Compugen Ltd.
Q1 2021 Earnings Call Transcript

Published: 13 May 2021

[Operator:]

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's First Quarter 2021 Results Conference Call . As a reminder, today's call is being recorded. With us from Compugen are Dr. Anat Cohen-Dayag; Ari Krashin, CFO and COO; and Dr. Henry Adewoye, Chief Medical Officer, who will be available for questions at the end of the call. Before we begin, I would like to read the following regarding forward-looking statements. During the course of this conference call, the company may make projections or other forward-looking statements regarding future events or future business outlook. Our development efforts and their outcome, our discovery platform, anticipated progress and time line for our programs, financial and accounting related matters as well as statements regarding our cash position.

[Anat Cohen-Dayag:]

Thank you, operator. Good morning and good afternoon, everyone, and welcome to our first quarter 2021 corporate and financial update. We have started 2021 from a strong position, building on our timely execution for our 2020 guidance and plans. We believe 2021 is poised to be an important year for Compugen as we continue our efforts to build a robust clinical pipeline with multiple clinical studies while further deepen the scientific foundation for our differentiated programs. We have developed a comprehensive clinical development program designed to systematically elucidate the role of our internally discovered and wholly owned anti-PVRIG and TIGIT assets across settings and combination regimens. With steady execution, we have made great progress both clinically and research wise in understanding the role of the DNAM axis members, PVRIG and TIGIT as potentially foundational immunotherapy checkpoint targets. Our work has identified PVRIG and TIGIT as key parallel and complementary inhibitory pathways in the DNAM axis, which also intersect with a well-established PD-1 pathway. Together, our data suggests that the D3 inhibitory pathways have different dominance in different tumor types and patients which means that in order to induce effective antitumor responses certain patient populations may require the blockade of different combinations of these three pathways. With this in mind, we have established a science driven and data informed clinical program, which evaluates different combinations of these axis members across indications that we believe will be most relevant in the clinic. On our last call, we shared data from the combination arm of the Phase I dose escalation study of COM701 in combination with Bristol-Myers Squibb nivolumab, as well as follow-up data from our monotherapy dose escalation and cohort expansion study. For the combination arm dose escalation, we provided complete data from all five dose levels in the study. Our encouraging results showed a disease control rate of approximately 67%, which is a significant accomplishment given the highly refractory heavily pretreated and advanced disease patient population.

[Ari Krashin:]

Thank you, Anat. Good morning, and good afternoon to everyone. Our financial results for the first quarter of 2021 released this morning continue to reflect a solid financial position with, as expected, increased research and development expenses due to a growing number of clinical trials. Research and development expenses for the first quarter of 2021 were $7.3 million compared with $4.7 million for the same period in 2020. This increase is attributed mostly to CMC related activities specifically manufacturing cost for additional drug supply of COM701 to support the planned expansion of our various clinical trials as well as expanded clinical team located in the US, which brings additional expertise to the company to ensure the successful management and execution of our ongoing and soon to be initiated clinical trials. As a reminder, our clinical expenses reflect costs associated with our expanded clinical programs, which we now include COM701 in monotherapy, dual and triple combination studies, as well as dose escalation study for COM902.

[Operator:]

The first question is from Mark Breidenbach of Oppenheimer.

[Mark Breidenbach:]

Congrats on all the progress, and I hope everyone is staying safe on your end. Just a couple for me. First of all, should we be expecting any additional patients from either the monotherapy or nivolumab combination cohorts to be included in the analysis presented at ASCO versus what we saw in February, or will it really just be the same set with more follow up time? And you mentioned that there might be some correlative data presented at ASCO as well. I'm wondering if you were able to track any specific markers of DNAM 1 activation or will these correlative data really be more generalized indicators of immune activation and response?

[Anat Cohen-Dayag:]

So I will take the correlative assessments and let Henry relate to the clinical. On the correlative assessment, as we stated in our last quarterly call, we were able to track with very initial data, obviously, immune activation seen by COM701 treatment as monotherapy and also in combination with nivolumab. So this data will be presented. With respect to DRAM access, this is really analysis in progress and if we'll show some data, it would be very, very initial. We will present the data as we will have it ready probably in additional later conference. Henry?

[Henry Adewoye:]

So Mark, what we previously disclosed in February was a snapshot of the data. At ASCO, we’ll present updated data, including all the patients who have been enrolled on the dose escalation arms of the study, so monotherapy dose escalation, the combination dose escalation, including follow up. We'll also disclose data on the patients who have been enrolled on the monotherapy expansion cohorts, including follow-up on those patients also. And particularly, we will disclose data on long term patients who have been on the study, especially the ones that we've highlighted in the prior disclosure we had in February. So it will be a summary of all the data that's been previously disclosed and new data, specifically new data in the last dose cohort of COM701 in combination with nivolumab both at the doses of 20 milligrams per kilogram body weight dose and 480 milligrams IV Q 4 weeks. So there will be a lot more of the safety data in those cohorts.

[Mark Breidenbach:]

And just also wondering if you were able to collect any postmortem biopsies from patients in the Phase I study, who were on drug at the time of death, just to be able to look for any evidence of target engagement and also do a little bit of PVRL2 expression profile in any of the Phase I patients?

[Henry Adewoye:]

As Anat mentioned in her script, there will be correlative data presented. And I'm giving the opportunity to Anat to further expatiate d on your question.

[Anat Cohen-Dayag:]

We were collecting on the monotherapy expansion. We're collecting pre and on treatment. I am not sure with respect to postmortem. I guess you'll need to wait for it. I'm not sure that we have postmortem for a specific patients.

[Operator:]

The next question is from Stephen Willey of Stifel.

[Stephen Willey:]

Maybe just to follow up on the last question. Can you maybe just kind of ballpark with respect to, I guess, how much pre and on treatment tumor biopsy data from patients we might see at ASCO? And I know you talked about some of the peripheral blood markers of immune activation, but I think there's been some increased interest in the changes in CD8 TIL fraction that are in the tumor, both pre and post treatment. So just wondering if that's an assessment that we might see at ASCO.

[Anat Cohen-Dayag:]

So as you correctly stated, we did speak about the blood markers. And with respect to liquid biopsies, we obviously have from the dose escalation as well as from the expansion. So here we have a little bit more -- the number is a little bit higher. On the tumor biopsies, as you remember, we had 20 patients in the monotherapy expansion. Obviously, we couldn't get biopsies from all of them as paired pre and on treatment. So it's only a portion of this group and taking into consideration that in some of them, obviously, we didn't see response. So I think that the data will be limited. It's initial. The data that we have is pointing to some preliminary, as we stated, preliminary activation upon COM701 treatment. What we're going to present will probably not be all the immuno-histochemistry data because this is in progress. We will present some of the data that we have. So just to address your question, it will be limited at this point in time, but we will make sure that we present all the data when we have it probably in a later conference.

[Stephen Willey:]

And then maybe just to throw a question at you that we're getting a lot. I know that there’s competitive trial readout, I think coming maybe later this quarter. And one of the backbone agents in that regimen that's being evaluated is an Fc silent TIGIT. So just kind of wondering what you’re maybe expecting to see out of that? And I guess, how you think that data might extrapolate out to what you’re personally with 902 right now?

[Anat Cohen-Dayag:]

Yes, it's a fair question that would be the first data that is derived from an Fc inactive TIGIT inhibitor as opposed to the rest of the data that is out there. So obviously, we're looking as well to see what the data will tell us. I guess that you are well familiar and not only you, Stephen, but also the community with our view about the need or actually the no need from our perspective, as we see it based on our data on having an Fc active. We hope this will support this view that we have, which is based on data. We recently published a paper on COM902, which is further strengthening what we're saying for quite some time. We have our own COM902 clinical study. This is now in dose escalation. We promised to show data in Q4. So obviously, our data will be outside as well. And so we're looking to see what the data will tell us from the other company, but also we're looking very carefully at our data as well. And we still didn't find in the public domain a reason to be concerned with our view with respect to Fc inactive performance in clinical studies. So we'll see.

[Operator:]

The next question is from Daina Graybosch of SVB Leerink.

[Daina Graybosch:]

A couple on the science side. I think we're seeing more companies talk about targeting tactile or CD96 sort of the other member that you don't have a program against from sort of the DNAM axis. And I wonder if -- the first question and then I'll have a follow-up. The first is, what do you think about CD96 and its role in DNAM signaling and whether you may need to target it in some patients or tumors as well.

[Anat Cohen-Dayag:]

CD96 actually is binding PVR, but it binds PVR with a lower affinity than TIGIT. So we think that the contribution is not really clear. Definitely PVRIG is addressing a completely different node, which is PVRIG/PVRL2. We believe that the PVRIG, PVRL2 and TIGIT PVR are the two pathways that needed to be blocked in order to generate meaningful antitumor activity. I would say that also whether CD96 is a positive costimulatory or negative costimulatory that's also a question, at least in our hands and in some papers outside. So we'll see, we'll wait and see. But it doesn't change our hypothesis.

[Daina Graybosch:]

And then a follow-up on the question that Stephen just asked on the competitor data. I wonder if you can remind us how similar are COM902 with Arcus’ TIGIT that’s going to have the data? Any notable differences in addition to the similarity that we should consider when looking at that data?

[Anat Cohen-Dayag:]

So first, our antibody is ITG4. I believe there is ITG1 mutated, but still Fc inactive. And in general, our antibody is ultra high affinity antibody that's an antibody that we've developed from day one to be complementary with COM701. And we tested it also benchmark to other TIGIT antibodies. We don't have a reason to believe that epitopes would play a role here, different epitopes like similarly to PD-1. But generally, the difference is the ultra-high affinity with respect to our antibody. So we'll see.

[Operator:]

The next question is from Ren Benjamin of JMP Securities.

[Ren Benjamin:]

Anat, you mentioned the additional data in the fourth quarter of this year. Can you give us a sense as to how many patients’ worth of data we might be seeing for both studies and would it be enough to make some reasonable conclusions about a path forward?

[Anat Cohen-Dayag:]

Henry, would you like to address this question?

[Henry Adewoye:]

So the two projected data that will be anticipated will be for the TIGIT antibody, like Anat mentioned, COM902. So for that, as you know, Reni, it's a design that has an accelerated portion to it. So we have single cell subject patient cohorts. And also, we have a three plus three subject level cohort. I cannot project for you now the total number of patients that we will expect to see. But certainly, it would be at least more than four patients that will enroll because we'll go past the single subject level cohorts. We'll continue to accumulate data on that study. So maybe at another presentation, we'll be able to hone in more on the absolute number of patients that we're projecting.

[Ren Benjamin:]

And then the triple comment?

[Henry Adewoye:]

So for the triple combination, we also have that ongoing. It's a three plus three study design also. The projection, when we started that dose escalation study, is to go as high as 20 milligrams per kilogram body weight dose with COM701 in combination with the other two agents. So the other two agents, the BMS-986207, the BMS TIGIT antibody and nivolumab. So far, as we keep on, we're on track. At a later teleconference, we will be able to tell you how many patients we expect. But certainly, the reason we are projecting that we'll get up to 20 milligrams per kilogram body weight dose of COM701 in combination with the other two agents is because, as you remember, the dose that we've recommended for expansion for COM701 is the 20 milligrams per kilogram body weight dose IVQ four weeks. So as we go along, we'll be able to further refine how many patients that we'll present at that time.

[Ren Benjamin:]

And then just regarding the biomarker data that you'll be disclosing at ASCO, as well as later on in the year, it seems to me that ultimately you are in search of a patient signature or some sort of signature that might allow you to identify patients that would respond to either 701 or the combination of 701 and 902. Am I thinking about that correctly that ultimately all these analyses will help you to identify the patients better or are you looking at these data more to boost the current clinical benefit rates that you're seeing to more of objective responses? Or do you kind of feel that Fcs right now are pretty good and if you can get more people with stable diseases, that would be just fine?

[Anat Cohen-Dayag:]

Actually, both and also for better understanding the mechanism of action of COM701 treatment. The biomarker strategy is broad enough in order to address tumor biopsies and also information gathered from blood samples, we have the component of the retrospective analysis and you also know that we have the component of patient selection basket study in the triplet. We are looking to understand what the tumors are telling us following COM701 treatment, monotherapy or combination. And whatever we can get to better understand what's going on in tumor macro environment, remodeling, et cetera. So both growth that you mentioned but also better understand the mechanism of action.

[Ren Benjamin:]

I guess just one final question for me. I'd love to just kind of get your thoughts on the TIGIT landscape as you see it right now, how it's unfolded with the data that we've seen to date. And kind of how 902 might be able to sort of thread the needle in the space?

[Anat Cohen-Dayag:]

I'll let Henry address it, but I'll just say that currently, the TIGIT studies that are ongoing across the different indications are mostly PD-L1 high. As we stated for quite some time, we believe that targeting PVRIG will be complementary. And you can see that our clinical strategy is addressing more the PD-L1 low and nonresponsive patient population. With our TIGIT, obviously, the key differentiating factor is the fact that we can combine it with COM701. But I'll let Henry address more the landscape and our strategy with COM902.

[Henry Adewoye:]

So Reni, I think what's key here is that this provides opportunities for better treatment options for patients who have advanced disease. Most of the data that's been presented prior to the release by Roche Genentech was this escalation by OncoMed Mereo. Now we have more data from Roche Genentech. And like Anat alluded to, this is more robust data because it's a randomized study in non-small cell lung cancer. And it appears that the activity of the combination of the TIGIT plus the PD-L1 inhibitor is better enhanced in patients who have high PD-L1 expression. The data from Merck also shows that the combination appears better in combination -- better results in combination with PD-1 inhibitor. So that's good for patients. What is currently -- at this time, I don't think personally speaking as an oncologist and looking at all the data that's been there, is whether there will be an impact with the kind of Fc that one has. We're looking forward to data disclosures by Arcus as they've iterated that they will have an interim analysis of their data. But we believe like Anat has mentioned that COM902 will have antitumor activity and that it will -- as a pure blocker that which show based on the science that there should be no difference in terms of whether there is an Fc enhanced or non-Fc enhanced. However, these data are all that we're collecting all ongoing and we'll see what Arcos presents also. I'd just like to add that Anat -- I completely aligned what Anat has said that what actually differentiates Compugen is that we are going to be testing a PD-1 and a PD-L1 free regimen, where it will be the combination of COM902 with COM701. We'll see what the preliminary safety, tolerability and antitumor activity of the combination will be. But also remember that we have a triple combination study that's ongoing in collaboration with BMS, obviously, where we are testing the DNAM hypothesis of complete inhibition of the various aspects of the DNAM axis. So it's all incredible and exciting data that we hope to see over the next several months and before the end of the year. And hopefully, this will all lead to clinical benefit for patients who desperately in need of better treatment options.

[Operator:]

The next question is from Asthika Goonewardene of Truist Securities.

[Asthika Goonewardene:]

I want to revisit updates here. On the triple, can you tell me what dose level of COM701 that you will begin the escalation? I just want to clarify, are you starting that at a dose with COM701 dosed at 20 mg per kg or something maybe around that area? And then I have another question. On the more complete IHC data that you noted that you'll follow up with at a later conference. Will that be something in the second half of 2021 as well that we can expect?

[Anat Cohen-Dayag:]

So I'll start with the IHC and then Henry will take the triplet dose escalation question. We did not share guidance. But as I said, this is in progress. Hopefully, we can still present it this year but we will give specific guidance when we know more.

[Henry Adewoye:]

So I'll speak with regards to the triplet combination. What we've disclosed is that will have approximately up to five dose level sequential dose escalation cohorts in combination with fixed doses of the BMS TIGIT antibody 98627 and nivolumab. So inherently that means that we will not be starting at 20 milligrams per kilogram body with dose of COM701 in combination with the other two agents.

[Operator:]

The next question is from Roger Song of Jefferies.

[Roger Song:]

Most of my question is related to Simon has been raised and answered, so I won't repeat. Maybe just a quick question related to that Johns Hopkins collaboration. So we know the myeloid target is one of the pillar of your competition and discovery platform. Maybe could you just provide some additional color in terms of the nature of the collaboration. I mean, maybe more specifically, what are the steps and the time line for the candidate nomination and the potential kind of R&D?

[Anat Cohen-Dayag:]

As much as we can relate it, we didn't disclose much. But I'll just say that the collaboration with Hopkins is it's very similar to how we conduct the collaboration for a few years now. Hopkins is part of executing the research on the candidate. As I stated, they were also part on some of the preclinical work on COM701. So this is the nature of the collaboration. Specifically for this myeloid target, this is a very early stage on. It still merits research in order to explore the therapeutic potential and we believe it's exciting. And as we disclosed, we've seen some tumor growth inhibition in generic depletion animal models. The mechanism seems interesting but it requires a lot of research and this is why we thought that it will be good to go hand-in-hand with the laboratory of Drew Pardoll and his excellent team that were used to work with them and do the work together. That's what I can say about this specific drug target.

[Roger Song:]

Yes, I won't leave Ari out of this conversation. Maybe, Ari, I believe you provide some kind of color around the OpEx and cash. Maybe just remind us what is the current guidance around the cash run rate?

[Ari Krashin:]

So we ended the quarter with about $190 million. As we stated before, the yearly run rate for --the yearly run rate expenditures would be roughly between $40 million to $42 million. So having said that, assuming we will not increase significantly the cash burn rate, we're talking about at least cash sufficient through the end of 2023. Having said that, again, if we do decide based on our clinical strategy to expand and to increase the clinical trials, obviously, this estimation might change.

[Operator:]

The next question is from Tony Butler of ROTH Capital.

[Tony Butler:]

A question on that and Henry is around 701 and 902, the combination trial. Henry, you alluded to the fact that for safety reasons, you wouldn’t want to see that combination but don't -- you actually get that with the triple. And I guess outside of dosing, that is the amount that you would use optimally with 701 with the optimal dose for 902. What else might you actually define, if anything, for the two -- for eliminating both co-inhibitors in the DNAM axis in the absence of a PD-1 antibody?

[Henry Adewoye:]

Remember that in the process of doing a dose escalation study, the intent is to evaluate what the safety and tolerability of that combination that you're testing. So if you have three study drugs that you're combining as part of a dose escalation, it is impossible to be able to extricate what the contribution to safety of either one of the components or two of the components are. So you can only speak to what that combination does in terms of safety and tolerability, especially within the DLT window that you've assigned for the course of the dose escalation and also intermediate and long term toxicity. Now for the dual -- so therefore, it will not be possible to allude completely to what a TIGIT inhibitor does separately as part of a triple combination. And also remember that even though we get some data from what the combination of a TIGIT inhibitor does as part of that triplet combination of COM701 nivolumab, it's a different TIGIT antibody. So the TIGIT antibody that we're using in the triple combination is the TIGIT antibody from BMS-986207. It's what we cannot miss -- it's a separate entity itself. So you cannot transfer the safety and tolerability of one antibody to the other. You can get an idea of what the relative toxicity is but you cannot transpose it to another antibody. So therefore, there is a need -- since the 2 agents that we'll be combining with ours, COM701, we know the safety and tolerability of COM701. As you remember, Tony, we started at 0.01 milligrams per kilogram both dose and we dose escalated through 20 milligrams per kilogram with dose IVQ four weeks. So we have a lot of data on COM701. It's an unapproved agent, so it's more -- it's an antibody that we're still collecting data on, but we're relatively comfortable with what we see in terms of its preliminary antitumor activity and safety and tolerability. COM902 is another new agent, it's a TIGIT antibody but remember that it has never been combined with COM701, which is another unapproved. So we have two unapproved agents. And as far as the regulations go and clinical practice and conducting clinical trials, you have to be able to compile the safety information of those two events separately without any other agents in combination, so it just be the dual combination. The expectation is because we know what the safety profile of COM701 is very well tolerated, we do not expect to see anything that is out of the blue, we would combine with COM902. But at any rate, that's why we're doing the clinical study. So even though the triplet will inform a little bit, it will still not be sufficient to fulfill regulatory obligations with the combination of COM701 and COM902. I hope that answers your question.

[Tony Butler:]

It does, Henry, and thank you for the clarity and please understand part of the rationale was would you find other information outside of safety. But I think you've made it very, very clear what the goal is, and I appreciate it.

[Operator:]

This concludes our Q&A session. I will now turn the call back to Compugen's President and CEO, Dr. Cohen-Dayag. Would you like to make your concluding statements?

[Anat Cohen-Dayag:]

Yes. Thank you. Thank you all for joining the call today. 2021 is poised to be an important year for Compugen, with meaningful milestones and multiple data readouts. We will continue to push forward as leaders in the DNAM axis space, advancing our wholly owned PVRIG and TIGIT assets to potentially drive immunotherapy responses in new and expanded patient population. Thank you for joining us today and your continued support. Stay safe and healthy.

[Operator:]

Thank you. This concludes the Compugen's Ltd. first quarter 2021 financial results conference call. Thank you for your participation. You may go ahead and disconnect.