Great. Good morning, everyone, or good afternoon, wherever you may be. Welcome to us kicking off our 35th annual Oppenheimer Healthcare Life Sciences Conference, again, doing it virtually this time. I'm Leland Gershell, one of the biotech analysts here at Oppenheimer. We're delighted to have with us the team from Compugen, for whom we most recently initiated coverage just earlier this year. We like the story very much for its oncology programs and platform. On behalf of the company, we have Anat Cohen-Dayag, the President and CEO, as well as Eran Ophir, who is Chief Scientific Officer, and will be leading a fireside chat with the team over the next half an hour or so. Welcome to you both, Anat and Eran.
Thank you. Thank you, Leland, for inviting us and for your support in Compugen.
Great. Of course, please feel free to lob in questions on your own, and I'll do my best to ask on your behalf. I think we'll just get right into some of your recent data, the triplet. You had recently presented data from the COM701 anti-TIGIT anti-PD-1 triplet combo in platinum-resistant ovarian cancer at SITC just a few months ago. I guess, Anat, if you could just review for us the key findings and what was the sort of initial, maybe the mechanistic rationale behind this combination therapy.
Sure. I'm happy to do that. The data that we shared in November was data from platinum-resistant ovarian cancer, where we evaluated the triplet combination of COM701, COM902, the COM701, the PVRIG antibody, COM902, the anti-TIGIT antibody, and pembrolizumab. This was also following data that we generated from a prior cohort in platinum-resistant ovarian cancer testing the same PVRIG, TIGIT, PD-1 blockade, but with different PD-1 and TIGIT antibodies. I think that I can say clearly that the data that we presented in November was consistent and supporting the data that we've already shared in the prior cohort. All in all, we have data in 40 patients of heavily pretreated platinum-resistant ovarian cancer patients showing that the triplet combination is active in the 20% overall response rate range and with disease control of about 45%.
Mainly, what we were able to see again is the durability of the responses. I'll let Eran relate in a minute for the COM701 mechanism of action, which we believe this data supports, and the DNAM axis hypothesis of why we've tested PVRIG, TIGIT, PD-1 blockade. I will say that durability-wise, we were presenting data in November showing that these patients that were responsive were for five, six months on study treatment, and the study is still ongoing. At the time that we shared the data, we had five patients on study treatment still. This was actually supportive of the prior cohort data that we presented, the prior 20 patients, which were showing durability of more than 16 months of patients that were responsive for this triplet.
All in all, we believe that the data that we shared is showing clinical relevance of COM701 combination with PVRIG and TIGIT in platinum-resistant ovarian cancer. Eran, I'll defer to you to go for the mechanism of action.
Yeah. PVRIG is part of the DNAM-1 axis, in which TIGIT is a parallel pathway, and PD-1 also intersects. We're investigating this pathway for quite a while. We identified computationally TIGIT around the same time Genentech did, and then later on PVRIG. What we identified is that if you co-blockade all these three pathways, PVRIG, TIGIT, and PD-1 together, you get synergistic immune activation. This is one part of it. Maybe the more important part is that it's not just a checkpoint combination, because PVRIG, and this we published earlier this year in Cancer Immunology Research, has a very different biology. I will not go through all the details now, but this unique biology, which is different from all the other checkpoints that we looked at and the approved ones, makes them relevant in this less inflamed indication.
If you block PVRIG with COM701, and this we have seen actually across cohorts in few indications, you see responses in places and indications which are typically not responsive to checkpoints. Therefore, while PD1 and TIGIT alone in historical data gave something like 8% response rate, 0% responses in PD1 negative, which have no TISSEL insights to begin with, we see across our cohorts, and specifically in this trial, that adding COM701 adds significant activity, adds responses in patients which are PD1 negative. We also had a response in monotherapy to COM701 in ovarian cancer, in PD1 negative patients. While data is preliminary, we do see this unique biology of COM701 translating into activity in less inflamed tumor types like ovarian cancer.
That's terrific. Great. Compugen recently announced plans to advance 701 as monotherapy, maintenance therapy for platinum-sensitive ovarian cancer. I guess maybe just why pursue this approach instead of simply continuing with the triplet? What data or insights support a monotherapy approach in platinum-sensitive?
I think I'll capitalize on what Eran was saying. We were taking the really hard way to present COM701 efficacy and durability and to present the mechanism of action. The patient population that we're selecting is the heavily pretreated patient population, patients that were already treated with BEV, PARP, sometimes ADCs, and really, the immune system is very much immune compromised, and it's less of a favorable condition for COM701 to present its mechanism of action. Seeing the data that we had, we thought that with this clinical relevance that we see in platinum-resistant, it may be best for us to pick a patient population where we can exemplify in a very nice way COM701 mechanism of action in patient population that is less heavily pretreated, in a patient population where the immune system is less immune compromised, so therefore, it would potentially better respond to COM701.
We also have a study where we present COM701 activity per se, not as part of combinations. This is where we identified the platinum-sensitive patient population, and specifically in the maintenance setting. Patients that have failed at least two platinum-sensitive platinum treatment cycles, and if they exhausted already BEV and PARP treatments as maintenance, these patients are getting nothing. They have no treatment options. They are being treated with the third cycle of platinum, and sometimes it's in the second already, and they're not candidates for BEV and PARP as treatment. These patients, we believe, fit to be treated with COM701 monotherapy, where COM701 may be able to present its unique mechanism of action and extend the time to disease progression for these patients because they're getting nothing and just sitting there for the disease to relapse.
We believe that it makes sense biologically and clinically to treat these patients with COM701. Biologically, these patients that are being treated already with platinum, not only that they will already be in CR or PR and then will be getting COM701 treatment as maintenance, but these patients being treated already with chemotherapy, we know from the literature that chemotherapy is inducing tertiary lymphoid structure and T-memory stem cells induction. We believe that it will sensitize even more the ability of these patients to respond to COM701. We believe that there is a strong rationale for us to go there. Also, the competitive landscape in this setting is much less competitive. ADCs that are now dominating clinical trials in the platinum-resistant ovarian cancer are aiming in the platinum-sensitive setting more to replace chemotherapy, and we're not competing on this.
We believe that for the biological, clinical, and the competition landscape, it makes more sense for us to test COM701, where we believe that it may shine. We'll see it in the data of this study.
Great. With these platinum-sensitive patients, what do we know about sort of their ability to respond to immunotherapy? Do CPS scores play a role? How do we think about these patients in terms of their potential responsiveness to IO-type therapies?
I think that I'll go back to what I was saying. I think that in terms of their immune system, the immune system is still much more intact than it is in platinum-resistant. Therefore, responding to immune checkpoints where the immune checkpoints are harnessing the immune system response against the anti-tumor immunity, it makes more sense. Having said that, we believe that COM701 mechanism of action may be unique on this front. Eran, maybe you want to relate to the uniqueness of the COM701 mechanism of action as compared to the PD1s because we do think that it will generate potentially different data.
Exactly. There is not much data in that specific setting for checkpoint blockade. I do not think looking at what we learned from the platinum-resistant settings, how COM701 is inducing activity, and also in other indications like MSS, CRC, that it is difficult to have lesson learned from PD-1 blockade in ovarian cancer to what we are going to see with COM701 because of that unique biology and because of the signals that we have seen until now.
I really think that we find really a sweet spot where COM701 can be relevant because, again, when looking at our results and after substantiating the activity in the platinum-resistant settings, if you look at the swimmers, you can actually see that some of the patients having benefit, long-term response, durable, safe, and some of the patients progressing so fast, probably they never even had a chance to respond to a treatment which is chemotherapy-free, like COM701. Now, going to the platinum-sensitive setting, treating patients that were, as Anat mentioned, probably synthesized to COM701 unique biology by inducing TSCM and TLS, and then having patients with less disease burden and less rapidly progressing tumor, probably because we're taking the PR and CR patients. For maintenance settings, a safe treatment like COM701 probably also bears a lot of relevance.
Therefore, we think this is really a good place to test our hypothesis and good settings for a checkpoint blockade with a unique biology like COM701.
Great. You're using an adaptive trial design here in maintenance. If you could just run us through the key benchmarks or endpoints that you're aiming to achieve here.
Sure. As you said, it's an adaptive platform trial design. We'll start with the sub-study one that will test COM701 as monotherapy compared to placebo. The patients that we're going to enroll are patients that experienced at least two cycles of platinum. These are patients that are not candidates for BEV or PARP treatment. This is going to be a randomized study and a blind study. Randomization will be two to one. We'll have all in all 60 patients. Forty will be for COM701 monotherapy treatment and 20 with placebo. It was important for us to have an internal control in the study to be able to present the COM701 activity. Endpoints-wise, the primary endpoint will be median PFS. We expect, based on the scientific literature out there, mostly very consistent data showing median PFS of about six months for patients that are with placebo.
We're looking to improve this by three months. It is a 50% improvement. We believe that if we're able to present with COM701 improvement of three months over the six months of median PFS, this is going to be having a major clinical relevance for this patient population, both for starting to speak with the FDA based on the future data for a relevant path for monotherapy treatment for these patients, but also as a way for us to think about COM701 as a backbone for combination therapy that could be tested in the next sub-studies in this platform trial. The trial is going to start in Q2 2025, in the next quarter. We anticipate to have interim analysis in the second half of 2026.
Okay. As we look at the PFS goals and your assumptions, do responses of the patients to prior platinum influence what we could see out of those? Like if they had stable disease or partial response, how those characteristics of the individual patients, could those maybe influence the assumptions you had mentioned, Anat?
We're going to enroll patients that are in CR or PR following the platinum treatment. The data that I referred to, the literature and what we think would be the median PFS, around six months, fits this patient population.
Okay, great. We look forward to seeing that go through. How large will the trial footprint be in terms of the sites? This is an international study. How quickly do you anticipate enrollment kind of running in the trial?
We did not share yet information about the geography of the sites, but we are going to have enough sites in order to be able to enroll this as quickly as possible. As I said, we look to have interim analysis in the second half of 2026, and we need to be able to enroll 60 patients for this study. We are going to open multiple sites. We believe that with the investigators that we already worked with in the prior study, we have the relationship, we have the network, and that we are able to do it. We will probably share additional guidance with respect to the sites and the geographies as we move forward.
In terms of the market opportunity, have you given any estimates here in terms of what you could see as sales potential in what could be the maintenance setting in platinum-sensitive?
We didn't give yet any guidance with respect to sales, but I can tell you that in terms of the patient population, the second line platinum-sensitive patient population is around 35,000 patients for this line of treatment. We believe that about 30% of them would go to the third line and not be eligible for BEV and PARP inhibitors, which would be the patient population that we will treat in this study. I want to mention, though, that we're testing this, evaluating this patient population for COM701 monotherapy treatment. I want to make sure that it is also clear that this is not the target population for COM701 treatment per se.
Showing this data for this patient population may open a door for us to go forward to assess what would be the right patient population for monotherapy, but also to be able to combine COM701 as a monotherapy treatment if it works as monotherapy as a backbone for combinations, and then go into additional combinations going earlier in the platinum-sensitive setting, second line, first line, et cetera. I want to make sure that this is not being seen as a finite sales assessment for COM701.
Terrific. Good. Let's talk a little bit about your partnership with AstraZeneca. There's a bispecific that Astra is developing, which is kind of a TIGIT anti-PVRIG, which the TIGIT component comes from Compugen. I think maybe just to help investors, we've seen we faced setbacks in the TIGIT space. I think maybe Merck recently had decided to halt their program. Maybe if you could just sort of walk us through how PVRIG blockade in COM701 provides with TIGIT provides sort of a differentiated approach and how that sets it apart maybe from other TIGIT and anti-PVRIG agents on their own.
Maybe I'll first start with what you mentioned about AstraZeneca. I have to say that we're so excited with the AstraZeneca partnership, with them taking the rights to develop a bispecific antibody based on our TIGIT antibody. I think that even now, specifically, when we see all the failures that are occurring with the TIGIT antibodies, we're even more enthusiastic because we believe that this is the right way to test TIGIT inhibition, both in terms of the indications, the patient population that is being selected, the isotype of the antibody, which we were always saying is the right isotype to be tested, FC silent as compared to the FC active that were tested. We believe that there is some data to show that the discontinuation rates with the FC silent is lower than the FC active.
We believe that AstraZeneca approach and broad strategy that they're taking have a better probability of success. Obviously, we'll need to see that. They're conducting now seven pivotal studies. That I'll say just with respect to AstraZeneca. I think that if we tie COM701 into it, look, we were never, and I'll let Eran go again to describe why it would make sense to tie COM701 into this TIGIT PD-1 story. I think that for us, we as a company never went after the strategy of testing TIGIT plus PD-1. We believe that there are patient populations and disease indications where it may be relevant. We still believe so. There are still five phase two randomized studies that are showing that there is benefit of adding TIGIT to PD-1. We need to see a good phase three study.
With this, we have two exposures for this as a company. One, through the AstraZeneca collaboration, we're eligible for milestones and royalties, and it will be great if it will be successful. It will also be good for us, for our COM902 asset, that we are one of these assets that is having a silent FC domain. I don't know of many other assets beyond AstraZeneca and Arcus that are Arcus Gilead that are well-known. That will take us again to the triplet combination. Eran, maybe you want to say again how PVRIG is being tied into this.
I think a few things. First of all, as I mentioned before, yes, if you combine PVRIG, TIGIT, and PD-1 blockade, you get synergistic immune activation. It is not only synergistic, but also when you add PVRIG to the story, then it probably, according to our preliminary clinical data and first national data and biological data, opens the door to PD-1 and TIGIT into less inflamed indications. We have seen data from AstraZeneca, for example, recently in non-small cell lung cancer, PD-L1 above 50%. This is an extremely inflamed indication. The data looks definitely compelling. Going into less inflamed settings, this is probably where COM701 is going to be needed. Regardless of that, we think that, as mentioned, PVRIG is a cousin of TIGIT, but it is not TIGIT. It has a very different biology.
As Anat mentioned, most of the setbacks of a company with active FCs, and us, AstraZeneca and Arcus, which have progressing probably more aggressively now, have a non-active FC. You asked us about differentiation of our own COM701. Also our own COM701, as our COM902, have a non-active FC, while some of the other PVRIG blocker competitors have an active FC. We will have to wait and see if in these settings also there will be a safety and maybe also some efficacy advantage for a non-FC agent like COM701 compared to the competitors.
Thanks. COM503, this is an anti-IL-18 binding protein antibody. You have recently begun enrollment in the phase one dose escalation study, both I think as monotherapy and also with Zimberelimab, which is Gilead. You have a partnership with Gilead on 503, and that is an anti-PD-1.
What role will you guys play as Compugen through this development, and how does that hand over to Gilead?
As part of the collaboration, we're responsible for the phase one studies. We're responsible also for the rest of the preclinical development and now the phase one study. Thereafter, Gilead will resume its rights to continue the development and for commercialization. We're now focusing on execution. It's not now. It's since the time that we initiated the program and then licensed it to Gilead. We licensed it in December 2023 when it was still a preclinical stage program. We got IND acceptance in July 2024. We initiated the study, opened the sites, and then dosed the first patient in January. We're just focused on the execution.
Many investors are familiar with the IL-18 pathway in autoimmune disease, but also it plays a role in oncology. Maybe you can just sort of help us understand what role IL-18 and IL-18BP play in the tumor microenvironment.
Yes, I'll make a stick into that. We used our computational discovery platform, Unigen, to examine resistance mechanisms of macrophages in the tumor microenvironment. The observation we made there took us into the world of cytokines. What we identified, that maybe first few words about cytokines and therapeutics, we all know that cytokines are very potent stimulatory agents for immunity, but the fact is that they are very lousy drugs. While there are cytokines approved, the last approval of a systemic administration of a cytokine was probably 30 years ago, IL-2 or interferons. The challenge is that you give these cytokines into the blood of the patient. They are so potent that in order to reach a significant amount of cytokine in the tumor to be active before you first reach toxicity in the blood, this is a major challenge.
There are numerous efforts and still really no recent approvals. What we identified, in the tumor microenvironment, there's a cytokine, a very potent one called IL-18. It's there naturally. It's induced by inflammasome. It's there in high levels. It's very low in the periphery because of that inflammasome biology. It's there in an inactive form. It's bound to an inhibitor called IL-18 binding protein. You have this complex of IL-18, IL-18BP floating in the tumor environment, non-active. What we developed is an antibody, a first-in-class potential antibody that inhibits the inhibitor, releases out IL-18BP. Now natural IL-18 is in the tumor environment and not in the periphery, doing exactly the opposite from the cytokines. This is what we have shown preclinically. Now we are eager to see how it's developed clinically.
It induces anti-tumor immunity, very potent one in the tumor, and the periphery remains completely clean. This is a really different approach for cytokine therapeutics by an antibody that we identified again using a Unigen computational discovery platform.
As we think about your partnerships with both Gilead and AstraZeneca, have you shared when we may see additional milestones from either of those? Will those be based on data? Do we have a sense of when—I know the AstraZeneca program has a number of late-stage trials. Do we have a sense of when we might see data from those?
I'll relate first to AstraZeneca. Yes, AstraZeneca already stated in their last conference call that they are going to share data from rilvegostomig in combination with ADCs this year, early data. Its phase three studies is beyond 2026 onward. Milestones-wise, we're eligible for up to $200 million milestone payments and mid-single digit tiered royalties. That's the AstraZeneca one. On the Gilead front, up until today, we got $90 million, $60 million as upfront, and $30 million as for IND acceptance. We're still eligible for more than $750 million in milestone payments and tiered royalties, which are going up to low double digit. We did not disclose any milestones. The only thing that I can say with respect to the phase one study that we do is that it is divided into two parts.
One part is the dose escalation, monotherapy and combo with Zimberelimab. The other part is expansion cohorts and mono and combo. That is what I can share.
Great. In the last minute, we have not spent too much time talking about the various characteristics of your in-house platform, which is quite robust. Maybe now you can just spend a few moments discussing how you are balancing, maybe looking at BD opportunities for the platform going forward versus internal pipeline development and when we might see additional preclinical candidates revealed by Compugen from there.
Yeah. We are using our computational discovery platform for our own internal pipeline establishment, both for the discovery of new drug targets, but also for support of the progress of a program in the pipeline. As you heard us say many times, we pick the indications and the patient populations and the combinations, et cetera. We do that. We are not yet harnessing, I am not saying that we will not do it yet, harnessing these capabilities in partnerships. At this point in time, I think that most of the partnerships that are being done with what you call computational discovery capabilities, usually termed as AI these days, are mostly done for the benefit of pharma to enhance their pipeline, but not as a way to, mostly as a service and not as a way to take a portion of the value of the product itself.
We're in the business of entering into collaborations where we have a skin in the game, but also retain more value from the asset and take milestones and royalties from the asset itself. It is still not there in the collaborations that we see out there, but we're not saying no. Obviously, this is an area that we have in the company, the Unigen platform that can serve for future collaborations with pharma.
Excellent. I think with that, we will come to a conclusion here. Thank you, Anat and Eran, for the discussion. Thank you all for zooming in here at our session with Compugen. Take care.
Thank you, Lynn.