Compugen Ltd (NASDAQ:CGEN) Q2 2020 Earnings Conference Call July 30, 2020 8:30 AM ET
Elana Holzman – Investor Relations
Anat Dayag – CEO
Henry Adewoye – Chief Medical Officer
Ari Krashin – CFO and COO
Eran Ophir – VP Research and Drug Discovery
Conference Call Participants
Stephen Willey – Stifel
Daina Graybosch – SVB Leerink
Matthew Biegler – Oppenheimer
Asthika Goonewardene – SunTrust
Colin White – Jefferies
Justin Walsh – JMP Securities
Tony Butler – Roth Capital
Ladies and gentlemen, thank you for standing by. Welcome to Compugen’s Second Quarter 2020 Results Conference Call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available in the investors section of Compugen’s website www.cgen.com. As a reminder, today’s call is being recorded.
I would now like to introduce Elana Holzman, Compugen’s Director of Investor Relations and Corporate Communications. Please go ahead.
Thank you, operator and thank you all for joining us today. With me from Compugen are Dr. Anat Cohen-Dayag, President and CEO; Dr. Henry Adewoye, Chief Medical Officer; Ari Krashin, CFO and COO; and Dr. Eran Ophir, VP, Research and Drug Discovery. 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. We wish to caution you that such statements reflect only the company’s current expectations and that actual events or results may differ materially.
You are kindly referred to the risk factors and cautionary language contained in the documents the company filed with the Securities and Exchange Commission including the company’s most recent Annual Report on Form 20-F filed on February 24th, 2020. The company undertakes no obligation to update projections or forward-looking statements in the future.
I will now turn the call over to Anat. Anat?
Thank you, Elana. Good morning and good afternoon everyone and welcome to our second quarter 2020 corporate and financial update. As Elana mentioned, with me today are Dr. Henry Adewoye, our Chief Medical Officer; Ari Krashin, our CFO and COO; and Dr. Eran Ophir, our VP, Research and Drug Discovery. After my prepared comments, Henry will review the progress across our clinical programs and Ari will review our financial statements and position. We will all be available for the Q&A session.
We have reached an exciting new phase of development at Compugen. Today, there are three clinical programs: COM701, COM902, and BAY 1905254 addressing drug targets we discovered computationally. COM701 and COM902, developed internally, are designed to strategically evaluate the DNAM axis as a potentially transformative checkpoint axis for cancer immunotherapy treatment. Henry will provide detailed updates across these programs later in the call, but first, I want to share what we believe are important developments for Compugen and the broader immuno-oncology space that leave us increasingly optimistic about our drug candidates and distinctive clinical development path.
As a reminder, Compugen’s internal computational discovery platform has enabled the discovery of two important new checkpoints in the DNAM axis: PVRIG, discovered by Compugen and TIGIT discovered by Compugen and, at the same time, also by others. Our lead program COM701 targets PVRIG while COM902, now also in the clinic, targets TIGIT. It is important to note that we identified that PVRIG and TIGIT are part of a parallel and complementary inhibitory pathway in the DNAM axis and we have pre-clinical data demonstrating that blocking PVRIG together with TIGIT may be required in certain tumor types in order to generate or enhance an antitumor immune response.
In addition, our pre-clinical work, supported also by others, provides the foundation of our hypothesis that there is an intersection between the two pathways on the DNAM axis, PVRIG and TIGIT and the PD-1 pathway. Specifically, our findings suggest that the simultaneous blockade of these three pathways has the potential to synergistically enhance antitumor immune responses in certain patient populations where the DNAM axis plays a role and who therefore, are probably not responsive to PD-1 inhibitors alone. As such, the blockade of these two DNAM axis pathways have the potential to expand immuno-oncology treatment options to cancer patients who are not responsive to currently available drugs. It is quite remarkable to think that just a few quarters ago, of these three targets, only PD-1 was clinically validated. We have come a long way in a very short time and are thrilled to now have initial signs of clinical activity by PVRIG and TIGIT validated in the clinic by others.
Taken together, these data increase our confidence in our hypothesis that in certain patient populations where these three pathways are dominant, blocking the DNAM axis and specifically, the addition of PVRIG blockade to TIGIT and PD-1 blockers may be a critical component in driving cancer immunotherapy treatment responses.
I want to dive in a bit more into PVRIG and TIGIT. It is important to recognize that while these are important complementary checkpoints in the same DNAM axis, they are in fact distinct. First, PVRIG and TIGIT bind preferentially to different ligands, PVRL2 and PVR, respectively. In addition, and highly relevant to our clinical programs, PVRL2 and PVR are differentially expressed on different tumor types. Importantly, PVRL2 expression is more dominant compared to PVR in certain cancers such as breast, endometrial and ovarian. This is significant because in these PVRL2 dominant indications, we expect that PVRIG must be blocked in order to drive antitumor immune responses.
Furthermore, PVRL2 is more expressed on various myeloid populations, mainly DC subsets. These immune cell types have been shown recently to be important in the PD-1 pathway. In addition, PVRIG and TIGIT are not necessarily expressed on same immune cell types. While both expressed on T cells and NK cells, TIGIT is highly expressed on Tregs relative to PVRIG. These findings with the totality of our functional data suggests that PVRIG blockade should support synergistic effects with PD-1 and/or TIGIT inhibitors and that these pathways are not redundant.
Therefore, as the only company with wholly owned clinical assets targeting both PVRIG and TIGIT, we believe we’re uniquely positioned to evaluate the blockade of the DNAM axis with and without PD-1 blockade and the safety [successive] potential to drive robust immune responses in patients. In line with our pre-clinical work, our initial clinical data suggests that COM701 treatment may indeed be relevant for certain cancer indications unresponsive to PD-1 treatment such as ovarian and colorectal.
As I discuss highlights from our trial, I would like to reiterate that our approach is strategic. We are rapidly advancing in parallel clinical programs that evaluate the potential of this candidate as monotherapy as well as in dual and triple combination regimens that we believe will allow us to comprehensively extract the value of our drug candidates addressing these new checkpoints.
So starting first with our COM701 clinical studies. In April, we presented at AACR the dose escalation data from both the COM701 monotherapy and combination arm with Bristol-Myers Squibb’s Opdivo. These data included all eight monotherapy dose escalation cohorts and four of a total of five cohorts from the dual combination arm. We were thrilled to observe two partial responses, one from each arm, with both having presented very encouraging durable responses of more than six months as of the data cut-off date.
We were also highly encouraged with both safety and tolerability and disease control rates in both arms. We believe the notable durability of responses observed in COM701 is particularly significant given that these results were achieved in a dose escalation setting and in heavily pre-treated patients. Together, these data serve as an important initial clinical validation of PVRIG as a new immune checkpoint with a role in cancer immunotherapy and we’re excited to continue advancing this program for the many patients who currently do not respond to available treatments potentially because the dominant inhibitory checkpoints in their tumors were not being targeted.
So what is next for COM701? This quarter, we initiated enrollment for the monotherapy expansion cohort, which is designed to evaluate the safety and tolerability of COM701 at the recommended dose for expansion. This study utilizes a biomarker informed strategy to focus on tumor types where we believe the PVRIG pathway may play a role based on our pre-clinical DNAM axis expression data and dose escalation clinical results.
We’re excited to start this study, which was also met with strong interest from our principal investigators and we’re excited to share that the enrollment is progressing as planned. We remain on track to complete enrollment in 2020 and report initial data from this trial, as previously indicated, in the first half of 2021. We recently completed enrollment in fifth and last cohort of the combination dose escalation study of COM701 with Opdivo and intend to provide the additional cohort data most likely at the same time as the initial monotherapy expansion cohort data in the first half of 2021.
Finally, moving to our triple combination study. We remain on track to begin the Phase 1/2 study to evaluate COM701 in combination with Opdivo and Bristol-Myers Squibb’s anti-TIGIT antibody in the second half of this year following the recent clearance of the IND by the FDA. We’re working closely with Bristol-Myers Squibb on this study and are very pleased with their continued support and involvement in our collaboration.
This program allows us to directly test our hypothesis of an intersection between the PVRIG, TIGIT and PD-1 pathways and that the simultaneous blockade of these three pathways has the potential to synergistically enhance antitumor immune responses in selected patient populations not responsive or refractory to PD-1 blockers alone.
As I have reviewed today, we believe there is now significant data, both clinical and pre-clinical, that support this strategy and we look forward to leveraging our position with our wholly owned clinical candidates against both PVRIG and TIGIT. We are highly enthusiastic about these targeted science-driven, clinical development program of COM701, which we believe has the potential to broaden the therapeutic benefit of checkpoint inhibitors to tumor types where they have previously not been successful.
Moving next to COM902, our anti-TIGIT therapeutic antibody. As I mentioned earlier in the call, new data presented by others over the past few months provided important clinical validation of TIGIT as an immunotherapy checkpoint. We’re thrilled to see these data, which we believe further supports our triple pathway hypothesis and we’re excited to initiate this quarter the dose escalation study of COM902. We anticipate disclosing initial data from this study next year.
I would like to reiterate that while TIGIT is now a clinically validated target being evaluated by us and others in biopharma, Compugen is the only company with clinical assets targeting both PVRIG and TIGIT in its portfolio allowing us to fully exploit the potential of blocking these parallel and complementary members of the DNAM axis to drive robust immune responses. Before I turn the call over to Henry, I would like to briefly touch upon the continued challenges associated with COVID-19. We’re fortunate in that we’re not experiencing significant impact on our activities for 2020. In fact, as indicated in our last call in May, we anticipate meeting our upcoming milestones and data readouts, including completing enrollment in the COM701 monotherapy expansion cohort this year and disclosing initial data from this study in the first half of 2021 together with the data from the additional cohort of the dose escalation of COM701 in combination with Opdivo as well as disclosing initial data from the COM902 dose escalation study in 2021.
COVID-19 has introduced challenges in our work and I am enormously proud of our team having watched them right to overcome the extraordinary circumstances we’re facing. Their dedication allows us to continue to advance our programs with the ultimate hope of broadly expanding the reach of cancer immunotherapy. We are grateful to our partners, investigators and shareholders and look forward to continued progress.
With that I will turn the call over to Henry to review our clinical programs.
Thank you, Anat and good day to everyone. As Anat already mentioned in April we presented at the first AACR virtual meeting the dose escalation data from both the COM701 monotherapy and combination arm with Bristol-Myers Squibb’s nivolumab. This data included all monotherapy dose escalation cohorts which is now completed with four or five cohorts from the dual combination arm.
We were highly encouraged with both safety and tolerability and initial anti-tumor activity with this data that showed disease control rates of 69% or 11 of 16 patients in the monotherapy arm and 75% or 9 out of 12 patients for the combination arm. We, as well as the principal investigator were also encouraged to observe two partial responses. One partial response was from the monotherapy arm in a patient with microsatellite stable platinum-resistant primary peritoneal cancer, a type of ovarian cancer. And the second partial response was from the combination arm in a patient with microsatellite stable colorectal cancer. Both patients presented very encouraging durable responses of more than six months. I’d also like to remind you that both indications, ovarian and colorectal cancer, are included in our COM701 monotherapy expansion cohort and we are eager to evaluate COM701 at the recommended dose for expansion in these tumor types that are generally unresponsive to immune checkpoint inhibition.
I would also like to highlight the durability of responses observed in our ongoing Phase 1 study with COM701. Across all cohorts we reported durable responses of at least stable disease or partial response for over six months in six out of 28 patients or 21% of patients and in two of six patients, 33%, in microsatellite stable colorectal cancer. At the time of the presentation, 50% of patients or six out of 12 in the combination arm remained on study with the number of patients on treatment for over 200 days. Taken together, the preliminary anti-tumor activity and durability of responses potentially serve as proof of concept that inhibition of PDI by COM701 is likely to translate into therapeutic benefit for patients.
Looking at the next steps in this program, we have completed enrollment in a dose escalation combination arm of COM701 with nivolumab and we continue to accrue clinical and laboratory data in these patients. In May, we announced that the first patient was dosed in the COM701 monotherapy cohort expansion. We plan to enroll a total of 20 patients with advanced solid tumors, including advanced non-small cell lung, ovarian, breast, endometrial and colorectal cancer who have exhausted all available standard therapies. The key objective is to evaluate the safety and tolerability of COM701 and the recommended dose for expansion.
Additional exploratory objective is the preliminary evaluation of the anti-tumor activity of COM701 monotherapy at the recommended dose for expansion. A third objective is to conduct retrospective biomarker analysis examining DNAM axis expression in biopsies obtained from patient before and during study treatment to inform on the DNAM axis and possibly to guide patient selection for other trials. We remain on track to complete enrollment in 2020 and report initial data from this trial in the first half of 2021.
Our triple combination study is also advancing to the clinic. We recently announced IND clearance from the FDA for our planned Phase 1/2 open label study, which will evaluate the safety, tolerability and more anti-tumor activity of COM701 in combination with nivolumab and Bristol-Myers Squibb anti-TIGIT antibody. This study will evaluate selected tumor types, namely ovarian cancer, endometrial cancer as well as the biomarker driven arm of tumor types with high expression of PVRL2. This study will dose escalate COM701 with fixed doses of nivolumab and BMS-986207. We remain on track to begin this study in the second half of this year.
Despite the challenges of COVID-19, we also initiated our Phase 1/2 escalation trial of COM902. Enrollment of patients in this study is on track. As of today, we have not observed significant impacts on enrollment of patients in our ongoing COM701 study. Having said that, we continue to remain in close contact with the principal investigators and sites to proactively monitor the situation. For us and the principal investigators, the safety of patients on the study remains our number one priority.
Before turning the call over to Ari, I would like to second Anat’s appreciation of the Compugen team for their strong execution in advancing our clinical study as well as to thank our investigators for their continued support and commitment to our study and of course our patients and their families.
Thank you, Henry. Good morning and good afternoon to everyone. Our financial results for the second quarter of 2020 released this morning continue to reflect a solid financial position with an improved cash balance, a leaner expense structure which gives us the flexibility and the ability to move fast and evaluate the potential of our clinical programs in the various indications and combination.
R&D expenses for the second quarter of 2020 were $4.4 million compared with $4.9 million for the same period in 2019. R&D expenses reflect costs associated with expanded clinical programs, which now include the COM701 monotherapy expansion cohorts, COM701 in combination with Opdivo dose escalation and dose escalation study for COM902.
Net loss for the second quarter of 2020 was $6.2 million or $0.08 per basic and diluted share, compared with a net loss of $6 million or $0.10 per basic and diluted share for the same period of 2019.
As of June 30, 2020, we had approximately $136 million in cash and cash related accounts compared with approximately and $121 million as of March 31st, 2020. The increase in our cash balances of approximately $15 million during the second quarter is attributed to approximately $21 million of net proceeds received from exercise of warrants, exercise of employee options and deposit exercise of underwriters option in connection with our recent public offering offset by our operating expenses and working capital needs.
Going into the second half of 2020, our ongoing R&D expenses are expected to increase slightly as planned compared to the first half of 2020 to support the initiation of our Phase 1/2 triple combination study. Our cash balance at the end of the year is expected to be above $120 million.
Thank you for joining us today and on behalf of the entire Compugen family, we hope you stay safe and healthy. Thank you. And with that, we will now open the call for questions.
Thank you. [Operator Instructions] The first question is from Steven Willey from Stifel. Please go ahead.
Yeah. Good morning everyone. Thanks for taking the questions and congratulations on the progress. Maybe just a couple of questions regarding the triple trial that’s going to initiate later this year. So I know the tumor type selection strategy here is going to be predicated on a PVRL2 biomarker. Can you speak to what you know about the correlation of PVRL2 high tumors and how that correlates to PDL1 expression? And I guess would you expect that the majority of these PVRL2 high tumors are going to be PDL1 low or lower just given that — I suppose that that would allow you to maybe better understand the contribution of COM701 to a backbone of TIGIT, PD-1 in the context of maybe these PVRL2 high tumors mostly being PDL1 low.
So — hi, Steve. So in general, the data that we have and we shared is that there are tumor types that have PVRL2 high that are also PDL1 low and these are mostly the tumors that we selected to focus our studies on, the monotherapy and the triplet as well. But also PVRL2 high is also found on tumor types where there is a PDL1 high. So it’s not that it is only characterizing the PDL1 low, but definitely when we look at the unmet need and where we think that the PVRIG pathway has a role and that’s the first that we want to test is that mostly on indications that are the breast, ovarian, endometrial, colorectal. But we also mentioned non-small cell cancer and obviously there are additional indications where there is a PDL1 high and PVRL2 high.
Okay. And then can you speak to what the starting dose of COM701 is going to be on a fixed background of TIGIT, PD-1? And I guess when you think about biomarker strategy for the triple what are the one or two biomarkers that you think will be the most important in terms of providing a surrogate of on-target PVRIG activity? Thanks.
So I’ll start with the biomarker question and then I’ll let Henry answer the dose of COM701 question. So on the biomarker front, obviously we have our hypothesis that is based on preclinical data and also analysis of human tumor samples that we were conducting. But at the end of the day, we’re still in the exploratory stage. We are going to test, not only PVRL2 by the way. We are looking to — look at different DNAM axis members. We’re also going to look at different and other biomarkers. We want to understand how the tumor microenvironment looks like pre-treatment and on-treatment. So we’re going to collect all these information and look at it. At the end of the day the study that we’re conducting, the triplet study that we’re conducting we do aim to look at PVRL2 high patient populations. But until we will get to this point, which we still need to go through the start the study and go through the dose escalation, we will collect biomarker information and be more educated about the hypothesis that we have.
All right. Thank you very much. Go ahead, Steve.
Oh, no, Henry I was just going to ask you about the starting dose.
Yeah. So the second dose, we haven’t disclosed. But safe to say that the dose we will select will be informed by the dose — will be informed by the dose that we’ve observed on the monotherapy study and also the dual combination dose escalation part of the COM701 study also. And the other things that we’re going to use to determine the starting dose are things that correlates with the PD and the PK of COM701. As the study starts to enroll and starts to generate data, we will be able to disclose the doses that we’ve used, both the starting dose and the dose escalation doses subsequently. But as a reminder, the doses BMS-986207 with TIGIT antibody and the dose of nivolumab are fixed. So they both are for 80 milligrams each and the dose that will be escalating will be the dose of COM701.
Understood. Thanks for taking the questions.
The next question is from Daina Graybosch of SVB Leerink. Please go ahead.
Hi. This is Daina. Thank you so much for the question. Two for me. The first sort of staying on the triplet and the plans for understanding the signal. I think with the triplet and single arm data, one worry I have is how we’re going to untangle the contribution from PVRIG, TIGIT and PD-1. I wonder if you can speak to what would be a really great signal. Do you think we can start to get an efficacy signal for the triplet in this sort of dose escalation and cohort expansion or can you speak to when you might plan to move into randomized trials to get a stronger signal?
So I’ll — Hi, Daina. I’ll start and I’ll let Henry add. I’ll just say that obviously it’s a Phase 1/2 study but we didn’t share the design yet. And this is obviously — it’s hard to answer your question without really being able to answer about to share the design. But this we will share the design after we start the study. Also I’ll say that while your question is completely relevant, I’ll just mention that we are addressing tumor types that are not responsive to PD-1 blockers. And this is — it may make it a little bit easier compared to historical data of these drugs and assess the contribution of COM701. But definitely you are correct. We — in our studies, we’re still at the stage of signal seeking. But in the triplet, obviously, we will need to relate to randomization at a certain point. So this is what I will say.
Henry, would you like to add anything on this?
Yeah, I’d just like to add that — it’s a very good question Daina. One of the things that is going to be helpful for us in determining the contribution of COM701 in the triplet study is the data that we’ve already accrued from the monotherapy study dose escalation and the patients that we’re also enrolling on the expansion cohort with COM701 monotherapy. In addition, the patients that we have on the dose escalation with COM701 nivolumab will also inform on what the relative contribution of COM701 is when added to nivolumab. What to note specifically is that we are fortunate in the sense that so for example for the monotherapy dose expansion cohort that is currently enrolling that we have patients that are very similar to the patients that we will enroll in the triplet dose expansion cohort. So that will inform in a way what the probable relative contribution of COM701 is. But at the end, in summary, I think the — the randomized study is what will actually be able to provide definitive proof of what the contribution of COM701 is.
The other thing to add, Daina, is you asked about what the response is and anti-tumor activity that will help us delineate the contribution — in further contribution of COM701. What Anat has already mentioned in our prepared comments is that the patient population that we are actually enrolling on this study, patients with ovarian cancer, patients with endometrial cancer, patients with high expression of PVRL2, these are patients who have exhausted all available therapies. And therefore, it really will not be too difficult to see when you compare it to historical control what the contribution of COM701 with the other two components are if that’s higher in the triplet compared to either what the patients came in with in terms of responses before they became enrolled on the study or historical data, data from patients who have been exposed to new checkpoints with ovarian cancer or breast — or endometrial cancer, which is typically low digit numbers at 9%, 10% and it was generous, maybe up to about 12%, 15%, if those numbers are higher in the triplet then you know we have a signal. So let’s look at the ways we are looking at it.
Maybe one follow-up on that. So it all makes a lot of sense. But I guess the challenge is we don’t have any data with TIGIT and PVRIG on its own to sort of tease out the relative contribution of those two novel and parallel pathways. And I wonder if you could speak to that.
So — yeah, go ahead, Henry. Go ahead.
Yeah. So it’s correct that we don’t have data, conclusive data that is, of course there are data in small subset of patients who have been enrolled on other studies, but not the study that we’re currently conducting. But Daina what’s important is that if we are looking at the patient population and the DNAM axis as a whole ad we are observing that the responses of the anti-tumor activity that we are observing in that study, the triplet study, is higher compared to what the historical data is that still leaves open the plan to have randomization where not only are we trying to figure out what the contribution of COM701 is, but the randomization will be done in such a way that we are also inclined what the contribution of the TIGIT antibody is. So it’s not just trying to figure out what the contribution of one component is. We’ll have to figure out the relative contributions through a randomized study of the other components also. And that’s the only appropriate way to determine this.
Yeah. That makes sense.
And one more piece of information for this and this — it’s not a direct comparison, but it would allow us to also better understand is our — the study that we are planning to conduct with our TIGIT inhibitor and COM701 as a doublet. And that will also allow us to better understand the relative contribution as compared to PD-1 itself. So there are different combinations here and we will need to make sure that we compare it well, apples to apples and do the right randomizations at the right time.
Great. And then one more question for me sort of on the biology, asking you to speculate and hear your hypothesis. I think we announced these three different triple or four different triple mechanism with TIGIT and PD-1. We see, of course, PVRIG. We see adenosine. We saw recently EMD Serono positive trial combining their TGF beta trap with their own TIGIT and then of course, chemo. And I wonder if you think across all of those mechanisms of triplet why PVRIG stands out to you as the best mechanism to add on top versus the other three.
It’s really based on our analysis as to where these pathways are dominant. And it won’t be relevant for all the patient populations, but in certain patient populations where these three pathways or two of them are dominant. You need to block and to release this negative costimulatory effect. So it doesn’t rule out that in other patients you’ll get some additional response when you combine with additional mechanisms of action. But we think that in tumor types where the two or three of the pathways are there and are signaling negative inhibitory signals you need to block them. So this is our focus.
Helpful. Thank you. That’s all from me. Thank you very much.
The next question is from Mark Breidenbach of Oppenheimer. Please go ahead.
Hey, guys. This is Matt on for Mark. Thanks for the update. Anat or or Henry, just wondering how you’re looking at the Roche’s TIGIT data and whether or not it’s affecting your development plans for 902. Should we expect further emphasis on lung cancers going forward or do you anticipate highlighting the data kind of guide you?
Hi, Matt. I’ll let Henry describe the clinical aspect, but I’ll just say that from our perspective being able to see the TIGIT pathway being clinically validated in a randomized study, yes, one indication. But it’s validated in a randomized study. It gives us more comfort, because as I mentioned in our prepared remarks, when we started this path and when we came up with these hypotheses only the PD-1 pathway was clinically validated. And right now we have some signs for the TIGIT. We have very initial signs for PVRIG. So we get more comfortable with our plan forward and with our strategy for a combination. So it’s just strengthening our belief in the hypothesis.
Our plan for COM remain the same, but I’ll let Henry — Henry would you like to relate it to the clinical front?
Yes. Thank you very much, Matt. The thing to say in addition to what Anat has said is that what we are doing strategically for COM902 is independent of what other competitors are doing. We are doing things with the science guiding essentially all the tumor types that we’re selecting, the combinations that we’re going to be doing and we’ve already disclosed in our corporate deck that for COM902 one of the key things is to look at the PD-1 and the PDL1 free regimen while we are combining COM902 and COM701 in the tumor types that are relevant. So the combination strategy is independent and it’s driven by the science like Anat has mentioned.
That makes sense. And then maybe another question on 902. Could you speak to any differences in the structure of the antibody, specifically between the Roche and Bristol TIGIT antibody? Are there any features that you think might improve on safety or efficacy? Thanks.
Yeah, I’ll let Eran answer this question.
Yes. So basically both antibodies are blockers of the TIGIT-PVR interaction. I would say that the main difference that is highly discussed also is the Fc and the binding to Fc receptors where obviously Genentech has the human IG 1 which bind up the receptors and BMS 7 has a mutated IG 1 which does not bind Fc receptors. And there a lot of debates about this issue whether Fc recoptor binding is important or not. And I think this could be looked at from three aspects. One is that the whole — the most of the motivation to use an antibody that bind Fc receptors or TIGITs mostly came from MURA studies. And actually the Fc receptor system and the MURA system is very different from the human, the composition, the identity of cell types, etc. So to use MURA studies to choose Fc — either type of antibody is a bit challenging and problematic.
The second part, which is highly linked to the first one is that the history taught us that this is — may be a problematic way for CTLA-4 for example in the MURA study, the very strong depletion of Tregs with CTLA-4 and actually ipilimumab does not touch that. And also PDL1 was shown to be more efficient option to acquire Fc receptor binding for its activity in the mouse. And this is not what we see in the clinic from antibodies that bind or the not bind PDL1. So this is for the transitionality from our team and Fc receptor binding.
And lastly, when you have human IG1 antibody like Genentech, while you have maybe the potential to deplete suppressive cells like T reg, you also have the potential to deplete a set of cells that you are — these are the same type of cells that you want to enhance their activity. So we chose to focus on a pure blocker since the — again the expression pattern of TIGIT is overlapping between the Tregs and receptor [Indiscernible] cells. So basically we chose to focus on pure blocker like the PD-1 blockers to enhance activity of T-cells and NK cells without the risk of depleting Treg and also NK [Indiscernible].
Awesome. Congrats on the targets guys.
The next question is from Asthika Goonewardene of SunTrust. Please go ahead.
Hi guys, Asthika from SunTrust here. Thank you for taking my questions. So the pre-clinical data has suggested that PVRIG inhibition induces TIGIT and PD-1 expression. So I’m wondering is there a logic to taking a sequencing strategy when you’re thinking of dosing your triple combination. Then I have a follow-up after that.
Yeah, well, it’s a interesting idea, but I think that this in vitro induction that we see, it will be difficult to translate into a dosing sequences in patients, basically in terms of biology, yes, the PVRIG are [related] to other pathways and this may expand in part the synergies in between all the three pathways, but I think that to link this into kinetics of upregulation in patients will be a bit challenging.
Got it, OK. And then I know COVID had a bit of an overhang in terms of recruitment for all clinical trials, but I’m just wondering, has the presentation at AACR impacted your recruitment rates on your ongoing study?
Yes, Asthika. So we’ve received a lot of inquiries about enrollment into our clinical study since Dr. Ryan Sullivan from Mass General Hospital presented at AACR. Like Anat said in our prepared comments, fortunately for us at this time, we have not been adversely impacted by the COVID pandemic. In fact, we’ve seen a lot of interest, not just by the investigators, but interest from also patient groups also wanting to participate in our clinical trial and hopefully this continues. So we haven’t been adversely impacted by COVID and in fact, we’ve been helped by the presentation that Dr. Ryan Sullivan gave at AACR.
Okay, thanks guys for taking my questions. That’s all from me.
The next question is from Colin White of Jefferies. Please go ahead.
Hello, it’s Colin White from Jefferies here. I just had one question. It was about, yesterday, GSK announced that they’ve moved their Anti-CD96 into clinical development. The first patient has been dosed in a Phase 1 study. So I just wondered if CD96 is obviously, with that target that you looked at, what do you think about that as a target. Like why you may be pursued PVRIG instead or if you think that might be a competitive threat or it might be something that could be used possibly in combination? Thank you.
Yes, thank you. So obviously, we have years of research of this DNAM axis. So, obviously, we’re taking a look or so on the CD96 related.
Yes, so basically CD96 binds PVR like TIGIT and it doesn’t bind PVRL2 like PVRIG. So I would say the pathway is related to PVRIG because of course it’s part of the DNAM axis, but it’s not highly related to PVRIG because it doesn’t bind the same ligand. In addition, the affinity of CD96 to PVR is actually one lobe lower than the affinity TIGIT to PVR. So then comes the question is how dominant is this target compared to TIGIT in terms of binding to PVR and activity.
And finally the biology of CD96 is a bit more complex. I mean, for example, there are some human mouse differences. In the human, there is a intercellular part, which is different from the mouse which actually indicates activator signal — potential activator signal and indeed in our hands, we actually checked and also published, we didn’t see any checkpoint inhibitor activity of CD96 basing blocking antibodies. Genentech recently published a paper in which it actually claimed that CD96 in the human is costimulatory molecule.
On the other hand, indeed the initial mouse studies did point for a inhibitory checkpoint activity of CD96 in the mouse and GSK are pursuing from what we understand from the press release, they are pursuing a blocker antibody. So the biology is may be complex and we need to see more data from GSK why they think differently from Genentech for example who published a costimulatory molecule. And again, even if it is a negative checkpoint, we need to see its dominance since its bind a bit weaker to PVR compared to TIGIT.
That’s great. Thank you very much.
The next question is from Reni Benjamin of JMP Securities. Please go ahead.
Q – Justin Walsh
Hi, this is Justin Walsh on for Reni. Given that the mechanism of action of COM701 the combination approach of course makes a lot of sense to us. Could you provide some color on your reasoning behind choosing to test nivolumab over other PD-1 or PD-L1 inhibitors and then to follow-up with that, if you do see positive results with nivo in either the doublet or the triplet, should we expect that you’d stick with nivo as a combo partner longer-term for COM701 or do you have plans to potentially explore other checkpoint inhibitors?
Yes, thank you. So the selection of nivo over other drugs was not specifically because we think that nivo is a very different PD-1 blocker compared to other PD-1 blockers. So we had our own business reasons and that’s the reason for selection. Obviously, as long as we have the collaboration with BMS, we will work closely with them, continue to work closely with them and use nivo. At the end of the day, we look at it as a proof of concept for the combination with PD-1 blocker and it doesn’t mean that in the future COM701 can’t be combined with a completely different PD-1 blocker. It’s really serving us as a way to prove the hypothesis and obviously to do business with BMS.
Q – Justin Walsh
Perfect, thank you very much. That’s all from me.
The next question is from Tony Butler of Roth Capital. Please go ahead.
Good morning. Thank you. I have three brief questions if I may and I’ll just recite them all at once, if that’s OK. Number one is that COM701, correct me if I’m wrong, but doses once every four weeks and obviously nivo and what you are attempting to do with 902 are every three weeks. Is there any thought as to perhaps creating a change such that it may be easier, certainly for the patient to come in and have dosing for all three, if you will, every three weeks as opposed to one which would be every four. That’s question one.
Number two is obviously Tregs in the tumor microenvironment are not necessarily beneficial. In a TIGIT positive Treg in the tumor microenvironment, you also have upregulation of TIM3. And some companies have moved forward with anti-TIM3 antibodies. I’m just curious of your view of TIM3 in a dominant negative regulatory sense and how that may stick out as a potential impediment, if you will, even under the triple combination scenario.
And then the final question is on PD-1 refractory patients. Do you know or can you hypothesize is PVRL2, does it change — does the expression change from say, potentially a naive tumor that hasn’t seen PD-1 to one that then has seen PD-1, it’s become refractory. One might anticipate that PVRL2 stays the same, alternatively that it diminishes in it’s expression. I’m just curious. I don’t know that data. I’m sure you do. Thank you very much.
So, yes, thank you. I’ll start with your last question about PVRL2 and that we are at the exploratory stage. We will collect data from biopsies pre-treatment on-treatment patients that did got treatment with the PD-1 and were refractory or not. So we will have this information. As of now, we still do not have any such clinical information. So we can’t really refer today. I’ll let Henry address the Q4 weekly question. Henry?
Yes, thank you, Anat. Tony, good question. So if you remember, we already disclosed the data on the PK profile of COM701 at SITC last year and with that data, we disclosed on the PK showed that we can actually dose COM701 at q3 weeks dosing also. And more recently, we disclosed data from Mass General, Dr. Ryan Sullivan’s presentation at AACR that we can also do q4 weekly. The dosing that we have selected for COM902 is based on what the pre-clinical data shows.
During the course of the clinical trial that we are currently undergoing now, we will be able to better define what the PK profile of COM902 is based on the data that we collect from the patients on the study and then that will inform what the eventual dosing paradigm that we’re going to use will be at the recommended dose for expansion of the selected dose. So that’s how we intend to do that. If it’s q3 weeks or q4 weeks, we’re in very good position because we can do either of those in combination with COM701.
Yes, thank you, Anat. Yes.
Yeah, with respect to TIM3 and TIGIT related.
Well TIM3 is obviously another player in the tumor microenvironment. Actually the most dominant expression of TIM3 is probably on maybe more on myeloid target. But in general, one is to look at the dominance of each of the pathway TIM3 and it’s ligands how dominant they are and till now the clinical results well, they are still evolving, but I’m not sure we’ve seen something very convincing to this point and so as TIM3, there are also other players in tumor microenvironment that maybe should be overcoming some tumor settings, but we are already moving into indication which we think that our pathways are dominant and pharmacological intervention in these tumor types will make clinical benefits.
Thank you for your time.
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 statement?
Thank you. We’re very pleased with the progress we’re making across our clinical programs. We have met important milestones so far this year and we anticipate providing multiple data readouts from our ongoing COM701 and COM902 Phase 1 studies in 2021 as I have detailed in my prepared comments.
Our clinical development plan is designed to strategically evaluate the DNAM axis as a potentially transformative checkpoint axis for cancer immunotherapy treatment and we’re uniquely positioned to test this hypothesis and the potential contribution of PVRIG in expanding immuno-oncology treatment options beyond PD-1 blockers.
Our confidence in the validity of our hypothesis, which we first introduced when only PD-1 was clinically validated, has grown in recent months given the preliminary antitumor activity of COM701 treatment we have shown and the clinical validation of TIGIT by others. We look forward to continue updating you on our progress throughout the year. Thank you all for joining us today. Stay safe and healthy.
Thank you. This concludes the Compugen Ltd second quarter 2020 financial results conference call. Thank you for your participation. You may go ahead and disconnect.