Compugen Ltd. (CGEN) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's Second Quarter 2023 Results Conference Call. [Operator Instructions]. As a reminder, today's call is being recorded. An audio webcast of this call will be made available on the Investors section of Compugen's website, www.cgen.com. I would now like to introduce Yvonne Naughton. Head of Investor Relations and Corporate Communications. Yvonne, please go ahead.

Thank you, operator, and thank you all for joining us on the call today. Joining me for Compugen for the prepared remarks are Dr. Anat Cohen-Dayag President and Chief Executive Officer; and Alberto Sessa, Chief Financial Officer; Dr. Henry Adewoye, Chief Medical Officer; and Dr. Eran Ophir, Chief Scientific Officer, will join us for the Q&A. Before we begin, we would like to remind you that during this call, the company may make projections or forward-looking statements regarding future events, business outlook, research and development efforts and our potential outcome, the capabilities of the company's discovery platform anticipated progress and plans, results and time lines for its programs, financial and accounting-related matters, including projected financial information as well as statements regarding the company's future cash position and other results and the company's future initiatives. We wish to caution you that such statements reflect only the company's current beliefs, expectations and assumptions, but actual results, performance or achievements of the company may differ materially. These statements are subject to known and unknown risks and uncertainties which could cause the company's actual results to differ materially from those projected in such forward-looking statements, and we refer you to the SEC filings for more details on these risks, including the company's most recent annual report on Form 20-F filed with the SEC on February 28, 2023. The company undertakes no obligation to update projections and forward-looking statements in the future. And now I'll turn the call over to Anat.

Thank you, Yvonne. Good morning, and good afternoon, everyone, and welcome to our second quarter 2023 update. At Compugen, our goal is to transform the treatment of cancer patients who have no effective treatment options by discovering novel drug targets and developing potential first-in-class drugs, on this front, we were efficiently executing on our differentiated clinical approach to evaluate the benefit of our chemotherapy-free triple cancer immunotherapy combination of COM701, COM902 and pembrolizumab blocking 3 pathways of the DNAM axis, PVRIG, TIGIT and PD-1. At ASCO this year, we were excited to see the positive momentum and interest of the industry and the scientific community in targeting the DNAM-1 axis as a potential novel approach in treating cancer reflected by our own data and data presented by others. Including AstraZeneca, Roche and Arcus Gilead. Looking at the totality of the data we have presented to date in hard-to-treat cancer patients there was enthusiasm among those we spoke with regarding responses demonstrated with our triple combination approach in patients with microsatellite stable endometrial cancer, who had failed standard of care, including prior pembro and lenvatinib treatment. For these patients, there were no other treatment options. In 9 patients, we showed an overall response rate of 22% and a disease control rate of 44%. The responses were durable and supported by immune activation better than what one would expect for an anti-PD-1 alone. This endometrial data is consistent with the antitumor activity we reported for COM701 based combinations in patients with other hard-to-treat tumors, including microsatellite stable colorectal cancer, platinum-resistant ovarian cancer and checkpoint inhibitor experienced non-small cell lung cancer patients. Reflecting on the totality of the data to date, in patients typically not responsive to standard of care, including immunotherapy. Our data suggests that our COM701 based combination have the potential to offer a treatment option with a favorable safety profile for hard-to-treat patients across the spectrum of PD-L1 expression levels in patients who are anti-PD-1 treatment refractory pointing to a potential COM701 mediated mechanism of action. Our immediate focus is on expanding our data in two indications, platinum-resistant ovarian cancer and MSS Colorectal Cancer, while continuing to invest in biomarker discovery which is important in efficiently setting our development path forward. However, we believe that the therapeutic potential of COM701 as part of the DNAM-1 axis may be much broader than these two indications. As mentioned earlier, AstraZeneca presented clinical results at ASCO on rilvegostomig, a PD-1 TIGIT bispecific antibody derived from our COM902, establishing its safety and pharmacokinetic profile and showing anti-tumor activity in patients previously exposed to checkpoint inhibitors and usually not responsive to immunotherapy. AstraZeneca continues to advance in rilvegostomig development in multiple studies, including a Phase II trial in checkpoint Inhibitor or naive non-small cell and cancer patients in a Phase II trial in hepatobiliary cancer and previously announced plans to initiate a Phase III trial this year. We know that not all anti-PD are designed the same. And like COM902, which is an anti-PD with reduced effect of function rilvegostomig to make was engineered to have an inactive Fc domain to enhance anti-tumor activity. Another program in this Fc inactive or reduced effector function can in Arcus anti-TIGIT. At ASCO, Arcus Gilead showed continued improvement in progression-free survivor, first is blocking PD-1 alone with a potentially better safety profile to what has been shown to date with Fc active anti-TIGIT. Another session that gained great interest at ASCO with Roche's anti-TIGIT liver cancer data. This is the third randomized trial showing the benefit of having an anti-TIGIT to standard of care. Blocking TIGIT restarted in a 4x greater overall response rate and a doubling the progression-free survival, on top of standard of care. And Roche has initiated a Phase III trial in first-line hepatocellular cancer based on these results. We were pleased that the discussions of Roche presentation highlighted the potential significance of adding PVRIG blockade in hepatocellular cancer. This is another hard-to-treat indication which may serve as a fit for COM701 treatment. The important role of PVRIG was also called out in another ASCO session on novel approaches to checkpoint inhibitors. In which the presenter was intrigued by our data presented by Dr. Mike Overman from MD Anderson at SITC, last year, showing that blocking PVRIG in combination with PD-1 led to responses in unexpected diseases like microsatellite stable colorectal cancer. It is great to see an increased awareness of PVRIG role in cancer immunotherapy. It is important to highlight Compugen's differentiated approach and how we stand out among all the players. Firstly, we have always said that blocking TIGIT may not be enough and that PVRIG may be needed. Our discovery of PVRIG and the extensive research we have conducted to test the effect of unlocking its biological function as a new drug target in the context of the DNAM axis support the need to block it. This diseases is consistently being reinforced as we roll out our clinical data across multiple indications. Secondly, we believe we have a potentially best-in-class reduced Fc effector function anti-TIGIT. The data available today suggest that Fc design of the TIGIT antibody may either not matter or it may be better to have a reduced or inactive Fc domain as we have. And finally, with COM701 and COM902, our 2 highly owned PVRIG and TIGIT programs were the leader in the unique chemotherapy-free triple combination approach of blocking 3 DNAM axis immune checkpoint, PVRIG, TIGIT and PD-1 with initial clinical data to support our hypothesis. Along with a very successful ASCO, I would like to refer to additional progress we have made in the first half of the year. We're advancing patient enrollment in our 2 follow-on proof-of-concept studies. Enrollment in the MSS-CRC study is on track to be completed by the end of the year. Enrollment is lower than planned in the platinum-resistant ovarian cancer study but we believe we can catch up on enrollment with a planned activation of additional sites. As a reminder, the goal of these studies is to obtain more data help us better understand the contribution of components and build on extensive biomarker work to identify the patients most likely to respond. We believe that this strategy provides the fastest way to efficiently set our development path forward and to potentially de-risk our lead assets, COM701 and COM902 in these 2 indications. In May of this year, we presented data on our potential first-in-class anti IL-18 binding protein antibody COM503 and the CIMT conference, Europe's Annual Immunology Conference. We believe there is excitement around our innovative approach, leading to the development of this COM503 program and its contention in addressing immunotherapy replacement. Finally, on the progress in the first half of 2023, we were delighted with the favorable ruling of the European patent office to uphold the broad claims in our PVRIG patent. This ruling of the European patent office is the win for our innovation, the discovery of PVRIG role as a novel immune checkpoint and a drug target for cancer. As a company that excels in the discovery of new drug targets, we have a broad patent strategy that takes advantage of our novel target discovery capability. Now moving on to what you should expect to see from us over the second half of the year. Third, we plan to report initial findings from our ongoing proof-of-concept studies by the end of the year and final data at a medical conference in 2024. Second, we're expecting to present new translational and initial biomarker data and long-term patient follow-up from our platinum-resistant ovarian cancer study presented at ESMO-IO, last year as well as additional data from our COM503 clinical program, all by the end of the year. We also plan to present new data from the metastatic breast cancer study of 17 patients treated with COM701 and nivolumab. Patients were enrolled into this cohort regardless of their ER, PR and HER2 status. These patients were heavily pretreated and had exhausted all available standard treatments which could include immune checkpoint inhibitors and ADC. Before handing over to Alberto, I will touch briefly on our finances and then Alberto will go into the details. We have an expected cash run rate through at least the end of 2024, which we believe is sufficient to support all planned operations and reach milestones to potentially de-risk our lead assets, COM701 and COM902. In terms of future funding, non-dilutive funding of our pipeline assets is our priority. On this front, it is worth noting that the trend in immunotherapy is to combine and treat earlier, and we believe, the profile of lead assets, COM701 and COM902 make them ideal combination candidates to be used in earlier treatment settings. Additionally, there is increasing excitement around the potential of IL-18 pathway modulation in immuno-oncology. And with COM503, we're happy that we have a differentiated approach to potentially harness this cytokine biology for optimal use in treating cancer. Finally, through our partnership with AstraZeneca we may become eligible for future milestone payments. And with that, I will hand over to Alberto for the financial update.

Thank you, Anat. I'm happy now to summarize our financial results. I will start with our cash balance. As of June 30, 2023, cash, cash equivalents and cash investments were approximately $66.5 million compared with approximately $83.7 million as of December 31, 2022 affirming our focus on capital efficiency while continuing our execution on our DNAM-1 axis hypothesis. The company has no debt. We recognize the importance of cash efficiency, and we are disciplined in how we deploy our cash services, ensuring we will focus on reaching came license with our available cash runway through at least the end of 2024. Expenses for the second quarter of 2023 were in line with our plans. R&D expenses for the second quarter of 2023 were $7.8 million, up from $6.8 million in the second quarter 2022. The increase is mainly due to the end of the amortization of deferred participation in R&D expenses on March 31, 2023. And an increase in freight clinical and CMC activities associated with plant COM503 activities, offset by a decrease in clinical trial expenses, head count and currency exchange effects. Our G&A expenses for the second quarter 2023 were $2.4 million compared to $2.6 million in the second quarter of 2022. For the second quarter of 2023, net loss was $9.3 million or $0.11 per basic and diluted share compared to a net loss of $9.1 million or $0.11 per basic and diluted share in the second quarter of 2022. With that, I will hand back to Anat to summarize.

Thank you, Alberto. To summarize, we continue to execute and deliver on our goals. With our most recent data in microsatellite stable endometrial cancer, we continue to provide evidence supporting the potential COM701 mediated clinical benefit in hard-to-treat patients who are not responding to standard of care and failed prior IO therapy. We're looking forward to presenting new translational and initial biomarker data and long-term patient follow-up from COM701 combination in ovarian cancer. First data in metastatic breast cancer as well as additional data from our COM503 preclinical program, all by the end of the year. We also plan to share initial findings from our two ongoing studies in microsatellite stable colorectal cancer and platinum-resistant ovarian cancer evaluating our leading triple combination blockade of PVRIG, TIGIT and PD-1 with COM701, COM902 and pembrolizumab by the end of the year. The opportunity we have to positively impact the lives of so many motivates every single employee within Compugen every day. With that and we turn the call over for questions. Operator?

Thank you. Ladies and gentlemen, at this time, we will begin the question-and-answer session. [Operator Instructions] The first question is from Stephen Willey of Stifel.

I guess just with respect to the Phase II platinum-resistant ovarian cancer study, you talked about enrollment, I guess, going a little bit slower than expected. Are you, is that just a function of the kinetics of site activation? Or do you now need to bring more sites than originally planned online in order to meet the target enrollment goal, which I believe was about 50% before the end of this year?

And Henry, would you like to address this question?

Yes, Anat ,Thank you very much, So first, let me say that there is a strong interest by the sites and investigators to participate on this study. There's a strong belief in the hypotheses in DNAM-1 axis with a triple combination of pembrolizumab, COM701 and COM902. At least based on the results we previously disclosed with the triplet that consisted of COM701, the BMS antibody, nivolumab, 20% response rate as we presented at ESMO IO. What we've observed is that there is a delay as a result of restricted resources at the sites, resources meaning personnel, mainly change in timing of IRB and FX coming to review cycles -- and a few competing studies in the platform resistant ovarian population also, we are in close contact to the sites and several additional sites are being considered who are more likely to recruit platform-resistant ovarian cancer patients, and they are very pleased to open now, which should get us back on track.

Okay. And I guess when you think about the year-end update, is there some threshold number of patients, specifically in ovarian that you want to have enrolled before you try to communicate something incremental?

So maybe I'll take this one. So in general, we're still guiding to the same guidance that we shared that we hope to enroll upto 20 patients by the end of the year. And that's when Henry saying that we believe we can catch up that what we mean. So we cannot, at this point in time, estimate any deviation from the guidance. But obviously, if there will be any, obviously, will we'll share that, and we believe that we will be able to share data as planned by the end of the year. I just want to remind that in any case, we indicated that for the 2 studies, this will be initial data from the study. And that as we enroll additional patients in the ovarian study in 2024, we'll share the full data disclosure.

Okay. And then maybe just lastly, I guess, you talked about having, I guess, these 2 data sets to present at a medical conference in '24. And -- just kind of wondering internally, is the goal at this point to be able to make some kind of registrational go-forward decision before the end of 2024 on the basis of these 2 studies? I'm just trying to think about what's kind of the next step here once we get the proof-of-concept data?

Yes. So maybe I'll start and here Henry, if you would like to add to chime in. But basically, the goal of the studies from the get-go for these 2 studies was to add more data to the data that we already have in these 2 indications, which seems promising to us and to assess some of the contribution of components and to build a path towards building a study that will take us to eventually to build a registration path. So that's the goal, yes. And we need to see as we go. With the studies or is the data, how it looks and as we said, previously, it's more than the over response rate. It is the additional products that were evaluating the durability, the safety profile, et cetera, this will allow us to gain the understanding of how we move forward. Henry, anything to add on this front?

No. Thank you, Anat. You've covered it all.

Okay. The next question is from Asthika Goonewardene of Truist Securities. Please go ahead.

I want to build on the question that Stephen asked here. So the update that we're getting for entire resistant ovarian cancer by year-end. I know the expectation is that initial data -- Can you just clarify what kind of efficacy at will we see in that presentation? And is it still right to assume that this is going to be fine more as an investor update and not a medical meeting update for the presentation of this year?

It will be an investor update and not a medical conference update from the 2 new proof-of-concept studies that we do. Yes. We tend to present data in medical conferences from studies that are that are more completed where we have more sites yes.

And then there's a question about what efficacy data will be in this to update? Just want to try and see that if you can -- is there going to be confirmed scan or is it just a proliferate can or should we reset different expectations?

Henry, would you like to address this?

Yes, Anat, thank you. The earliest readout one can get -- for this patient population will be response rates. We obviously will be interested also in looking at other important clinical endpoints, such as duration of response or possibly progression-free survival. Now that being said, this will depend on enrollment and our ability to catch up, like we think we will be able to -- we project we'll be able to do, but those are the key endpoints, the most important being response rates.

Got it. And then on the issue with the -- with the delays, I certainly appreciate that there's some personal restrictions and [ constraints ] to IRB are happening. I'm just wondering, is there any impact of the ADC launch in platinum-resistant ovarian cancer is also maybe causing any delays here? And then related to that, have you seen any delays in recruitment for the colorectal study?

Henry?

Thank you, Asthika. In speaking with the investigators and all the sites that we have, we haven't observed or we haven't reported back to us that the ADCs have contributed meaningfully to the delays that would just highlighted as you recall, Asthika, the ADC that we're talking about here is mirvetuximab, which is actually -- which has acted approval in platform resistant ovarian cancer. That has not been the communication received back. And that accelerated approval is also in a restricted biomarker-limited population folate receptor alpha positive patient population. So that has not been a part all of the reason for the minimal delay that we've disclosed.

Got it. And so -- and also just want to double check, That's been known delays on the colorectal side, right? And obviously, there's no competing products there, but is that recruiting well as well [indiscernible]?

The fact that we have reputing well with colorectal cancer. As you know, the patient population with microsatellite stable colorectal cancer is very underserved one. There are lots of patients, unfortunately, that are need of newer therapies for microsatellite stable colorectal cancer. And we haven't experienced that much of a significant delay with that population.

The next question is from Daina Graybosch of Leerink Partners.

This is Jeff LaRosa on for Daina. I guess the first is, what do you hope to show the breast cancer update that will be supportive of your plans and strategy in ovarian cancer and MSS-CRC? And for the initial -- I mean, the updated translational initial biomarker data in block with Bristol's TIGIT. How comparable is the status set to your own study with your TIGIT? Any differences there you could point to? And regarding the ASCO data, in HCC. Was that a tumor type that you sort of predicted would be amenable to PVRIG blockade? And what's your interest in that indication?

So Henry, you start, Henry you start with the breast and then Eran will take the biomarker and HCC expression.

Yes. Thank you for the question. With regards to breast cancer data, all I can see at this point is that the patient population that we've enrolled patient population that's heterogenous with respect to whether the ER, PR positive or ER, PR negative or HER2 is negative -- this is a patient population that has exhausted all available standard of care therapies, including therapies that are approved, such as [indiscernible]. Now the important thing that we're looking for in this patient population is to see a signal of anti-tumor activity, and that will confirm to us that there is activity with the combination that we are pursuing with COM701 plus nivolumab. So that's what would be of interest to us, especially in these hard-to-treat patient population that have possibly received several lines of therapy.

Yes. Then for the questions about the biomarker. So yes, we anticipate that the same biomarkers that would inform that we learn from -- in the study of using the BMS TIGIT should be relevant also for the other studies that we are doing, both BMS TIGIT and our own COM902 are Fc inactive. And in general, this -- that was a study of blocking triple blockade of TIGIT, PD-1 and PVRIG. So biologically, it should be very similar to the study that we are currently conducting -- and if you will identify some new translational or potential predictive biomarkers in that study, we definitely think it could be and should be relevant also to the follow-up study that we are currently doing. Now about the HCC -- so we identified ovarian endometrial as one of the top indications with dominance of the pathway, and that's why we went to these indications also breast. But HCC is definitely one of the top expressed of the pathway. We couldn't start with all of them and PVRL2, is quite broadly expressed in many indications. So HCC is definitely in an indication in which the pathway is dominant and it's a target indication that we definitely see a potential in.

And just in terms of the -- whether we're going to test the indication to your specific question, I think that it is being shown by now that the PVRIG blockade potential, the COM701 therapeutic potential is much broader than the 2 indications that we're focusing right now. We took to focus on these 2 indications where we have data and where we believe that additional data that we will expand with the studies may allow us to better design the path forward. But I want to stress that again and again. The potential of COM701 is much beyond these 2 indications and it include endometrial cancer and non small cell lung cancer and MCP. And as we said, would present data and breast towards the end of the year. That's very encouraging to us.

I think one of the other questions you asked was if there was any substantial difference between the triplets that we're currently exploring in the ovarian cancer space which is the triple I'm referring to now is COM902 plus COM701 nivolumab versus the earlier triplet, which is the triplet with the BMS TIGIT antibody BMS-986207 and nivolumab. We did -- if you -- as a reminder, we did have a press release where when we enrolled the first patient in to the current triplet of COM902-COM701 nivolumab. And as part of what one of the, what we said was that we did not -- this is one of the investigators on that study. The initial observation is that this combination, which is the pembrolizumab continuing triplet of COM902 COM701 and Pembro is very well tolerated as observed, at least in the patient population of microsatellite stable colorectal cancer in the initial study that we enrolled. So there are no differences observed so far. And this is earlier on as we enrolled colorectal patients microsatellite cancer patients. We do not expect there to be any substantial differences in terms of safety and tolerability. I hope that answers your question.

It does.

The next question is from Tony Butler of EF Hutton.

I would like to go back to this notion of PVRL2 dominance at least over PVRIG, which seems to be a recurring theme in some of the cohorts in which you're attempting to move forward with the triple combination and in particular, of course, 701. And that's back to ASCO, where you had some really good data in endometrial cancer. The cutoff as I recall, was in April, the 2 responses and then 2 patients who had stable disease? And I wondered if there was any additional information on follow-up that is where patients actually able to show an additional reduction consumer size of those responses and/or those patients who had stable disease? Thank you.

Eran, would you like to address the PVRL2 portion?

So the PVRL2 portion, I think that is not only PVRL2. I mean, in general, it's the PVRIG pathway dominant PVRL2 an important part of it. And this is, again, a measure that we looked at in both endometrial, which have a dominant and also another indication. As mentioned before.

Henry anything you want to add?

Nothing more to add to what Eran mentioned.

But anything more on the patients for additional follow-up that were presented at that time?

So we -- so we are going to present a follow-up data on these patients. Remember that when we shared the data in December at ESMO-IO, December '22, we had patients that were still on study treatment responsive patients and some of them had durability of more than 9 months, we are going to present data by year-end a follow-up date for these patients. So I guess that you'll have answers to some of your questions then.

And that I just want to be sure that will include the endometrial patients? That's what I'm focusing on.

No. It will relate to the ovarian. Sorry, I misheard your question it will relate to the ovarian. No, we didn't plan yet to have any follow-up on the ovarian on the endometrial cancer patients.

Okay.

This concludes the Q&A session in Compugen's Investor Conference Call. Thank you for your participation. You may go ahead and disconnect.