Compugen Ltd.

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's fourth quarter and full year 2021 results conference call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available in the 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, Operator, and thank you all for joining us on the call today. Joining me to present a prepared remarks are Dr. Nat Cohen-Diag, President and CEO, and Ari Krashen, Chief Financial and Operating Officer. For the Q&A session, we will also be joined by Dr. Henry Adewoye, Chief Medical Officer, and Dr. Eran Ofer, Vice President, Research and Drug Discovery. Before we begin, we'd like to remind you that during this call, the company may make projections or forward-looking statements regarding future events, business outlook, development efforts and their outcome, the company's discovery platform, anticipated progress, results and timelines of our programs, financial and accounting-related matters, as well as statements regarding our cash position. We wish to caution you that such statements reflect only the company's current beliefs, expectations, and assumptions. but actual results, performance, or achievements of the company may differ materially. These statements are subject to known and unknown risks and uncertainties, and we refer you to the SEC filings for more details on these risks, including the company's most recent annual report on file form 20F filed with the SEC on February 25th, 2021. The company undertakes no obligation to update projections and forward-looking statements in the future. With that, I now turn the call over to Anat.

Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to our fourth quarter and full year 2021 update. I'm proud to say that Compugn made excellent progress in 2021. Our fundamentals have improved and we're delivering on our promises. COMPIGEN has done groundbreaking work on the biology of the key targets of the DENAM axis, PVRIG, and TIGIT. This is evidenced by our numerous publications and patent filings. We are pioneers in an uncharted territory. We're the first to test in the clinic two agents never combined before, primarily focused on PD-1 non-responsive patients. Our differentiated clinical strategy with our potential first-in-class anti-PVRIG antibody COM701 is to lead the next wave of innovation by executing a unique combination approach to realize the full potential of TIGIT and PVRIG. Immune checkpoint inhibitors have become multibillion-dollar drugs and are having a major impact on cancer care. However, As most patients do not respond to immunotherapies, there is a need for new drugs for these cancer patients. At Compugen, we believe that immune checkpoint inhibitors that target the denim axis have the potential to be a game changer in the treatment of cancer. As we continue as leaders in the denim axis by unlocking the potential of both PVRIG and TGIT pathways, with a vision to deliver the next transformational drugs. We're excited to see the growing interest in the space by major pharma companies, providing further validation of our hypothesis and the possibility of opening additional opportunities for us in the future. Data from our clinical studies presented in 2021 with COM701 and COM902 support our hypothesis that treatments that target the denim axis could be effective in inflamed or even more exciting, less inflamed tumors. Our studies show early signals of anti-tumor activity with immune activation across studies and a good safety profile in mono, dual, and triple therapy settings. Today, we would like to update you on our clinical program, upcoming anticipated milestones, and report on our financial results for the fourth quarter and full year 2021. I'll start by updating you on our key 2021 accomplishments and 2022 anticipated milestones. Then I will review the clinical program with you. Ari will summarize our financial results, and then I will come back to make a few closing remarks. 2021 has been a year of progress for Compugen with a strong execution across our differentiated clinical strategy. I want to highlight three of our important accomplishments in 2021. First, in keeping with our goal to develop first-in-class or best-in-class immune therapies for cancer patients who are not responding to currently available therapies, we delivered on our clinical milestones to complete dose escalation studies and begin expansion cohorts across all our programs. These encouraging results from our initial clinical studies reported at major medical and scientific meetings throughout the year paved the way for a comprehensive evaluation of Compugen's Dynamaxis hypothesis in our ongoing expansion cohort studies. Second, In keeping with our goal of maximizing value for patients, we expanded our collaboration with Bristol-Mell Squibb and are happy to see AstraZeneca progressing their TGPD-1 bispecific derived from our COM902 into the clinic. In addition, we expanded our research collaboration with Johns Hopkins University. These partnerships support our focus on expediting our early and clinical stage programs and bringing them to the market. Third, in keeping with our leadership position in the field and our goal to advance immune oncology research, throughout 2021, we presented new research and translational data at scientific conferences to support the unique biology of PVRIG, and the potential of its blockade to target less inflamed tumor types. In addition, along with one of our trusted advisors and long-term collaborators, Professor Drew Pardol, we co-authored a review on the biology and potential therapeutic relevance of the DENAM assays in cancer immunotherapy in the prestigious high-impact journal, Cancer Discovery. Looking ahead to 2022, we're conducting three very important phase 1-2 combination studies. As you know, our clinical strategy has been designed to allow us to systematically evaluate our hypothesis that simultaneously blocking three pathways, PVRIG, TGIT, and PD-1 in selected biomarker-informed tumor types may produce game-changing results for cancer patients with inflamed, or less inflamed tumors. PVRIG, which is differentiated from TG10PD1, may be the missing piece when current immunotherapies have failed by potentially generating new waves of T cells to infiltrate the tumor microenvironment, turning it to a more inflamed environment. Our ongoing combination studies are signal-seeking studies evaluating preliminary antitumor activity of COM701 in addition to safety and tolerability in multiple indications. These studies also include a parallel comprehensive translational analysis assessing immune activation to further evaluate our unique drug mechanism of action and potential biomarker identification that may be of relevance for future patient selections. Based on establishing proof of concept in specific indications, we will share our path forward in such indications, targeting the fastest path for registration to maintain our first mover advantage. Our studies have been designed to efficiently identify the optimal inhibitor combinations and tumor types. Although these are signal-seeking studies, this approach which includes some overlapping indications across studies, is intended to help us understand the contribution of each study drug. Enrollment is underway in our ongoing clinical studies. The first study, initiated at the end of June 2021, is designed to evaluate an anti-PVRIG PD-1 combination with COM701-Evalumab in patients with ovarian, endometrial, breast, and microsatellite-stable colorectal cancer. The second study, initiated in July 2021, is designed to evaluate the anti-TGIT-PVRIG-PD1 triple combination with COM701, nivolumab, and bristomersquibs anti-TGIT in patients with ovarian, endometrial, and head and neck squamous cell carcinoma, plus a cohort of subjects who have high expression of PVRL2, which we will start enrolling following the assessment of correlation between PVRL2 level of expression and response. The third study, most recently initiated in November 2021, is evaluating an anti-tigit PVRLG combination with our wholly-owned COM902, COM701 drug candidates, in patients with head and neck squamous cell carcinoma, non-small cell cancer, and microsatellite stable colorectal cancer. Our intention is to report data from fully enrolled cohorts of each of these studies, taking into consideration that certain cohort indications enroll faster than others and use the results to define our regulatory strategy on a cohort-by-cohort basis. Based on the current enrollment rate, first data from combination studies are expected to be reported in Q4 2022, starting with a microsatellite-stable colorectal cancer cohort from the COM701 Nivolumab study. And we expect to complete enrollment in all cohorts by end of 2023. As enrollment progresses, we plan to share further guidance with respect to the other cohorts. Microsatellite-stable colorectal cancer is a tumor type that has so far been immunologically unresponsive. There is no approved therapy specifically for these MSS CRC patients, and immune checkpoint inhibitors have demonstrated limited or no activity in this patient population. Treatment in this setting is typically regorafenib or LUNSERV, which show ORR of 1%, median PFS of 2 months, and median OS of 6 to 7 months. As of today, we have presented data from 12 patients using various doses of COM701 with or without nivolumab across studies and have shown encouraging preliminary antitumor activity with a disease control rate of 58%, including one partial response of 44 weeks. Our current COM701 Evolumab study consists of additional 20 MSS CRC patients, which will help us further assess the potential of this drug combination in this setting. Looking back over 2021, I've been very pleased with the encouraging data in our Phase I studies across mono, dual, and triple therapy in multiple tumor types, as presented at ASCO and CITI, as well as the expansion of our collaboration with Bristol-Mass Quibb based on the data we've presented to date. Three observations from our overall translational data set stand out to me. First, Our most recently presented translational data demonstrating immune activation across our COM701 studies with the most potent immune activation in triple blockade of PVRIG, TGIT, and PD-1 supports our suggested drug mechanism of action as well as the differentiation of PVRIG from that of TGIT and PD-1. Second, I'm pleased that our approach to develop our anti-TG antibody using an IgG4 backbone, similar to the leading anti-PD-1 antibodies with less effects of function than IgG1, appears to be an appropriate strategy. Indeed, in our COM902 dose escalation study, which represented at 60, we showed that there is no depletion of the CD8 plus T cells, the most effective anti-tumor immune subsets. We were the first to present clinical data with an IgG4 antitigit antibody with low FC effector function, and we believe this may also come with additional benefits on the safety side to be confirmed in the clinic. Third, our initial data suggests that COM701 may have potential to address less inflamed tumor types where other immune checkpoint inhibitors have not been successful in line with supportive data from our PVRIG research. In addition, we achieved encouraging signals of antitumor activity in our studies with several notable durable responses in heavily pretreated patients who had exhausted all available therapies with a good safety profile. To summarize, our translational observations coupled with our encouraging data to date, suggest a differentiated profile for COM701 and COM902 with the potential to unlock the value of denim axis as a game changer in the treatment of cancer. I'm enthusiastic about our program and look forward to sharing the results of our ongoing studies with you. Before I turn the call over to Ari, I would like to thank the patients and their families caregivers, investigators, and study sites.

Thank you, Anat. I'm happy to summarize our financial results. I'll start with our cash balance. As of December 31st, 2021, we had approximately $118 million in cash compared with approximately $124 million as of December 31st, 2020. The company has no debt. Our cash balance reflects Bristol-Myers Squibb's strategic investment of $20 million and a $6 million milestone payment from AstraZeneca received during the fourth quarter. Going into 2022, we expect our cash burn to be in the range of between $44 to $46 million. Financially disciplined, we are a company targeting our extensive and unique knowledge in this space on specific tumor types and comprehensive clinical strategy to increase our probability of success of our drugs to help patients. At the current level of operations, we expect current cash will be sufficient to fund our operating plans into 2024. For revenue, we reported no revenue for the fourth quarter of 2021 and of $6 million for the year ended December 31st, 2021, compared with $2 million for each of the comparable periods in 2020. 2021 revenues are related to the milestone payment from AstraZeneca for dosing the first patient in their Phase 1-2 study of a TGIT bispecific monoclonal antibody derived from our COM902. With respect to R&D, R&D expenses for the fourth quarter and year end of December 31, 2021 were $5.8 million and $28.7 million, respectively, compared with $8.1 million and $22.8 million for the comparable period in 2020. The increase in R&D expenses during 2021 is attributed mainly to higher expenses associated with our various clinical studies as well as increase in headcount as we continue to grow our U.S.-based clinical team to support the expansion of our studies. The decrease in the quarterly period is due to a decrease in manufacturing and related expenses. Our G&A expenses for the fourth quarter and year-end of December 31, 2021, were $2.7 million and $10.9 million, respectively. compared with approximately $2.7 million and approximately $9.8 million for the comparable periods in 2020. The increase is mainly due to increased DNO insurance premium costs that affected the overall industry. During the fourth quarter of 2021, we reported a net loss of $8.6 million, or 10 cents per basic in diluted share, similarly to a net loss of $8.6 million or 10 cents per basic and diluted chair in the comparable period of 2020. Net loss for the year ended December 31st, 2021 was $34.2 million or 41 cents per basic and diluted chair compared with a net loss of $29.7 million or 37 cents per basic and diluted chair in the comparable period of 2020. Now, I'll turn the call back to Anat.

CombiGen has done groundbreaking work on the discovery of the PVRIG pathway and the DENAM axis hypothesis and we're well positioned to maintain our leadership in this new area of cancer immunotherapy. We're actively enrolling in three important combination studies that will guide our registration strategy and we expect to report the first clinical results in Q4 2022. We have a solid balance sheet with a cash balance of $118 million that will support our clinical program and our operations into 2024. I'm very enthusiastic for what's to come for Compugen and look forward to updating you on our progress throughout the year. I want to send a special thank you to the amazing team at Compugen, whose dedication has enabled our remarkable accomplishments, and to you all for joining us today and taking time to follow the company. And with that, we'll 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 a 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 Stifel. Please go ahead.

Yeah, good morning. Thanks for taking the questions. Can you maybe just share with us what your current expectations are regarding efficacy data that will be emerging out of the colorectal cohort by year end and, I guess, what needs to be seen to potentially inform a go-forward decision? And then, I guess, second to that, can you make that decision about going forward before you see combo data from the 701 and io2 combo in the same tumor type?

Thank you, Steve. I'll just say I'll refer this question to Henry. I'll just say that in general, for most of the tumor types that we're addressing, these are tumor types that are not responsive to checkpoints, and the patients do not have many options, so we think that the bar is not important. very high in terms of numbers. Obviously, this is a very hard-to-treat patient population, but I'll let Henry relate to more specifics.

Yeah, thank you very much, Anat. Thanks, Steve, for the question. Yeah, I just want to remind you and everybody also listening that these are signal-seeking studies, even though they're expansion cohorts, right? So we have 20 patients in each of these cohorts that you're mentioning. So it's actually what we're looking for, a combination of various things. So number one, we're looking for efficacy in terms of adipatial response. We're also looking for antitumor activity in terms of stable disease and the durability of the stable disease. So it will be premature to start assigning numbers that will be of interest to us. But that being said, I think it bears mentioning, just like Anat mentioned in her prepared comments, that a particular tumor type where you see a patient with a partial response, for example, colorectal cancer, that stays on for 44 weeks is actually notable. It is notable for the following reasons, and one of it being that this tumor type is typically not responsive to immune checkpoints or they have very limited activity. So that itself shows that we have a signal just there. That's one patient. And the other reason that's important is the fact that we've also disclosed that at ASCO just last year, the caliber of patients that were enrolled into the colorectal cancer cohort of the 12 patients we enrolled, we saw patients, and this is also listed in our swimmer plot, those patients that actually surpassed what is typical for the median progression-free survival in this patient cohort. So those are the parameters that we're interested in. And we'll continue to accrue into all other cohorts and then see what the results are and be able to make a more informed judgment as to antitumor activity and the next steps for CompuGen.

Steve, I'll just add one more thing that relates not only to the clinical data, but also, as you know, we have a comprehensive translational program that we apply on all the different studies and on all the cohorts. So we really look also on the translational data as very important parameters. So this will be taken into consideration as well. And obviously for COM 701 and COM 902 combination, the data, it's open studies. We see the data. So definitely this is a parameter that we'll take into consideration.

Okay. That's helpful. And then maybe just lastly, is the year end 23 guidance that you're providing here for completing enrollment in all cohorts, is that in any way rate limited by the diagnostic work that you're doing to establish a PBRL2 expression threshold for enrollment into the basket cohort?

That's not limited. The program is ongoing. We're doing a lot of work in order to make sure that we have the samples and that we can test the expression profiles of the Dynamexis members and specifically PBRL2 so at the time that we'll feel that we have enough in order to correlate expression to response, we would start the basket study. Okay.

Thanks for taking the questions.

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

Hey, guys. Good morning. Thanks for taking the questions. I guess just starting off, you know, the timing for the dose expansion studies has kind of thrown me off a little bit. Can you just give me a sense as to what are the factors that are, you know, leading you to think that enrollment would only be complete by the end of 2023? I always assumed that once the dose expansion was done that the expansion studies would enroll, you know, a lot quicker. So if you can give us a sense of that, and then I have a follow-up.

Sure. Basically, there are two parameters. It's the enrollment rate that is very different for different indications. CRC by nature is more prevalent, less treatment, so it is enrolled faster. There are indications that are harder to enroll, and the pace is slower. So this is one parameter. And also, I want to remind everyone, true, these are studies, these are signal-seeking studies, and we have 20 patients per cohort, but we have many cohorts and many studies ongoing. So the total number of patients that we're enrolling is very large. So it is important for us to make sure that we do this analysis of the dynam axis in a way where we maximize the opportunities and that we maintain the leadership in this, evaluating this axis, and also to make sure that these are not only signal-seeking studies, so we can really relate to the contribution of components But let's make sure that we remember that these are not small studies, and we're really enrolling fast. We're on execution, and we will start sharing data in Q4, and these studies will continue to enroll, and we will continue to share guidance and data. But that's the two parameters, the enrollment and the size of the studies.

Got it. And just as I think about news flow, I have a sense of obviously how the news flow from the company is coming out. Can you talk a little bit about maybe your partnership programs and any sort of a sense as to when we might see news flow from those programs? And I understand these are partner programs. You might not have as much control or insight into that. I guess just related, you have an early pipeline. I think you have some myeloid candidates and the like. Can you give us an update as to how those might be progressing and when we might see an IND for a new agent?

Sure. So for the partner programs, there is the AstraZeneca program, which is a bispecific that is based on our COM902. It's a It's a TGPD-1 bispecific, and it just recently started clinical studies. And obviously, I'll say that now, and it also relates to Bayer, and you rightly so, you mentioned this. The progress of this program is really dependent on our partners, and the sharing of the information is dependent on our partners. So obviously, we cannot relate to it, but they're progressing. And the Bayer program, the last update that we shared was the fact that it is being tested in combination with the Keytruda. So it's a LDR2 antibody that is being tested in combination with the Keytruda. And Bayer is focusing on first-line IO-naive head and neck cell carcinoma. And again, in this case, the progress is dependent on Bayer and they control the news flow, but this program is progressing as well. With respect to our early stage pipeline, so yes, we did not share information about it. I'll repeat what we were saying and I'll relate to the reasons why we're not discussing it in the public domain, but basically we're focusing these on a number of programs We're focusing, all of them are programs that were predicted by our computational discovery capabilities. Remember, we're not a me-too company. We're focusing on modulating the immunosuppressive cells in the tumor microenvironment. And we will share information about these programs depending on their development stage and also depending on the competitive landscape. it is clear to us that it's like PVRIG, right? At the time that we shared information about PVRIG, the clock started ticking with respect to competition. And you now see it is validating as well that there is competition on new targets that we identify, but we also want to make sure that the development stage is as such that we can maintain our leadership.

Terrific. Thanks for taking the questions.

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

Hi, good morning. This is Jacqueline for Mark from Oppenheimer. Thanks for taking our question. My first question is, are you taking any steps to limit the number of prior therapies for patients enrolling in the extension cohorts? versus what we saw in the all-commerce study population at the FITC conference? Thank you.

Henry, I guess you'll address that one.

Yeah, yeah, I will. Thank you, Kathleen, for the question. We are not taking any active steps to limit the number of private therapies. What we are doing actively is speaking with the investigators in ensuring that the subjects or the patients who are enrolled onto these clinical trials are patients who meet all the eligibility criteria for the particular studies that we're doing. And in addition to that, we're also ensuring that they're fit enough as per eligibility for the clinical trial. And then the other thing that we're also doing is ensuring that the appropriate therapies have been administered to these patients before they come onto this study. and we'll meet with the investigators very, very frequently, and we review each patient before they come on. Now, if you remember, and I'll just go back to the guidance document by the FDA, for phase one studies where we're testing investigational new drugs, the guidance from the FDA is that the patients who are enrolled onto the studies must have exhausted all available standard of care therapies. Therefore, you can see, that depending on the tumor type, the number of prior therapies that patients must have been exposed to will vary. So including in those instances where the standard of care is shifting, even as we conduct the studies for, for example, endometrial cancer, where the standard of care has now shifted into patients receiving lenvatinib and pembrolizumab. What we do encourage the investigators to do, and this is why we speak to them, is that when patients have exhausted those available standard of care therapies, that they consider the clinical trials that we're doing, and they're seriously considering this. So I think that's where the change will come from. So that they're offered the opportunity to enroll on our clinical trials earlier on before they receive other investigational agents. So, for example, for the COM902 studies that we're doing, we're ensuring this. for the triplet study that we're doing the same thing and for the COM7-1 plus and the Volumark study. So it's an ongoing engagement with the investigators that we're ensuring.

Thank you. My second question is the R&D expenses were sharply down in 4Q. How should we think about modeling going forward in 25Qs?

So, yeah, we had a slight reduction in the fourth quarter. It's mostly shifting between quarters. It's a good question. And basically going forward, you should assume that the run rate would be more similar to the third quarter, which was roughly $8 million, $9 million, and that's probably what you're going to see in 2022 as well.

Okay, thank you. That's it for me. Thank you for taking my questions again.

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

Thanks very much. A couple of questions, if I may. The basket trial with PVRL to high level, how are you defining, or please remind us how you're defining high, and then I have two follow-ups, if I may.

So yes, Tony, thank you. This is exactly what we do now. So we need to explore what does it mean high and low for enrollment. And this is defined in correlation with anti-tumor activity. So we're now evaluating the expression levels as compared to response in all the studies that we have. And when we will set the threshold, we will then initiate enrolling for the basket study. So this is still not being enrolled.

Yeah, thanks. That's very helpful. Thank you. In the doublet for non-small cell lung cancer, it's interesting to enroll a cohort and treat them with the doublet, assuming that they have, of course, failed prior PD-1 therapy. But I am curious why it may not also be in the triplet. And the second, and part B to that question, do you think that anti-PD-1 actually drives, at least in combination with anti-TIGIT and anti-PVRIG, actually drives increased exhaustion for T cells. In other words, they become no longer, I guess, CD8, CD28-positive.

So I will relate to the triplet first, or maybe as you alluded from the doublet of the COM701, COM902, that is in a PD-1 free regimen, to the triplet. We focused on the triplet on tumor types that are not responsive to PD-1 inhibition other than the head and neck that is more inflamed as compared to the other indications that we have. We limited the study. It does not mean that we will not expand triplet assessment in non-small cell lung cancer, but at this point in time, we're not assessing non-small cell lung cancer in the triplet. A later run relates to the triplet or blocking the three pathways with respect to driving increased exhaustion. Eran?

Yes, so overall PD-1, like many other checkpoints, are reinvigorating exhausted cells. And PVRAG actually is expressed also in exhausted cells like other checkpoints, But what's interesting is PVRLG has even a more dominant expression in cells with earlier differentiation. And these cells normally have higher proliferative states. So if you block PVRLG and we start to see some early signals in clinical trials, you are able to enhance interaction of early memory cells, less exhausted, with embryonic cells. This could induce additional waves of effector cells that will penetrate your microenvironment. And over there, the cells probably will adopt the PVRIG, TGIT, and PD-1 triple expression. And then the triple blockade, or maybe in some cases, in which they are less dominant of some of the parts, maybe even the specific doublets could be meaningful. So overall, we think that PVRIG could bring to TGIT and PD-1, or maybe in some cases, even in the absence of PD-1, could bring treatment options to patients that normally are not responding to checkpoints because of this unique expression profile. And this is what we're evaluating clinically.

Thank you, Aron. Last question is around scopal effects, especially in CRC. I don't know, and I don't think this has been addressed, but were any of the patients stage 4 colorectal cancer patients, at least previously treated, and importantly, assuming then by definition they have liver mets, has it been determined at all or observed? that those METs also were in fact stable and or were maybe part of that partial response patient that was observed in the previous cohort of CRC patients. Thank you very much.

Henry?

Yeah, Tony, good question. Thank you. So I will not be able to point to specific patients. But what I can point to is to go back and remember, remind all of us about the way the assessments are conducted. And that will probably provide a reasonable answer to your question. So if you remember, Tony, what we're using to, what the investigators are using to determine responses on this various studies that we're doing, and in particular colorectal cancer, is to look at RASIST version 1.1. So in that case, they're looking at patients who have, especially in the expansion cohorts, patients who have target lesions. So all the patients that we have enrolled on the colorectal cancer cohorts have, by definition, stage four disease. So stage four disease, that means they have disease sometimes in the liver, sometimes in the lungs, and other body cavities also. Those target lesions are then accounted for in terms of the assessments. So what we've observed, at least in some of the patients, is that the investigators have selected some of the target lesions that are either in the liver or in the lung, and then they measure these lesions and follow them. And this accounts for how the patient's response assessments are then reported. whether it's stable disease, meaning there's no appreciable increase in the size of these target lesions, whether there's a reduction, as in the partial response we observed, we reported in that patient with colorectal cancer, microsatellite stable, or whether there was progression. So that's the way it's assessed. And sometimes some other lesions, that are non-target lesions are also reviewed to see if there's any increase in terms of subjectivity for these lesions. So we cannot rule out the abscopal effect in these patients, but certainly we're using more refined and more established criteria in the assessment of responses in these patients. Henry, thank you very much.

I appreciate it. Maybe just to add in this regard, and actually linking this to the previous comment about the PVAG expression on early memory cells. So we have recently actually presented in that CLT patient who responded clinically, we followed up a pre- and non-treatment biopsy taken from liver metastasis, which is normally an immunosuppressive environment. And we have seen a dramatic immune modulation. We have presented it in the last FIGI Summit. So we see actually a huge increase in influx of new T-cell clones penetrating that specific lesion in the liver. And we saw increasing clonality, increasing immune activation. And this is one of these observations I mentioned, preliminary observation, that supports, especially in this indication, because normally you wouldn't expect to see this kind of modulation following NEVO alone. So this is very encouraging to see such immune modulation and increased T-cell infiltration in such a liver mass of MSS colorectal cancer patients.

Very important, Iran. Thanks very much for the clarity.

The next question is from Diana Graybosh from SVB Learing. Please go ahead.

Thank you. Thank you, guys. I'm going to make a statement that I've been thinking about and I think a lot of the questions are thinking about. If you're enrolling A lot of patients, approximately 220. And I think our worry is collectively that you've set the ambition and bar so high because of your belief in being able to have PBRG, stimulate an immune response, and these harder to treat patient populations, whether it be like colorectal or ovarian or in lung after they've exhausted other IO treatment. So, you know, I think that the risk that I think a lot of us are considering is could you have a good hypothesis and a good treatment, but then you enroll all these patients and we still fail to see a really strong signal because the threshold is so high. And I wonder, as you look at that, can you point to any cohort or combination where you think the threshold is not so high that we are more likely to see a signal. And I'll make an example. Like with TIDGET, if these cohorts had been enrolled for TIDGET, I don't think we'd be where we are with TIDGET today. We're excited about TIDGET because Roche Genentech did a frontline study, which they could, because they were combining on top of standard of care, and which you guys also have standard of care, Updivo, that you could do a strategy like that with the combinations that include Updivo. have chosen not to. So I just love for you to react to that statement and tell us all where we could have some optimism that you haven't set the threshold too high.

So Dana, thank you. And it's a very good question, obviously, as always. And we picked this strategy of going after people mainly the non-responsive patient population, the less inflamed tumor types, the PD-1 non-responders. Yes, in a data-driven manner that is based on what we believe is the groundbreaking science that we have in hand. So that's correct, and this is the plan. Yes, we do have more inflamed tumor types that are the head and neck and the non-small cell and cancer, but yes, these are In head and neck, we have IO naive arm, but indeed, this is targeting less inflamed. I will say that as we move forward, all options are on the table for us also to make sure to pursue inflamed tumor types. It was very important for us with these studies that we pursued this time to go ahead and try to address what we think is the edge that PVRIG may bring to the table. But it is a higher risk. As a company, we are considering various options to also lower the risk, and all options are on the table now.

That was very helpful. Thank you, Anat. That's it for me.

Thank you.

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

Yes, thank you, Operator. Thank you for joining us today and your continued support. Stay safe and healthy.

Thank you. This concludes the CompuGen LTD fourth quarter 2021 financial results conference call. Thank you for your participation. You may go ahead and disconnect.