anti-tumor activity data for an Fc reduced effector function antibody at a scientific conference. These dose escalation studies have paved the way for us to initiate multiple expansion cohort studies aimed at broadly evaluating the DNAM axis in cancer immunotherapy and advancing the development of our two leading programs, COM701 and COM902. Henry will go over the data from our dose escalation studies during the call. Before that, I would like to provide a high-level overview of our long-term strategy's four key pillars and our clinical strategy. Moving to Slide 4. Our first pillar is to advance immuno-oncology research with the ultimate aim of developing new therapies. We have an excellent track record of discovering new targets and pathways in immuno-oncology, evidenced by our cutting-edge work published in peer-reviewed papers and the development of a clinical stage pipeline stemming from this research. Our validated computational target discovery platform has generated a pipeline of promising new candidates currently being evaluated in phase 1 clinical trials by us and our partners. This includes our potentially first-in-class anti-PVRIG antibody, COM701, our high-affinity IgG4 Fc reduced effector function anti-TIGIT antibody, COM902, and Bapotulimab, an anti-ILDR2 antibody being developed by Bayer and AstraZeneca's TIGIT bispecific antibody program derived from COM902. I am proud of our talented team of scientists with expertise in immuno-oncology and translational medicine, as we push forward the science of new, unexplored biological pathways while developing first-in-class therapeutics targeting these pathways. This leads us to our second pillar, which is to expand the number of patients benefiting from treatment by developing potentially first-in-class therapies for those who do not respond to existing therapeutics. The unique biology we uncovered regarding the PVRIG pathway has formed the basis for our research into the different combinations of PVRIG, TIGIT, and PD-1 inhibitors in selected biomarker-informed tumor types that generally do not respond to checkpoint inhibitors. What sets us apart is that we are the only company evaluating the combination of PVRIG, TIGIT, and PD-1 blockers in clinical trials. It is exciting to be leaders in the DNAM axis, especially given the recent advances and increasing interest in this area. Our third pillar is focused on maximizing value for patients, emphasizing our goal of rapidly and efficiently bringing new treatments to market. We seek collaborations and strategic partnerships with leading biopharma companies that have complementary capabilities worldwide to accelerate our early and clinical stage programs and facilitate their market entry. Our partnerships with BMS, AstraZeneca, and Bayer exemplify the value of our strategy in broadening the potential reach of our products to more patients. Finally, our fourth pillar is to safeguard our innovation while developing drugs for patients by securing intellectual property rights. We have developed a robust IP portfolio that offers potentially broad protection for our drug candidates. Moving to Slide 5. We have implemented a comprehensive clinical strategy to evaluate our DNAM axis hypothesis. We designed multiple combination studies that assess the simultaneous blockade of the three pathways, which are currently running in parallel across multiple tumor types selected based on biomarker insights. Each of these studies includes extensive translational data analytics to further elucidate our drug’s mechanism of action and to identify and assess potential biomarkers relevant for future patient selection. Additionally, our combination studies are being pursued in some overlapping indications, allowing us to evaluate the contribution of each drug within these combinations. By focusing on non-responsive tumors, we aim to clarify the role of COM701. The data from these multiple studies will guide us in selecting the combinations and tumor types to further our program. Moving now to Slide 6. I am pleased to report that we have achieved all our targeted milestones for this quarter and for the year. 2021 has been significant in reinforcing our leadership position in the DNAM axis, characterized by steady and impressive execution. We have completed all our dose escalation studies, including COM701 monotherapy, COM701 plus nivolumab, COM902 monotherapy, and triple combination studies. We have now progressed to expansion cohorts across all our programs, allowing us to concentrate on selected indications as per our translational data-driven strategy. Our achievements through 2021 also highlight the strength of our partnership approach in diversifying our portfolio, underscored by a milestone payment from AstraZeneca following the first patient dose in their Phase 1 study of the TIGIT bispecific derived from COM902. Additionally, we are excited to announce the expansion of our collaboration with BMS and believe that the recent $20 million strategic equity investment in Compugen will enhance our relationship and our joint efforts to bring innovative therapies to cancer patients through advancing our collaborative clinical studies. As part of this collaboration's expansion, a joint steering committee has been established to facilitate strategic oversight and guidance. This committee will operate alongside the existing joint development committee, which manages operational duties. With that, I will now turn the call over to Henry, who will provide an overview of our data released at CT today.

Thank you, Anat. Let's move to Slide 7. I'm happy to share an overview of the preliminary results from our ongoing Phase 1/2 study assessing the combination of COM701, our potential first-in-class anti-PVRIG antibody, with nivolumab and BMS's anti-TIGIT antibody BMS-986207, which we announced today at SITC. The study included 13 evaluable patients with various advanced solid tumors, all of whom had undergone extensive prior treatments, with a median of 10 previous therapies and a maximum of 19. We evaluated escalating doses of COM701 alongside fixed doses of nivolumab and BMS's anti-TIGIT antibody. The main goal of this study was to assess safety and tolerability. The study reported no dose-limiting toxicities, and the combination exhibited a favorable safety profile and was well tolerated. Achieving this important milestone allows for a thorough evaluation of Compugen's DNAM axis hypotheses regarding the triple blockade of PVRIG, TIGIT, and PD-1 pathways in specific biomarker-informed indications. Additionally, a dose of COM701 at 20 milligrams per kilogram IV every four weeks was identified as the recommended dose for further expansion. The expansion cohorts have started, and we are enrolling patients with platinum-resistant ovarian cancer, endometrial cancer, and head and neck squamous cell carcinoma. We also observed preliminary anti-tumor activity, with three patients showing stable disease, including one patient with prostate cancer who remained on study for over 100 days of treatment. Now, moving to Slide 8, our partner BMS and we found the translational data significant, indicating that the immune system was activated following treatment across various parameters, including interferon gamma induction, enhanced T-cell activation, and memory T-cell proliferation at all doses of COM701. These results are noteworthy for several reasons. They were consistent across various measures and patient responses. The effect's magnitude surpassed what we've seen in monotherapy and other combination settings for COM701, as well as results reported for other TDV antibodies in both mono and combination studies. They support a strong activation of the immune system after the triple blockade of PVRIG, TIGIT, and PD-1, aligning with extensive preclinical work. Importantly, immune activation was demonstrated in traditionally cold tumor types, such as ovarian, colorectal, and prostate cancer. Collectively, these findings reinforce Compugen's earlier conclusions regarding the potential of triple blockade to elicit synergistic immune activation, and we anticipate further evaluating our hypothesis in ongoing biomarker-informed expansion cohorts. Sticking with the theme of translational data, I would like to briefly mention some preliminary findings that will be presented at SITC in our research booster. Building on our observation that PVRIG may serve as a unique and dominant checkpoint in stem-like memory T-cell and dendritic cell interactions, we analyzed serum from two patients who responded to the combination of COM701 and nivolumab. Notably, we observed an increase in markers of dendritic cell activation in these patients when compared to non-responders. This suggests that the clinical response may involve enhanced dendritic cell and T-cell interaction influenced by COM701. It's exciting to see how our research on PVRIG's potential mechanism of action translates into preliminary clinical findings, further distinguishing PVRIG from TIGIT and PD-1. This implies a unique profile for COM701, capable of targeting both inflamed and less inflamed tumor types where existing checkpoint inhibitors have faced challenges, and also clarifies the expectation for more potent immune activation when combining COM701 with these other inhibitors. Moving on to Slide 9, we present data from our Phase 1 dose escalation study involving the high-affinity anti-TIGIT antibody COM902, designed with reduced Fc effector function. This study enrolled 18 patients with advanced solid tumors, all of whom had exhausted available standard therapies, with a median of 7 prior therapies and a maximum of 16. The primary objectives for the COM902 monotherapy dose escalation study were to establish safety and tolerability, the recommended dose for expansion, and the pharmacokinetic profile of COM902. Overall, COM902 showed a favorable safety and tolerability profile. In this study, we reported two patients with dose-limiting toxicities: one in the single subject dose cohort who experienced grade 2 vomiting at a 0.01 milligram per kilogram dose, and another who had grade 3 atrial fibrillation at a 1 milligram per kilogram dose, based on investigator assessment. Importantly, there were no dose-limiting toxicities reported at other doses, including higher doses up to 10 milligrams per kilogram, and the maximum tolerated dose was not reached. Notably, in the repeat dose preclinical study of COM902, no ECG changes were observed. The recommended dose for expansion was established at 2 milligrams per kilogram administered subcutaneously every three weeks. Additionally, COM902's pharmacokinetics were dose proportional, supporting this dosing schedule. We were encouraged by preliminary anti-tumor activity, with 50% of patients, or 9 out of 18, achieving a best response of stable disease; six patients, representing 67%, had confirmed stable disease, and three patients, or 17%, maintained stable disease for at least six months. While we view TIGIT as a combination therapy, achieving a disease control rate of 50% in this heavily pre-treated patient population is promising. These preliminary results hold particular significance for Compugen and the broader TIGIT landscape. There has been considerable debate regarding the relevance of the Fc domain for anti-tumor activity with TIGIT inhibitors. Our strategy has consistently focused on an anti-TIGIT antibody with reduced Fc effector function, believing it diminishes the risk of depleting CD8 positive T-cells, which are vital for anti-tumor activity. This indicates preliminary anti-tumor activity with COM902 monotherapy, corroborating that our reduced Fc approach is a suitable strategy, further supported by the translational data I will outline in the next slide. Lastly, on Slide 10, we present translational data from our study that further investigates this. Cytometry analysis of peripheral blood from patients treated with COM902 showed no significant changes in the counts of CD4 and CD8 T-cells and NK cells. This is crucial as these findings reaffirm that our reduced Fc strategy avoids depleting major TIGIT positive lymphocytes, essential for anti-tumor immunity, thereby supporting our choice of an IgG4 Fc reduced effector function anti-TIGIT antibody. Before handing the call back to Anat, I want to extend my gratitude to the patients and their families, investigators, and study sites. Anat.

Thank you, Henry. Slide 11, please. This year has been significant for Compugen, marked by strong execution of our unique clinical strategy, solidifying our leadership in the DNAM axis. We are the sole company targeting PVRIG, TIGIT, and PD-1 in clinical settings, maintaining a first-mover advantage for PVRIG inhibition and specifically for our three-pathway hypothesis. The validity of this hypothesis has been enhanced through new translational data, indicating robust immune activation via triple blockade, consistent across two different types of immune measures. Furthermore, we have deepened our understanding of PVRIG biology, supported by preclinical and translational data that outline PVRIG's distinct profile as an immune checkpoint. Exciting findings show an increase in activator DC markers in the serum of two patients who responded positively to treatment with COM701 plus nivolumab, suggesting that the interaction between dendritic cells and T cells initiated by COM701 may drive patient responses and could potentially address both inflamed and less inflamed tumors. Regarding TIGIT, our ultimate strategy involves combination therapies, and we are uniquely positioned to assess PVRIG and TIGIT in clinical settings through our ongoing COM701 combination study. We were pleased to share translational data supporting our choice of an anti-TIGIT antibody with diminished Fc effector function. Results indicate that COM902 successfully avoids the depletion of key TIGIT positive lymphocytes like CD4 and CD8 T-cells and NK cells, all while maintaining anti-tumor efficacy comparable to other TIGIT assets. We are encouraged by the increasing interest in the DNAM space and our three-pathway hypothesis, while also safeguarding our first-mover advantage and strong intellectual property protections. I am proud of our achievements, which include numerous significant data readouts and the launch of multiple expansion cohort studies, underpinned by translational data and more data readouts on the horizon, enabling us to advance our program for the potential benefit of patients. I am very excited about what lies ahead and grateful for the exceptional team at Compugen whose commitment has led to our significant accomplishments. I will now hand the call over to Ari to discuss our financials. Ari.

Thank you, Anat. So, moving to Slide 12. Our financial results for the third quarter of 2021 we did this morning continue to show our strong financial position as we execute across our expanding clinical programs. The $6 million in revenue this quarter relates to the AstraZeneca milestone triggered by the dosing of the first patient in AstraZeneca's Phase 1/2 study of a TIGIT bispecific derived from our COM902. Cost of revenues of $0.7 million are attributed mainly to royalty and milestone payments. Research and development expenses for the third quarter of 2021 were $8.7 million, compared with $5.5 million for the same period in 2020. The increase reflects the expansion and initiation of additional clinical studies during 2021, as well as increased drug manufacturing activities. Net loss for the third quarter of 2021 was $6.2 million or $0.07 per basic and diluted share, compared with a net loss of $7.8 million or $0.09 per basic and diluted share for the same period in 2020. As of September 30th, 2021, we had approximately $102 million in cash and cash-related accounts compared with approximately $111 million as of June 30th, 2021. With the recent $20 million equity investment by Bristol Myers Squibb, as well as the collection of the $6 million payment from AstraZeneca expected in the fourth quarter, our year-end cash balance is expected to be in the range of $130 million to $116 million. The Company has no debt. Thank you, and with that, we will now open the call for questions.

Thank you. Ladies and gentlemen, we will now start the question-and-answer session. Do you have a question? Please hold on while we gather your questions. The first question is from Mark Breidenbach of Oppenheimer. Please go ahead.

Good morning, everyone, and thank you for taking my questions. I'd like to start with 902 and the dosage you've decided to use for the expansion cohorts. It appears to be somewhat lower than what we observe with other TIGIT antibodies, including the fixed dose used in BMS-986207 in your triple study. Could you provide some insight into why you believe you have adequately dose-escalated and are confident in the 3 mg per kg dose moving forward? Additionally, what factors might make 902 potentially more effective than other TIGIT antibodies that have progressed to late-stage trials? Thank you.

Sure. Thank you, Mark. And Henry, would you like to start, and maybe Eran will have any additions later.

Sure, I can start. Thank you, Mark, for the question. We considered several factors when selecting the recommended dose for expansion, which is 3 milligrams per kilogram body weight administered intravenously every three weeks. One important factor was receptor occupancy, specifically peripheral receptor occupancy. As you know, COM902 is a high affinity TIGIT antibody, and we observed that we achieved peripheral receptor occupancy at a dose of 0.1 milligrams per kilogram body weight. We also increased the dose of COM902 up to 10 milligrams per kilogram body weight. After reviewing the data, including the pharmacokinetics, we, along with the investigators and study authors, concluded that increasing the dose beyond 3 milligrams per kilogram body weight would not provide additional clinical benefits for patient outcomes. This is why we chose the 3 milligrams per kilogram body weight dose. When benchmarking this dose against peripheral receptor occupancy, there is at least a margin of 30, indicating sufficient tissue penetration in the tumor microenvironment. While I won't comment on the metrics of other companies, I believe that if you look back at how they demonstrated their receptor occupancy and selected their doses, it is very similar across the industry. So, we are actually aligned with mainstream practices.

To add, when we compared COM902 to other leading TIGIT benchmarks, we found that COM902 exhibits superior binding, better blocking, and functional activity in vitro that is at least as good or better. We are pleased to see this translate into achieving full occupancy at a relatively low level compared to published data. Additionally, as Henry mentioned, we believe the chosen dose is adequate for maintaining full-year occupancy in the tumor microenvironment.

Okay. And just with respect to that one Grade 3 atrial fibrillation, is this a toxicity that's been seen in other studies of TIGIT antibodies, is there any chance in your mind that this is a class effect or you think this is a one-off?

Yes, that's a good question. We believe this is an isolated case for several reasons. We will review the pre-clinical data. We conducted repeat dose toxicity studies before beginning the human clinical trials, and those studies did not show any EKG abnormalities as mentioned in my prepared comments. Additionally, we did not observe any further toxicities when we increased the dosage to 10 milligrams per kilogram body weight, as I previously stated. Regarding that specific patient, I can provide some more details. The patient was diagnosed with atrial fibrillation, which resolved on the same day of the visit, approximately a week into the first dosing interval of the first cycle. Therefore, we believe it's an isolated effect. We are unsure if other companies with TIGIT inhibitors report all their data, so it's possible that reported data might only reflect a small number of patients, which could lead to the omission of single-digit toxicities. However, based on our preclinical data, we do not think this incident is related to COM902. That is our assessment.

Okay. Thanks for taking the questions. I'll jump back into the queue.

The next question is from Stephen Willey of Stifel. Please go ahead.

Good morning. Thank you for taking the questions. To follow up on COM902, the lack of lymphocyte depletion on TIGIT positive cells is interesting. Can you remind us what magnitude of decrease you would expect to see in these cell subtypes with the enhanced effector TIGIT antibodies?

Yes. Some of the companies reported their results, which indicate a significant reduction in peripheral blood. This is not a minor decrease. As we know, depleting cells in the tumor microenvironment is typically much more difficult, so we cannot confirm if there is any depletion there. However, in peripheral blood, they observed a considerable reduction of CD8 positive TIGIT positive cells, and this reduction was substantial.

Okay, that's helpful. And then on the triple combo biomarker data that you have again, I guess it appears to support the hypothesis that PVRIG is contributing something. But I know the way that the data is presented, it's a function of all doses. Is there anything that you can say with respect to there potentially being a dose dependency to some of these changes in biomarkers that you're seeing as a function of escalating COM701?

Okay. So, in this trial in the treatment study, the dose response range was not as big as we had in the past, so absolutely started in 1 patient in all three and then already moved to 1 mg per kg which is the already 4-step that you can see. So, in this specific context, we haven't seen much of a dose response. I reminded in the past and we had provided a range of responses, concentrations we did see a dose response of COM701 in combination with nivo etc.

And maybe you can just lastly, talk about how the expanded Bristol collaboration intersects with the fact that you are now through dose escalation with COM902. You're going to be interrogating various combinations with that agent. How do those two things overlap with each other if at all? And are you guys, I guess on the guardrails in place embedded within the collaboration such that you're kind of each day in your own way.

I agree with you, Steve. This expansion of our collaboration highlights the long-standing relationship between our two companies. It speaks for itself and is aimed at enhancing our strategic partnership. It will support the studies we have planned and assist Compugen in executing them. Currently, on the clinical strategy front, we have completed all the dose escalation studies we intended to conduct and have already initiated the expansion cohort. Keep in mind, we now have two combination studies with Bristol, focusing on both the volumes hub and the triplet, conducted across multiple tumor types. We have a comprehensive translational program addressing PD markers and immunohistochemistry, and we are committed to investing in technology centered around our patients. The collaboration is continually growing, and both parties believe it would be beneficial to establish a Joint Strategic Oversight Committee that operates alongside the Joint Development Committee, which is responsible for operational tasks. With all studies being expanded, this is the ideal time for us to align on our strategy regarding data interpretation and our thoughts on the next steps.

Alright. Thanks for taking my questions.

The next question is from Daina Graybosch of SVB. Please go ahead.

Hi. Thank you for the question. And congratulations on the data, guys. I wonder first on COM902, if you could give us any more details about the nature of these stable diseases. Did you see tumor shrinkage? Was there not so much shrinkage and a lot of stable? Any notable case studies that gave you a lot of confidence.

Thank you for the question, Daina. We examined the metrics for the enrolled patients and collaborated with the investigators to determine that the data presented in the poster effectively informed us about the clinical profile of the subjects involved in the study. Our focus was on the treatment journeys of the patients, as illustrated in the plots. We believe the plot best represents the extent to which those patients were pre-treated. We also included icons to indicate patients who had received prior immune checkpoint therapies and those with treatment refractory disease. Additionally, it's important to note that for patients in dose escalation, which is the only aspect we're reporting, the assessment of measurable disease was not a criterion for eligibility. Therefore, we didn't view it as relevant to determining tumor reductions. While patients could be evaluated based on RECIST, we felt the most effective way to showcase the anti-tumor activity of COM902 was through the plots. We did observe a few patients with tumor regressions, but upon closer inspection of the swimmer plot, it best illustrates how patients were responding in the study. That's why we chose to highlight the swimmer plot.

A follow-up then. How many of these patients do you know started with measurable disease and which ones did not?

We chose not to include that information because it was not part of the eligibility criteria, and many patients did not have measurable disease. Instead, we wanted to highlight the findings related to anti-tumor activity, including confirmed stable disease that we observed. Of the 18 patients, 9 had a best response assessment of stable disease, and out of these, two-thirds or 67% had confirmed stable disease. Additionally, there were 3 patients who maintained stable disease for 6 months or longer. The icons we presented give a surrogate assessment of how COM902 as a monotherapy with dose escalations offers some clinical benefit to the patients enrolled. Overall, if you reflect on this information, it provides a good indication of how the patients are faring in the study.

Okay. Maybe one more follow-up. For the patients of prior immune checkpoint inhibitor, do they follow, let's say, the 50 guidelines, for washout of between the periods that confirmed progression on the checkpoint?

We set specific benchmarks in the protocol regarding eligibility for enrollment in the study. Out of the 18 patients we enrolled, 8 had previously received immune checkpoint treatments. If you examine the plot, it clearly shows the various patients. We had one patient with existing carcinoma, one with peritoneal cancer, another with small cell lung cancer, one with prostate cancer, one with renal cell carcinoma, and one with caustic cancer. We adhered to the guidelines concerning washout periods.

Perfect, okay. Thank you very much.

No worries.

The next question is from Chris Howerton of Jefferies. Please go ahead.

Hi. Good morning. Congratulations on your progress, and thank you for addressing the questions. Several good questions have already been asked, but I have two of my own. First, could you provide any insights regarding safety observed in the triple combination study? Were there any notable toxicities or indications of immune activation, such as CRS? My second question may be a bit more challenging, but it seems significant that the patient populations here have been heavily pretreated, with a median of 10 previous therapies. How should we assess the potency of 902 in the context of patients with healthier immune systems, and what factors will you be monitoring as you move forward? Thank you.

I can start by saying that we did not observe cytokine release syndrome in our study involving the triplet or COM902. This was not anticipated in our preclinical assessments, and based on the data we have received, neither we nor the investigators have reported any instances of this condition. Despite inquiries and lab work conducted on patients, no cases have been observed. Considering the mechanism of action of COM902 and its role in the triplet therapy, the toxicities we have noted are either common across treatments or unique to the triplet itself. Our data on COM701, which I will discuss first, shows that it is very well-tolerated as a monotherapy with a favorable safety profile. We also have sufficient information regarding the combination of COM701 with nivolumab, which we will present at ASCO, and it has also been well tolerated with a good safety profile. We did not record the toxicities you referenced, with fatigue being the most frequent side effect for both COM701 alone and in combination with nivolumab, typically at grade 1 or 2. Other toxicities seen in combination related to the cancer itself, such as elevated liver function test results due to liver progression or obstruction from the cancer. Overall, nothing unusual has been observed so far. Specifically for COM902, it is also well-tolerated. Regarding patients with atrial fibrillation, we believe this is an isolated incident based on our preclinical data, and we did not see sacroiliac syndrome present. Additionally, most patients have responded well to the treatment, with only one subject discontinuing due to atrial fibrillation linked to prostate cancer. I'll stop there.

Okay. Alright then. That's great. Thank you very much, Henry.

The next question is from Tony Butler of ROTH Capital. Please go ahead.

Thank you very much. I have a couple of questions. First, in the triple study with a small number of patients, what qualifies as a high expressor of PVRL2? Second, regarding the translational data, which I greatly respect, I'm curious about the pharmacokinetics of 701, especially in relation to low vs. high doses. Is there any correlation between the dose level and duration of treatment? And, do you have any theory on why we aren't seeing greater tumor shrinkage, considering that the translational data is primarily peripheral? We lack information on the dosage at the tumor site unless you have insights on that. I'm aware these patients are very sick and have undergone multiple therapies, but I would like to hear your thoughts on this matter. Thank you.

Okay. Thanks. I think I can take it. So first of all, for the high expressor of PVRL2, as you may remember, we published quite extensively in the past that certain tumor types have higher expression of PVRIG and PVRL2. And these are the indication which we're moving forward to now. So just indication which PVRL2 in terms of age score, if you wish, it's probably 200, 300 at least for the first one. Then for the dose and duration, Henry, you probably want to take this one and I could take the third one.

You're correct that the duration is a reflection of the heavy pre-treatments that diplomas on the studies we're on. Just as a matter of fact, we did indicate that in our prepared comments and also on a poster that in the median of ten prior therapies with a range of one through 19, and if you think of the COM701 nivo study, this was the median of five. So, it's actually essentially a doubling of the media anti-therapies. If patients are unable to stay as long, then you probably will not be able to see this correlation that is of interest to you, that is also of interest to us. So, it's all based on the heterogeneity of the patient population and the length of time patients stay on. Those are the key metrics that inform on the relationship with treatment outcome.

We are very excited about the translational data and our partnership with BMS. We have been studying this pathway for over a decade, establishing the biology and preclinical data that shows combining three agents modulates the DNAM axis and achieves synergy in multiple clinical models. For the first time, we are observing such a strong response in patients, evident in the potency and consistency of the results across various assessments. This transition of data into the patient context is thrilling. When we compare this data to our own results with COM701, both in monotherapy and combination settings, as well as all published data on TIGIT, our findings continue to appear more robust and potent. This suggests that the triplet therapy is working differently compared to combinations of the agents used individually. Regarding the tumor microenvironment, it is important to note that this trial involves heavily pretreated patient populations. More needs to occur in the macro environment to observe actual tumor shrinkage. We have conducted several biopsies and aim to expand the trial to further explore the micro-environment. The peripheral immune effects we are seeing are significant; however, in these heavily pretreated patients, they might not be adequate to sufficiently influence the macro-environment needed for tumor reduction. We are eager to see how this regimen performs as we move forward with our market-driven expansion.

Excellent am grateful. Thank you very much.

The next question is from Reni Benjamin of JMP Securities. Please go ahead.

Hey, good morning, guys. Thanks for taking the questions. I guess just starting off with the triplet and Henry, some of the comments you have made regarding the extension cords. Did I hear right that prostate wasn't one of the ones that you will be expanding into and if I did hear right, I was just kind of curious given the long-standing SD that you have here, why that is.

Thank you. Reni. So, for the expansion cohort, for the triplet, we're focused on the biomarker-informed patient population. We are focused on ovarian cancer, we are focused on endometrial cancer, we're also now focused on head and neck squamous cell carcinoma, and we also have a basket cohort. This is of interest to us also, prostate cancer. But understandably, we think we need to prioritize the indications that are of interest to us. And that's why we're focused on what we have now currently at the start of the expansion for the triplet.

Okay. As you have reviewed this data, are there any new insights related to biomarkers that you can share? Have you discovered anything new that could influence your expansion cohorts?

So, the main observation is that biopsies are not mandatory in this part of the trial, but this is a work in progress. We are collecting samples from all the patients, particularly since the expansion cohorts will follow with correlations to different biomarkers we explore, and we will also explore modulation in the tumor microenvironment. However, this is all a work in progress.

Reni, I want to emphasize that we are seeing significant immune activation in both the triplet and the doublet with COM701 alone. This observation supports our hypothesis regarding the PVRIG pathway and its combinations. It was crucial for us in the dose escalation phase to gain confidence before moving into the expansion cohort. We have a lot of work ahead in advancing these studies and ensuring we are active on all fronts with our translational approach. While we are still evaluating the data we have, we are encouraged by our findings.

Got it. Finally, given these results with the triplet and how pleased you are with them, why not consider evaluating 902 and 701 alongside either a PD-1 or PD-L1 inhibitor compared to the ongoing 902 and 701 studies? When we look at Roche's data, the response rates with the PD-L1 inhibitor are notable. Is there a biological reason to continue with Opdivo? I understand the considerations from a cost perspective and the Bristol collaboration, but is there a thought process or something you're currently considering regarding evaluating different combination partners? Thanks.

On the AstraZeneca dose, if you have any additional insights, we have launched the studies we aimed to conduct, collaborating with Bristol-Myers Squibb and using nivolumab. These studies are intended to help us explore relevant drug combinations for various patient populations across different indications and evaluate which ones we should prioritize for future investigation. However, we are open to the possibility of using additional PD-1/PD-L1 inhibitors in the future. Currently, through our partnership with BMS, we are focused on this approach to gather the necessary data for a more in-depth analysis of specific indications and combinations. Would you like to add anything?

I think you've said most of it. Just one little part of it that I think you've articulated very well before in the past, and continuously, Anat, and that's not just to look at the PD-1 / PD-L1 access, but also to rely on the strength that Compugen has with its antibodies. We also think strategically of a PD-1 and PD-L1 free regimen. And as a consequence of that, we have this ongoing study with an expansion cohort of COM701 and COM902 and learning patients with non-small cell lung cancer, head and neck squamous cell cancer, and also colorectal cancer. So that's the other strategy, which I think might be of interest to you also. And I know you remember these, Reni, so not just the PD-1, PD-L1 combination, but one that is free of those agents.

Great, thanks for taking the questions.

This concludes the Q&A session. I will now turn the call back to Compugen's President and CEO, Dr. Cohen-Dayag. Would you like to make your concluding statement?

Yes. Thank you, Operator. Thank you for joining us today and for your continued support. We hope to see your safety. Stay safe and healthy.

Thank you. This concludes the Compugen Ltd, third quarter 2021 financial results conference call. Thank you for your participation. You may go ahead and disconnect.