Compugen Ltd. (CGEN) Earnings Call Transcript
September 16, 2020
Earnings Call Speaker Segments
Good morning, everybody. It's Albert Wong from Morgan Stanley. Welcome to the third day of our Virtual Health Care Conference. I have with us Compugen, very exciting company based in Israel. I will hand it off to Anat, the CEO; and Ari, the CFO, who can introduce the rest of the team. And we will go through a presentation for a few minutes and then open it up to Q&A. Anat?
Thank you, Albert, and thank you for Morgan Stanley to invite us to the conference. Today, with me today, as Albert was saying, Ari Krashin, the CFO of the company. But also Dr. Henry Adewoye, the CMO of the company; and Dr. Eran Ophir, which is heading the research and drug discovery at Compugen. And I'll start with a brief overview we'll go to the Q&A. You can look at Slide #3. Compugen is a therapeutic discovery and development company. We discover new drug targets, and we developed first-in-class drugs to address these drug targets. We're focusing the field of cancer immunotherapy, specifically antibody therapeutics. And the way we discover new drug targets, actually new biological pathways, is by a computational platform that we developed for many years in the company. If you look at Slide #4, we'll be able to discuss the three key building blocks of the company, which are the innovative immuno-oncology portfolio of the company, which is totally based on computer predictions of new drug targets and new biological pathways. The strategic collaborations that the company has with leading pharma companies and the computational engine that actually allows us to feed our own pipeline with new drug targets. So in the innovative immuno-oncology portfolio, we have today, 3 programs in the clinic and an early-stage pipeline that is following this clinical stage pipeline. The early-stage pipeline consists of multiple programs that are addressing the immunosuppressive tumor microenvironment, mainly focusing on myelin targets. And I describe a focus more on the 2 leading programs of the company, COM701 and COM902, targeting PVRIG and TIGIT. The Bayer program is a program that we entered into a license agreement with Bayer for a new drug target that we discovered, and this program is now pursed in the clinic by Bayer. The strategic collaborations that we have are three collaborations. They're very different from one another. The collaboration with Bristol is a clinical collaboration, under which BMS applied to us, Nivo and their own TIGIT inhibitor, which is an investigational drug. And we conduct the studies. Under this collaboration, Bristol entered into equity investment in Compugen, and they own about 3% of the company. And for the Bayer collaboration, this is a development and commercialization agreement that related to BAY 1905254, the target that was developed -- the antibody that was developed together addressing LDR 2 target. And under this collaboration up until today, we got $30 million in upfront payment and milestones, and we're still eligible for over $250 million and mid- to high single-digit royalties. And the third collaboration is with AstraZeneca. This is actually a license agreement where we licensed to AstraZeneca, the rights to develop bispecific antibodies to one of the programs that is in our pipeline. We kept the rights for monotherapy and combination therapy, and we licensed to AstraZeneca, the right to develop bispecific antibodies. We got $10 million upfront, and we have -- we're eligible for packages of milestones and royalties. For each and every product that is going to be developed based on this program. The third key building block is the computational engine. And here, we have an engine that have a proof-of-concept, which is highly differentiating Compugen in this space of computational target discovery in life sciences today. We moved 3 programs from computer prediction of the drug target to an antibody proven successful in clinical studies, by the way, not only by Compugen, but with Bayer as well. And for TIGIT, it was done with additional companies in the industry and with programs that have clinical data. Now TIGIT and early-stage data for PVRIG in the clinic as well. The second key differentiating factor for Compugen's computational engine is the fact that in one company, we have the engine itself but also the drug development capabilities and starting with the end-in-mind matters in order to be able to discover well drug targets that could be translated to drugs at the end. So if you look at Slide #5, we'll dive just a little bit into the pathway biology of TIGIT and PVRIG and then to our clinical strategy and the data. We actually sent TIGIT to publication after we discovered it in 2009 back to back with Genentech. We identified this pathway as a negative costimulatory pathway. And then we discovered also, PVRIG few years later as a negative costimulatory pathway. Our data suggests that PVRIG and TIGIT are distinct pathways that are working in parallel and in complement to one another. And what we discovered is that PVRL2 is the ligand of PVRIG and we think, based on our data, that PVRL2 is not ligand of TIGIT as being considered in the scientific literature. So basically, there are two pathways here, TIGIT PVR and PVRIG, PVRL2, and we're saying that in tumor types where the 2 pathways are operative, you'll need to block the 2 pathways in order to get sufficient immune response. And not only in order to release the blockade over TIGIT and PVRIG as negative inhibitory pathways receptors, but also in order to release PVR and PVRL2 to stimulate DNAM, which is a positive costimulatory pathway. So you really need to release the blockade of the 2 in order to be able to fully stimulate the system. But there is one more angle to this story, and this is in Slide #6. The left side is describing what I was just telling you about PVRIG, PVRL2 and TIGIT PVR. But on the right side, you'll see the PD-1 pathway. And there is data in the literature in the last 2 years that started to appear, indicating that there is a molecular intersection between the PD-1 pathway and the DNAM axis. And this is supported also by a preclinical data. We think about this as a 3 pathway story. And we think based on our data, that in different tumor types and in different patient populations, you'll get different dominance and effect of these 3 pathways. And while in some tumor types, the PD-1 pathway will be dominant and you treat these patients with the PD-1 blocker and their respond. In some of the patients, it will not be enough and you still need to block the PVRIG and/or TIGIT pathways. And this was the underlying understanding that we had building our own clinical strategy. One more thing. We were asking ourself what are the tumor types where the PVRIG, PVRL2 pathway is more dominant in order to be able to address these tumor types and hopefully increase our probability of success in the clinical studies, testing COM701. And by analyzing the expression process of the receptors and ligand of this axis, we identified that high PVRL 2 is present in tumor types like breast, ovarian, endometrial, but also in non-small cell lung cancer in PD-L1 low and high patient populations. And with this, we moved into designing the clinical studies. Today, we pursue 3 different type of studies, COM701 monotherapy, dose escalation and monotherapy expansion in the tumor types that we actually found that are relevant for the COM701 pathway. To this, we added also colorectal and that's based on clinical data that we got when we started to pursue the dose escalation portion of the studies, and I'll explain and the -- we also pursue the dual combination study of COM701 plus nivolumab together with Bristol-Myers Squibb. And last week, we actually announced that we started first patient dosing for the triplet study dose escalation, which will be followed by cohort expansion in the same indications that I just mentioned, ovarian, endometrial and the basket study that will include high PVRL2 expression tumor types. So I'd just say that the colorectal for the colorectal portion of the study, the data that we shared from the monotherapy dose escalation in a portion of the dual combination study, we found out that we have responses in primary peritoneal cancer, which is a type of ovarian cancer in monotherapy of COM701. And MSS colorectal cancer in the combination of COM701 plus Opdivo. And due to this, although colorectal cancer is presenting in to medium extent, the PVRIG, PVRL2 pathway, we decided that will add also colorectal cancer to the -- to our assessment of the COM701 effect. With this, the last slide, Slide #8, just some guidance in respect to value drivers and data readout. So we -- at recent ASA, we presented encouraging data from the monotherapy and combination study with Opdivo -- COM701 and Opdivo. And we completed the enrollment for the Opdivo, COM701 dose escalation study. We initiated the enrollment of the monotherapy expansion cohorts, and this is an ongoing study now. And we also initiated, as I said, last week, the Phase I/II triple combination study with Opdivo, BMS TIGIT inhibitor and COM701. For 2021, on the COM701 front, we expect to share data from the monotherapy expansion cohorts as well as the rest of the data from the combination of the doublet of Opdivo and COM701 in the first half of 2021. And on the COM902 front, our own TIGIT antibody that we develop in order to make sure that as the only company that has a clinical stage PVRIG antibody, we also control the other arm of the axis, the TIGIT axis. We developed our own COM902, which initiated Phase I studies on March, and it is progressing in the dose escalation study. We expect to share data of the dose escalation by -- during 2021. And the idea is to be able to test the potential of the combination of COM701 and COM902, namely inhibiting PVRIG and TIGIT in a PD-1 free regimen. That's the potential for COM902, while we continue to pursue together with BMS to, ultimately, test hypothesis and push forward the triplet study for TIGIT, PVRIG and PD-1 blockade. So that's -- other than the additional partner programs and the discovery capabilities, these are the value drivers of the company as of today. And with that, we can move to the questions.
Great. Maybe I'll start. So you had mentioned the combination of PVRIG and TIGIT, both as acting as inhibitory on the T-cell. Can you go into a little bit more detail on why it's important to target both of them at the same time and not as effective as in targeting just TIGIT?
Yes. I think that Eran can address it from this -- understanding the science behind these 2 pathways, Eran?
Yes. So basically, yes, TIGIT PVRIG are both expressed by T-cells and by NK cells. But as Anat mentioned, they bind different ligands. And DNAM, which is the mutual player -- mutual to 2 pathways, engage PVR and PVRL2, and it needs to engage probably both of them to get optimal signaling. Now especially in certain tumor types, which PVRL2 is more dominant. Probably, in this cases, you need to block also PVRIG. While in addition, there are certain aspects in PVRIG biology that PVRIG by itself is expressed by T cells and CD-8 and NK, TIGIT [indiscernible] also by [indiscernible]. So it's not the same molecules, even though they're coming from the same pathway. The ligands have different expression pattern both PVRL2 and PVRL are expressed, yes, in PDL-1 low and high patients, but PVRL2 has different expression pattern also [indiscernible] cells on some types of [ dendtritic ] cells. So in these cases, blocking PVRIG might add additional effects which are not simply coming from blocking TIGIT. So to summarize, it's coming from the different patterns of the ligands and the target, which give a bit different angle for biology. And specifically in some tumor types in which PVRL2 is very dominant in this case, it partly blocking PVRIG, might be also very, very important also in the 2 macro environment itself.
Okay. And PVRIG seems to be unique for you guys. I mean you discovered it. Have others tried this before or are others working on this as well? Is this something that is a theme that you guys have discovered? Or is it something that others are working on?
So we discovered it computationally, working it for quite some time. We're the only clinical-stage company targeting PVRIG but there is a paper of University of Colorado that is describing PVRIG as well. There is another company that is addressing it preclinically at this stage. And our working assumption is that there are others. Remember that the first 2 papers that we published that are comprehensively actually looking at the biology or unlocking the biology of PVRIG, were really published by us on 2018, which is very recently. Together with Johns Hopkins with the [indiscernible], which is a long-term collaborator of Compugen. Two papers describing the human biology and the mouse biology, that's very different from the time that we published and Genentech published the data, the first time discovery of TIGIT, which was 2009, and we now see the huge competition behind it. So it's very different in timelines.
Okay. And then thinking of the competition in TIGIT, the Roche data, and then I think Mark published TIGIT data, was it on Monday. Or abstracts came out. How do you think that supports your thesis with PVRIG?
So I'll first relate to it in general and then Henry can speak to it. I'll say first that just in terms of competition to TIGIT, I just want to make sure that everyone understands that for us, it's not about the competition with TIGIT. The key differentiating factor for Compugen is the fact that we have PVRIG and we're using TIGIT in order to be able to extract the full potential of COM701. But the second thing I'll say is that we speak for 3 years, more than 3 years about this 3 pathway story. And the DNAM Axis. And when we started this path, only the PD-1 pathway was validated. And today, we're sitting here with some initial clinical data for PVRIG pathway that we generated that is supporting our hypothesis. And also with clinical data that was just shared by Genentech and recently by Merck, that is actually proving the -- validating the TIGIT pathway. So today, out of the 3 pathway, we have more support for these 3 pathways, and we feel that we have more support for our hypothesis moving forward. So we're more encouraged. I'll let Henry discuss more the clinical front of this.
Yes. Okay. That's a very good question. And as you can see, what announces are articulating for you in is the fact that it appears the field is now catching up to what Compugen has been seeing over the last several years. And I say this because now -- we now have data both beginning from [indiscernible] through the America present initial presentation like this ITC a couple of years ago and now more essentially the data with a randomized study by [indiscernible]. It demonstrates the fact that this 2 pathway story and eventually the 3 pathway story with inhibition of the blockade of the [ completing ] of axis is probably the way to go. And the reason we say is just looking at the Roche and Genentech data with a very significant housed ratio in the intensive tree population. And now there are these three studies that they have launched already. [indiscernible] that there's likely a clinical benefit that will be derived from the Phase III study in addition to the fact that the [indiscernible] lung cancer study that they already disclosed, was very significant in terms of the hazard ratio that was demonstrated. In that vein, that's why we're doing our own COM902 study with dose escalation. And eventually, like Anat also mentioned, which was going through this slide, where we have the 3 -- the triple competition, where we're looking at complete blockade of the members of the DNAM axis, we're fully be able to see what that looks like in terms of clinical outcomes like PFS, response rate, duration of response, et cetera. So I think it just brings the story together for Compugen and what we've been saying over the last several years.
Okay. And speaking of your 701 trial and data, what have you seen in your data so far that has encouraged you to continue pursuing? And what do you see that's exciting about it?
Yes. So two things. So the [indiscernible] responses that we've observed one in monotherapy, which is in patients with primary [indiscernible] cancer, microsatellite stable [indiscernible] cancer that is platinum resistant. The partial response was observed. And at the time we did [indiscernible] the presentation was done by [indiscernible] Hospital. We observed the [indiscernible] on for 25 weeks. Typically, when you go back and look at the historical data for patients with this type of -- tumor type, it's typically about 3 months to about 4 months that you have on study treatment for this type of cancer. Now for monotherapy that was demonstrated in these patients, we actually saw a natural response at the first imaging assessment. Remember, this is a patient that system disease before I came on to the study. And then the subsequent assessment should actually [indiscernible] that response. The full deck that we have for presentation shows the CT [indiscernible] I can go back and look at. And it actually shows that, that response stays the same. So it's confirmed for 25 weeks at the time when the presentation was given. So that's very encouraging that a typical tumor type that is not responsive to immune checkpoint, we can see this kind of response that is durable. The second response that's encouraging is a microsatellite stable colorectal cancer. Another tumor type that is typically unresponsive to in checkpoint. And I think -- I mean, there's a litany of erosion checkpoints that have been evaluated in this space. So more recently, you're probably familiar with the impassion [indiscernible] started by Roche and Genentech in Phase III study in about 400 patients, 3 Arm study where we are evaluating [indiscernible] editions with microsatellite stable colorectal cancer in combination with [indiscernible] or looking at [indiscernible] also. The medium PFS in that patient population, typically is in 2 months. That's it. In our study, we first observed that the patients we presented at SITC in 2018. This seemed to be a premonition of the time on study treatment meaning that the PFS was very much higher than what is typically observed in patients with microsatellite stable colorectal cancer, which is about 2 months. So it was very encouraging for us when we then saw in decent with -- in the combination Arm of COM701 and nivolumab with the passion respond that was confirmed, that means we repeated [indiscernible] assessment by [indiscernible] 1.1 for with the passion response of duration of 44 weeks, to 11 months. That's significantly, significantly higher than what is typically recorded. And again, that [indiscernible] again is typically unresponsive to immune checkpoint. So that's a very encouraging result. Now the last thing to say is that if you go back and look at the disease control rate for this for the 2 Arms of the study. So monotherapy, dose escalation and combination with escalation, the disease control, meaning passion response for stable diseases, 69% on the monotherapy around this escalation and 75% on the [indiscernible] now. So in common balance, essentially always say is at least 69% of patients on the monotherapy are derived some form of clinical benefit and 3/4 of the patients on the combination of direct, some form of chemical benefit. So that's very significant for monotherapy for a novel first-in-class agent, which supports the mechanism of action as the checkpoint in this patient population. So like Anat mentioned, given the use expansion now for the monotherapy we also have demonstrated that the safety profile of COM701 alone and in combination with nivolumab shows that it's very well tolerated. [indiscernible] subjects came on study treatment as a result of toxicity. So that's -- those are very encouraging signals for this study.
Okay. Maybe just a couple of questions on 902. That's obviously your own TIGIT. I see the trial with Bristol with the PD-1 and their TIGIT is ongoing. Can you talk about the dynamics and how you're going to do trials with their TIGIT? And then as yours continues to develop, how that will play out?
Yes, definitely. This is -- the partnership with BMS is a win-win for both sides. And we're happy to continue and extend this collaboration as much as possible based on data and also based on BMS interest. So getting an access to the BMS TIGIT, which was tested in the clinic already with nivo, allows us just to titrate in COM701 and test -- accelerate our time lines to test the triple pathway story, the hypothesis and be able to go ahead with this. And as much as this will be successful, we're happy to move forward with BMS, and there is no need to replace it with our own TIGIT. Our own TIGIT is really serving us, first, in order to be able to control the 2 Arms of the axis as a company, but also in order to have the potent to be able to act for testing the potential of COM701, COM902 combination that is PD-1 independent. And also now when TIGIT pathway is validated, we're not ignoring a situation where we can test it as a pathway on its own with other agent. So we have now in our pipeline, an asset that is targeting a clinically validated pathway, which is TIGIT. So outside of the DNAM axis, that may have a potential as well. And we're not going to ignore it. So this is how we see it. Obviously, this is all with plans, but it is generating a safer profile for the company.
Okay Maybe just in the last couple of minutes, if you can highlight what your near-term milestones are, so that people will know what to look for, maybe either at conferences or just when you think data will come out, that sort of thing? And then any closing remarks?
Sure. So we did give guidance to data readout, and I'll just make sure that I repeat it. On the monotherapy expansion cohorts, we're going to -- we expect to share data in the first half of 2021. This will also include data from the rest of the doublet dose escalation of COM701 plus Opdivo, the rest of the data that following ACR 2020. And the triplet study that just started a week ago, we did not share guidance yet to data readout, but we will share -- going forward, we will share how we see data readouts for the triplet study. And for the COM902 program, we shared that we will share data in -- during 2021. So this is going forward. With respect to closing remarks, I'll just say that Compugen is actually in a very unique position at this stage. We actually -- we are the only company that has a control of two clinical-stage assets for the 2, what we think are the relevant pathways from the DNAM axis, the TIGIT and PVRIG. And together with BMS, were both equipped in order to test this hypothesis as needed in a triplet study or any other forms of studies to test the contribution of the different components. And I think that with the 3 programs in the clinic that were discovered by computer prediction, we're also one of these companies that prove the computational engine that we generated in this field. So it gives us an edge to discover more and more and to feed our own pipeline.
Okay. Great. Well, that takes us to the end here. Thank you very much, and we appreciate your participation. Hopefully, everybody learned a little bit more about Compugen. Thank you.
Thank you, Albert, and thank you, everyone.
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