Compugen Ltd (CGEN) 2022 Q3 法說會逐字稿

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 a listen-only mode. An audio webcast of this call is available in the Investors section of Compugen's website, www.cgen.com. As a reminder, today's call is being recorded. I would now like to introduce Yvonne Naughton, Head of Investor Relations and Corporate Communications. Yvonne. Please go ahead.

Thank you, Jamie, and thank you all for joining us on the call today. Joining me from Cumpogen are Dr. Cohen-Dayag, President and Chief Executive Officer; Dr. Henry Adewoye, Chief Medical Officer; Dr. Eran Ophir, 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 time lines for our programs, financial and accounting related matters as well as statements regarding our cash businesses. 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 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'll now turn it over to Anat.

Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to our third quarter 2022 update, fresh after a great C2 conference in Boston last week, where we had 2 hour presentation.

In the first 9 months of the year, we've continued to execute and meet our guidance. We presented clinical data from the MSS CRC expansion cohort at 60 last week. And in 3 weeks' time, we will present clinical data from the 2 ovarian expansion cohort at ESMO IO. During our first oral presentation at SIFI, Dr. Michael Aberman from MB Anderson presented encouraging overall response rate following treatment with COM701 in combination with nivolumab in heavily pre-treated metastatic MSCs patients, a hard-to-treat tumor type, typically not responsive to immunotherapy. Over 70% of the patients from this study has liver metastasis, typical of this patient population who are resistant to treatment. Responses in these patients with liver mass is a key differentiator for COM701 and the unique achievement.

On the safety side, there were no serious adverse events deemed by the investigator as related to study drug. During our second oral presentation at SITC, Eran presented data showing that COM701 in combination with nivolumab results in potent immune modulation in the 2 MSS-CRC patients with liver mass who responded to treatment. Suggesting that the clinical responses we observed in such a called 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 PVRIG and PD-1 with and without blocking TIGIT. We're looking forward to presenting this data at FIO 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 nonresponsive tumor types. The combination of our translational data from patients tumor centers, 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 TIGIT and PD-1 blockade. We believe that a triple blockade of the Dinanaxis unleashing the 3 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 are planning a triple combination study in NSCLC patients with our own potential first-in-class COM701 in combination with our own potential best-in-class anti-TIGIT Connal 2 and an anti-PD-1. Our anti-TIGIT, CONAI 2 was engineered to reduce SP functionality with the potential to enhance antitumor 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 the preclinical data as Astrazeneca recently presented at SITC on their PD-1 TV bispecific derived from CONAI 2, also engineered to have reduced FC function.

Moving to ovarian cancer. We believe the encouraging data in platinum-resistant ovarian cancer merit further development in this indication, which opens the door for us in a much less crowded competitive landscape, compared to non macellan cancer. For this reason, we have decided to pursue platinum-resistant ovarian cancer, and we are now evaluating the various options for the planned non mecellan cancer studies.

Following the disclosure of the data from the 2 ovarian cancer studies at SMA-I, 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 are committed to this guidance and our focus on 2 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 Sessa, 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 SITC. Eran will then provide an overview of the research and translational data that he presented at SITC. I will then set the expectations ahead of the data in platinum-resistant ovarian cancer patients, which we will present at SMO. 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'm 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 PAS 102, which show an overall response rate of 1% to 2%, median PFS of 2 months and median overall survival of 6 to 7 months. Most patients with metastatic MSS-CRC have metastases to deliver and studies show that presence of liver metastases corrolates with lack of response to checkpoint inhibitors. The data we presented includes 2 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 metastases. Patients were heavily pre-treated with a median of 3 prior therapies and 32% had prior treatment with regorafenib or TAS-102, which is current standard of care. The objective response rate was 12% in the 17 patients with liver metastases. With 2 patients with partial responses also had RAS 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 2 casual responses and 4 patients with stable disease. Observing 2 patients with antitumor activity, one stable disease and 1 patio response for 6 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 pre-treated and the median overall survival in this patient population is slightly less than 6 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 investigator as related to study drugs.

The totality of our data, combined with the mechanism of action of COM701 justifies a further development of the triple blockade of the DNAM axis with PVRIG, CD-and PD-1 in this patient population. As Anat mentioned earlier, we are moving ahead with the evaluation of the triple combination in a proof-of-concept study.

I would like to extend as you see a 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 SITC on Friday, which supports the data just presented by Henry. True to COM701, in combination with nivolumab in MSS-CRC patients were associated with potent immunoactivation and geo macro environment. We also show data supporting the unique expression of PBRG on the ever-differentiated stem-like (inaudible), which are key players in driving T cell proliferation in the tumor microenvironment.

To go into details, we share translational data from 13 patients with a static MSS-CRC. As I mentioned, treatment with COM701 in combination with nivolumab when associated with potent human activation. Importantly, in the 2 patients who had partial responses, we serve more potential activation in the tumor environment. Such magnitude of immunoactivation for (inaudible) blockage is not typical for cold-tumor MSS-CRC. The clear immunoactivation seen also in all responding patients may suggest that the full blockade of the denomaxisbedy antigenic antibody might tip the balance towards enhancing immunoactivation and subsequent further improved clinical outcome. This is supported by our preclinical and clinical data across our studies.

We also presented translational data in 5 patients with another cold tumor, platinum-resistant ovarian cancer treated COM701 in monotherapy. Also here, treatment was associated with clear immunoactivation in the tumor environment. The pre-treatment biopsy of 1 patient who had a durable partial response to COM701 monotherapy showed an immune desert with no T-cell in the tumor environment and sending negative for PD-1. COM701 induced a robust increase in intertrial gamma in the peripheral blood of the responding patients from who we didn't have post written biopsy. Also here, the clear immunoactivation seen also in nonresponding patients with only people at (inaudible) blockade may suggest that the full blockade of (inaudible) access might tip the balance towards enhanced in clinical antitumor activity. Such triple data blockade in ovarian cancer patients will be presented by us at ESMO.

Finally, on the research side, we described unique attributes of PBRG that may provide biological rationale for these antitumor and trocession activity of COM701 in indications typically not responsive to checkpoint inhibitors. Using cutting edge technologies and anti (inaudible) analysis, we showed that PBRG compared to checkpoints at 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 antitumor T cells burst that may be inhibited dominantly by PBRG. Therefore, and missing this blockade by COM701 may efficiently drive T cells in the tumor microenvironment. And in doing so, making cultures like MSS-CRC and platinum-resistant ovarian cancer, more responsive to anti-PD-1 and potentially other TIGIT as part of the cross stock of these 3 pathways.

With that, I'm now turning back to Anat.

Thank you, Eran and Henry.

Moving now to setting expectations ahead of the platinum-resistant ovarian cancer data, which we will present at ESMO on December 8. We will present preliminary data, including overall response rate, duration of response, safety and very initial translational data from 20 patients with platinum-resistant ovarian cancer who are treated with COM701 in combination with nivolumab and 20 patients who were treated with COM701 in combination with nivolumab and BMS anti-TIGIT.

We're excited to be seeing encouraging data following dual and triple blockade of the denim access in this patient. Effective treatment options for patients with platinum-resistant ovarian cancer are limited. Specifically, standard of care in patients with platinum-resistant ovarian cancer, a single-agent chemotherapy and responses range from 8% to 12% with median progression-free survival of 3 to 4 months and overall survival of around 1 year. Also, immune-checkpoint inhibitor 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 ESMO on December 8. During this call, we will discuss the data presented at that conference, including in platinum-resistant ovarian cancer patients in non macellan cancer. The metastatic non macellan 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, CON5403, 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, Anat. I'm delighted to be on board and excited with the opportunity to work closely with you and the Compugen experienced 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 option 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 31, 2021. The company has no debt.

For the third quarter of 2022, we reported a net loss of $11.7 million or $0.14 per basic and diluted share compared with a net loss of $6.2 million or $0.07 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 2 prioritized indication starting 2023, we expect our ongoing R&D cash expenditure to be lower than the current run rate. 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.

This concludes. 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 pull for your questions. The first question is from Stephen Wiley of Stifel. Please go ahead.

Yeah, good morning, and thanks for taking questions. And congrats on the updated SITC.

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 PVR and PVRL2. 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're correct. So when we started the program based on preclinical data and also based on expression profiles in tumor (inaudible) taken from patients, not patients in our study, we were prioritizing ovarian, endometrial, breast and normalcy cancer. Later, when we started to see the dose escalation data, we also prioritize MSS-CRC. And I'll just say that when we returned back to look at the CRC data, the expression was somewhat lower then the indications that were prioritized, but still high. Maybe I'll ask Eran to say a few words about the expression profit of the medians and the receptor.

Yes. So Anat mentioned, the MSS-CRC definitely have a dominant expression of the PBG pathway. Basically, every tumor that we ever tested for MSC--CRC 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 lion of TIGIT is also high. And actually, MSS-CRC is one of the indications with the highest expression compared to other indications of PVR, the lion of TIGIT.

Okay. That's helpful. And then, maybe you can just talk a little bit about some of the factors that you have considering in terms of your decision to move forward to lung. And I guess, with 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 yes. So maybe first, try to remind why we picked non macellan cancer. As you know, this was not part of the cohort expansion studies that we had in the combination, any of them. And actually, it was in the (inaudible) the PD-1 (inaudible) 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 noninflamed one and an inflame one.

I have to say that we recognized at that time, and we were relating to it to data, it's a more competitive area for us to get in. If data matured with the ovarian cancer and we sold 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 many checkpoints are not showing great things there. But still, the way for us to exemplify signal would probably be easier as compared to non macellan cancer, where we would need to get to much higher numbers.

So we're encouraging data that we have in hand. We thought that that it would be better for us to switch the indications. I'd say that for the non macellan cancer, we're still evaluating our options for doing the study internally, maybe at different time lines or to do it externally, investigator-sponsored studies. We have a great relationship with our investigators and -- and we'll try to assess what are -- what's the right path for us in non macellan 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 committed to the guidance of the cash runway, but also still peak 2 indications where we feel that we have higher probability of success. And I think that ovarian is included in this definitely.

Going forward, I think that in general, you know, we're now -- we're going to start the studies, and we're continuing to evaluate the data that we have, obviously, and we'll make sure we don't leave value on the table with respect to COM701.

Alright, thanks for taking my questions.

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

Hey, thanks for taking the questions. I really appreciated Eran's presentation at SITC 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 Nivo plus 701 in a doublet combination.

And then a second question is, obviously, at SITC, we saw some encouraging data from a CTLA-4 PD-1 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 combination versus that IO combo, maybe highlight distinct patient groups that one combination may be more appropriate for than the other. Thank you for taking 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 are doing from the D1 access preclinically definitely show that if you combine PD-1 TIGIT and PVR blockade to completely unleash denom activity, then you get an optimal and enhance this 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, and that's stage is what we have done. And we can see really important immunoivation with triple blockade in patients treated with the treatment of blockade of COM701 with COM701 TIGIT and PD-1 blockers.

Finally, in our cohort of patients treated in the MSS-CRC with COM701 plus nivo, Yes, the responding patients were immune modulated very significantly. But we also have many patients that were immune modulated a bit to lesser extent, we do see increase in this infiltration, things are happening in the tumor microenvironment, but not sufficiently to drive activity probably.

Now we do know that when you have more sets in the tumor macro environment, TIGIT is then more active. So what we think that in these patients that we were able to drive immunity but not in sufficient level to drive clinical activity, ending in our digits should add enhancing immune activity that will translate also to enhance clinical activity, and this is exactly what we are going to test.

And Mark, to your other question with respect to other agents, CTLA-4, I'll 7. I think that there are 2 -- first, it's encouraging data, obviously, it's encouraging data, what has been seen in MSS-CRC it's great for patients. I assume that the 2 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 then we can allow work on this. And also the fact that we see signals in liver mass. And again, Henry will relate to it, but I'll just say, other than the reg (inaudible) study in Japan, there are all the studies that are showing 0 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 in MSS-CRC for MSS-CRC patients. And Henry every feel free to elaborate on the safety and on the data.

Yes. So Mark, thank you very much for your question. With all the caveats of comparing across trials, you can do the Phase I trials, -- and the caveats with comparing different class of agents. It is repeating that on all the studies that were conducted, not just the one we 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 IDQ 4 weeks as monotherapy and in combination with nivolumab and in combination with nivolumab and BMS-986207, which is a TIGIT antibody, we haven't reported any increase in the toxicities of either of any of the agents that is being combined with. And specifically, if you go back and look at our data, I would reported at SITC, with Dr. Overman, we didn't report aiming sub debt coming off -- coming off study drug as a result of any toxicity. The most common treatment emergent adverse event that we've seen in at least 4 subjects with anaemia and most of these were grade 1, grade 2 in about 1/3 of the patients, likely related to the disease itself, hypoaline and (inaudible). Overall, it's Grade 1, Grade 2 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 this 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 study that 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 1/3 of patients with diarrhea, they upgrade 5 events, including colitis and intestinal operation. This might possibly be related to sometimes the disease, but we do say it's related to the study drug because their treatment-related adverse events.

So COM701 alone, COM701 in combination with nivolumab, COM701 in combination as it tripled to BMS-986207 very well tolerated favorable safety profile. And even at the doses we 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 mentioned this, and it's borne out in the report at SITC and in other prior publications.

Okay thanks Henry, super help. Thank you.

Just to add one mechanistic insights about basic and fundamental biology of CTLA-4 versus PBRG. CTLA-4 is a major player controlling peripheral tolerance. And that's why from the mine study all the way to the patients we see this toxicity, where PBRG was just shown now in SITC that much of the activity is happening in the tumor macroenvironment , this all hypothesis and what we show that PBRG is dominant in these structures in the tumor micro environment in which (inaudible) proliferating. And we have shown that actually that most of the activity, the most dominant clone proliferating in the responding patients is in the tumor environment.

So biologically, since the PBRG plays a less of a relevant role in (inaudible) tollerance and much of the defense activity of (inaudible) proliferation is in the tumor macroenvironment.

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 SITC.

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 dragolumab doesn't show a survival benefit, kind of what are the implications to Compugen. And then I have a follow-up.

Thank you, Randy.

Yes, it will have implications on Compugen, obviously. If data is positive, then great, I guess that interest in digit will resume in the industry and -- and we will continue to be there to make sure that people understand that PG without PVRIG is not the way to go in certain tumor times, definitely not those that are not responding to PD-1 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 strong biology. We have data from patients, clinical responses as well as immune - as well as data from the tumor macro environment. And we have the assets. We have 2 independent assets, and we're going to pursue it. That's our plan. So is it 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 a gray zone. And -- but still, we -- in any scenario, we're moving forward.

Got it. 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 in your mind? What do you need to see?

So we will not go too much into detail with this, you know, when the data is out, will be able, 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 second resistant to varying cancer patients in general, not alluding to our data. Henry?

Yes. So thank you very much Reni. In our prepared remarks, Anat already previously mentioned, what one would expect. And if you look at the NCCN guidelines also with respect to platinum resistant ovarian cancer is what concerns us that what is recommended for most patients in that category is monotherapy. And the results are typically in the range of single digits, like I mentioned, and PFS 3, 4 months and then we can (inaudible).

So 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 alone in combination with any of the other agents like BLS 97 or in combination with Nebo. So as you know, really, there's been a lot of unfortunately, spillers with trying to investigate what immune checkpoint activity it is in platform resistant ovarian cancer.

So, the results is that 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 conducted with chemotherapy. So that's as far as I will go until we formally disclose the data at ESMO IO.

Got it. Okay. And my final question is for Eran, I guess, would love to get an idea as to how the biomarker kind of patient selection work that's being done at Compugen is going? And I guess where I'm where my question is going with this is you guys saw significant immune activation in those 2 PRs presented at SITC. And -- but at baseline, they -- all the patients look the same, right? It's kind of like a 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. So of course, this is very important. And we are doing extensive work, both with the normal ISAs and also we're sequencing the tumors. We're doing user (inaudible) 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 many for PD-1. And in our case, we don't see pure correlation is PD-L1, right? I mean also talking about the ovarian cancer responses have seen. If there is any checkpoint activity response in ovarian cancer is normally in PD1/CPS above 1, even in the America PD-1 plus TIGIT study where you have some responses that 0 responses in PD-L1 CPS of 0. We already have results in ovarian cancer patient treated in monotherapy that was PD-L1 0, who responded to COM701 monotherapy. We also have results now from the CRC call. Some patients are really not in plan tumor environment. Actually, the patient with the highest PDL1 level before treatment relapsed. So at this point, PD-1, maybe because that's unique biology PBLG have been able to work in also less tumor types seems less relevant. Of course, we will continue to vary. And we are evaluating all the (inaudible) members, and this is work ongoing.

Great, thanks for taking the questions.

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

Hi, thank you for the questions. I have 2 as well. The first one for Henry.

I wonder if you could talk, Henry, more about the second responder with MSS-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?

Yes, Daina. Yes. So that subject that Dr. Overman presented was a patient, obviously, we care as mutant tumors and had bulky disease. -- the liver lesions, they are common lesions also. And (inaudible), the investigator had to select the -- of all the tumors, which ones were measurable for assist and which ones will be deemed non measurable that will be followed subjectively persist. So they selected the ones in the (technical difficulty) that. Now of the 2 patients, the first one we reported previously at AACR, we did see that there was -- that the liver lesions were selected and there was a reduction per receipt in the target lesion.

In the second patient, which was presented by Dr. Overman, there was a significant reduction in the target lesions that are 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 that previously received that there was no progression in terms of those target in terms of the liver lesions. But there was significant reduction when it came to the target lesions that were selected. Unfortunately, the subject like we did mention, relapse to the brain, while at the same time, maintain the responses that we observed at the time when they had the assessment for the imaging assessment of (inaudible). Does that answer your question, Daina?

It does. And then another one for Eran. I think somewhat similar but a different twist to one that everybody has been asking you about, really the mechanistic rationale for why CBRE and MSS-CRC. You clearly showed the CRC responses were immune-driven. And I think you also clearly show the translational differentiation of PVRIG.

I'm wondering how do you think you could or have you linked those 2 pieces of evidence? So do you have any translational or going back into (inaudible) models planned that can help us understand and confirm the role of PVRIG in MSS-CRC, particularly or in the liver. Thank you.

Thanks, Daina. So -- the other study to do will go into the neuron settings and then to test mechanistically in a very relatively easy way. The issue is that PBRG in the mice is not -- the beverage is a bit different than in human. We don't go through the details, but in general, PBRGs different in its biology. And specifically, this version, we discussed about the dominance and ability to triplet of serves 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 leading, as you mentioned, the biology with the transfusion observation, PBRG seems to be very dominant and probably in controlling this T cell proliferation event. And this kind of immunitiation that we see in MSS-CRC suggest that we were so dominantly controlling T cell proliferation in the tumor macro environment and also outside of it that it can drive activity also in this kind of less-intenindication. And specifically, one of the patients in which that biopsy was taken from the liver, we could easily see almost completely as you expect maybe from a liver biopsy, almost complete bezel biopsy, becoming completely inflamed or COM701 and evolumab treatment. So we think that this unique observation, suggestion PBRG is dominant enough in controlling T-cell proliferation to be active also in patients with MSS-CRC in liver mass, 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 look at the tertiary pilymphoid centers and the expression of PBRG. Were those primary tumors? Or are those metastatic tumors? Can you tell them anything more about those particular tumors or patients that they came from?

Yes, there were a mix. I don't think there's anything specific we can say or identified to this point that the patients 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, but also outside of MSS-CRC.

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

Thanks very much. Two questions for Eran. Eran, this is back to biology and mechanism, as well. Is -- 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 look to the tumor, what happens with PVRL2. Again, the same question. Is it a PVR L2 constitutively express -- or is it dependent on prior therapy, for example, with chemotherapy. Thank you.

Okay, thanks. So both the target (inaudible) and the ligand have considerative expression. Of course, it can be modulated. We don't have any data specifically showing if PBRGs moderating phono-specific treatment. In general, if you have T cells in a tumor micro environment or even if (inaudible) in a micro environment, (inaudible) will be there, and it will be normally dominant again on the early differentiated cells. And for PVRL2, it might be approbated 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 Baltic space and the resilience of the competent 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.

This concludes the Compugen Q3 2022 Conference Call. You may go ahead and disconnect.