Q4 2021 Compugen Ltd Earnings Call

Unknown Executive: files with the SEC on February 25, 2021. The company undertakes no obligation to update projections and forward-looking statements in the future.

On February 25 2021.

The company undertakes no obligation to update projections and forward looking statements in the future.

Anat Cohen: With that, I now turn the call over to Anat. Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to a fourth quarter and full year 2021 update. I'm proud to say that Compugen made excellent progress in 2021. Our fundamentals have improved, and we're delivering on our promise. Compugen has done groundbreaking work on the biology of the key targets of the denim axis, PVRIG and TIG.

With us I'll now turn the call over to enough.

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 comp again made excellent progress in 2021.

Our fundamentals have improved and we are delivering on our promises.

Competition has done ground breaking work on the biology of the key targets of the denim X is P. D R I G and PG.

Anat Cohen: This is evidenced by our numerous publications and patent filings. We are pioneers in 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 TGIT and PVRIG. Immune checkpoint inhibitors have become multi-billion dollar drugs and are having a major impact on cancer care.

This is evidenced by our numerous publications and patent filings.

We're pioneers in an uncharted territory.

The first test in the clinic two agents never combined before primarily focused on PD, one nonresponsive patients.

Our differentiated clinical strategy with our potential first in class NTP Vieira G antibody come. So then the one is to lead the next wave of innovation by executing a unique combination approach to realize the full potential of <unk> and P. V. R. I G.

Immune checkpoint inhibitors have become multi billion dollar drugs and they're having a major impact on cancer care.

Anat Cohen: 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 adenine axis have the potential to be a game changers in the treatment of cancer.

However, as most patients do not respond to immunotherapy there is a need for new drugs for these cancer patients.

At <unk>, we believe that immune checkpoint inhibitors that target the DRAM axis have the potential to be a game changer in the treatment of cancer.

Anat Cohen: As we continue as leaders in the DINAM Act by unlocking the potential of both the PVRIG and TIGIT pathways with a vision to deliver the next transformational drug, 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, 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.

As we continue as leaders in the DRAM axis.

Unlocking the potential of both <unk> and <unk> 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 we'd come seven one and comment on to support our hypothesis the treatments that target the denim X. These could be effective in inflamed or even more exciting less inflamed tumors.

Anat Cohen: Our studies show early signals of anti-tumor respiratory activity, with Immune Activation Across Studies and a Good Safety Profile in Mono, Dual, and Triple Therapy Sets. 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.

Our studies show early signals of antitumor activity with immune activation across studies and a good safety profile in monarch 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 would you.

Anat Cohen: 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 strong execution across our differentiated clinical strategy. I want to highlight three of our important accomplishments in 2021.

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 competition with a strong execution across our differentiated clinical strategy.

I want to highlight real far important accomplishments in 2021.

Anat Cohen: 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 those 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 deenomaxis hypothesis in our ongoing expansion cohort studies.

First in keeping with our goal to develop a 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 competence Dino Maxis hypothesis in our ongoing expansion cohort studies.

Yeah.

Second in keeping with our goal of maximizing value for patients.

Anat Cohen: In keeping with our goal of maximizing value for patients, we expanded our collaboration with Bristol-Myers Squibb and are happy to see AstraZeneca progressing their TGPD-1 bispecific derived from our COM902 into the clinic. In addition, we extended 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. In keeping with our leadership position in the field and our goal to advance 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.

We expanded our collaboration with Bristol Myers Squibb and are happy to see Astrazeneca progressing their ticket PD one by specific derived from our continental to into the clinic.

In addition, we extended 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 go to advanced immuno oncology research.

Throughout 2021, we presented new research and translational data at scientific conferences to support the unique biology of P. B R E G and the potential of its blockade to target less inflamed tumor types.

Anat Cohen: 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 DINAM-S in Cancer Immunotherapy in the prestigious high-impact journal Cancer Discovery.

In addition, along with one of our trusted devices and long term collaborators Professor Drupal doll, we co authored a review on the biology and potential therapeutic relevance of the denim etsy.

In cancer immunotherapy in the prestigious high impact Journal cancer discovery.

Anat Cohen: Looking ahead to 2022, we're conducting three very important Phase I-II combination studies. As you know, our clinical strategy has been designed to allow us to systematically evaluate our hypothesis that simultaneously blocking three pathways, PDRG-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 TIGIT and PV1, 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 into a more inflamed environment.

Looking ahead to 2022, we're conducting three very important phase one two combination studies.

As you know our clinical strategy.

It's been designed to allow us to systematically evaluate our hypothesis that simultaneously blocking three pathways P. Gary G T J <unk> and PD one in selected biomarker informed tumor types may produce game changing results for cancer patient with inflamed or less.

Inflamed tumors.

P D R. I G, which is differentiated from <unk> and PD, one may be the missing piece when current immunotherapies have failed by potentially generating new waves of T cells to infiltrate the tumor microenvironment turn engaged to a more inflamed environment.

Anat Cohen: 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 selection. Based on establishing proof of concept in specific indications, we will share a 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.

Our ongoing combination studies are seeking those seeking studies evaluating preliminary antitumor activity of <unk> 71. In addition to safety and Tolerability in multiple indications.

These studies also include a parallel comprehensive translational analyses.

Setting immune activation to further evaluate our unique drug mechanism of action and potential biomarker identification that may be of relevance for future patient selection.

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.

Anat Cohen: 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 COM-701 Evolumab 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-PVRL-GPD-1 triple combination with COM701, nivolumab, and bristol-melsquib's anti-TGIT in patients with ovarian, endometrial, and head and neck squamous cell carcinoma, plus a cohort of subjects who have high expression of PVRL-GPD-1, which we will start enrolling following the assessment of correlation between PVRL2 level of expression and response.

Although these are signal seeking studies. This approach which include some overlapping indications across studies is intended to help us understand the contribution of each study drug.

Anat Cohen: The third study, most recently initiated in November 2021, is evaluating an NTTG-PVRG combination with our wholly owned COM-902 and COM-701 drug candidates in patients with head and neck squamous cell carcinoma, non-small cell cancer, and microsatellite stable cholera cell cancer. Our intention is to report data from fully enrolled cohorts of each of these studies, taking into consideration that certain indications enroll faster than others, and use the results to define our regulatory strategy on a cohort-by-cohort basis.

Enrollment is underway in our ongoing clinical studies.

Anat Cohen: 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 volume-up 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.

The first study initiated at the end of June 2021.

Is designed to evaluate and NTP V or a G. PD one combination we'd come seven Hawaii volume up in patients with ovarian endometrial breast and microsatellite stable colorectal cancer.

Anat Cohen: 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 Regoraphenib or Lunsurf, which show an ORR of 1%. Median PFS of 2 months and median OS of 6-7 months. As of today, we have presented data from 12 patients using various doses of COM-701 with or without nivolumab across studies and have shown encouraging preliminary anti-tumor activity with a disease control rate of 58%, including one partial response of 44 weeks.

Anat Cohen: Our current COM7-1 eVolumab study consists of an 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 CT, as well as the expansion of our collaboration with Bristol-Myers Squibb based on the data we've presented to date.

The second study initiated in July 2021 is designed to evaluate the N T. P. T. J P V. R. A G. P D. One triple combination with comps up in the one new value mob and Bristol Myers Squibb's NTT Jade in patients with ovarian endometrial and.

The next squamous cell carcinoma, plus a cohort of subjects, who have high expression of PV or attitude.

Which we'll start enrolling following the assessment of correlation between P. P. L. Two level of expression and response.

Anat Cohen: Three observations from our overall translational data set stand out. First, our most recently presented translational data demonstrating immune activation across our COM701 studies, with the most potent immune activation in triple blockade of PDRG, TG10, and PD-1 supports our suggested drug mechanism of action, as well as the differentiation of PDRG from that, Fidget, and Petey One.

The third study most recently initiated in November 2021 is evaluating and NTT G. P. V. R. A G combination with our wholly owned come nano to come 71 drug candidate in patients with head and neck squamous cell carcinoma, non small cell lung cancer and microsatellite.

Anat Cohen: I'm pleased that our approach to develop our anti-PD antibody using an IDG4 backbone similar to the leading anti-PD1 antibodies with less effects of function than IDG1 appears to be an appropriate strategy. Indeed, in our COM902 dose escalation study, which we presented at CITSI, we showed that there was no depletion of the CD8 plastesis, the most effective anti-tumor immune substance. We were the first to present clinical data with an IgG4 antipygic antibody with low FC effector function.

Stable colorectal cancer.

Our intention is to report data from fully enrolled cohorts of each of these studies.

Taking into considerations that certain cohorts indications and rose faster than others and use the reserve to define a 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.

Talking with the microsatellite stable colorectal cancer cohort from the comfort of knowing the volume up 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 these patient population.

Treatment in this setting is typically rig roughing it.

Ola surf, we'd show or are of 1% median PFS of two months and median O S of six to seven months.

And today, we have presented data from 12 patients using various doses of <unk> seven to one we don't without the volume up across studies and have shown encouraging preliminary antitumor activity with a disease control rate of 58%, including <unk>.

One partial response of 44 week.

Our current comps are in Hawaii volume up 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 2020 , one I've been very pleased with the encouraging data in our phase one studies across mono dual and triple therapy in multiple tumor types as presented at our school and C. T as well as the expansion of our collaboration with Bristol Myers Squibb.

Based on the data we've presented to date.

Three observations from our overall translational dataset stand out to me.

First most recently presented translational data demonstrating immune activation across our Com 71 studies.

With the most potent immune activation in triple blockade of PD L. G T J and PD one.

Supports our suggested drug mechanism of action.

Well as the differentiation of PV energy from that team.

<unk> and PD one.

Second.

I'm pleased that our approach to develop our anti <unk> antibody using and arguably for backbone similar to the leading anti PD, one antibodies with less effector function than <unk> Q1.

It appears to be an appropriate strategy.

Indeed in our come nine O two dose escalation study, which we presented at city. We showed that there is no depletion of the C. D plus T says the most effective antitumor immune subset.

We were the first to present clinical data with an IGD for anti <unk> 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.

Anat Cohen: 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 supporting data from our PVRIG research. In addition... We achieved encouraging signals of anti-tumor activity in our studies with several notable durable responses in heavily pre-treated 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 COM-7.1 and COM-9.0.2 with the potential to unlock the value of Dinam-Apsis as a game-changer in the treatment of

Third our initial data suggest that comes out of the one may have potential to address less inflamed tumor types with other immune checkpoint inhibitors have not been successful.

In line with supportive data from our P. B R. I G research.

In addition, we achieved encouraging signals of antitumor activity in our studies with several notable durable responses in heavily pretreated patients who have exhausted all available therapies with a good safety profile.

To summarize our translational observations coupled with encouraging data to date suggest a differentiated profile for comps have been wanting to come in I know too with the potential to unlock the value of DRAM axis is a game changer in the treatment of cancer.

Ari: I am enthusiastic about our program and look forward to sharing the results of our ongoing studies. 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 banners. 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.

I'm enthusiastic about our programs 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 site.

Thank you I'm not I'm happy to summarize our financial results.

I'll start with our cash balance.

As of December 31, 2021, we had approximately $118 million in cash compared with approximately $124 million.

December 31st 2020 <unk>.

The company has no debt.

Ari: 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 of specific tumor types and comprehensive clinical strategy to increase the probability of success of our drugs to help patients.

Our cash balance reflects Bristol Myers Squibb strategic investment of 20 million $20 million and a $6 million milestone payment from Astrazeneca received during the fourth quarter.

Going into 2022.

Our cash burn to be in the range of between $44 million to $46 million.

Financially disciplined where a company targeting our extensive and unique knowledge in this space or specific tumor types and comprehensive clinical strategy.

Increase our probability of success of our drugs to help patients.

Ari: 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 $6 million for the year ended December 31, 2021, compared with $2 million for each of the comparable periods in 2020.

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 a $6 million for the year ended December 31, 2021, compared with $2 million for each of the comparable periods in 2020.

Ari: 2021 revenues are related to the milestone payment from AstraZeneca for dosing the first patient in their Phase 1-2 study of a TG-Bispecific Monoclonal Antibody derived from our COM-902. With respect to R&D, R&D expenses for the fourth quarter and year-ended December 31, 2021, were $5.8 million and $28.7 million, respectively, compared with $8.1 million and $22.8 million The increase in R&D expenses during 2021 is attributed mainly to higher expenses associated with our various clinical studies, as well as increased headcount as we continue to grow our US-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.

2021 revenues are related to the Muslim payment from Astrazeneca for dosing the first patient in their phase one two study of a digit bispecific monoclonal antibody derived from our 902.

With respect to R&D R&D expenses for the fourth quarter and year ended December 31st 2021 were $5 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.

Well as increase in headcount as we continue to grow our U S based clinical team to support the extension and expansion of our studies.

The decrease in the quarterly period.

Two a decrease in manufacturing and related expenses.

Ari: Our G&A expenses for the fourth quarter and year-end of December 31st, 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 D&O insurance premium costs that affected the overall industry. During the fourth quarter of 2021, we reported a net loss of $8.6 million, or $0.10 per basic diluted share, similarly to a net loss of $8.6 million, or $0.10 per basic diluted share in the comparable period of 2020.

Our G&A expenses for the fourth quarter and year ended December 31st 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 D&O 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 and diluted share.

Similarly to a net loss of $8 $6 million or 10 cents per basic and diluted diluted share in the comparable period of 2020.

Ari: The net loss for the year ended December 31, 2021 was $34.2 million, or $0.41 per basic and diluted share, compared with a net loss of $29.7 million, or $0.37 per basic and diluted share, in the comparable period of 2020.

Net loss for the year ended December 31st 2021, with $34 2 million or 41 cents per basic and diluted share compared with a net loss of $29 $7 million or <unk> 37 cents per basic and diluted share in the comparable period of 2020.

Anat Cohen: Now, I'll turn the call back to Anna. Compugen has done groundbreaking work on the discovery of the PVRIG pathway and the DINAM 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 2020. We have a solid balance sheet with a cash balance of $118 million that will support our clinical program and our operations into 2024.

Now I'll turn the call back to on that.

Competition has done ground breaking work on the discovery of the P. D. R. I G pathway and the DRAM axis hypotheses.

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 100, and a $10 million that will support our clinical program and our operations in into 'twenty 'twenty four.

Anat Cohen: I'm very enthusiastic about 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.

I'm very enthusiastic for what's to come for country Jin.

And look forward to updating you on our progress throughout the year.

I want to send a special thank you to the amazing team, it's coffee, Jim whose dedication has enabled our remarkable accomplishments and to you all for joining us today and taking time to follow the company.

Operator: 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.

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 one if you wish to decline from the polling process.

Press Star two if you are using speaker equipment currently with the handset before pressing the numbers. Please standby, while we poll for your questions.

Operator: Please stand by while we poll for your questions. The first question is from Stephen Wiley of Stifel. Please go ahead. Yeah, good morning.

The first question is from Stephen Wiley of Stifel. Please go ahead.

Stephen Willey: Thanks for taking the questions. Can you maybe just share with us what your current expectations are regarding efficacy data that will be emerging from 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 701902 combo? Thank you, Steve.

Yeah. Good morning, Thanks for taking the questions.

Uh huh.

Can you maybe just share with us what your car.

Current expectations are regarding efficacy data that will be emerging out of the core cohort by year end.

Yeah.

I guess what needs to be seen essentially inform a go forward decision.

And then I guess second to that can you make that decision about going forward.

Or you see combo data from the study.

Okay.

Yeah.

Anat Cohen: 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 patients do not have many options. So we think that the bar is not 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.

And thank you, Steve and I'd, just say I'd refer this question to Henry I'd, just say that in general for all the most of the tumor types that we're addressing.

These are two more times than not responsive to checkpoint and and the patients do not have many options. So we think that the bar.

Is not that is not to.

Very high in terms of numbers. Obviously this is a very hard to treat patient population.

But I'll, let Henry relate to two more specifics.

Yeah. Thank you very much and thanks, Jim for the question Yeah, I just want to remind you and everybody also listening.

Anat Cohen: Thanks, Steve, for the question. Yeah, I just want to remind you and everybody else listening that these are signal-seeking studies, even though they're expansion cohorts, right? So, we have about 20 subjects in each of these co... 20 patients in each of these cohorts that you're mentioning. So, it's actually what we're looking for is a combination of various things. So, number one, we're looking for efficacy in terms of a partial response. We're also looking for anti-tumor activity in terms of stable disease and the durability of the stable... So it will be premature to start assigning numbers that will be of interest to us.

These are signal seeking studies, even though the expansion cohorts right.

Two subjects in each of these transitions in each of these cohorts that you are in Michigan.

It's actually what we're looking for a combination of those things. So number one we're looking for.

That's what you've seen in terms of whether your partial response.

So looking for anti tumor activity in terms of stable disease, and the durability of stable disease. So it would be premature to start signing numbers that will be of interest to us.

Henry Adewoye: With 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, one of them being that this tumor type is typically not responsive to immune checkpoints, or it has very limited activity. So that itself shows that we have a signal just there, that that's one patient.

But that being said I think it bears mentioning just like Oh, that's mentioned in her prepared comments that particular tumor type where you see.

Nutrition with a partial response for example, colorectal cancer.

Steve one for 44 weeks.

Notable.

Notable for the following reasons and what else is being that this tumor type is typically not responsive to immune checkpoints or they have very limited activity.

So it shows that we have received no just the divestment of completions and the other reason that's important is the fact that we've also disclosed that our school just last year.

Henry Adewoye: And the other reason that's important is that, at ASCO just last year, the caliber of patients that we enrolled into the colorectal cancer cohort, of the 12 patients we enrolled, we saw patients, 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.

The caliber of Ah patients that were enrolled into the colorectal cancer cohort.

Of the 12 patients enrolled we saw pretty Sean. This is also listed a swimmer plot.

Those patients.

I actually saw.

What is typical for the medium progression free survival in this patient cohort. So that's we'll do so.

Those are the parameters that we're interested in.

Henry Adewoye: And we'll continue to accrue data into all other cohorts and then see what the results are and be able to make a more informed judgment as to anti-tumor activity and the next steps for completion. I'll just add, 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 to all the different studies and all the cohorts. So we really look at the translational data as a very important parameter.

And we will continue to accrue into all of the cohorts and then see what the results are unable to make a more informed judgment.

Judgment us.

As to anti tumor activity the next steps for computer.

I just.

Yes, 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 going on all the cohorts. So we really look also on.

The translational data is very important parameter. So this will be taken into consideration as well and obviously for <unk> 701 and call nano two combination the data.

Anat Cohen: So this will be taken into consideration as well. And obviously, for COM 701 and COM 902, 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 PBRL-2 expression threshold? enrollment into the basket. That's not limited to

Open studies, we see the data so definitely this is a parameter that would take into consideration.

Okay.

That's helpful and then.

Maybe just lastly.

Is the year end 'twenty three guidance that you provided here.

Does that does that in any way.

And by the diagnostic work.

You are doing.

What's your P BRL two expression.

Enrollment.

That's not limited to the program is ongoing where they can get out of work in order to.

Operator: 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 Dynamaxis members and specifically PVRL2. So at the time that we feel that we have enough in order to correlate expression to response, we will start the basket. Okay, thanks for taking the question. The next question is from Ren Benjamin of JMP Security. Please go ahead.

Make sure that we have the samples and that we can test the expression profile slipped a denim excess members and specifically the PV era too. So at the time that we will feel that we have enough in order to correlate expression to respond. So we would start the basket study.

Okay. Thanks for taking the question.

Okay.

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

Ren Benjamin: Hey guys, good morning. Thanks for taking the questions. I guess just starting off, you know, the dose and timing for the dose expansion studies. Can you just give me a sense as to what the factors that are...

Hey, guys. Good morning, Thanks for taking the questions I guess, just starting off you know the.

Does 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 leading you to think that enrollment would only be complete by the end of 2023.

Anat Cohen: I always assumed that once the dose expansion was done, that the expansion... Sure. Basically, there are two parameters. It's the enrollment rate that is very different for different indications. CRC, by nature, is more prevalent, and less treated, so it is enrolled faster. There are indications where it is harder to enroll, and the pace is lower, so this is one parameter.

I always assume that once the dose expansion was done that the pension 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.

Anat Cohen: And also, I want to remind everyone that these are studies, these are significant 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 dynum axis in a way where we maximize the opportunities.

Sure basically there are two parameters that the enrollment rate that is very different for different indications and CRC by nature is more prevalent lesser treatment. So.

It is enrolling 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 seen as seeking study is and we have 20 patients per cohort.

But we have many cohort 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 DRAM axis in a way where we maximize the opportunities.

And then we maintained the leadership in this area in this and evaluating this and access and also to make sure that these are not only signal seeking studies. So we can really relate to the two.

Due to the contribution of components, but let's make sure that we remember that these are not small studies and we're really enrolling faster we're on execution.

And we will start to sharing data in Q4.

And these studies will continue to enroll and we will continue to share guidance end to end data, but that's the two pharmacist enrollment and the size of the studies.

Got it and just as I think about news flow out of a sense of obviously, how the news flow from the companies coming out can you talk a little bit about maybe your partnership programs.

And you know any sort of a sense as to as to when we might.

C news flow from from those programs.

Anat Cohen: 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 agency? Sure so for the 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 and obviously I say that now and it also relates to Bayer and you rightly so you mentioned this this said 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 are 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 an LDR2 antibody that is being tested in combination with the Keytruda and Bayer is focusing on first-line ion-naive head and neck cell carcinoma and again in this case the progress is dependent on Bayer and they control the the muce flow but this program is progressing as well and with respect to our early stage pipeline so, Yes, we did not share information about it.

And I understand you know these are producer partner programs, you might not have as much control or insight into that Ah 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 in INV.

Uhm.

Sure so for the for the partner programs and there is the Astrazeneca program, which is a bi specific that is based on our common name or two it's a it's a tedious PD one by specific end them.

And it just recently started clinical studies and and obviously I'll say desk now and it also relates to bear and you you rightly. So you mentioned this they said the progress of this program is really dependent on our partners and the sharing of information is dependent on our partners. So obviously, we should not really.

To do it but they're progressing.

And the bare program and the last update that we shared was the fact that it is being tested in combination with keytruda for it out of their two antibody that is being tested in <unk>.

Combination with Keytruda.

And they are focusing on first line Io naive head and neck squamous cell carcinoma.

And again in this case, the progress is dependent and Bayer and they control then and then use flow everybody's program is progressing as well.

And with respect to our early stage pipeline so.

Anat Cohen: I'll repeat what we're saying, and I'll relate to the reasons why we're not discussing it in the public domain, but basically, we're focusing on these a number of programs. We're focusing all of them are programs that were predicted by our computational discovery capabilities. Remember, we're not in need of a company.

Yes, we did not sharing information about it I'll repeat what we're saying and then related to the reasons why we're not discussing do you think the public domain, but basically we're focusing these a number of programs we're focusing.

All of them are and programs that were predicted by our computational discovery capabilities and remember we're not to me to company and were focusing on modulating the immune suppressive there.

First in the tumor microenvironment.

And then 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 P V. Our idea right at the time that we shared information about PV array G and the clock starts ticking with respect to competition and you now see it is validating as well that there is competition on new targets that we identify button, but we also want to make sure that the development stage.

He 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.

Operator: Thanks for taking our questions. 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-comer study population at the Henry, I guess you'll address that one. Yeah, yeah, I will.

Hi, Good morning, this exactly mark from Oppenheimer. Thanks for taking our questions. My first question is are you taking any steps to limit the number of prior therapies for patients enrolling in the expansion cohorts versus what we saw in the all comer study population.

She's not offered.

Thank you.

Henry I guess, he will address that one.

Operator: Thank you, Kathleen, for the question. We are not taking any active steps to limit the number of prior treatments. If you, what we're actively doing is speaking with the investigators to ensure that the subjects of the patients who are enrolled in the 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 for the, 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 the patients before they come onto the study. And we meet with the investigators very, very frequently.

Yes, yes, thank you Katherine for the question.

We're not taking any active steps to limit the number of prior therapies.

If you were doing actively speaking with the investigators and ensuring that the subject to the patients who are enrolled onto this clinical trials patients who meet the eligibility criteria for the particular studies that we're doing.

And in addition to that we're also ensuring that they are sweet enough.

For the.

What's your ability 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 into the study.

I would like to be the inverse the investigators are very very frequently.

Henry Adewoye: 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 I studies where we're testing investigational new drugs, the guidance from the FDA is that the patients who are enrolled in the studies must have exhausted all available standard-of-care therapies. Therefore, you can see that, depending on the tumor type, the number of paratherapies that patients must have been exposed to will vary.

We view each patient before they come on.

No if you remember and I'll just go back to the guidance document by the FDA.

For Phase one studies, where we are testing investigational new drugs the guidance from the SBA.

The patients who are enrolled onto their studies most have exhausted all available standard of care therapies. Therefore, you can see that depending on the tumor type.

<unk> kind of therapies that patients have been exposed to.

Henry Adewoye: 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 to patients receiving lenvartinib and pembrolizumab. What we do encourage the investigators to do, and this is why we split..., is that when patients have exhausted all available standard of care therapies, they consider the clinical trials that we So, I think that's where the change will come from, so that they're offered the opportunity to enroll in our clinical trials earlier on before they receive other investigational agents.

Gary.

No.

In those instances, where the standard of care are shifting even as we conduct this study as well for example, endometrial cancer, where the standard of care is now shifted.

And two patients receiving.

The advancing the Penguin Lisa.

What we do encourage the investigators to do and this is why we stick to them.

Is that when patients.

Have exhausted all available standard of care therapies that would be considered the clinical trials that we're doing and they seriously considered considering this so I think thats, where the change will come from so that they are offered the opportunity to enroll on our clinical trials.

Before the Ebola investigational agents. So for example for the Continental to studies that we're doing we're ensuring base for the triplet study that we're doing the same thing for the <unk> hundred one closing remark study sorry.

Henry Adewoye: So, for example, for the COM 902 studies that we're doing, we're ensuring this. For the triplet study that we're doing, the same thing. And for the COM 71 plus, the volume up study. So, it's ongoing engagement with investigators that are in charge. Thank you. My second question is: R&D expenses were sharply down in 4Q. How should we think about modeling going forward in 5Q

Ongoing engagement with the investigators that were insuring.

Okay.

Okay. Thank you and my second question.

R&D expenses were sharply down in <unk>, how should we think about modeling going forward.

Yeah.

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.

Unknown Executive: 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 eight, nine million dollars. And that's probably what you're going to see in 2022 as well.

It would be more similar to the third quarter, which was roughly $89 million and thats, probably what youre going to see in 2021.

Unknown Executive: 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.

Okay. Thank you that's it for me. Thank you for taking my questions I guess.

Thank you.

Yes.

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

Operator: Thanks very much. A couple of questions, if I may. The basket trial for PVRL to a high level, what, how are you defining high, or please remind me, How You're Defining High. And then I have two follow-ups if I... So, yes, Tony, thank you. This is exactly what we do now.

Thanks, very much couple of questions if I may.

The basket trial with <unk>.

Two high level.

How are you defining please remind us how.

How are you defining high.

And then I have two follow ups department.

Anat Cohen: So, we need to explore what means 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 set the threshold, we will then initiate enrollment for the basket study. So, this is still not being an, Yeah, thanks.

So yes, Tommy. 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 the and with antitumor activity.

So were now evaluating the expression levels as compared to response in all the studies that we have and then when we will set a debt threshold. We would then initiate to enrolling for the basket study. So this is still not being enrolled.

Yeah.

Anat Cohen: That's, 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 doublets similarly, that they have, of course, failed prior PD-1 therapy. But I am curious why it may not also be in the trip. Second, and part B to that question, do you think that Antipede one actually derives, at least in combination with antipaget and antipaget?

Yes. Thanks.

Very helpful. Thank you.

The doublet for non small cell lung cancer, it's interesting too.

Two.

Enrolled a cohort.

Treat them with the doublet assuming of.

Of course failed.

PD, one therapy, but I am curious.

Why it may not also be in the triplet and the second important because that question do you think.

Hmm.

Anti <unk> anti PD, one actually drives at least in combination with an anti <unk>.

Anat Cohen: PBRG actually drives increased exhaustion for T cells. In other words, they have become. You know, no longer, I guess, CD8, CD28 positive. So I will relate to the triplet first, and or maybe as you alluded to 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, which is more inflamed as compared to the other indications that we have. We limited the study to

<unk> actually drive.

The increase.

Exhaustion for T cells in other words they become.

No longer I guess, CDA actually 28, Oh positive.

So I will relate to the triplet first and or maybe as you alluded from the doublet of the comps are in the one come nano to there isn't a PD one free regimen.

Anat Cohen: It does not mean that we will not expand triplet assessment in non-small cell and cancer, but at this point in time, we're not assessing non-small cell and cancer in the triplet. I let Eran relate to the... A triplet or blocking the three pathways, and... with respect to driving increased exhaustion. Eran?

And to the triplet we focused on the triplet on tumor types that are and that are not responsive to PD one inhibition other than the head and neck. If there is more inflamed as compared to the other indications that we have we're limited to study it does.

Not mean that we will not expand and triplet assessment in non small cell lung cancer, but at this point in time.

We're not assessing those will sit on caffeine that triplet.

Iran relate to them.

The triplet and or blocking the three pathways.

And with respect to driving increased extortion.

Iran.

Yes, so overall PD one like any other checkpoints are reinvigorating exhaustive.

Eran Ophir: Yes, so overall, PD-1, like many other checkpoints, is reinvigorating exhaust. And PVRG actually is expressed also in the lost cells, like other checkpoints. But what's interesting is PVRG has even a more dominant expression in cells with earlier differentiation, and these cells normally have higher proliferative states. So if you block PVRG, and we start to see some early signals in clinical trials, you are able to enhance the interaction of early memory cells, less exhausted, with embryonic cells. This could induce additional waves of effector cells that will penetrate a true microenvironment.

And Peter G. Auctions expressed also in the lawsuit says like other checkpoints.

So interesting is people.

More luminous expression earlier differentiation and these sales are normally have hopefully first refers to the stage.

If you block G and we start to see some early signals into clinical trials you are able to.

Hum interruption, Italy memory says less exhausted within critics run this could induce additional waves of effector cells.

The tumor microenvironment and over there the sales probably will adopt.

Eran Ophir: And over there, the cells probably will adopt a PVRG-TGTNPD1 triple expression. And then the triple blockade, or maybe in some cases, in which they are less dominant in some of the parts, maybe even this presentation. Thank you, Eran. My last question is around the obscopal effect, especially in CRC.

N PD one expression and then the truth located there maybe in some cases in which there are less dominant or solve the puzzle maybe even.

Pacific Doublets could be meaningful.

Overall, the thing that people, who could bring to teachers and PD, one or maybe in some cases, even in the absence of PD one.

<unk> treatment option to patients with pneumonia and look responded to checkpoints because of this unique expression profile and.

We reevaluate it clinically.

Thank you Ron last question is just around Abscopal effects, especially in CRC.

Tony Butler: 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, by definition, they have liver mets? It hasn't been determined at all or observed that those mets also were, in fact, stable and or maybe part of that partial response patient that was observed in the previous cohort of CRC patients. Thank you very much. Henry

I don't know.

And I don't think this has been addressed but.

Any of the patients stage for colorectal cancer patients.

At least previously treated and importantly.

Assuming then by definition they have liver Mets.

Has it been determined.

Or observed that those that's also where in fact stable <unk>.

<unk>.

Part of that.

Partial response patients.

Was observed in the previous cohort of CRC patients. Thank you very much.

Henry.

Yeah.

Henry Adewoye: 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.

Yes, Tony Good question. Thank you so.

I will not be able to point to specific patients.

What I can point to is to go back and remember remind all of us about the way the assessments are conducted and that would probably provide.

A reasonable answer to your question.

Sure. So if you remember Tony when we use them to what the investigators are using to determine responses on this too.

Henry Adewoye: So if you remember, Tony, what we're using to, what the investigators are using to determine responses in this, in the various studies that we're doing, and in particular, colorectal cancer, is to look at RESIST version 1.2. So in that case, they're looking at patients who have, especially in the expansion cohort, patients who have the target. So all the patients that we have enrolled in the colorectal cancer cohorts are, by definition, stage four disease. So stage four disease means they have disease sometimes in the liver, sometimes..., in the lungs and other body parts of the other body cavities also.

This great start.

Studies that we're doing and in particular colorectal cancer.

If you look a racist version one one.

So in that case, we're looking at patients who have especially in the expansion cohort patients.

Who have target lesions. So all the patients that would have enrolled in the colorectal cancer cohorts by definition.

<unk> disease, so stage four disease that means they have disease, sometimes in the liver or sometimes in the end.

The lungs.

Therefore, the coverage is also.

Henry Adewoye: So those target lesions are then accounted for in terms of the assessment. 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. With stable disease, meaning there's no appreciable increase in the size of this target lesion, whether there's a reduction, as in the partial response we observed, reported in that patient with colorectal cancer microsatellite stable, or whether there was progression.

So those target lesions than accounted for in terms of the assessments. So what we've observed actually seen some of the patients is I think.

The investigators have selected somewhat struggled lesions that are either in the liver or in the lung and then we measure this nations and followed them.

And this accounts for how Depletions response assessments I've been.

Reported where that stable disease.

There is no appreciable increase in the size of this target lesions.

It basically reduction as in the partial response, we have we observed were reported in the accretion.

Colorectal cancer microsatellite stable.

Henry Adewoye: 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 this patient, but certainly we're looking at, we're using more refined and more established criteria in the assessment of responses in this.

Or whether there was progression.

So that's the way it's assessed and some times. Some other nations that are non target lesions are also reviewed to see if there's any.

Amy increase in terms of subjectivity for.

Our distributions so we cannot rule out the abscopal effect in these patients.

Secondly, we're looking we're using more refined and more established criteria in the assessment of responses in these patients.

Eran Ophir: Henry, thank you very much. And maybe just to add in this regard, and actually link this to the previous comment about the PVRG expression on early memory cells, so we have recently presented in that CLC patient who responded clinically, we followed up a prey and untreated biopsy taken from a liver metastasis, which is normally in an immunosuppressive environment. And we have seen dramatic immune modulation, and we presented it at the last DigiSonic.

Andrew Thank you very much.

Maybe just to I think you saw gods and actually linking linking this to the previous comment about the Pea Ridge excursion on Italy memory cells. So we have recently actually presented and that CLC Fisher to respond and clinically we followed up an.

And on treatment biopsies taken from a liver metastasis.

Which is normally in the muni suppressive environment than we have seen a dramatic immune modulation you presented it and good luck. Thank you Simon so we see actually a huge increase of an influx of new T cell clones penetrating that specific lesion in the Liza and.

Eran Ophir: So we actually see a huge increase in the influx of new T-cell clones penetrating that specific lesion in the liver. And we see increasing clonality, and increased immune activation. And this is one of these observations I mentioned, a preliminary observation, that supports the treatment, especially in this indication, because normally you wouldn't expect to see this kind of modulation following Nivo 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.

And we saw increasing quality and can be seen good activation and this is one of the these observations I mentioned preliminary observation that's of course, especially in this indication but globally.

We see this kind of population pulling me go alone.

It's very encouraging to see such a NIM regulation and increased penetration in such a lethal Mister pharmaceutical like for consultation.

Eran Ophir: Very important, Eran, thanks very much. The next question is from Daina Graybosch from SVB Lyrinc. 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 about what I'm thinking about. 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 it's harder to treat patient populations, whether it be like colorectal or ovarian or lung, after they've exhausted other I.O.

Very important Ron thanks, Thanks, very much for the court.

Okay.

The next question is from Diana Gray Bosch from SBB Leerink. Please go ahead.

Thank you. Thank you guys I'm going to make a statement I've been thinking about and I think a lot of the questions are thinking about you're enrolling a lot of patients approximately 220, and I think our worry is collectively.

You've set the ambition in bars, so hard because of your beliefs and being able to have P. B R. A G. Stimulate an immune response in these harder to treat patient populations, whether it would be like colorectal or ovarian or in long after they have exhausted other I O treatment.

Eran Ophir: So, you know, I think that the risk that I and 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 Tidbit. These cohorts have been enrolled in TIDGET. I don't think we would be where we are with TIDGET today.

You know I think that the risk that I and 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 felt fail to see 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 you know the threshold is not so high.

At you that we are more likely to see a signal in and I'll make an example, like with Tibet if.

These cohorts had been enrolled for T. J I don't think we'd be where we are with does it today. We're excited about two digit because Roche genentech did a frontline study, which they could because they were combining on top of standard of care and what did you guys also have standard of care Opdivo that you could do a strategy like that with the combination of that.

Daina Graybosch: We're excited about TIDGET because Roche and Nentech did a frontline study, which they could do because they were combining on top of standard of care, and which you guys also have standard of care, Updevo, so you could do a strategy like that with combinations that include Updevo but have chosen not to. So I would just love for you to react to that statement and tell us all where we can and have some optimism that you haven't set the threshold too high.

<unk>, but.

Have a chosen not to do.

Just like Love you Love for you to react to that statement and tell us all where we could have some optimism that you havent set the threshold too high.

So Dana Thank you and it's a very good question and obviously as always and we pick this strategy of going after than mainly the nonresponsive patient population there.

Daina Graybosch: So, Daina, thank you. And it's a very good question, obviously, as always. We picked this strategy of going after 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-supersonic cancer, but yes, these are IO. In the head and neck, we have an IO naive arm, but indeed this is targeting less inflamed tumors.

The less inflamed tumor types there.

PD one non responders.

Yes.

In a data driven manner that is based on the what we believe is the ground breaking 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 they had neck and then also southern cancer, but yes. These are I O N E.

Neck with I O naive.

And arm, but eh, but indeed this is targeting less inflamed.

Anat Cohen: 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 are conducting at this time to go ahead and try to address what we think is the edge that we, 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.

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 would they say Ah studies did we pursue at this time to go ahead and try to address and.

What we think is the edge.

Did we P V R. I G may bring to the table at but it is a higher risk and as a company. We are considering various options and to also lawyer lowered the risk and all options are on the table now.

Anat Cohen: That was very helpful. Thank you, Anat. This concludes our Q&A session. I will now turn the call back to Compugen's President and CEO, Dr. Cohen Dayag.

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

Thank you.

Operator: 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.

This concludes our Q&A session I will now turn the call back to coffee Jones, President and CEO . Dr. Cohen <unk> would you like to make a concluding statement.

Okay.

Yes, thank you operator.

Thank you for joining us today, and your continued support stay safe and healthy.

Thank you. This concludes the comp you Jan L T D.

Fourth quarter 2021 financial results conference call. Thank you for your participation you May go ahead and disconnect.

Anat Cohen: And, of course, the most important thing, the most important thing, is that you are a good person. Thank you. Thank you. Thank you. Thank you. Thank you.

[noise].

Operator: Beep. Beep. Beep.

Anat Cohen: We're focusing on modulating the immunosuppressive self 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 that it is validating as well that there is competition for new targets that we identified, 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.

Anat Cohen: And that we maintain the leadership in evaluating this axis, and also make sure that these are not only significant 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 faster. We're in 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.

Anat Cohen: But those are the two parameters, the enrollment and the Science of the Study. And, and just as I think about, Slow, I have a sense of obviously how, out. Can you talk a little bit about maybe your partnership program? And, you know, any, White.