Compugen Ltd (CGEN) 2024 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 2024 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, Vice President, 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 David Silberman, Chief Financial Officer. Dr. Michelle Mahler, Chief Medical Officer; and Dr. Eran Ophir, Chief Scientific Officer, 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 the potential outcome. The company's discovery platform, anticipated progress and plans, results and timelines for our programs, financial and accounting related matters, as well as statements regarding our cash position and cash runway.

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

And with that, I'll turn the call over to Anat.

Thank you, Yvonne, and a warm welcome to everyone joining our call today. On today's call, I will highlight some of our key achievements in 2024 and outline our strategic priorities for 2025.

Starting with our potential first-in-class anti-PVRIG COM701. In 2024, we presented data showing the treatment with a triple blockade of PVRIG, TIGIT, and PD-1 with COM701, COM902, and pembrolizumab in platinum resistant ovarian cancer patients who typically do not respond to immunotherapy, resulted in encouraging durable responses and was well tolerated.

As of mid-February 2025, a few patients remained on study treatment. The data from this study is important because it is consistent with data we previously presented and further demonstrates COM701 is active, results in durable responses, and has a good tolerability profile.

Based on the totality of the data we've presented to date, including monotherapy and combination data, and with the support from ovarian cancer experts, we announced at the end of 2024 that we would advance development of COM701 as a maintenance treatment option for patients with platinum sensitive ovarian cancer.

We believe that advancing COM701 in this maintenance setting of platinum sensitive ovarian cancer has a strong clinical and biological rationale and represents a less competitive landscape. As part of our 2025 strategic priorities, we are on track to initiate in the second quarter of 2025 an adaptive platform trial starting with a randomized double blinded sub-trial.

The first sub-trial will evaluate single agent COM701 as a maintenance therapy versus placebo in a total of 60 patients with platinum sensitive ovarian cancer who are not candidates for bevacizumab or PARP inhibitors. The primary endpoint will be median progression free survival, where the placebo benchmark is expected to be approximately six months.

We believe that showing a three-month improvement over the median progression free survival of the placebo would be clinically meaningful. We expect to share interim analysis from this sub-trial in the second half of 2026. Positive data may allow us to both engage in discussions with the regulatory authorities on a path for COM701's registration as a single agent. And to extend the opportunity for COM701 to serve as the backbone for future drug combinations.

Moving next to the TIGIT landscape. In 2024, there have been several setbacks for the TIGIT antibody class, resulting in study or program discontinuations, which led to skepticism about the benefit that TIGIT blocker combinations could bring. These study discontinuations occurred with Fc active TIGIT antibodies.

Setting aside the importance of selecting the appropriate tumor types and patient populations that in some cases might not have been an ideal fit for TIGIT blocker's assessment. We consistently have advocated that Fc inactive antibodies may serve as the better antibody format for targeting TIGIT.

In line with this, current clinical trials suggest that Fc inactive anti TIGIT may have a safety advantage in certain patient populations which could ultimately support a potential efficacy advantage due to the patient's durability on study treatment. We therefore believe that the current Phase 3 trials conducted with Fc inactive TIGIT antibodies are important to confirm or refute the benefit that TIGIT blocker combinations could bring.

If success is achieved by one of these upcoming Phase 3 trials, it could validate TIGIT antibodies as a drug class, and open new opportunities for Compugen based on our TIGIT antibody. We're one of the few companies with a clinical stage Fc inactive TIGIT antibody COM902. We differentiate ourselves not only by the unique properties of COM902, but also by our clinical strategy.

We continue to believe that blocking TIGIT in combination with PD-1 blockers may be effective in certain PD-L1 high tumors. But we also believe the TIGIT PD-1 blockade may need to be combined with the PVRIG inhibitor to expand their use to less inflamed PD-L1 low tumors.

In addition, our partner AstraZeneca has most recently initiated their seven Phase 3 clinical trials with rilvegostomig. The PD-1 TIGIT by specific, the TIGIT component of which is derived from our COM902. Since we last reported in November 2024, AstraZeneca has initiated two Phase 3 trials evaluating rilvegostomig combinations first the standard of care, with one trial in first line squamous non-small cell lung cancer, expressing PD-L1 and the other trial as first line treatment in HER2 positive gastric cancer.

AstraZeneca's broad development strategy for rilvegostomig to replace existing PD-1 or PD-L1 inhibitors represents a significant potential revenue source for Compugen as we're eligible for both future milestone payments and meet single digit tiered royalties on future sales.

In 2024, AstraZeneca presented promising rilvegostomig data at the World Conference of Lung Cancer and ESMO, showing promising efficacy and the manageable safety profile in both lung and gastrointestinal cancer. In 2025, AstraZeneca plans to share early data on the combination of rilvegostomig with their ADCs.

Moving next to GS-0321 previously named COM503. As a reminder, GS-0321, a potential first-in-class anti-anti-IL18 binding protein antibody licensed to Gilead, represents a novel way to harness IL18 pathway biology for the treatment of cancer by using an antibody against IL18 binding protein and therefore potentially avoiding the challenges presented by administration of therapeutic cytokines.

The license by Gilead of GS-0321 further validates our computational discovery, research, and drug development capabilities. It is also a testament to the differentiation of our antibody program targeting the IL18 binding protein.

In 2024 we also made great progress on GS-0321. In the third quarter of 2024, we received a $30 million maximum payment from Gilead for achieving the FDA IND clearance. In the fourth quarter of 2024, we initiated the Phase 1 trial for GS-0321, and the first patient was dosed in early January 2025. As part of our strategic priorities in 2025, we're focused on the efficient execution of the GS-0321 Phase 1 trial.

Finally, beyond our clinical stage programs, our talented teams are working on multiple innovative undisclosed research programs. These efforts leverage computational predictions to identify novel ways to activate anti-tumor immunity.

This work is powered by Unigen, our computational prediction discovery platform already validated by our multiple clinical stage potential first and best-in-class antibodies, as well as our partnerships with AstraZeneca and Gilead. It is a strategic priority for us to advance our programs to continue to feed our own pipeline.

With a diverse pipeline and strong focus on execution in 2025, we believe Compugen is well positioned for growth. Cash runway, assuming no further cash inflows, is expected to last into 2027, and we anticipate using this runway to advance the projected COM701 single agent sub-trial interim analysis. And to support the progression of GS-0321 in the clinic, together with continuing investment in our early-stage research pipeline.

Of course, none of this would be possible without our extraordinary team here at Compugen, who continuously performs at the highest level of excellence. I'm excited for 2025 to be another year of advancing our efforts to make a meaningful impact on cancer patients' lives.

With that, I will hand over to David for the financial update before we open the floor for Q&A.

Thank you, Anat. I'm delighted to say that we're advancing into 2025 with a solid balance sheet with no debt and with a cash runway to support our operating plans in 2027.

Going into the details, I will start with our cash balance. As of December 31, 2024, we had approximately $103.3 million in cash, cash equivalents, short term bank deposits, and investments in marketable securities. The cash balance at the end of 2024 includes the $60 million upfront payment from Gilead for the licensing of GS-0321 in December 2023. And the $30 million milestone payment for its IND clearance in 2024 after withholding taxes at source on those payments.

In addition to $15 million in milestone payments from AstraZeneca on building the first patient in the first and second major indications for rilvegostomig in Phase 3 trials. Our cash runway takes into account the planned development of our clinical assets and continued investment in our early innovative pipeline.

On the revenues front, we reported approximately $1.5 million in revenues for the fourth quarter of 2024, and approximately $27.9 million for the year ended December 31, 2024, compared to approximately $33.5 million in revenues for each of the comparable periods in 2023. Revenues for 2024 include the portion of the upfront payment and the IND milestone payment for the license agreement with Gilead and the $5 million clinical milestone payment from AstraZeneca.

Moving to expenses. R&D expenses for the fourth quarter of 2024 and for the year ending December 31, 2024, were approximately $5.9 million and $24.8 million respectively, compared with approximately $10.9 million and $34.5 million for the comparable periods in 2023. The decrease in 2024 was mainly due to the classification of expenses related to GS-0321 to cost of revenues and to lower CMC and IND enabling activities related to GS-0321 partially offset by an increase in clinical expenses.

Our G&A expenses for the fourth quarter of 2024 and for the year ending December 31, 2024, were approximately $2.2 million and $9.4 million respectively compared with approximately $2.5 million and $9.7 million for the comparable period in 2023.

Finally, on net loss. For the fourth quarter of 2024, we reported a net loss of approximately $6.1 million or approximately $0.07 per basic and diluted share compared to a net income of approximately $9.7 million or approximately $0.11 per basic and diluted share in the comparable period of 2023.

Net loss for the year ended December 31, 2024, was approximately $14.2 million or approximately $0.16 per basic and diluted share compared with the net loss of approximately $18.8 million or approximately $0.21 per basic and diluted share in the comparable period in 2023.

With that, I will hand over to the operator to open the call for questions.

(Operator Instructions)

Asthika Goonewardene, Truist Securities.

Hi, this is Karina from Truist. I had a question on AstraZeneca's recent -- they announced the initiation of Phase 3 endometrial study. For the B7-H4 DCPSAM., they're evaluating in the Phase 1/2 Blue Star, as a monotherapy and then combo with the rilvegostomig. Can you confirm whether rilvegostomig will be included in the Phase 3 study design?

Hi, Karina. Actually, we cannot relate to anything that AstraZeneca did not put in the public domain. So I think that we cannot address this question. We're very happy with the seven pivotal trials that they opened, across indications and as they stated that they will open up to 10 trials. They're really moving forward faster, aggressively testing with the rilvegostomig with ADCs, with chemo as a standalone, we just need to wait and see.

Okay. And I had a follow-up. Can we expect any new term data from them that could clarify contribution to efficacy for the TIGIT part?

So they were -- in a minute, I relate to contribution of efficacy, but they've stated that they will present data during 2025 from the combination of rilvegostomig with ADC.

So that -- this is expected, I don't know to say more about the contribution of rilvegostomig as part of the ADC, but they did present data from rilvegostomig in non-small cell lung cancer and in gastric cancer. So I think that the data is showing promising efficacy and the safety profile.

Okay. And a follow-up is, which of the ongoing Phase 3 trials is expected to read out first and the anticipated timeline for that?.

So again, they -- AstraZeneca did not share any information about this. If you look at their debt from the Investor call, they are referring to the Phase 3 trials as beyond '26, but we cannot relate to more than that.

Okay. Thank you so much.

Daina Graybosch, Leerink.

Hi, thanks for the question. I wonder if you could talk more about your design of the ovarian study. I understand that it's randomized in 20 patients. Can you help us understand what it's powered to show in terms of PFS hazard ratio? And given it's small, are you going to ensure you have balance between the two arms and why not go for a larger study to help ensure baseline balance? Thank you.

Michelle.

Sure. Hi, Daina. The design of the study is still an exploratory, Phase 1b study, so it's not powered to detect an improvement in terms of a full -- like a full pivotal trial. It's designed to be able to allow us to evaluate the single agent activity of COM701 so that we will be able to outline or accelerate a pathway to an approval.

So the design that we're using is used quite frequently at this point in time in Phase 2 drug development or Phase 1b, Phase 2 drug development with an adaptive trial design, and we're using Bayesian statistics to be able to evaluate what the probability is of improvement by more than three months when you compare the active arm to the placebo.

And Daina, I'll just add with respect to a larger study, obviously, if we will see -- we anticipate to have the interim analysis in the second half of '26, if you will see that there is a reason for us to add more patients and turn into a larger study. That's also something that we can do, but we decided that we focus our resources on trying to see if what we believe should work in platinum sensitive and maintenance setting and is delivering the data that we expect to see.

Can you talk about how you're going to help both arms be balanced? And maybe I'll add on a second question to this. You said that patients can be not eligible for [BEV] and not eligible for part. How does that bias this patient group to performance status or any other sort of clinical disease or patient characteristics with that particular criteria? And are there benefits and risks to that?

Okay. So the study is going to enroll patients who are already in a PR or CR following the platinum chemotherapy, and there are patients who would not be recommended to get standard of care maintenance. So they've -- if they are eligible to get BEV, they will get BEV beforehand. If not, they won't to see Bev. Similarly, if they meet the criteria for the label and guidelines to get PARP inhibitors, they will.

So this effectively captures what would be considered the third line patient population and by virtue of the fact that they've been able to tolerate chemotherapy, you're already selecting for a more well patient population. We do have a stratification factor when we randomize. So that is how we will achieve balance between the arm, and even though there's a 2:1 randomization, the stratification is for PARP inhibitor use.

So patients who have not seen PARP inhibitors are placed differently in terms of the analysis. And let me know if I've answered all the questions you had on there, but happy to keep going.

Got it. I guess it's one more follow-up. Why prior PARP as your stratification versus anything else?

Because the biology is slightly different among the patients who've had PARP inhibitor use and so that has the potential to result in an imbalance at the time of analysis. So patients who have PARP inhibitors can often be the ones that remain platinum sensitive with multiple relapses more often than patients who've seen data source on that, or who have not been treated at all with their full part.

Leland Gershell, Oppenheimer.

Hey, good morning. Thanks for the update and for taking our questions. Just one from us. Just on 0321, just curious, in addition to studying this in and solid tumors, just wondering if there's interest in evaluating this asset in hematologic malignancies, and or with maybe combination with products like rituximab just given other campaigns in the past, along the IL-18 access that have looked at those candidates in such settings?

Thank you.

Yes. This is an interesting question.

(multiple speakers) Eran, I'll just say, we -- obviously, later on related from the biology perspective and what could be done. Obviously, we cannot go beyond what's written in ClinicalTrials.gov in the description of the study with the solid tumors. But Eran, go ahead.

Yeah, it's an interesting question. Obviously, it's right that in the past, IL-18 has shown some combination of rituximab. For us, we're focusing now in solid tumors. This is where we did most of our research. This is where we saw the observations of this unique activity, specifically inside the tumor microenvironment and not the periphery.

So hematological could be interesting. But as Anat mentioned, the focus now in solid tumors, we think we have an edge there versus other IL-18 agents. And yeah, this is where we go first.

Great. Thanks. And then just with respect to the study in platinum sensitive, if you could just remind us if it's an adaptive platform trial, just what the adaptive nature of that design is?

Sure. So it's adaptive because it allows -- we declare upfront that we would add additional arms to the study or after our interim analysis, there's an opportunity, as Anat alluded to, that we could also increase the sample size. So those are the adapt patients and it allows us to be able to be much more flexible in terms of what our next steps will be pending the interim analysis data.

Okay. And I guess just a follow-on to the earlier question, have you indicated what sample size you may be looking to raise the size of the trial to?

No, it will be dependent on the magnitude of effect size that we get at the interim analysis.

Got it. Great, thanks very much.

Tony Butler, Rodman & Renshaw.

Michelle, just one or two follow-ups on the same topic. One is, what are your expectations for rate of enrollment? Importantly, when do you think you could reach roughly 60 patients in total?

And the second is, in a real-world setting, what's the rough percentage of patients that actually don't see BEV or PARP in the platinum-sensitive setting? Thank you.

Okay. So in terms of -- I'll take the first question. The percentage of patients -- sorry, I'm going to take the second question first, and I'm going to ask you to repeat the first question, I apologize. So the percentage of patients is PARP inhibitors, if a patient is eligible for a PARP inhibitor, meaning that they have one of the mutations associated with the response, they're absolutely treated.

And so that's really driven by the underlying genetics of the patient population. And off hand, I think it's about a third of patients that have the mutation. Among the patients who are eligible for bevacizumab, there's a lot of different factors that will be taken into consideration.

However, in the clinical trial, patients that had a very high-risk disease and high risk for disease progression, when we did the clinical trials, the progression-free survival with adding bevacizumab was improved, but except for the patient population that had high-risk features, there wasn't an improvement in overall survival. So there are a group of patients that are not always treated upfront in the first-line setting with bevacizumab.

And they are investigators who elect to hold off treatment until the patient has platinum-resistant disease. Not here exactly what percentage of patients that is, but it tends to be a smaller percent than what we would expect. And we know that in the third-line patient population, about 40% of those patients who relapse off to second line remain platinum-sensitive. The rest become platinum resistant.

Thank you. The first question was rate of enrollment in the studies.

Yes. So from all the investigators that are in touch with us with respect to participation, there's a lot of support for the study to enroll rapidly. One of the reasons being is that there aren't too many other clinical trials right now open for this specific patient population. So it would appear that we should have a pretty fast rate of enrollment. And as we have stated before, our plan is to have an interim analysis in the morning.

Thanks Michelle.

Stephen Willey, Stifel.

Yeah, good morning, thanks for taking the questions. Maybe just to follow-up on the substudy one question. So can you speak to what specifically triggers the interim analysis that will be conducted in the study? Is it an event rate-driven analysis? And I guess, is there also a predefined futility threshold that will be evaluated at time of this interim?

Yes. There is a futility rate based on the assumption that after nine months of follow-up after we enroll the last patient in, we will evaluate because -- so let me take a step back and explain. Because we know that the patients who don't get maintenance treatment from the literature, the median progression-free survival, when you look across all the big registration studies and big cooperative group studies, the median progression-free survival is approximately six months, okay.

There are some outliers in that approximation. There's one study where it was 8.4 months and one study where it was 3.8 months. But when you put all the data together, it's approximately six months. So we are looking for a three-month improvement, and we do have a futility boundary. And the way we will analyze this using the agent statistics will be to say what is the probability of seeing an improvement of three months at the time that we look at the interim analysis.

We will also follow the event. So if we are hitting an event-driven improvement before we get to the planned interim analysis, we will then potentially also consider unblinding the study at that point. But that's why we will have an independent data review committee who will be looking at the data as the study progresses.

Okay. So the interim is triggered by PFS event rate, not by some prespecified.

It's a combination. So we have the event rate, and we also are triggering it based on follow-up. So once we know that we've gone according to the particular follow-up and the hypothesis, we will then look at potentially cutting the data.

And if we meet either the futility boundary or we exceed it from the point of view that we are positive with the greater than 80% chance of that observation, then we will consider that the study is positive or at least the interim analysis is positive and then take additional steps to move forward.

Okay, got it. And then just quickly on the 0321 dose escalation study. Can you speak to whether pre or post-treatment biopsies are mandatory? And then just, what PD data will you be collecting both in the tumor and I guess, also the periphery to confirm on-target activity?

So I can't speak to all the [minute] details within that question. I can only speak to what we've had in the ClinicalTrials.gov, but suffice to say we do have certain cohorts that we will obtain on treatment biopsy so that we will be able to look more deeply into some of the pharmacodynamic properties of the compound.

Okay, thanks for taking the questions.

Thank you. This concludes the Q&A session and Compugen's Investor Relations conference call. Thank you for your participation. You may go ahead and disconnect.