Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's Q2 2023 Results Conference Call. At this time, all participants are in a listen-only mode. 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, 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 their potential outcome, the capabilities of the company's discovery platform, anticipated progress and plans, results and timelines 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. 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. Now I'll turn the call over to Anat.
Thank you, Yvonne. Good morning and good afternoon, everyone, welcome to our Q2 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 three 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 how 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 nine 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 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 combinations 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-...
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 antitumor activity in patients previously exposed to checkpoint inhibitors and usually not responsive to immunotherapy. AstraZeneca continues to advance rilvegostomig development in multiple studies, including a phase II trial in checkpoint inhibitor, naive non-small cell cancer patients, and 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-TIGIT are designed the same, and like COM902, which is an anti-TIGIT with reduced Fc effector function, rilvegostomig was engineered to have an inactive Fc domain to enhance antitumor activity. Another program in this Fc inactive or reduced effector function camp is Arcus anti-TIGIT.
At ASCO, Arcus/Gilead showed continued improvement in progression-free survival versus 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 was Roche TIGIT liver cancer data. This is the third randomized trial showing the benefit of adding an anti-TIGIT to standard of care. Blocking TIGIT resulted in a four times greater overall response rate and a doubling the progression-free survival on top of standard of care. Roche has initiated a phase three trial in first-line hepatocellular cancer based on these results. We were pleased that the discussant 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, supports the need to block it.
This belief 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 suggests 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. Finally, with COM701 and COM902, our two wholly owned PVRIG and TIGIT programs, we're the leader in the unique chemotherapy-free triple combination approach of blocking three DNAM axis immune checkpoints, 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 two follow-on proof of concept studies.
Enrollment in the NSCLC study is on track to be completed by the end of the year. Enrollment is slower than planned in the platinum-resistant ovarian cancer study, but we believe we can catch up on enrollment with the 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 Compugen, and build on extensive biomarker work to identify the patients most likely to respond. We believe that this strategy provides the fastest way to reset our development path forward and to potentially de-risk our lead assets, COM701 and COM902, in these two indications. In May of this year, we presented data on our potential first-in-class anti-IL-18 binding protein antibody, COM503, at 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 potential in addressing immunotherapy resistance. 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 a win for our innovation, the discovery of PVRIG's 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 harness the 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.
First, 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 studies, presented at ESMO IO last year, as well as additional data from our COM503 preclinical 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 ADCs.
Before handing over to Alberto, I will touch briefly on our finances, then Alberto will go into the details. We have an expected cash runway 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, we believe the profile of our 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.
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. 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 dollar 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 resources, ensuring we will focus on reaching key milestones with our available cash runway through at least the end of 2024. Expenses for the Q2 of 2023 were in line with our plans.
R&D expenses for the Q2 of 2023 were $7.8 million, up from $6.8 million in the Q2 of 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 preclinical and CMC activities associated with planned COM503 activities, offsets by a decrease in clinical trial expenses, head count, and currency exchange effects. Our G&A expenses for the Q2 of 2023 were $2.4 billion compared to $2.6 million in the Q2 of 2022.
For the Q2 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 Q2 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 a 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, I will turn the call over for questions. Operator?
Thank you. Ladies and gentlemen, at this time, we will begin the question and answer session. If you have a question, please press star one. If you wish to decline from the polling process, please press star two. If you are using speaker equipment, kindly lift the handset before pressing the numbers. Please stand by while we poll for your questions. The first question is from Stephen Willey of Stifel. Please go ahead.
Hey, good morning. Thanks for taking the questions. I guess, just with respect to the phase two platinum-resistant ovarian cancer study, you talked about enrollment, I guess, going a little bit slower than expected. 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?
Henry, Steve, hi. Henry, would you like to address this question?
Yes, Anat. Thank you very much, Stephen. First, let me say that there's a strong interest by the sites and investigators to participate on this study. There's a strong belief in the hypothesis in inhibiting the DNAM-1 axis with the triple combination of pembrolizumab, COM701 and COM902, and it's based on the results we previously disclosed with the triplet that consisted of COM902-- COM701, the BMS antibody and 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, changing timing of IRB and ethics committee review cycles, and a few competing studies, in the platinum-resistant ovarian population also. We are in close contact with the sites, and several additional sites are being considered, who are more likely to recruit platinum-resistant ovarian cancer patients, and they're very close to opening now, which should get us back on track.
Okay. 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?
Maybe I'll, I'll take this one. In general, we're still guiding to the same guidance that we shared, that we hope to enroll up to 20 patients by the end of the year. That's when Henry is saying that we believe we can catch up, that, is that what we mean? We, we cannot, at this point in time, estimate any deviation from the guidance. Obviously, if there will be any, obviously, we'll, we'll share that, and we believe that we'll be able to share data as planned by the end of the year.
I just want to remind that in, in any case, we indicated that for the two 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. Then maybe just lastly, I guess, you talked about having, I guess, these two data sets to present at a medical conference in 2024. Just kind of wondering, internally, is, is, 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 two studies? I'm just trying to think about what's kind of the next step here once we get the proof of concept data. Thanks.
Yeah. Maybe I'll start, and Henry, if you, if you would like to add, please chime in. Basically, the goal of the study from the get-go for these two studies was to add more data to the data that we already have in these two 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, to build a registration path. That's the goal, yes. And we need to, we need to see as we go with these studies, what is the data, how it looks like, and as we said, previously, it's more than the overall response rate.
It is the additional parameters that we're evaluating, the durability, the safety profile, et cetera, that will allow us to, to gain the understanding how we move forward. Henry, anything to add on this front?
No, thank you, Anat. You've covered it all.
Okay, thanks.
The next question is from Asthika Goonewardene of Truist Securities. Please go ahead.
Hey, guys. Good morning. Thanks for taking my questions. I'm gonna build on the questions that Stephen asked here. For the updates that we're getting for platinum-resistant ovarian cancer by year-end, I know the expectation is the initial data. Can you just clarify what kind of efficacy data will we see in that presentation? Is it still right to assume that this is gonna be kind of more as a, as an investor update and not a medical meeting update for the presentation update this year?
It will be an investor update and not a medical conference update from the two new proof of concept studies that we do. Yes. We, we tend to present data in medical conferences from studies that are that are more completed, where we have more insights. Yes.
Okay. Then, the question about what efficacy data will be in these two updates? Just wanted to try and tease out if you can, if there's gonna be confirmed scans, or if it's just preliminary scans, or should we set different expectations?
Henry, would you like to, to address this?
Oh, yes, Anat, thank you. The earliest readouts one can get for this patient population will be response rates. We also obviously will be interested also in looking at other important clinical endpoints, such as duration of response or possibly progression-free survival. Now, all 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. Those are the key endpoints, the most important being response rates.
Got it. On, on the issue with the, with, with the delays, I totally appreciate that there's some personal restrictions and there's some changes to IRB etc., happening. I'm just wondering, is there any impact of, the ADC launch in platinum-resistant ovarian cancer that is also, maybe causing any delays here? Related to that, have you seen any delays in recruitments 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 they haven't reported back to us that the ADCs have contributed meaningfully to the delay that was just highlighted. As you recall, Asthika, the ADC that we're talking about here is mirvetuximab, which has accelerated approval in platinum-resistant ovarian cancer. That has not been the communication we've received back. And that accelerated approval is also in a restricted, biomarker, limited population, folate receptor alpha-positive patient population. That has not been a part of the reason for the minimal delay that we've disclosed.
Got it. And so... And, and, and just also just wanted to double check, there's been no delays on the colorectal side, right? Obviously, there's no competing products there, but, is that recruiting well as well, guys?
The, the sites that we have are recruiting well with colorectal cancer. As you know, the patient population, with microsatellite-stable colorectal cancer is a very underserved one. There are lots of patients, unfortunately, that are in need of newer therapies for microsatellite-stable colorectal cancer. We haven't experienced that much of a significant delay with that population.
Hi, this is Jeff LaRosa for Dana. Thanks for taking our question. I guess the first is, what do you hope to show the breast cancer update, that'll be supportive of your plans and strategy in ovarian cancer and MSS CRC? For the initial, I mean, the updated translational initial biomarker data, in proc with Bristol's TIGIT, how comparable is this data set to your own study with your TIGIT? Any differences there you could point to? You know, regarding the ASCO data in HCC, was that a tumor type, that you sort of predicted would be, amenable to PVRIG blockade? What's your interest in that indication? Thank you.
Henry.
We thought that the patient population that we've enrolled, a patient population that's heterogeneous, with respect to whether they're ERPR positive or ERPR negative or HER2 negative. This is a patient population that has exhausted all available standard of care therapies, including therapies that are approved, such as, Trodelvy. Now, anti-tumor activity, and that will confirm, to us that there is activity, with the combination, that we're pursuing with COM701 plus nivolumab. 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. For the questions about the biomarkers. Yes, we anticipate that the same biomarkers that would inform or that we learn from in the study of the using the BMS TIGIT, should be relevant also for the other studies that we are doing. Both BMS TIGIT and our own COM902 are, are, are Fc active, and in general, that was a study of blocking triple blockade of TIGIT, PD-1 and PVRIG. Biologically, it should be very similar to the study that we are currently conducting. If you, if you will identify some a 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're currently doing. About the HCC.
you know, we identified ovarian endometrial as one of the top indications with dominance of the pathway, and that's why we went to this, to this indication, also breast. HCC is definitely one of the top expressors of the pathway. you know, we couldn't start with all of them, and PVRL2 is quite broadly expressed in many indications. HCC is definitely an indication in which the pathway is dominant, and it's a target indication that we definitely see a potential in.
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 two indications that we're focusing right now. We've took to focus on these two indications where we have data and where we believe that additional data that we will expand with these studies, may allow us to better design the path forward. But I want to stress that again and again, the therapeutic potential of COM701 is much beyond these two indications, and it includes endometrial cancer and non-small cell lung cancer and HCC. As we said, we'll present data in breast towards the end of the year. That's very encouraging to us.
Yeah. I, I, I think one of the other questions you asked was if there was any substantive difference between the triplets that we're currently exploring in the ovarian cancer space, which is the triplet I'm referring to now is COM902 plus COM701 plus pembrolizumab, 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 into the current triplet of COM902, COM701, and pembrolizumab. 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-containing triplet of COM902, COM701, and pembro, is very well tolerated as observed, at least in the patient population with microsatellite colorectal cancer in the initial study that we enrolled. So there are no differences observed so far. This is earlier on as we enrolled colorectal patients, microsatellite colorectal cancer patients. We do not expect there to be any substantive differences in terms of safety and tolerability. I hope that answers your question.
It does. Thank you all. Appreciate it.
The next question is from Tony Butler of EF Hutton. Please go ahead.
Good morning. I would like to go back to this notion of PVRL2 dominance, at least over PVR, 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, COM701. That's back to ASCO, where you had some really good data in endometrial cancer. The cutoff, as I recall, was in April. The two responses, and then two patients who had stable disease. I wondered if there was any additional information on follow-up. That is, were patients actually able to show an additional reduction in tumor size of those responses and, or of those patients who had stable disease? Thank you.
Eran, would you like to address the PVRL2 portion?
Sure. The PVRL2 portion, I think that it's not only PVRL2. I mean, in general, it's the PVRIG pathway dominance. PVRL2 obviously is important part of it, and this is again, a measure that we looked at in both endometrial, which have a dominance and also another indication, as mentioned before.
Henry, anything, more 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?
We, so we are going to present, follow-up data on these patients. Remember that when we shared the data in December, at ESMO, December 2022, we had patients that were still on study treatment, responsive patients, and some of them had durability of more than nine months. We are going to present data, by year-end, a follow-up data for these patients. I guess that you'll have answers to some of your questions then.
I just want to be sure that'll include the endometrial patients. That's what I'm focusing on.
Oh, no, it will relate to the, to the ovarian. Sorry, I, I misheard your question. It will relate to the ovarian. No, we didn't plan yet to have any follow-up on the ovarian cancer, on the endometrial cancer patients.
Okay. Thank you.
This concludes the Q&A session in Compugen's Investor Conference Call. Thank you for your participation. You may go ahead and disconnect.