Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's Fourth Quarter and Full Year 2022 Results Conference Call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available in the Investors section of Compugen's website, www.cgen.com. As a reminder, today's call is being recorded. I would now like to introduce Yvonne Naughton, Head of Investor Relations and Corporate Communications. Yvonne. Please go ahead.

Thank you, 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 for 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 more details on these risks, including the company's most recent annual report on Form 20-F, filed with the SEC on February 28, 2022. The company undertakes no obligation to update projections and forward-looking statements in the future. And now, I'll 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 inhibitors 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 antibody in combination with PD-1 inhibitor may function in PDL1 high expressing patients, our data consistently show that the addition of an anti-PVRIG may sensitize tumors to respond to PD-1 and TIGIT blockade even in PDL1 low expressing patients. As leader in the DNAM axis space, we believe that evaluating the triple combination of our potential first-in-class anti-PVRIG COM701 with our potential best-in-class anti-TIGIT COM902 and the 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 therapies. First in 2022, we took a strategic decision to narrow down our broad significant study to focus on two indications with high unmet medical needs 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…

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, [trigged] by initiation of AstraZeneca Phase 2 study evaluating that PD-1 TIGIT bispecific derived from our COM902. The company had 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 types and clinical strategy to increase the probability of success of our drugs to patients. Based on our current plans, 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 of revenues respectively for each of the comparable period of 2021. Our revenue in 2022 are related to the milestone payments received from AstraZeneca. Now regarding the expense front. 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 period in 2021. The increase is mainly due to higher expenses associated…

Thanks, Alberto. So to summarize upcoming milestones. In MSS CRC, we're on track to dose the first patient with our triple combination study 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 finding 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 triple is completed, we intend to evaluate the inclusion of an additional arm of COM701 and pembrolizumab in the absence of COM902 to gain more insight on contribution of components. We also continue to monitor the patients in the cohort expansion studies with Bristol Myers Squibb and expect to report findings from these studies, including longer follow-up and translational data from the platinum resistant ovarian forward expansion study in 2023. We plan to present on COM503 during the medical conference in 2023 and to file an IND for COM503 in 2024. Finally, this is a big year for TIGIT results, and we expect to see reach through to Compugen. To this end, I want to emphasize why we believe we have an edge with our differentiated clinical strategy. Firstly, we have a combination approach with a 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're being followed by others. PVRIG is gaining traction as a relevant testing in our immunology targets with more and more competitors joining these rates, including GSK, while 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 unique biology different than other checkpoints may be exemplified and has the potential to generate better outcomes in these patients, and we would share initial findings from our proof-of-concept study by the end of the year. With that, I will turn the call over to question. Operator?

[Operator Instructions] The first question is from Stephen Willey of Stifel. Please go ahead.

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 typically 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, PDL1 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 the matched mutation population. And then I have a follow-up.

Henry, I guess you want to take this one?

Yes, I will take it. Yes, Steve, it's actually 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-and-apples comparison of what the triplet is doing and what the doublet will possibly do.

And Stephen - I'll add just -- 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 better understanding of the patient population.

Okay. That makes sense. And then just quickly, I guess, on COM503. Now 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 kind of suggesting that the disruption of this pathway can lead to pathological inflammation. So I guess, just wondering if this is kind of 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?

Eran, I think that one's for you.

Yes. 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-18 binding protein with an antibody or anything like that in the literature. So we're the first to show that if you tackle this pathway preclinical model, you can actually get anti-cancer activities. And yes, again, there are literature about IL-18's role in inflammatory diseases and that exactly plays to the same role that inhibiting IL-18 binding protein is effectively canceled.

Okay. Thanks for taking the questions.

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

Hi. 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 AstraZenaca to present data this year from any of its early studies of the bispecific antibody, kind of justifying their plans to advance into the Phase III 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 decision to decide when they're disclosing what, so we cannot relate to it and -- and Alberto, do you want to take the milestone one?

Yes, 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 kind of actively integrated into patient selection strategies for the two proof-of-concept trials, or are those protocols kind of fixed right now with regards to what kind of patients and selection criteria that you're going to use?

At this point in time, the protocol is -- our intentions and plans are fixed moving forward. But also the studies that we're doing are designed in order 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 a biomarker. As I related to it in the prepared remarks, it is not a given. It is not an easy path to identify 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 technologies that we're using and with being the first in the 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 studies are fixed, but we're one company and we can be opportunistic and we'll make sure that we act on what we have.

Okay. Thank you so much for taking the questions.

The next question is from Asthika Goonewardene of Truist Securities. Please go ahead.

Hi, guys. Good morning and thank you for taking my questions. Just wondering, so the data for COM701 and -- would the data in COM701 and 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 scan for majority of patients? I guess sort of related to that, you gave some thought on what the bar is for ORR. But what kind of duration of response you think might be meaningful in the CRC and 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 related to two type of guidance. One guidance relates to the study that is still ongoing. And under the expansion cohorts being done with nivolumab plus TD. And that follow-up data that we may disclose later in the 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 additional patients increases and we will consider adding a doublet after we have enrolled 20 patients. In this case, the initial findings and -- not necessarily in a medical conference. It depends on the rate of enrolment, et cetera. But definitely, the full data disclosure will be in a medical conference.

Yes. So thank you, Asthika, for the question. 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 having 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 is approximately two months also with all the data that's seen, including data from using a PD-L1 inhibitor as in IMblaze 370, where the median progression-free survival of the -- are beyond two months also. So we expect that there will be a substantive increase based on the data that we probably will show. And I would like to remind you that -- remember that for ovarian cancer, platinum-resistant, we already presented data in one subject who had primary colorectal cancer. It was on study treatment for 18 months. That's a lot to be on 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 treatment on ovarian cancer, have been known for approximately 9 months. So that's clinically relevant for those patients. For patients with microsatellite stable colorectal cancer, anything that's beyond six months 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 with regorafenib is approximately six months. So patients who can be on study treatment will be on this period of time will have derived substantive clinical benefit from study treatment of either in doublet or in triplet. Does that answer your question, Asthika?

Yes, Henry. Thank you. Maybe if you can have a quick follow-up. What do you think of 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 CRC population with liver metastasis? I know, about 70% of patients present with metastasis. Is that a viable option for you [indiscernible]?

Yes. So all options are on the table. From the data we presented so far, I think it probably would be best to pursue what the triplet will show us, because the Dynavax 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 sort out the contribution of components with either a doublet also and then a discussion with regards to whether monotherapy should be added in this case, the monotherapy and -- that seems reasonable to compare to the 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 question, guys.

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

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

So I'll take that. So first, just to say, partnering strategy from our perspective, we are open for collaboration arrangements. We do want to make sure that we broaden the patent 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 think specifically on COM701 and COM902, obviously, we cannot share any details or -- on any possible discussions that we had or have with partners. But I think that in general, COM701 being differentiated in the field, we're leaders, we're leading these test fields. We have the substantial amount of biology and supports the mechanism of action they choose. As to PD-1 and possibly to TIGIT, and 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. And our intention with this new study is to add additional -- to add to the [indiscernible] size that we have, as I said in the prepared remarks, to strengthen the evidence in order to able to 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 and mainly the PD-L1 low pace 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 expression tumor types. So that's in general. So one, I'm not commenting on specific discussions, that's the general perspective.

Thank you. My second question is on the 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? 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 and the tax -- and the data you could get in last year you had, how different are these new studies in terms of line from the last enrollment?

Henry?

Yes. So let's stick 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 prior lines in platinum -resistant setting. So we're not considering patient 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 -- 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 therapy, most have received all the standard of care therapies include FOLFOX and FOLFIRI and more than three prior lines also for those patients.

Great. Thank you.

The next question is from Tony Butler of EF Hutton. Please go ahead.

This is Charles on for Tony. The trial as it appears on ClinicalTrials.gov today, at least there are six trial 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 -- have more trial sites enrolling more patients?

Henry?

So 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 currently enrolling, 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 will be on track, just like Anat mentioned.

Yes, yes. 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 trials sites?

Yes. Yes. It's very likely to be listed under the same trial cohort. And it will be enrolling in the sites also that are listed -- currently listed on ClinicalTrials.gov and will look the necessary public disclosures as soon as we can. We will also be looking for additional sites also, and we expect that to be on track, just like Anat mentioned in her prepared comments. I may -- let me go back to Daina's question because I think Daina asked me 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 and as you remember, we had two presentations, one by Dr. Yeku from Mass General Hospital. Remember, this was a population of [indiscernible] platinum-resistant ovarian cancer, and it was the drug combination, meaning COM701 plus nivolumab. The number of median number of lines in that recent population of 20 was 6. That's the number of median parallel lines with a range of 2 to 9, 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 110. We expect that most of the patients will fall within this range for this new triplet expansion cohort that will be including -- that will consist of COM701, COM902 and Pembrolizumab.

Thank you.

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