Compugen Ltd Q3 FY2022 Earnings Call

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 Compugen are Dr. Anat 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 timelines 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 now turn over to Anat.

Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to our third quarter 2022 update. We're just coming off a great Citi Conference in Boston last week where we had two oral presentations. In the first nine months of the year, we have continued to execute and meet our guidance. We presented clinical data from the MSS-CRC expansion cohort at SITC last week. In three weeks’ time, we will present clinical data from the two ovarian expansion cohorts at ESMO-IO. During our first oral presentation at SITC, Dr. Michael Overman from MD Anderson presented encouraging overall response rates following treatment with COM701 in combination with nivolumab in heavily pre-treated metastatic MSS-CRC 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 that are resistant to treatment. Responses in these patients with liver mass are 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 the 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 two MSS-CRC patients with liver mass 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 PVRIG and PD-1 with and without blocking TIGIT. We are looking forward to presenting this data at ESMO-IO in December. I am excited that the totality of our data suggests a COM701 mediated effect, especially as it is observed in hard-to-treat non-responsive tumor types. The combination of our translational data from patient tumor centers along with our preclinical and clinical data suggest that the increased infiltration of T cells into 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 DNAM axis, unleashing these 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 are planning a triple combination study in MSS-CRC patients with our potential first-in-class COM701 in combination with our potential best-in-class anti-TIGIT COM902 and an anti-PD-1. Our anti-TIGIT COM902 was engineered to reduce Fc functionality with the potential to enhance anti-tumor activity. 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 preclinical data AstraZeneca recently presented at SITC on their PD-1 TIGIT bispecific derived from COM902, also engineered to have reduced Fc function. Moving to ovarian cancer, we believe that 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 lung cancer. For this reason, we have decided to pursue platinum-resistant ovarian cancer and we are now evaluating various options for planned non-small-cell lung 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. We are committed to this guidance and our focus on two indications where we believe we have 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 am delighted to have Alberto as part of my management team 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 expectations ahead of our data in platinum-resistant ovarian cancer patients, which we will present at ESMO, and Alberto will bring you through the third quarter financials. 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 is 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%, a median PFS of 2 months, and median overall survival of 6 to 7 months. Most patients with metastatic MSS-CRC have metastases to the liver, and studies show that the presence of liver metastasis correlates with a 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 the patients having liver metastasis. Patients were heavily pre-treated with a median of three prior therapies, and 32% had prior treatment with regorafenib or TAS-102, which is the 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 KRAS 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 overall population of 22 patients, 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 where the median overall survival in this patient population is slightly 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 the 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 DNAM axis with PVRIG, TIGIT, 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 am delighted to share the robust translational and research data I presented at SITC on Friday, which supports the data just presented by Henry. Due to this COM701 in combination with nivolumab in MSS-CRC patients, we observed potent immune activation in the tumor microenvironment. We also show data supporting the unique expression of PVRIG on the undifferentiated 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 MSS-CRC. As I mentioned, treatment with COM701 in combination with nivolumab was associated with potent immune activation. Importantly, in the two patients who had partial responses, we observed more potent immune activation in the tumor microenvironment. Such magnitude of immune activation for a checkpoint blockade is not typical for a cold tumor like MSS-CRC. The clear immune activation seen also in non-responding patients may suggest that the full blockade of the DNAM axis by the anti-TIGIT antibody might tip the balance towards enhancing immune activation and subsequently may improve 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 immunoactivation in the tumor microenvironment. The pretreatment biopsy of one patient had a durable partial response to COM701 monotherapy, showing an immune response with no T-cells in the tumor microenvironment and was negative for PD-1. COM701 induced a robust increase in interferon-gamma in the peripheral blood of the responding patients, whom we didn’t have a post-treatment biopsy. Also here, the clear immune activation seen in non-responding patients with only some having triple blockades may suggest that the full blockade of the DNAM axis might tip the balance toward enhancing clinical anti-tumor activity. The triple data blockade in ovarian cancer patients will be presented by us at ESMO-IO. Finally, on the research side, we described the unique attributes of PVRIG that may provide biological rationale for the anti-tumor activity of COM701 in indications typically not responsive to checkpoint inhibitors. Using cutting-edge technologies and patient analysis, we show that PVRIG, 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-cell bursts that may be inhibited dominantly by PVRIG. Therefore, unleashing this blockade by COM701 may efficiently drive T-cells in the tumor microenvironment. In doing so, making cold tumors like MSS-CRC and platinum-resistant ovarian cancer more responsive to anti-PD-1s and potentially anti-TIGITs as part of the cross-talk of these three pathways. With that, I am 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-IO 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 treated with COM701 in combination with nivolumab and 20 patients treated with COM701 in combination with nivolumab and BMS anti-TIGIT. We are excited to be seeing encouraging data following dual and triple blockade of the DNAM axis in these patients. Effective treatment options for patients with platinum-resistant ovarian cancer are limited. Specifically, standard of care in these patients is typically 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. Additionally, immune checkpoint inhibitors as monotherapy and as part of immunotherapy combinations have demonstrated limited activity in this patient population. Also here, PVRIG's unique biology is different from other checkpoints and has the 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 and non-small-cell lung cancer. The metastatic non-small-cell lung cancer data we will present will be 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, COM503, which has first-in-class potential. We will elaborate more on this program during the end-of-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 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 two prioritized indications starting in 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. With that, we will now open the call for questions.

Thank you. The first question is from Stephen Willey of Stifel. Please go ahead.

Yes, 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 samples taken from patients, not patients in our study, we were prioritizing ovarian, endometrial, breast, and non-small cell lung 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 Eran to say a few words about the expression profile of the medians and the receptor.

Yes. So as Anat mentioned, the MSS-CRC definitely has a dominant expression of the PBG pathway. Basically, every tumor that we tested for MSS-CRC is positive for PVRL2 for sure and actually has abundant expression. It is a bit lower than ovarian, which is even higher, but definitely PVRL2 is present in all the patients we tested. And PVR, the ligand of TIGIT, is also high. In fact, MSS-CRC is one of the indications with the highest expression compared to other indications of PVR, the ligand of TIGIT.

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

So yes. So maybe first, I’ll try to remind why we picked non-small cell lung 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 doublet in the PD-1 pre-regimen, but not with PD-1. The reason we picked this indication is that we thought that focusing on an indication that is immune checkpoint sensitive, that is responding inflamed, would set a different bar for us. We wanted to pick both a non-inflamed one and an inflamed 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 into. If the data matured with ovarian cancer and we solidify it, we understood that there is an opportunity for us to get into an area that is less competitive. The enrollment rate would be easier to address, the signal that we would need to present, even though ovarian cancer is a hard-to-treat tumor type and many checkpoints are not showing great results. But still, the way for us to exemplify the signal would probably be easier compared to non-small cell lung cancer, where we would need to get much higher numbers. With the encouraging data we have in hand, we thought that it would be better for us to switch indications. For non-small cell lung cancer, we’re still evaluating our options for doing the study internally, maybe at different timelines or using investigator-sponsored studies. We have a great relationship with our investigators, and we will assess what the right path for us in non-small cell lung cancer is. But at this point in time, it was very important for us as a company to stay focused on one hand and ensure we commit to the guidance of the cash runway, while also selecting two indications where we feel we have a higher probability of success. I believe ovarian cancer is included in this definitely going forward. I think that in general, we are now starting the studies, and we are continuing to evaluate the data we have. Obviously, we will ensure we don’t leave value on the table regarding 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 the addition of a TIGIT antibody to the COM701 nivolumab doublet can perform better than what you’re already seeing in terms of tumor microenvironment modulation and immune activation that you’ve seen with the doublet combination? And then a second question is, obviously, at SITC, we saw some encouraging data from a CTLA4 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 with nivolumab combination versus that IO combo, and 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. There are a few lines of evidence to support that. First, the research we are doing on the DNAM-1 axis pre-clinically definitely shows that if you combine PD-1 TIGIT and PVR blockade to completely unleash DNAM activity, you get optimal and enhanced activity. In patients treated with the triplet, this is what we have seen. It was exciting to see that when you have a triplet, you can follow the patient’s blood, and we can see significant immunization with triple blockade in patients treated with COM701 combined with COM701 TIGIT and PD-1 blockers. Finally, in our cohort of patients treated in the MSS-CRC with COM701 plus nivolumab, yes, the responding patients were immune-modulated significantly. But we have many patients that were immune-modulated to a lesser extent. We see increases in T-cell infiltration; however, this wasn’t sufficient to drive activity. We know that when you have more sets in the tumor microenvironment, TIGIT becomes more active. Therefore, we believe that in patients where we were able to drive immunity, but to a limited extent, adding TIGIT should enhance immune activity that will translate to improved clinical activity, and this is exactly what we are going to test.

And Mark, regarding your other question about CTLA-4, L7, it’s indeed encouraging data. What has been seen in MSS-CRC is great for patients. The two major things to remember regarding our studies and our data are the safety profile and the ability to work on this. Additionally, we see signals in liver masses. Other than the regulated study in Japan, all the studies show a zero response rate in this patient population, which consists of approximately 70% of the population. This is why we believe that the data we are showing are encouraging specifically for MSS-CRC patients. Henry, feel free to elaborate further on the safety and data.

Thank you very much for your question, Mark. All the caveats of comparing across trials, comparing the Phase 1 trials and the caveats of comparing different classes of agents apply here. It’s important to note that from all the studies conducted, not just the one we reported recently at SITC 2022, beginning in 2018, we have been able to show no increase in the toxicities of any of the agents that are being combined with. Specifically, in our data reported at SITC, we didn’t report any patients discontinuing study drugs due to toxicity. The most common treatment-emergent adverse event seen was anemia, and most of these were Grade 1 and Grade 2, likely related to the disease itself. Overall, it’s Grade 1 and Grade 2 toxicities, and remember this is in combination with nivolumab. I would not want to elaborate more on the CTLA-4 antibody because we all know the toxicity profiles of these agents and the challenges they present. That question was asked during SITC, with respect 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. In their report, they mentioned around a third of patients had diarrhea, and grade five events including colitis and intestinal operation were noted. So, COM701, alone and in combination with nivolumab, as well as the triplet with BMS-986207, has shown to be very well tolerated with a favorable safety profile. We haven’t reported any increased adverse event profiles of the drugs we are combining with. The investigators we meet with regularly have mentioned this, and it’s supported by the reports at SITC and other prior publications.

Okay, thanks, Henry. Super helpful. Thank you.

Just to add one mechanistic insight about basic and fundamental biology of CTLA-4 versus PVRIG. CTLA-4 is a major player controlling peripheral tolerance, which is why we see this toxicity. PVRIG is different; it’s shown that most of the activity is happening in the tumor microenvironment. This hypothesis has been supported by our clinical data. PVRIG seems to be dominant in these structures, driving T-cell proliferation in the tumor microenvironment, suggesting it may have less relevance in tolerance.

The next question is from Reni 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 am kind of curious how you guys are thinking about the implications if 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 tiragolumab doesn’t show a survival benefit, kind of what are the implications for 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 TIGIT will resume in the industry, and we will continue to ensure that people understand that PD without PVRIG is not the way to go in certain tumor types, definitely not those that are not responding to PD-1 blockers. So, that’s an important thing, and we will continue to make sure that this is being heard, and we are pursuing it as well. 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 are 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 responses and data from the tumor microenvironment. We have the assets, two independent assets, and we are going to pursue them. That’s our plan. It may be harder if the sentiment isn't strong, but we will present it. We believe we will show good positive data that will be convincing. At the end of the day, it may be a gray zone, but in any scenario, we are moving forward.

Got it. Second question is just in terms of expectations for the platinum-resistant ovarian cancer. 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 what you are looking for to help frame a go/no-go decision in your mind? What do you need to see?

So, we will not go into too much detail with this. When the data is out, we can speak about it in a more informed way. I think I will let Henry relate to the field regarding what should be seen in ovarian cancer, specifically in platinum-resistant ovarian cancer patients. Henry?

Yes. Thank you very much, Reni. As Anat mentioned, what one would expect, if you look at the NCCN guidelines with respect to platinum-resistant ovarian cancer, is that most patients in that category are recommended for monotherapy. Typical results are in the range of single digits, with PFS three to four months and median overall survival typically around one year. We will be expecting to see an improvement in any of those parameters, including also quality of life, which we hear more about from clinical trials with COM701 alone or in combination with agents like BMS-96 or 97 or in combination with nivolumab. Unfortunately, there have been a lot of challenges investigating immune checkpoint activity in platinum-resistant ovarian cancer. We are encouraged by what we see in our study. Those are the metrics we will look for with respect to the standard of care in this patient population. Those are fair metrics since they can be benchmarked to what’s been reported in larger studies conducted with chemotherapy. 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, I'd love to get an idea as to how the biomarker patient selection work that’s being done at Compugen is going. Where my question is headed is you saw significant immune activation in those two PRs presented at SITC. However, at baseline, all patients looked the same. I’m curious, have you made any more headway in selecting those patients or excluding patients that may or may not respond?

Yes. This is very important. We are doing extensive work both with the normal ICSAs and sequencing the tumors. We are looking into potential capabilities to identify less obvious candidates for patient selection. So this work is ongoing. One important thing to mention is that the obvious biomarker we are looking at for other checkpoints mainly works for PD-1s. In our case, we don’t see a pure correlation with PD-L1. For ovarian cancer responses, if there is any checkpoint activity responsein ovarian cancer, it is normally in PD-L1. CRC above 1, even in the American PD-1 plus TIGIT study where you have some responses that report zero responses in PD-L1 CRC of zero. We already have results from ovarian cancer where a patient treated with COM701 monotherapy was PD-L1 zero, yet responded. We also see results from the CRC call; some patients don’t have tumor responses; the patient with the highest PD-L1 level before treatment relapsed. So at this point, PD-L1 seems to be less relevant given PVRIG's unique biology. We will continue to evaluate it, and this is ongoing work.

The next question is from Daina Graybosch 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 more about the second responder with MSS-CRC. I think you said or the presenters said they had unmeasurable liver metastasis. I wonder what that specifically means 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 presented by Dr. Overman was a patient with KRAS mutant tumors. They had bulky disease. The liver lesions were selected for assessment subjectively because investigators had to identify measurable lesions for assessment. Of the two patients, the first one we reported previously at AACR did show a reduction in the targeted lesion. The second patient presented by Dr. Overman showed a significant reduction in the target lesions selected in the lungs, while liver lesions appeared stable, meaning they didn’t worsen. This, in itself, is significant because that shows that despite the number of prior therapies the subject received, there was no progression in the liver lesions. However, the significant reduction was noted in the targeted lung lesions. Unfortunately, this subject relapsed to the brain but still maintained the responses that we observed during the imaging assessment.

It does. Thank you. And then another one for Eran. I think somewhat similar but with a different twist than what has been asked. You showed that CRC responses were immune-driven. You also showed translational differentiation of PVRIG. I wonder how you think you could, or have you linked those two pieces of evidence? Do you have any translational or in vitro models planned that can help us understand and confirm the role of PVRIG in MSS-CRC, particularly in the liver?

Yes. The study we plan will go into the neuron settings to test mechanistically in a relatively easy way. The issue is that PVRIG is different in the animal models; the biology differs slightly from humans. Without going into the details, PVRIG's functions differently in different settings. What we’re doing is following the clinical samples. What we observe is that PVRIG is observed to be very dominant. It likely controls T-cell proliferation in the tumor microenvironment and potentially outside of it, which can drive activity in less insensitive indications. Specifically, one patient had a biopsy taken from the liver, and we noted that this biopsy became completely inflamed due to treatment with COM701 and nivolumab. We believe this unique observation suggests that PVRIG is dominant in controlling T-cell proliferation.

One follow-up for me then. 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 PVRIG, were those primary tumors, or are they metastatic tumors? Can you tell anything more about those particular tumors or patients that they came from?

Yes. There were a mix; I don’t think there was any specific observation we can identify that patients with liver metastasis were any different from the other patients with MSS-CRC. This seems to be a wide observation for PVRIG biology, which also extends 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. Does the expression of PVRIG get 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 at the tumor, what happens with PVRL2? Again, the same question. Is PVRL2 constitutively expressed, or is it dependent on prior therapy, for example, with chemotherapy? Thank you.

Okay. Thanks. Both PVRIG and PVRL2 have considerable expression. Of course, it can be modulated. We don’t have any specific data showing if PVRIG is modulated by treatment. In general, if you have T-cells in a tumor microenvironment or even outside of it, PVRIG will be present, and will normally be dominant on early differentiated cells. For PVRL2, it might be regulated by some chemotherapies, but in general, it shows high expression, and you can see it considerably before and after treatment.

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 the 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 Compugen team is commendable, driven by our vision to transform the lives of patients with cancer. I am very proud to be leading this vision. Thank you.