Compugen Ltd (CGEN) 2022 Q4 法說會逐字稿

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's fourth quarter and full year 2022 results conference call. (Operator Instructions) 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 from Compugen for the prepared remarks are Dr. Anat Cohen-Dayag, President and Chief Executive Officer; and Alberto Sessa, Chief Financial Officer. Dr. Henry Adewoye, Chief Medical Officer and Dr. Eran Ophir, Senior Vice President, Research and Drug Discovery, will join us in the Q&A.

Before we begin, we would like to remind you that during this call, the company may make projections or forward-looking statements regarding future events, business outlook, development efforts, and their potential outcome; the company's Discovery platform, anticipated progress and plans, results, and timelines for its programs; financial and accounting-related matters, as well as statements regarding the company's future 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 details on these risks, including the company's most recent annual report on Form 20-F filed with the SEC on February 28, 2022. The company undertakes no obligation to update projections and forward-looking statements in the future.

And now I turn the call over to Anat.

Thank you, Yvonne. Good morning and good afternoon, everyone and welcome to our fourth quarter and full year 2022 update. Immunotherapy has been a revolution for the treatment of many patients with cancer. 2022 annual sales of PD-1 pathway inhibitor alone were greater than $35 billion.

But still, as we all know, there remains an urgent unmet medical need for the majority of the cancer patients who are resistant to anti-PD-1. To address the needs of these patients, many drug combinations are being evaluated, including IO/IO combination. Compugen is the leader in the triple IO/IO combination blocking PVRIG, PD, and PD-1.

While TIGIT blocking antibodies in combination with PD-1 inhibitor may function in PD-L1 high-expressing patients, our data consistently shows that the addition of an anti-PVRIG may sensitize tumors to respond to PD-1 and TIGIT blockade, even in PD-L1 low-expressing patients.

As leader in the DNAM axis space, we believe that evaluating a triple combination of our potential first-in-class anti-PVRIG COM701 with our potential best-in-class anti-TIGIT, COM902, and a PD-1 inhibitor has the potential to maximize clinical benefit for patients.

On this front, we have made significant progress. And I would like to share our top highlights for 2022, which we believe set us up for success in realizing our vision to transform the lives of patients by extending the reach of cancer immunotherapy to those who are resistant to anti-PD-1 therapy.

First, in 2022, we took a strategic decision to narrow down our broad significant studies to focus on two indications with high unmet medical need and less competitive landscape, microsatellite-stable colorectal cancer and platinum-resistant ovarian cancer. We believe that this focus provides us with a high probability of success for several reasons.

One, these are indications where we have shown encouraging clinical benefit supported by immune activation that aligns with the COM701 mechanism of action backed with a biological rationale and which we believe provides the fastest route to additional meaningful data to inform on the next steps in building a path to registration.

Two, as a result of our decision to prioritize two indications, we concluded our collaboration with Bristol Myers Squibb, thereby enabling us to focus our time and cash on two indications as well as switch to evaluate our own potential best-in-class, anti-TIGIT COM902 as part of our triple combination going forward.

And now this COM701 is no longer restricted, we also have the opportunity to advance and partner both our potential first-in-class, anti-PVRIG COM701 in addition to COM902. And lastly, the decision has enabled us to extend our cash runway through at least the end of 2024, which is sufficient time to complete our small proof-of-concept study aimed at strengthening the evidence and derisk our lead asset in these two indications.

Moving now to the second highlight of 2022, which was the encouraging clinical data we presented in the fourth quarter of 2022 in two indications. The first set of data we presented was in patients with microsatellite-stable colorectal cancer, at Citi Conference in November 2022. And the second set of data was in patients with platinum-resistant ovarian cancer, which we presented at ESMO Immuno-Oncology Conference in December 2022.

As far as we are aware, we are the only company reporting clinical benefit with an immune checkpoint inhibitor supported by an underlying biological rationale in this patient population with microsatellite-stable colorectal cancer and liver metastases, which makes up approximately 70% of the MSS CRC patients in this metastatic setting.

This is encouraging as this is an indication with a high unmet medical need and these patients have no approved treatment option after failure of standard-of-care therapy. In these patients with platinum-resistant ovarian cancer, there was a lot of excitement from investigators reporting durable shrinking or stabilization of tumor in some of their patients who had previously progressed on all available treatment options.

The totality of the clinical benefit in these patients, including a 20%-overall response rate, with several patients responding over nine months with responses also achieved in hard-to-treat, high-grade serous adenocarcinoma patients along with a favorable safety profile is encouraging compared to current standard of care. The translational work with samples taken from these patients is in progress. And we expect to share this data in one of the upcoming medical conferences during 2023.

In both indications, the clinical benefit is supported by biological rationale and points to a COM701-mediated mechanism of action, increasing T-cell numbers and mediating anti-tumor immunity in tumor type and in patient populations that could not be addressed otherwise.

And the third highlight is AstraZeneca's rapid progress and continued expansion of their PD-1/TIGIT bispecific rilvegostomig, which is derived from our COM902. This progress and continued investment by global leader in oncology, in our opinion, exemplifies belief in the TIGIT mechanism of action; and more specifically, in our differentiated anti-TIGIT COM902.

Like COM902, which is a high affinity reduced the Fc effector function anti-TIGIT antibody, rilvegostomig was engineered to reduce the FC effector functionality with the potential to enhance the antitumor activity. With (inaudible) Gilead's randomized Phase 2 data with an Fc silent TIGIT antibody and AstraZeneca's antibody design strategy, we believe our choice of a reduced Fc effector function anti-TIGIT is well reinforced.

Last year, AstraZeneca (inaudible) rilvegostomig into Phase 2 development in metastatic non-small cell lung cancer. And since then AstraZeneca has a standard development for the treatment of naive non-small cell lung cancer and gastric cancer patients. AstraZeneca announced they also plan to initiate a Phase 3 study this year and has suggested that it could be one of its 10 programs with a blockbuster potential.

This is great news for us as we may be entitled to receive up to an aggregate of $200 million in milestones for these products as well as tiered royalties on future product sales. We look forward to the success of rilvegostomig.

During our call today, I will provide an overview of the opportunity and path forward in our prioritized indication, microsatellite-stable colorectal cancer and platinum-resistant ovarian cancer. I will go on to describe our next pipeline asset, COM503, which is the lead asset in our early pipeline and why we're excited about its potential. Alberto will take you through the financials. I will summarize our upcoming milestones. And then we will open the call up for questions.

Starting with the opportunity and path forward with our prioritized indication. We're initiating two proof-of-concept studies in platinum-resistant ovarian cancer and in microsatellite-stable colorectal cancer. The goal of these proof-of-concept studies is to strengthen the evidence, help us better understand the contribution of components and build on the extensive biomarker work we're doing to try and understand the patients most likely to respond with the purpose of building a path to registration in this indication.

Colorectal cancer is the third most common cancer in the US. It is estimated that in 2023, approximately 153,000 new cases will be diagnosed in the US. And about 52,000 patients will die from this cancer in the US. Microsatellite-stable colorectal cancer represents about 95% of the colorectal cancer patients with limited treatment options.

Around 70% of the patients with metastatic colorectal cancer have metastases to the liver. And as far as we are aware, we are the only company who has reported clinical benefit in this patient population with a checkpoint inhibitor. I'm delighted to report that we have multiple sites open, which are actively screening patients to enroll in our MSS CRC treatment combination proof-of-concept study.

Patients will be eligible if they are PD-1 naive and have received up to three prior lines of therapy. And we will be including patients with liver metastases. With the enthusiasm of our study investigators and the lack of good treatment options for these patients, we anticipate completing enrollment of up to 20 patients and plan to share initial findings this year, with full data disclosure expected in the first half of 2024.

In terms of what success looks like, we believe that even if we repeat the 12% overall response rate in patients with liver metastases and also take into consideration other clinically relevant endpoints, such as progression-free survival, durability of antitumor activity, depth of response, safety, presence of coexisting adverse prognostic features, such as KRAS mutation, we would be informed on next steps for a potential path to registration ideally with the right partner.

Moving to platinum-resistant ovarian cancer, where there is also an urgent unmet medical need as these patients have very limited treatment options. Platinum-resistant ovarian cancer is a hard-to-treat tumor type with limited T-cell infiltration, which are required for immune checkpoint inhibitors to be effective.

Historically, most immune checkpoint inhibitors have demonstrated limited activity in such tumors. It is estimated that in 2023, in the US alone, approximately 20,000 new cases will be diagnosed and 13,000 patients will die of this cancer. We believe that PVRIG's unique biology, different than other checkpoints, has the potential to generate different outcomes in these patients. I'm delighted to say that we are on track to dose the first platinum-resistant ovarian cancer patients in our triple combination proof-of-concept study in the second quarter of this year.

Immune checkpoint inhibitor naive patients will be eligible if they have received up to three prior lines of therapy. And we will include patients of all histologies. We plan to employ a staged approach. We will enroll up to 40 patients in total in the triplet, with the first 20 patients until the end of the year and the full cohort in the first half of 2024.

Once we complete enrollment of the first 20 patients on triplet, we intend to evaluate the inclusion of an additional doublet arm of up to 20 patients, which is a combination of COM701 and pembrolizumab without COM902 to help us better understand the contribution of the component.

We plan to report initial findings by the end of this year. Together with the data we have in hand, this triplet study is expected to bring us to an overall assessment of up to 60 platinum-resistant ovarian cancer patients on triplet treatment, which we expect will inform us on next steps in building a potential path to registration, which again, ideally, would be done with the right [party].

In terms of what success looks like, we believe that if we see at least 20% overall response rate in these additional patients, along with the safety profile reported to date, and taking into consideration tumor histology and other clinically relevant endpoints like durability of antitumor activity, depth of response, and progression-free survival, we would be informed on the next step towards a potential path to registration.

Of course, in both indications, the identification of the biomarker would greatly contribute to further defining a study population to most likely derive clinical benefit. While identifying biomarkers in the field of checkpoint inhibition is not a given, with our years of expertise in understanding the underlying biology of the DNAM axis, evident by the quality of the translational data we have generated from patient biopsies using cutting-edge technology and our computational capabilities, we believe we are well suited to identify biomarkers which can help define the patients who may benefit from our COM701 combination and will, therefore, allow us to better design and execute targeted, well-defined, randomized studies.

Moving next to our leading early pipeline asset, COM503. We're very excited about the progress we have made with our early-stage program originating from our computational discovery engine. While PVRIG and TIGIT were totally new targets and pathways upon discovery, our next program is different. Here we are targeting a known pathway in a completely unique way with a potential first-in-class therapeutic candidate.

We identified a potential dominant immunosuppressive mechanism, which is used by macrophages in tumors to escape the immune system. This is the Interleukin-18 binding protein and Interleukin-18 complex. The inflammasome-induced pro-inflammatory cytokine are Interleukin-18 is present at high level in the tumor microenvironment where it is expected to naturally activate antitumor effector cells, such as T and NK cells.

But IL-18 is one of the rare cytokines that is naturally blocked by an endogenous high-affinity inhibitor called Interleukin-18 binding protein. Cytokines are powerful tools and are used therapeutically. However, there is a challenge of giving them systemically at levels high enough to reach and modulate the tumor microenvironment without causing systemic side effects.

As a result of their narrow therapeutic window conventional recombinant cytokines are limited in terms of efficacy. Some recent clinical failures exemplifies this challenge. Specifically, IL-18 has been administered to cancer patients in the past, but failed; most probably because of general limitations of recombinant cytokines just mentioned and potentially because IL-18 is inactivated by natural blocker IL-18 binding protein.

With that in mind, we have developed a potential first-in-class, fully human, high-affinity monoclonal antibody COM503, which targets IL-18 binding protein to release endogenous naturally occurring IL-18 to activate T and NK cells in the tumor microenvironment. In our preclinical models, we have shown that blocking IL-18 binding protein can displace IL-18 from IL-18 binding protein in the tumor microenvironment, enabling the physiological IL-18 to have immune stimulating activity and in turn, mediate potent antitumor efficacy.

We believe the one major advantage of using an IL-18 binding protein antibody over administration of IL-18 cytokine is a better therapeutic window due to IL-18 pathway upregulation confined to the tumor microenvironment. We have shown that an antibody against IL-18 binding protein modulates the tumor microenvironment for potent antitumor immunity without affecting peripheral immunity.

We believe that our COM503 program represents a new and differentiated approach to harness cytokine biology for cancer characteristics. The program is now advancing in IND-enabling studies with the goal to file IND in 2024. We plan to present this new approach at a scientific conference in 2023.

With that, I'll turn the call over to Alberto.

Thank you, Anat. I'm happy to summarize our financial results. I will start with our cash balance. As of December 31, 2022, we had approximately $83.7 million in cash compared with approximately $117.8 million as of December 31, 2021, affirming our focus on capital efficiency and bold execution on our DNAM-1 axis hypothesis.

During 2022, we used $41.6 million to fund our operations. And we received in the fourth quarter, a $7.5 million payment received by initiation of AstraZeneca Phase 2 study evaluating their PD-1 TIGIT bispecific derived from our COM902. The company has no debt.

Going into 2023, we expect our cash burn to be in the range of between $37 million to $39 million. We understand the importance of our cash balance. And we are financially disciplined. We are constantly monitoring our expenses. But at the same time, we are targeting our extensive and unique knowledge in this space on specific tumor type and clinical strategy to increase the probability of success of our drugs to help patients. Based on our current plan, we expect that our current cash will be sufficient to fund our operating plan at least through the end of 2024.

On the revenue front, as just mentioned, we reported $7.5 million revenue from the fourth quarter and for the year ended December 31, 2022, compared with no revenue and $6 million revenue respectively for each of the comparable period of 2021. Our revenues 2022 are related to the milestone payments received from AstraZeneca.

Now regarding the expense fronts. R&D expenses for the fourth quarter of 2022 and for the year ended December 31, 2022, were $7.3 million and $30.6 million, respectively, compared with $5.8 million and $28.7 million for the comparable periods in 2021. The increase is mainly due to higher expenses associated with our CMC activities, offset by higher BMS participation in R&D expenses.

Research and development expenses as a percentage of total operating expenses were 73% in 2022 compared to 71% in 2021. Our G&A expenses for the fourth quarter of 2022 and for the year ended December 31, 2022, were $2.5 million and $10.3 million, respectively, compared with approximately $2.7 million and approximately $10.9 million for the comparable period in 2021.

For the fourth quarter 2022, we reported a net loss of $3.1 million, or $0.04 per basic and diluted share compared to a net loss of $8.6 million or $0.10 per basic and diluted share in the comparable period of 2021. Net loss for the year ended December 31, 2022, was $33.7 million or $0.39 per basic and diluted share compared with a net loss of $34.2 million or $0.41 per basic and diluted share in the comparable period of 2021.

I'm moving now to the 2023 outlook. Going into 2023, we expect our cash burn to be in the range of $37 million to $39 million. In 2023 we are planning to have a similar level of R&D expenses compared to 2022, mainly to support our upcoming MSS CRC and platinum-resistant ovarian cancer proof-of-concept studies, as well as our leading early pipeline asset COM503. We understand the importance of our cash reserves. And we believe we have sufficient cash to execute on our plan and guidance.

With that, I will hand back to Anat to summarize what you should expect from Compugen in 2023.

Thanks, Alberto. So to summarize upcoming milestones, in MSS CRC we're on track to dose the first patient with our triple combination soon, to complete enrollment of up to 20 patients and report initial findings this year. In platinum-resistant ovarian cancer, we are on track to dose the first patient with our triple combination in the second quarter of this year. We plan to complete enrollment of 20 patients and report initial findings this year and plan to complete the full enrollment in the first half of 2024.

Taking a staged approach, once the enrollment of the first 20 patients in the triplet is completed, we intend to evaluate the inclusion of an additional arm of COM701 and pembrolizumab in the absence of COM902 to gain more insights on contribution of components.

We also continue to monitor the patients in the cohort expansion study with Bristol Myers Squibb and expect to report findings from these studies, including longer follow-up and translational data from the platinum-resistant ovarian cohort expansion study in 2023. We plan to present on COM503 during a medical conference in 2023 and to file an IND for COM503 in 2024.

Finally, this is a big year for TIGIT readout. And we expect to see read-through to Compugen. To this end, I want to emphasize why we believe we have an edge with our differentiated clinical strategy. Firstly, we had a combination approach with the leading anti-PVRIG COM701 against a novel target which our data suggests may sensitize tumors to respond to PD-1 and possibly TIGIT blockade. And we are being followed by others. PVRIG is gaining traction as a relevant (inaudible) immunology target with more and more competitors joining this race, including GSK, who are following our triple combination approach.

Secondly, we have a differentiated Fc reduced effector function, high-affinity anti-TIGIT COM902, which we believe was reinforced recently. And finally, we're targeting tumor types typically not responding to immunotherapy where we believe that PVRIG's unique biology, different than other checkpoints, may be exemplified and has the potential to generate better outcomes in these patients. And we will share initial findings from our proof-of-concept study by the end of the year.

With that, I will turn the call over to questions. Operator?

(Operator Instructions) Steven Willey, Stifel.

Yes, good morning. Thanks for taking the questions. I guess with the decision to add a doublet cohort to platinum-resistant ovarian cancer, will there be any attempt to try to enroll patients into that cohort that I guess are phenotypically similar to the triplet cohort? And I'm just talking about perhaps an effort to try to match baseline characteristics with respect to things like histology, PD-L1 expression so that you can get a better kind of apples to apples comparison of what triplet is buying you above and beyond doublet in a matched patient population. And I have a follow up.

Henry, I guess you want to take this one.

Yes, I will take it. Yes, Steve, that's a very good question. And that's the overall intent because that provides us an opportunity, as you rightly pointed out, to be able to have an apples to apples comparison of what the triplet is doing and what the doublet will possibly do.

Yes, Steve, I'd just add that taking an advantage of the amount of work that we do on biomarker in the studies that we just completed, as well as in these new ones, that's also a reason to consider including a doublet and allow ourselves to get a better understanding on patient selection.

Okay. That makes sense. And then just quickly, I guess, on COM503, you talked about how the targeting of IL-18 binding protein gives you a wider therapeutic window versus IL-18 administration alone. But I know that there's some literature out there suggesting that the disruption of this pathway can lead to pathological inflammation. So I guess just wondering if this is something that you've seen within preclinical models, and whether or not you've evaluated the asset in models of inflammatory disease to see if this somehow gets exacerbated. Thanks.

Eran, that's a good one for you.

Yeah, I think like every, many of the IO assets, if you take them to the other direction, they also might play a role in inflammatory diseases. There is a literature about the targeting IL binding protein with an antibody or anything like that in the literature. So we are the first to show that if you tackle this pathway in preclinical models, you can actually get, I think, anticancer activities. And yes, again, there are literature about [IL-18's] role in inflammatory diseases that exactly plays to the same role that [inhibiting] IL-18 binding protein is effectively cancelled.

Okay. Thanks for taking the questions.

Mark Breidenbach, Oppenheimer.

Hey. Good morning. Thanks for taking the questions and congrats on the progress. Just a few quick ones for me. First of all, I'm wondering if you're aware of any plans from AstraZeneca to present data this year from any of its early studies of the bispecific antibody, justifying their plans to advance into a Phase 3 trial.

And one for Alberto is if any of his guidance on operational runway includes assumptions about additional milestone payments from AstraZeneca or is the guidance completely independent from that? And then I have maybe one follow-up.

So I'll start with the disclosure, it's AstraZeneca's decision to decide when they're disclosing what. So we cannot [relate with them]. And Alberto, do you want to take the milestone one?

Yeah, sure. As Anat said, we have no control on what AstraZeneca is going to do. So all our guidance do not include any fund whatsoever from AstraZeneca. So it's net of.

Okay. That's super helpful. And then just with respect to the biomarker data that you're planning to present later this year. Is that going to be actively integrated into patient selection strategies for the two proof-of-concept trials? Or are those protocols fixed right now with regards to what kinds of patients and selection criteria that you're going to use?

At this point in time, the protocol is that our intentions and plans are fixed and it's moving forward. But also these studies that we're doing are designed to allow us to continue to collect data and to better inform the data that we have in order to see if we can employ such as biomarker. As I related to it in the prepared remarks, it's not a given; it is not an easy path to identify a biomarker in the [terms] of cancer immunotherapy.

And I do think that we are well positioned to do this work computationally, experimentally with the translational cutting-edge technology that we're using and being the first into PVRIG space. But having said that, we're designing carefully the studies and the work that we do in order to identify. So at this point in time, the timings are fixed. But we are a small company. And we can be opportunistic. And we'll make sure that we [exploit] what we have.

Okay. Thank you so much for taking the questions.

Asthika Goonewardene, Truist Securities.

Hi, guys, good morning and thanks for taking my question. Just wondering, so the data of COM701 -- that's me. That's my puppies in the background playing with a squeaky toy. Would the data in COM701, CRC, and ovarian cancer be at a medical conference? And then what do you think the data will look like? Will you aim to have first scans from a majority of patients?

I guess sort of related to that, have you given some thought on what the bar is for ORR but what kind of duration of response do you think might be meaningful in the CRC and the PROC population? And then I have a quick follow up after that.

Okay. So I'll take the first one. And then Henry will relate to the duration of response in both indications. But in the platinum-resistant ovarian cancer we're related to two types of guidance. One guidance relates to the study that is still ongoing. And under the -- the expansion cohorts are being done with nivolumab and nivolumab plus TIGIT. And that's follow-up data that we may disclose later in a medical conference. That's one.

The second type of guidance related to the new study that is being taken in a staged approach, 20 patients and then an additional 20 patients in triplet. And we will consider adding a doublet after we have enrolled 20 patients. In this case, the initial findings it's not necessarily in a medical conference. It depends on the rate of enrollment, et cetera. But definitely the full data disclosure will be in a medical conference.

Yeah, so thank you, Asthika for the questions. So with respect to the duration of response in patients who have colorectal cancer, microsatellite stable and also ovarian cancer platinum resistant, maybe historical context will provide some information here as I provide the response. So as you remember, patients who have platinum-resistant ovarian cancer have a median PFS of approximately three to four months.

So that means within about a three- to four-month period of time, in all the patients enrolled, most of them would have progressed. Now for colorectal cancer, the median PFS in approximately two months also with all the data that's in, including data from using a PD-L1 inhibitor as in IMblaze 370 where the median progression-free survival are beyond two months also. So we expect that there will be a substantive increase based on the data that we will probably show.

And I'd like to remind you that remember that for ovarian cancer platinum resistant, we already presented data in one subject who had primary peritoneal cancer and was on study treatment for 18 months. That's a lot to be on a study treatment for where we, like I already previously said, the median PFS is approximately three to four months. So if you're seeing patients who are on for six months or more, that's significant.

And we've already disclosed in Anat's previous prepared statement that some of our patients who were on the triplet on ovarian cancer have been on for approximately nine months. So that's clinically relevant for those patients.

For patients with microsatellite-stable colorectal cancer, anything that's beyond six months is also relevant. And the reason I say that is, if you recall, the median overall survival with standard of care now, whether it's TAS-102 or regorafenib is approximately six months. So patients who can be on study treatment way beyond this period of time will have derived substantive clinical benefit from study treatment of either a doublet or a triplet. Does that answer your question, Asthika?

That does, Henry. Thank you. Maybe if you can have a quick follow-up. What do you think are the next steps in colorectal cancer, microsatellite-stable colorectal cancer? Do you think there's a fast path to market with a single-arm study if you go after a CRC population with liver mets? I know about 70% of patients present with liver mets but is that a viable option for you?

Yeah. So all options are on the table. From the data we've presented so far, I think it probably would be best to pursue what the triplet will show us because the DNAM axis appears to be very active also in several cancers, including as we think in microsatellite-stable colorectal cancer. And that's the reason for pursuing the triplet in that indication.

Now depending on the results we get from the triplet there, of course, will be a discussion with regulatory agencies with regards to either considering the triplet as a regimen or trying to see if we need to set out the contribution of components with either a doublet also and then a discussion with regards to whether monotherapy arm should be added.

And in this case, the monotherapy arm that seems reasonable to compare to standard of care, which would be either TAS-102 or regorafenib. So at this point, the strategy we have is to pursue the triplet. And like Anat said in her prepared comments, we'll have data disclosures.

Excellent. Thanks for taking my questions, guys.

Daina Graybosch, SVB Securities.

Hi, guys. Thanks for the question. Two from me. The first one is I'd like to understand more [if we can] about your partnering conversations. So have partners been coming to you? Have you been going to partners? Which assets specifically have they been interested in, which data set? And have they advised at all on the (inaudible) concept study?

So I'll take that. So first, just to say, partnering strategy from our perspective, we are open for collaborative arrangements. We do want to make sure that we broaden the pipeline opportunities through studies that will be done with a partner and we also view it as a way to add non-dilutive funding to the company. That's our first priority. So that's just in general.

I'd say specifically on COM701 and COM902, obviously we cannot share any details or any possible discussions that we have or don't have with our partners. But I'll say that in general, COM701 being differentiated in the field, we are leaders. We are leading these test fields. We have a substantial amount of biology and support for the mechanism of action they choose.

As to PD-1 and possibly to TIGIT, we have the ability to do the biomarker work, as I stated before that. And in general, there is interest in what PVRIG is generating. That's on one hand. Our intention with this new study is to add additional -- to add to the sample size that we have. As I said in the prepared remarks, to strengthen the evidence in order to be able understand the path forward in a better way and to also solidify this difference that we're getting in tumor types that are hard to treat in mainly the PD-L1 low [space] that is of high interest in the industry.

We're differentiating ourselves not only on the PVRIG asset, but also on the fact that we are targeting this PD-L1 low expressor tumor types. So that's in general. So while I'm not commenting on specific discussions, that's the general perspective.

Thank you. My second question is on the (inaudible) concept study. I think you said for both MSS CRC and platinum-resistant ovarian that you're enrolling patients with up to three prior lines. Does that mean these could be treatment-naive patients? And how early do you expect to be able to enroll patients on these studies? And can you remind us how many lines on average in the range in the past in the data you presented last year you had so how different are these new studies in terms of line from the last data?

Henry?

Yes. So let's deal with the ovarian cancer question first, Daina. So for ovarian cancer, what we are referring to or what Anat just mentioned in her prepared comments, is for the number of up to three prior lines in platinum-resistant setting. So we're not considering patients who've had platinum sensitive disease, in which case, they might have received platinum a number of times. So it is strictly for the platinum-resistant setting, okay, where the standard of care is chemotherapy for now.

And I know yes, we have a study drug that's been conditionally approved or accelerated approval on EDC. Yes. So that's what we mean by up to three prior lines. And then for colorectal cancer also, this is not in the earlier setting. This is in patients who have been exposed to standard of care therapies, must have received all the standard of care therapies, include FOLFOX or FOLFIRI and no more than three prior lines also for those patients.

Great. Thank you.

Tony Butler, EF Hutton.

Hi, good morning. This is [Tash] on for Tony. The trial as it appears on clinicaltrials.gov, today at least, there are six central sites. I wonder if you could tell me how many of these trial sites are enrolling patients for the colorectal cancer arm? And then whether you intend to have more trial sites enrolling more patients.

Henry?

Yes. So the -- what we have on clinicaltrials.gov is current. All the sites that we have listed for the dual combination study and for all the other studies that we have are currently enrolling, are open to enrollment for the colorectal cancer cohort. We expect that just based on the number of patients who have this unfortunate illness, that enrollment should be brisk and be on track, just like Anat mentioned.

Thank you. And what about -- yeah, yeah, thank you for that. And what about ovarian cancer patients? Will that cohort be listed as a separate under this same trial? And the same question about trial sites.

Yes. Yeah, it's very likely to be listed under the same trial cohort. And it will be enrolling in the sites. Also, there are listed -- currently listed on clinicaltrials.gov. And we will [do] the necessary public disclosures as soon as we can. We will also be looking for additional sites also. We expect that to be on track, just like Anat mentioned in her prepared comments.

If I may Anat, let me go back to Daina's question because I think Daina asked the question on the number of prior lines that we saw on our prior disclosures at ESMO IO, for example, and also at SITC, Dr. Overman's presentation.

So Let me start with ovarian cancer first, Daina. So for the ovarian cancer cohort, at ESMO IO, as you remember, we had two presentations, one by Dr. Yeku from Mass General Hospital. This was a population of patients with platinum-resistant ovarian cancer. And it was the dual combination, meaning COM701 plus nivolumab. The number of -- median number of lines in that patient population of 20 was six. That's the number of median prior lines with a range of two to nine, okay.

And then for the triplet combination that was presented by Dr. John Moroney at University of Chicago, 20 patients also. The number of median lines was four with a range of one to 10. We expect that most of the patients will fall within this range for this new triplet expansion cohort that will consist of COM701, COM902, and pembro also.

Thank you.

This concludes the QA session and Compugen's investor conference call. Thank you for your participation. You may go ahead and disconnect.