Compugen Ltd.

Ladies and gentlemen, thank you for joining us today. Welcome to CompuGen's third quarter 2022 results conference call. At this time, all participants are in the 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, Yanni, and thank you all for joining us on the call today. Joining me from Compogen are Dr. Anako Undayak, President and Chief Executive Officer, Dr. Henry Adewoye, Chief Medical Officer, Dr. Iran Ofer, Senior Vice President, Research and Drug Discovery, and Alberto Sessa, Chief Financial Officer. 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 our programs, financial and accounting-related matters, as well as statements regarding our cash business. 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. With that, I now turn over to Anat.

Thank you, Yvonne. Good morning and good afternoon, everyone. And welcome to our third quarter 2022 update, fresh after a great CITSE conference in Boston last week, where we had two oral presentations. In the first nine months of the year, we've continued to execute and meet our guidance. We presented clinical data from the MSS CRC expansion cohort at CITSE last week. And in three weeks' time, we will present clinical data from the two ovarian expansion cohorts at ESMO-IO. During our first oral presentation at SIFI, Dr. Michael Overman from MD Anderson presented encouraging overall response rates following treatment with COM701 in combination with nivolumab in heavily pretreated metastatic MSS-CSC patients, a hard-to-treat tumor type, typically not responsive to immunotherapy. Over 70% of the patients from this study had liver metastasis, typical of this patient population who are resistant to treatment. Responses in these patients with liver mets is a key differentiator for COM701 and a unique achievement. On the safety side, there were no serious adverse events deemed by the investigator as related to study drugs. During our oral presentation at CITSE, Eran presented data showing that COM701 in combination with nivolumab results in potent immune modulation in the two MSS-CRC patients with liver mets who responded to treatment, suggesting that the clinical responses we observed in such a cold tumor type are linked to a COM701-mediated effect. He also presented data showing immune modulation in platinum-resistant ovarian cancer patients treated with COM701 monotherapy. This data in an additional cold tumor type, typically not responsive to immunotherapy, is further supported by encouraging data in platinum-resistant ovarian patients treated with dual and triple combination therapy, blocking PDR-IG, and PD-1 with and without blocking TIGIT. We're looking forward to presenting this data at ESMO IO in December. I'm excited that the totality of our data suggests a COM701-mediated effect, and this is specifically encouraging as it is observed in hard-to-treat, non-responsive tumor types. The combination of our translational data from patients' tumor samples along with our preclinical and clinical data suggest that the increased infiltration of T cells to the tumor microenvironment following blockade of PVRIG may be needed to sensitize the tumors to TGIT and PD-1 blockade. We believe that a triple blockade of the denim axis unleashing the three pathways may result in turning cold tumors like MSS-CRC and platinum-resistant ovarian cancer more responsive to such immune checkpoint inhibitors. As a result, we're planning a triple combination study in MSS-CRC patients with our own potential first-in-class COM701 in combination with our own potential best-in-class anti-TGIT COM902 and an anti-PD-1. Our anti-TGIT COM902 was engineered to reduce FP functionality with the potential to enhance anti-tumor activity, and we believe this is the optimal design to pursue clinically and look forward to seeing how this plays out in the clinic. This is further supported by by the preclinical data AstraZeneca recently presented at SITC on their PD1-TG bispecific derived from COM902, also engineered to have reduced the FC function. Moving to ovarian cancer, we believe the encouraging data in platinum-resistant ovarian cancer merits further development in this indication, which opens the door for us in a much less crowded, competitive landscape compared to non-small cell and cancer. For this reason, we have decided to pursue platinum-resistant ovarian cancer, and we're now evaluating the various options for the planned non-small cell and cancer studies. Following the disclosure of the data from the two ovarian cancer studies at ESMO-IO, we will host an investor call to describe the totality of our data and provide details on our studies. We have a solid balance sheet with cash expected to support operations at least through the end of 2024, and we're committed to this guidance and our focus on two indications with what we believe has the highest probability of success. On that note, I would like to welcome on board our new Chief Financial Officer, Alberto Cessa, who is with us today for his first conference call with Compugen. I'm delighted to have Alberto as part of my management team and as we continue to focus on execution and delivering meaningful clinical data and value to our stakeholders. During today's call, Henry will start by providing an overview of the MSS CRC data presented at CITI. Eran will then provide an overview of the research and translational data that he presented at CITI. I will then set the expectations ahead of the data in platinum-resistant ovarian cancer patients, which we will present at ESMO-IO. Alberto will then bring you through the third quarter financials, and then we will open the call for questions. With that, I will hand over to Henry.

Thank you, Anat. I am very happy to provide an overview of the data that Dr. Overman presented at SITC 2022. There is an urgent medical need for patients with MSS CRC who have very limited treatment options. Microsatellite stable colorectal cancer is a cold tumor type with limited T cell infiltration which, as you know, are required for immune checkpoint inhibitors to be effective. Historically, most immune checkpoint inhibitors have demonstrated limited or no activity in such tumors. Standard of care in the third line or greater metastatic CRC setting is typically regorafenib or TAS-102, which show an overall response rate of 1% to 2%. median PFS of two months, and median overall survival of six to seven months. Most patients with metastatic MSS-CRC have metastasis to the liver, and studies show that presence of liver metastasis correlates with lack of response to checkpoint inhibitors. The data we presented includes two patients from the combination dose escalation cohort study and 20 patients from the combination cohort expansion study. The baseline characteristics are typical of a patient population with metastatic MSS-CRC with 77% of patients with liver metastasis. Patients were heavily pre-treated with a median of three prior therapies, and 32% had prior treatment with regorafenib or TASC-102. which is current standard of care. The objective response rate was 12% in the 17 patients with liver metastasis. The two patients with partial responses also had HERAS mutations, an additional adverse prognostic factor. Observing responses in patients who would typically have been poor responders and with poor prognosis is unique and highly encouraging. The objective response rate was 9% in the 22 patients in the overall population, and the disease control rate was 27% with two partial responses and four patients with stable disease. Observing two patients with anti-tumor activity one stable disease and one partial response for six months or longer is encouraging, considering that this is a hard-to-treat tumor type in which the patients on the study have been extensively pretreated, and the median overall survival in this patient population is likely less than six months when compared to standard of care. In terms of safety and tolerability, COM701 combined with Nivolumab showed a favorable safety profile and was well tolerated. No patients discontinued study treatment due to the toxicity of any of the study drugs. Notably, no serious adverse event was assessed by the investigators as related to study drugs. The totality of our data combined with the mechanism of action of COM701 justifies the further development of the triple blockade of the DNM axis with PVRIG, TGIT, and PD-1 in this patient population. As Anat mentioned earlier, we are moving ahead with the evaluation of this triple combination in a proof-of-concept study. I would like to extend our sincere thanks to the investigators, study staff, patients, and their families participating in our clinical trials. With that, I will hand over to Eran.

Thank you, Henry. I'm delighted to share the robust translational and research data I presented at CITC on Friday, which supports the data just presented by Henry. Truth of this COM701, in combination with nivolumab in MSS-CRC patients, was associated with potent immune activation in Tumor microenvironment. We also showed data supporting unique expression of TBRG on the early differentiated stem-like memory T-cells, which are key players in driving T-cell proliferation in the tumor microenvironment. To go into details, we shared translational data from 13 patients with the static MSS CRC. As I mentioned, treatment with COM701 in combination with Divolumab was associated with potent human activation. Importantly, in the two patients who had partial responses, we saw even more potent immunactivation in the tumor macroenvironment. Such magnitude of immunactivation for a checkpoint blockade is not typical for a cold tumor like MSS-CRC. The clear immunactivation seen also in home-responding patients may suggest that the full blockade of the genome access by the anti-treated antibody might tip the balance toward enhanced immunactivation and subsequent further improved clinical outcomes. This is supported by our preclinical and clinical data across our studies. We also presented translational data in five patients with another cold tumor, platinum-resistant ovarian cancer, treated with COM701 in monotherapy. Also here, treatment was associated with clear immune activation in the tumor macroenvironment. The pre-treatment biopsy of one patient who had a durable partial response to COM7-1 monotherapy showed an immune desert with no T-cells in the tumor macroenvironment and sending a negative for PD-L1. COM7-1 induced a robust increase in interferon gamma in the peripheral blood of that responding patient from whom we didn't have post-treatment biopsy. Also here, the clear immune activation seen also in non-responding patients with only PVLG blockades may suggest that the full blockade of the DENM axis might tip the balance toward enhancing immunoclinical antitumor activity. Such triple data blockade in ovarian cancer patients will be presented by us at ESMO I.O. Finally, on the research side, we describe unique attributes of PVRLG that may provide biological rationale for these anti-tumor and translational activity of COM701 in indications typically not responsive to checkpoint inhibitors. Using cutting-edge technologies and computational analysis, we show that PVRLG, compared to checkpoints like PD-1 and TIGIT, is uniquely and dominantly expressed on early differentiated stem-like memory T-cells in tertiary lymphoid structures. These cells could drive proliferative anti-tumor T-cells burst that may be inhibited dominantly by PBRG. Therefore, unleashing this blockade by COM7-1 may efficiently drive T-cells into tumor microenvironment, and in doing so, making cold tumors like MSS-CRC and platinum-resistant ovarian cancer more responsive to anti-PD-1s and potentially anti-TGITs as part of the crosstalk of these three pathways. With that, I am now turning back to Anat.

Thank you, Ron and Henry. Moving now to setting expectations ahead of the platinum-resistant ovarian cancer data, which we will present at SMIO on December 8. We will present preliminary data, including overall response rates, duration of response, safety, and very initial translational data from 20 patients with platinum-resistant ovarian cancer who were treated with COM701 in combination with nivolumab, and 20 patients who were treated with COM701 in combination with nivolumab and BMS antitigid. We're excited to be seeing encouraging data following dual and triple blockade of the DENAM axis in these patients. Effective treatment options for patients with platinum-resistant ovarian cancer are limited. Specifically, standard of care in patients with platinum-resistant ovarian cancer is single-agent chemotherapy, and responses range from 8% to 12%, with median progression-free survival of three to four months, and overall survival of around one year. Also, immune checkpoint inhibitors as monotherapy and as part of immunotherapy combinations, have demonstrated limited activity in this patient population. Also here, PVRIG unique biology, different than other checkpoints, have potential to generate different outcomes. Finally, we plan to host an investor call following our data presentation at SMIO on December 8th. During this call, we will discuss the data presented at that conference, including in platinum-resistant ovarian cancer patients and non-small-cell cancer. The metastatic non-small-cell cancer data we will present is long-term follow-up of a very small number of patients already presented at ASCO in 2021 treated with COM701 with or without nivolumab. In the call, we will also provide details on our planned studies, and we plan to share initial findings and progress on these studies during 2023. We're also making progress on our preclinical pipeline and are very excited about our lead program, COM 503, which has first-in-class potential. We will elaborate more on this program during the end of the year investor call in early 2023. I will now hand over to Alberto.

Thank you, Annette. I'm delighted to be on board and excited with the opportunity to work closely with you and the CompuGen experience management team to ensure the company will continue to execute and deliver value to our stakeholders. Our financial results for the third quarter of 2022 are in line with our forecast and working plans. We have a solid balance sheet with sufficient cash, which is expected to support operations at least through the end of 2024, and we are committed to continue delivering meaningful clinical data. As of September 30, 2022, we had approximately $88 million in cash compared with approximately $118 million as of December 31st, 2021. The company has no debt. For the third quarter of 2022, we reported a net loss of $11.7 million, or 14 cents per basic and diluted share, compared with a net loss of $6.2 million, or 7 cents per basic and diluted share, in the comparable period of 2021. R&D expenses for the third quarter of 2022 were $9.3 million, compared to $8.7 million for the comparable period of 2021. As a result of our decision to focus on two prioritized indications, starting 2023, we expect our ongoing R&D cash expenditure to be lower than the current trend rates. This is expected to extend the cash runway to at least the end of 2024. G&A expenses for the third quarter ended September 30, 2022, were $2.6 million, compared with approximately $2.8 million for the comparable period in 2021. And with that, we will now open the call for questions.

Thank you. Ladies and gentlemen, At this time, we will begin the question and answer session. If you have a question, please press star 1. If you wish to decline from the polling process, please press star 2. If you are using speaker equipment, kindly lift the handset before pressing the numbers. Please stand by while we poll for your questions. The first question is from Steven Wiley of Stifo. Please go ahead.

Yeah, good morning. Thanks for taking the questions. And congrats on the updated CIDC. I guess the selection of tumor types within the original development program that you guys outlined, I guess it was at some point last year, really prioritized biomarker expression. I think both PBR and PBRL2 What can you say about the expression of these biomarkers in colorectal, which I know was not originally included in the tumor types of interest?

Thank you, Steve. Yes, you are correct. So when we started the program, based on preclinical data and also based on expression profiles in tumor samples taken from patients, not patients in our study, We were prioritizing ovarian, endometrial, breast, and non-small cell cancer. Later, when we started to see the dose escalation data, we also prioritized MSS-CRC. And I'll just say that when we returned back to look at the CRC data, the expression was somewhat lower than the indications that were prioritized, but still high. Maybe I'll ask Iran to say a few words about the expression profits of the ligands and the receptor.

Yes, so as I mentioned, the MSS-CRCs definitely have a dominant expression of the P-Bology pathway. Basically, every tumor that we ever tested for MSS-CLC is positive for PVRL2 for sure and actually has abandoned expression. It is a bit lower than ovarian, which is even a bit higher, but definitely PVRL2 is there in all the patients we have tested. And PVR, the ligand of digits, is also high. And actually, MSS-CLC is one of the indications with the highest expression compared to other indications of PVR, the ligand of digits.

Okay, that's helpful. And then maybe you can just talk a little bit about some of the factors that you're now considering in terms of your decision to move forward into lung. And I guess, would the decision to pursue lung or any other tumor types beyond colorectal and ovarian have a meaningful impact on the current cash runway? Thanks.

So, yeah, so maybe first I'll try to remind why we picked non-small cell and cancer. As you know, this was not part of the cohort expansion studies that we had in the combinations, any of them. Actually, it was in the doublet in the PD-1 free regimen, but not with PD-1. The reason we picked this indication is because we thought that focusing on an indication that is immune checkpoint sensitive, that is responding, inflamed, would set a different bar for us. And we wanted to pick a non-inflamed one and an inflamed one. I have to say that we recognized at that time, and we were relating to it, that it's a more competitive area for us to get in. As data matured with the ovarian cancer and we saw the data, we understood that there is an opportunity for us to get into an area that is less competitive. Enrollment rate would be easier to address. The signal that we will need to present, even though ovarian cancer is a hard to treat tumor type and mainly checkpoints are not showing great signals there, but still, the way for us to exemplify signal would probably be easier as compared to non-small cell cancer where we would need to get to much higher numbers. So we did encouraging data that we have in hand. We thought that it would be better for us to switch the indications. I'll say that for the non-fungal cell cancer, we're still evaluating our options for doing the study internally, maybe at different timelines, or to do it externally. investigator-sponsored studies. We have a great relationship with our investigators, and we'll try to assess what's the right path for us in non-fungal cancer. But at this point in time, it was very important for us as a company to stay focused, on one hand, and make sure that we commit to the guidance of the cash runway, but also still peek to indications where we feel that we have higher probability of success, and they think that Ovarian is included in this definitely. Going forward, I think that in general, you know, we're now going to start the studies, and we're continuing to evaluate the data that we have, obviously, and we'll make sure we We don't leave value on the table with respect to Comp 701. All right.

Thanks for taking the questions.

The next question is from Mark Breidenbach of Oppenheimer. Please go ahead.

Hey, thanks for taking the questions. I really appreciated Iran's presentation with all the translational data. I guess one of my main questions is, what are you guys seeing as the best evidence that addition of a TIGIT antibody to the 701 Nivo doublet can do even better than what you're already seeing in terms of tumor microenvironment modulation and immune activation that you've seen with TIGIT? NIVO plus 701 in a doublet combination. And then a second question is, obviously, at CITSE, we saw some encouraging data from a CTLA-4-DD1 combination in microsatellite-stable CRC. I was wondering if you could take a moment to just compare and contrast the safety profile of your combination, the COM701 plus NIVO combination. versus that I-O combo, maybe highlight distinct patient groups that one combination may be more appropriate for than the other. Thank you for taking the questions.

Thanks, Mark. So for your first question, it's a very important one. So I think there are a few lines of evidence to support that. First, the research we're doing on the D9-1 axis preclinically definitely shows that if you combine PD-1 TGIT, and PVLG blockade to completely unleash DNM activity. Then you get an optimal and enhanced T cell activity. Later on, in patient samples treated with the triplet, this is what we have seen. It was very exciting to see that when you get a triplet, you can follow the patient's blood. At that stage, this is what we have done. And we can see really important immune activation with triple blockade in patients treated with the triplet of blockade of COM701 with COM701, TGIT, and PD-1 blockers. Finally, in our cohort of patients treated in the MSS-CRC with COM7R plus NEVO, yes, the responding patients were immune-modulated very significantly. But we also have many patients that were immune-modulated a bit to a lesser extent. We do see increase in tissue infiltration. Things are happening in the tumor microenvironment, but not sufficiently to drive activity probably. Now, we do know that when you have more tissues in the tumor microenvironment, TGT is then more active. So what do we think? that in this patient that we were able to drive immunity, but not in sufficient level to drive clinical activity, adding now digits should enhance immune activity that will translate also to enhance clinical activity, and this is exactly what we're going to test.

And Mark, and to your other question with respect to other agents, CTLA-4, IL-7, I think that there are two, first it's encouraging data, obviously. It's encouraging data, what has been seen in MSS-CRC, and it's great for patients. I think that the two major things that one needs to remember that are highly differentiated in our studies on our data is the fact that the safety profile, and Henry can elaborate on this, And also the fact that we see sickness in liver mass. And again, Henry will relate to it, but I'll just say, other than the regular study in Japan, all the studies are showing zero response rate in this patient population. Now, remember that this specific patient population is actually consisting about 70% of the population. So... That's the reason we think that the data that we're showing are encouraging specifically for MSS CRC patients. And Henry, feel free to elaborate on the safety and on the data.

Yeah, so Mark, thank you very much for your question. With all the caveats of comparing across trials, even though they're phase one trials, And the caveat with comparing different class of agents, it bears repeating that in all the studies that we've conducted, not just the one we've reported recently at SITC 2022, but beginning from 2018 when we started to report data on all the ongoing trials, we've been able to show that even when we use COM701 as monotherapy, up to 20 milligrams per kilogram body weight dose IVQ for weeks as monotherapy, And in combination with nivolumab, and in combination with nivolumab and BMS-986207, which is a CT antibody, we haven't reported any increase in the toxicities of any of the agents that it's been combined with. And specifically, if you go back and look at our data that we've reported at SITC with Dr. Overberg, we didn't report any subject coming off study drugs as a result of any toxicity. The most common treatment emergent adverse event that we've seen in at least four subjects was anemia, and most of these were grade 1, grade 2 in about a third of the patients, likely related to the disease itself, hypoalbuminemia and fatigue. Overall, it's grade one, grade two toxicities. And remember, this is in combination with nivolumab. I wouldn't want to elaborate a lot more on the CTLA-4 antibody because we all know what the toxicity profile of these agents are. There has to be, and that question was asked during SITC, actually to the presenter with regards to trying to select patients for their studies that he will subsequently conduct, trying to exclude patients who've had prior toxicities or discontinuation from immune checkpoints. And specifically in their report, they have about almost a third of patients with diarrhea. They have grade five events, including colitis and intestinal perforation. This might possibly be related to sometimes the disease, but they do say it's related to the studied drug because they're treatment-related adverse events. So COM701 alone, COM701 in combination with nivolumab, COM701 in combination as a triplet with BFS96207, very well tolerated, favorable safety profile, and even at the doses we've selected, we have not reported any increase in the adverse event profile of the drugs that we're combining with. So very favorable, and the investigators that we meet with regularly mention this, and it's borne out in the report at SITC and in other prior publications.

Okay, thanks, Henry.

Thank you. Just to add one mechanistic insight about basic in the fundamental biology of CTLA-4 versus PBRG. CTLA-4 is a major player controlling peripheral tolerance, and that's why from the mice studies all the way to the patients, we see all this toxicity. Well, PVRG was just shown now in SATC that much of the activity is happening in the tumor microenvironment. This whole hypothesis and what we show that PVRG is dominant in these structures in the tumor microenvironment in which tissues are proliferating. And we have shown that actually that most of the activity, the most dominant clone proliferating in the responding patient is in the tumor microenvironment. So biologically, it seems that PVRG plays a less of a relevant role in peripheral tolerance and much of the defense activity of tissue proliferation is in the tumor microenvironment.

Got it.

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

Hey, good morning, everyone. Thanks for taking the questions and congratulations on the progress at CITSE. I guess maybe just starting off, I'm kind of curious how you guys are thinking about the implications if, you know, Roche's data at some time in 2023 pan out, kind of what are the implications for Compugen? And then maybe even more importantly, if, you know, triaglumab doesn't show a survival benefit, kind of what are the implications to Compugen? And then I have a follow-up.

Thank you, Rennie. Yes, it will have implications on Configen, obviously. If data is positive, then great. I guess that interest in TGIT will resume in the industry, and we will continue to be there to make sure that people understand that TGIT without PVRIG is not the way to go in certain tumor types. Definitely not those that are not responding to P1 blockers. So that's an important thing and we'll continue to make sure that this is being heard and we're pursuing it as well. I'll say that my answer will be somewhat similar if it is negative. If it is negative, yes, I guess that the sentiment in the market would not be that great, but it doesn't mean that what we're doing is not the right thing. We have the biology to support us, strong biology. We have data from patients, clinical responses, as well as data from the tumor microenvironment. And we have the assets. We have two independent assets, and we're going to pursue it. That's our plan. So it is going to be probably harder if the sentiment is not there. But we are going to present it, and we believe that we will show good, positive data that will be convincing. I think that, you know, at the end of the day, it may also be somewhere in the gray zone, but still, any scenario, we're moving forward.

Got it. The second question is just in terms of expectations for the platinum-resistant ovarian cancer, you know, you mentioned during your prepared remarks kind of where the typical objective response rate is, where the typical median overall survival is. Can you talk a little bit about, you know, what you're looking for, what helps frame a go, no-go decision, you know, in your mind? You know, what do you need to see?

So we will not go too much into detail with this. You know, when the data will be out there, we can speak about it in a more informed way. But I think that I'll just let Henry relate to the field and what should be seen in ovarian cancer, in platinum-resistant ovarian cancer patients in general, not alluding to our data. Henry?

Yeah, so thank you very much, Reni. In her prepared remarks, Annette already previously mentioned what one would expect. And if you look at the NCCN guidelines also with respect to platinum resistance ovarian cancer, there is wide consensus that what is recommended for most patients in that category is monotherapy. And the results are typically in the range of single digits, like Annette mentioned. and PFS, three, four months, and median overall survival, about a year. Essentially, what we will be expecting is to see an improvement in any of these parameters, including quality of life also, which we seem to be hearing a lot more with respect to our clinical trials with COM701 and Lono in combination with any of the other agents like BMS9-8607, all in combination with NEBO. As you know, Renny, there have been a lot of, unfortunately, failures with trying to investigate what immune checkpoint activity is in platinum-resistant ovarian cancer. So the results, at least that, you know, we're encouraged by what we're seeing in our study, and those are the metrics that we'll be looking for. with respect to what standard of care will typically be in this patient population. And I think there are fair metrics in the sense that at least you can benchmark these to what's been reported in larger studies that's been conducted with chemotherapy. So that's as far as I will go until we formally disclose the data at ESMO-IOC.

Got it. Okay. And my final question is for Arun, I guess. We'd love to get an idea as to how the biomarker kind of patient selection, you know, work that's being done at Compugen is going. And I guess where my question is going with this is, you know, you guys saw significant immune activation in those two PRs, you know, presented at CITSEE. But at baseline, all the patients look the same, right? It's kind of like after you've been treated, you see this activation. I'm kind of curious, have you been able to make any more headway in terms of selecting those patients or excluding patients that may or may not respond?

Yes, of course, this is very important, and we are doing extensive work, both with the normal IHC assays, and also we're sequencing the tumors. We're using our computation capabilities to try to identify maybe less obvious candidates for patient selection. So this work is ongoing. One important thing to mention that one obvious biomarker that you're looking at, and for other checkpoints, it's worked mainly for PD-1s, and in our case, we don't see a clear correlation. It's PD-L1, right? I mean, also talking about the ovarian cancer responses I've seen, if there is any checkpoint activity response in ovarian cancer is normally in PD-L1 CPS above one, even in the American PD-1 plus digit study, where they have some responses, there are zero responses in PD-L1 CPS of zero. We already have results in ovarian cancer patients treated in monotherapy. That was PD-L1-0 who responded to COM7-1 monotherapy. We also have results now from the CRC code. Some patients are really not inflamed tumor environment. Actually, the patient with the highest PD-L1 level before treatment relapsed. So at this point, PD-L1, maybe because of that unique biology of PVRG, being able to work also in less inflamed tumor types seems less relevant. Of course, we continue to evaluate, and we are evaluating all the DINAMAXIS members, and this is work ongoing. Thank you.

Great. Thanks for taking the questions.

The next question is from Dana Graybosh of SVB Securities. Please go ahead.

Hi. Thank you for the questions. I have two as well. The first one for Henry. I wonder if you could talk, Henry, more about the second responder with MSF CRC. I think you said or the presenter said they had unmeasurable liver metastasis. I wonder what that means specifically and whether you had any signal of benefit in the liver with the combination therapy, either radiographic or clinical or symptomatic.

Yeah, Dana. Yeah, so that subject that... Dr. Overman presented was a patient, obviously, who cared as a mutant tumor and had a bulky disease. They had liver lesions. They had pulmonary lesions also. And per assist, the investigator had to select, of all the tumors, which ones were measurable per assist and which ones would be deemed non-measurable that would be followed subjectively per assist. So they selected the ones in the Now, of the two patients, the first one we reported previously at AACR, we did see that the liver lesions were selected and there was a reduction in the target lesions. In the second patient, which was presented by Dr. Overman, there was a significant reduction in the target lesions that were selected in the lungs. The liver lesions appeared stable. meaning they didn't get any worse. So that in itself is significant because that shows with the number of prior therapies that a subject had previously received that there was no progression in terms of those target, in terms of the deliberations, but there was significant reduction when it came to the target patients that were selected. Unfortunately, the subject, like we did mention, relapsed to the brain, while at the same time maintaining the responses that were observed at the time when they had the imaging assessments performed per assist. Does that answer your question, Tina?

It does. Thank you. And then another one for Iran, I think somewhat similar but a different twist to one that everybody's been asking you about, really the mechanistic rationale for why PBRG and MSS-CRC. You clearly showed the CRC responses were immune-driven, and I think you also clearly showed the sort of translational differentiation of PBRG. I'm wondering how you think you could or have you linked those two pieces of evidence. So do you have any translational or going back into in vitro mirroring models planned that can help us understand and confirm the role of PVRIG in MSS-CRC, particularly, or in the liver? Thank you.

Thanks, Dana. So, the obvious study to do would go into demurant settings and then to test mechanistically in a very relatively easy way. The issue is that PVRIG in the mice is not, the biology is a bit different than in human. We don't go through all the details, but in general, PVRG is different in its biology, and specifically this biology we discussed about the dominance and ability to provide proliferation of cells is a bit different in the mice. So, therefore, what we are doing is following the clinical samples. And what we see over there is that, as you mentioned, the biology with the translational observation, PVRG seems to be very dominant and probably in controlling these T cell proliferation events. And this kind of immune modulation that we see in MSS CRC suggests that PIVR-AD is so dominant in controlling T-cell proliferation in the tumor microenvironment and also outside of it, that it can drive activity also in this kind of less inflamed indication. And specifically, one of the patients in which the biopsy was taken from the liver, we could easily see almost completely, as you expect maybe from a liver biopsy, almost complete desert biopsy, becoming completely inflamed following COM701 and Evolumab treatment. So we think that this unique observation suggests that PBRG is dominant enough in controlling tissue proliferation to be active also in patients with MSS-CRC and liver meds, obviously also in other indications.

One follow-up for me then. In the data you showed with data from patients not on this trial, but patients with MSS-CRC, where you looked at the tertiary lymphoid centers and the expression of PBRG, Were those primary tumors or those metastatic tumors? Can you tell me anything more about those particular tumors or patients that they came from?

Yeah, they were a mix. I don't think there was anything specific we can say or identify to this point that the patient with liver metastasis has something which is very different from the other patients with MSS-CRC. It seems that this is a wide observation for PBRG biology also outside of MSS CLC.

Thank you. The next question is from Tony Butler of Roth Capital. Please go ahead.

Thanks very much. Two questions for Ron. Ron, this is back to biology and mechanism as well. Does expression of PVRIG, is it affected by prior therapy? In other words, do you have any evidence that it is constitutively expressed and or only expressed under certain conditions? That's point one. And number two, if you looked at the tumor, what happens with PVRL2? Again, the same question. Is it PVRL2 constitutively expressed, or is it dependent on prior therapy, for example, with chemotherapy? Thank you.

Okay, thanks. So both the target, PVRL2 and the ligand, have constitutive expression. Of course, it can be modulated. We don't have any data specifically showing if PVRL2 is modulating following specific treatment. In general, if you have T cells in a tumor environment or even if you feel this in a tumor environment, PVRL2 will be there, and it will be normally dominant, again, on the early differentiated cells. And for PVRL2, it might be upregulated by some chemotherapies, but in general, it has high expression, and you can see it considerably before treatment and after treatment.

Thanks a lot.

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 all for joining us today and taking time to follow the company. I want to thank the Compugen team for their dedication and commitment to the company's ambition in the third quarter. We all know that this is not an easy time to be in the biotech space, and the resilience of the Configent team is commendable, driven by our vision to transform the lives of patients with cancer, and I'm very proud to be leading this vision. Thank you.