Compugen Ltd Q1 FY2024 Earnings Call

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's First Quarter 2024 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 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 from Compugen for the prepared remarks are Dr. Anat Cohen-Dayag, President and Chief Executive Officer; and Alberto Sessa, Chief Financial Officer. Dr. Michelle Mahler, 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 of forward-looking statements regarding future events, business outlook, development efforts and their potential outcome, the company's discovery platform, anticipated progress and plans, results and timelines 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 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 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. The company undertakes no obligation to update projections and forward-looking statements in the future. With that, I now turn the call over to Anat.

Thank you, Yvonne, and thank you everyone for joining us on our first quarter 2024 call. Today, I will cover the significant progress we have made across our pipeline in the first quarter of this year, and I will then move to our planned catalysts through the rest of 2024. But before I go there, I thought I would start on a question which we frequently get asked, is Compugen an AI company? And the answer is yes. Compugen is a pioneer in the computational discovery of novel drug targets, and not just in theory, but in practice, which is a significant differentiator. We successfully moved our newly discovered drug targets from computer prediction to drug discovery to preclinical and clinical trials, continuously feeding our own pipeline with potential significant opportunities to address cancer immunotherapy resistance. The Gilead deal on COM503 highlights the most recent asset discovered through our computational discovery capability. Our discovery platform is a validated AI/ML powered platform. This platform is the engine fueling our competitive advantage and pipeline and has already delivered multiple fully-owned clinical programs, multiple validating strategic partnerships, and multiple early-stage undisclosed assets, which are expected to feed our future pipeline and opportunity to deliver long-term value creation. We plan to speak more on our discovery platform at future events. So now I will move to the focus of today's call. In the first quarter of the year, we again executed on our promises. Firstly, at the annual ASCO conference in June, we will present preliminary anti-tumor activities of COM701 in combination with COM902 and pembrolizumab in patients with MSS-CRC and liver metastasis from our ongoing proof of concept study. Secondly, we completed enrollment of more than 20 patients in our platinum-resistant ovarian cancer study, and we're on track to report initial findings in the fourth quarter of this year. Thirdly, the progress we have made unlocking novel biology of new drug targets and in diversifying our approach to address cancer immunotherapy resistance was reflected by our presentations at the Keystone Symposium and the American Association of Cancer Research Conference in March and April this year, along with the publication of our COM503 and PVRIG papers in cancer immunology research. At both conferences, we presented data supporting the unique biology of PVRIG, suggesting its role in sensitizing tumors to the other immune checkpoints, TIGIT and PD1, and additionally, data supporting the targeted potential of our high affinity, potential first-in-class anti-IL-18 binding protein antibody, COM503, showing its activity localized to the tumor microenvironment with the potential advantage of a wider therapeutic window than systemically delivered cytokines. Finally, in the first quarter of 2024, our partner AstraZeneca continued to rapidly advance the development of rilvegostomig. We're delighted that they are initiating a second Phase 3 trial, TROPION-Lung10, in non-squamous non-small cell lung cancer. The study will assess rilvegostomig as monotherapy and in combination with Dato-DXd, a TROP2 directed ADC being developed in collaboration with Daiichi Sankyo, compared to pembrolizumab as first-line treatment for patients with advanced or metastatic non-squamous lung cancer with high PDL-1 expression. As a reminder, we recently received a $10 million milestone payment upon dosing of the first patient in the Phase 3 study of the first indication, biliary tract cancer. Under this agreement, we're eligible to receive development milestone payments for the first and second indications. The progress into a second Phase 3 trial addressing a major indication such as non-squamous non-small cell and cancer reinforces our partnering strategy to broaden opportunities for our pipeline and brings us closer to realizing additional future milestone payments and royalties. As a reminder, the TIGIT component of rilvegostomig is derived from our potential best-in-class anti-TIGIT COM902, and both rilvegostomig and COM902 fall in the Fc reduced inactive function camp. Moving on now to what's planned for the rest of the year. 2024 is planned to be a catalyst-rich year for us, with multiple data readouts and updates expected from our diversified portfolio. At ASCO in June, we plan to present data from our ongoing proof of concept study in MSS CRC patients, including those with liver metastasis, who have been treated with the triple IO combination of COM701, COM902, and pembrolizumab. MSS CRC and in particular such patients with liver metastasis represent significant unmet medical need and a hard-to-treat patient population. At SITC in 2022, we presented data from our first cohort of 22 patients treated with a dual combination of COM701 and nivolumab, and we were the first and only company to report responses to IOs in this population of patients with liver metastasis, reporting a 12% overall response rate and stable disease in addition to immune activation supporting PVRIG biology and COM701 mechanism of action. Although this indication was not initially selected based on dominant PVRIG pathway expression levels, following this encouraging clinical data and with an aim to assess the strength of our findings in liver metastasis patients in a larger cohort, we initiated our ongoing study in 20 patients with MSS-CRC and added our anti-TIGIT COM902 to the drug combination to see if we could improve on the responses seen with a dual combination. Enrollment was rapid, reflecting the significant unmet need, and we enrolled the last patient in September '23. The data will be presented at the upcoming ASCO on June 1st with a data cut-off date of April 5th, 2024 and remains supportive of COM701 mediated activity and safety with some patients continuing treatment at the data cutoff date. However, with the totality of the data we have in hand, we believe that an IO-IO approach is not the way forward in this notoriously IO-resistant patient population of MSS-CRC with liver metastasis. Yet, the total clinical activity observed to date in the two evaluated cohorts suggests the effects are COM701 mediated and, due to the unique biology of PVRIG, may warrant further evaluation of COM701 with other agents in MSS-CRC. Therefore, the door remains open for other COM701 combinations in this patient population. However, this will not be the focus of our internal resources at this time. It is important to note that observations made in tumors, which are biologically distinct from each other, such as MSS-CRC and platinum-resistant ovarian cancer, are not considered indicative of each other. With this, I will remind you that we have reported more dominant PVRIG pathway expression levels in ovarian cancer. This brings us to our next catalyst. The next catalyst for our triple combination will be the presentation of our data in platinum-resistant ovarian cancer for which we have completed enrollment. Data presentation is on track for the fourth quarter of 2024, and our plan is to present this data at a medical conference. We believe the totality of the data we have reported to date in platinum-resistant ovarian cancer patients is encouraging compared to the current standard of care. Based on the data we reported at ESMO IO in December 2022 from the first cohort of 20 platinum-resistant ovarian cancer patients treated with a triple combination, investigators were excited to report durable shrinking or stabilization of tumors in some of their patients who had previously progressed on all available treatment options. We presented a 20% overall response rate with some patients responding for over 16 months, which is favorable considering the median duration of response for single-agent chemotherapy is around three to four months, and in ADC is around six to nine months. Responses were achieved in the hard-to-treat high-grade serous adenocarcinoma patients along with the favorable safety profile. We also presented preliminary biomarker data showing an association between PVRL2 expression and clinical benefit. Of note, we also previously presented data showing COM701 monotherapy activity in a patient with ovarian cancer whose tumor microenvironment was immune desert. This patient had a partial response of more than 18 months. For the ongoing study, we plan to present data in the fourth quarter of the year, including the baseline characteristics, safety, overall response rate, disease control rate, preliminary data on duration of responses, and potentially biomarker data. Data showing clinical benefit in platinum-resistant ovarian cancer is expected to allow us to pursue the next study toward registration, which depending on data may employ a predictive biomarker enrichment strategy. In addition, we're also on track to submit the IND for COM503 in the second half of this year and expect that IND clearance for which we're eligible for $30 million maximum payments from Gilead will be achieved in 2024. With that expectation, we're in advanced stages of planning the Phase 1 study. Finally, in the second half of this year, AstraZeneca expects data from their Phase 1/2 ARTEMIDE-01 trial in non-small cell lung cancer in the frontline setting. Before passing over to Alberto to go through the financials, I would like to take this opportunity to warmly thank him for his commitment and leadership since he joined us in 2022. Alberto has been a great partner to me and the rest of the team here at Compugen. David Silberman will take over the reins from Alberto as Chief Financial Officer effective August 15th. David has experience in the healthcare industry as Chief Financial Officer of a biotech company traded on the NASDAQ, and I'm looking forward to introducing you to David when he joins. I also want to emphasize that while benefiting from our solid cash position to enhance and advance Compugen to additional milestones, we're also financially disciplined. We have two potential first or best-in-class unrestricted assets along with multiple undisclosed early-stage assets with the possibility to address a significant unmet need in immuno-oncology. In addition, we have two strong validating strategic pharma partners, Gilead and AstraZeneca, on rilvegostomig and COM503 respectively, and from whom we are eligible to receive future milestone and royalty payments. With that, I will hand over to Alberto for the financial update.

Thank you, Anat. I'm happy to summarize our financial results. I will start with our cash balance. As of March 31, 2024, we had approximately $101.3 million in cash compared with approximately $51.1 million as of December 31, 2023. This cash balance includes a $60 million upfront payment from Gilead related to the licensing of COM503 and $10 million milestone payments from AstraZeneca on dosing the first patient in the Phase 3 trial in biliary tract cancer. We recognize the importance of cash efficiency and we are disciplined in how we deploy our cash reserves while making sure we focus on reaching key milestones. We have a cash runway into 2027 taking into account the expected milestones payment of $30 million from Gilead for COM503 IND clearance expected in the second half of 2024. It is important to emphasize that this does not include any additional potential cash inflow from our partners. I remind you that the company has no debts. Revenue for Q1 2024 was approximately $2.6 million compared to no revenue for the comparable period in 2023. The revenue reflects recognition of a portion of the upfront payment from the license agreement with Gilead. Expenses for the first quarter of 2024 were in line with our plans. R&D expenses for the first quarter of 2024 were $6.4 million, reduced from $7.4 million in the first quarter of 2023. Our G&A expenses for the first quarter of 2024 were $2.4 million compared to $2.6 million in the first quarter of 2023. For the first quarter of 2024, net loss was $7.3 million, or $0.08 per basic and diluted share, compared to a net loss of $9.3 million or $0.11 per basic and diluted share in the first quarter of 2023. With that, I will hand back to Anat to summarize.

Thank you, Alberto. To summarize, Compugen stands out as a clinical stage immuno-oncology target discovery pioneer. We're differentiated by our validated discovery platform, which is powered by the mix of human expertise with AI and machine learning to fuel our first-in-class pipeline. We're on track to deliver a catalyst-rich 2024 across our diversified pipeline and planning to present data for our COM701, COM902 triple combination at ASCO in MSS-CRC, as well as data from our platinum-resistant ovarian cancer at the end of the year. We are planning to submit COM503 for IND in the second half of this year and are advancing our planning for the initiation of Phase 1 for this program. With the pipeline that is being advanced internally and by our partners, this is an exciting time for Compugen, and we believe that we have the fundamentals in place to bring value to our shareholders and cancer patients. I am proud of what we are achieving here at Compugen. I would like to thank all our Compugen colleagues for their collaborative spirit and daily dedication, resulting in a well-executed first quarter of the year and setting us up for future success. With that, I will turn the call over for questions.

The first question is from Stephen Willey of Stifel. Please go ahead.

Hi, this is [indiscernible] on for Steve. Thank you for taking my question and congrats on the progress. We have two questions. The first is about colorectal trials. I know that ASCO abstracts will be available this week, but how much additional detail should we expect in the actual presentation compared to the abstract? After this presentation, what will be the path forward for this study? The second question is about COM503. Do you anticipate disclosing any clinical data following IND submission for these assets? Thank you.

Thank you. I'll start with the second question regarding COM503. The decision to disclose clinical data from a Phase 1 study will be made in collaboration with Gilead, as this asset was licensed to them. I cannot speak for them at this time, but I will provide guidance once we have more information. Before that, we need to file the IND and begin the study, which we expect to complete in the second half of this year. Regarding the CRC data, the abstract will be released this week, and we will present the data on June 1st for Compugen. This will include information from 20 enrolled patients, covering antitumor reactivity, durability, translational data, safety, and patient baseline characteristics. As previously mentioned, the data supports the antitumor activity of COM701 and its mechanism of action in relation to PVRIG biology. However, based on the data we have, we believe that IO-IO only combinations are not the appropriate approach for targeting the MSS-CRC with liver metastasis, which makes up 70% of the patient population. We feel that while there may be potential for COM701 in MSS-CRC with liver metastasis, possibly in other combinations or earlier treatment lines, we are not pursuing that route at this time.

Thank you.

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

Hi, everyone. Good morning, and I appreciate your insights. I’d like to discuss colorectal further and get your thoughts on what might be lacking in this area. It seems that 701 biology is effective, but could you clarify if you require more immune activation and less checkpoint blockade, or perhaps more debulking? What do you believe is the missing element considering the positive activity we noticed previously with this approach? Additionally, regarding 701 and 902, how should we view the other paths you plan to explore with this combination? Is your next focus to possibly revisit efforts in CRC with a different combination to tackle the gaps, or have you found another tumor type to target? Thank you.

Okay. Thanks, Asthika. I'll start by saying that, look, we can't get really to the specifics of the data, and maybe this discussion will be worth taking following the presentation in June 1st. Maybe Eran wants to add, but I'll just say that with IO only, we believe that what we see is not enough in order to pursue. But maybe, Eran, do you want to say anything about it more than that?

Yeah. So with the unique biology of PVRIG and what you have seen previously, definitely with the activity in places where normally checkpoints are not working in MSS-CRC, with liver metastasis, immune modulation, increase in T cells. But we've seen it in part of the patients, right? And eventually to move forward, you need to have sufficient activity in sufficient amount of the patients to really consider to go towards approval. And as you understand, what we see in a pure IO combination of the triplet. In this very difficult and not immunogenic indication, what you have seen is not enough to convince ourselves to move forward as is. And yes, as discussed, maybe not at this point in time, but there are other rational-based combinations that could be employed to increase IO activity in this kind of difficult indication that is something to consider for the future, but again not at this point in time.

Regarding your second question about additional tumor types, we have data indicating that COM701 is active in non-inflamed tumor types where PD-1 treatments have limited effectiveness. While we are currently focusing on platinum-resistant ovarian cancer, where we have a robust set of data, we anticipate that additional data from over 20 patients will aid us in deciding how to proceed. There are several potential avenues for exploration, both in non-inflamed and inflamed indications. While we have not previously tested inflamed indications, we chose this path based on the biology of PVRIG, which allowed us to demonstrate the activity of COM701 in combination in single-arm studies without questioning whether PD-1 inhibition was responsible for the observed effects. We are also considering combinations with other therapies. For now, however, our emphasis remains on platinum-resistant ovarian cancer, and we will determine our next steps in this area throughout the year.

And maybe I would just add that in addition to what we're focusing on at the moment, you pre-identify a few indications with dominant PVRIG pathway. Ovarian is one of those, but there are other indications, for example, like non-small cell lung cancers, and I've mentioned more inflamed settings. So definitely there are multiple opportunities and combining this with the safety profile of COM701 that really will enable us safe combinations maybe in other indications, maybe in early lines. So again, the opportunities are there and there are quite a few, but we are focusing now on the ovarian cancer which we have seen until now quite promising data.

The next question is from Daina Graybosch of Leerink. Please go ahead.

Thank you for your question. I would like to continue discussing your strategy for PVRIG moving forward, particularly in ovarian cancer. I'm curious about your thoughts on combining it with other standard treatments such as chemotherapy or VEGF agents like bevacizumab. Looking back at colorectal cancer, there are two approaches: one is trying to make a pure IO therapy successful, and the other involves combinations, which could indicate a different type of study. I would like to know your perspective on this. Additionally, I remember you had considered a chemotherapy combination for lung cancer, but I am not sure if you ever began enrolling for that. Could you remind us why that enrollment did not start and what specific path you envision for cancer if we reach that stage? Thank you.

Thank you, Daina. I'll begin, and Eron and Michelle can join in whenever they like. Let me start with ovarian cancer. Firstly, in response to your inquiries about combinations, we are currently focused on the immuno-oncology combination we’re pursuing. With the data package we have, including the initial biomarker correlations, we believe that if the results are consistent, we will observe clinical benefits. There is a potential pathway for us to target different patient populations, including those progressing on antibody-drug conjugates and those either receiving standard care or who are ineligible. Nevertheless, it’s important to note that combining our treatment with chemotherapy, VEGF, or antibody-drug conjugates may be significant. This consideration is based on the mechanism of action of PVRIG in conjunction with cytotoxic agents, as well as the safety profile mentioned by Eran. While our focus remains on ovarian cancer and gathering data from this study, we will also take into account the competitive landscape. Regarding colorectal cancer, I will allow Eran and Michelle to contribute as they see fit for each indication. However, in colorectal cancer, we see potential for advancement in combination with standard care. Mechanistically and safety-wise, especially in earlier lines of treatment, the risk profile for microsatellite-stable colorectal cancer with liver metastasis indicates that, at this stage of our company, we should be cautious with resource allocation, but this avenue remains open for future exploration. That sums up the situation for colorectal cancer.

Anat, I didn’t ask about CRC. I asked about non-small cell lung cancer. What would be potential for there?

Sorry. Sorry. Yeah. And this is correct that we planned at a certain point in time to move based on the data that we had that Eran mentioned, data in patients that already experienced checkpoint blockade. We had very nice data, seven patients though, but very nice data, and we thought of pursuing non-small cell lung cancer with chemotherapy as a small study. The reason that we decided to focus on the non-flamed indications at the end of the day was the fact that we were with the cash limitations that we had at that time, we decided to focus on indications where we will not need large studies in order to prove the activity of COM701 combinations. Single arm, small study that we can tease out the contribution of COM701 quickly and move forward. And this is still on the table and as I said, as a company in general, we're thinking about indications that we can pursue internally by ourselves, and indications that we may pursue, as I was saying all the time, partnering is also a priority for us, and larger indications that could be pursued in partnerships. And, Eran, Michelle, anything to add in ovarian and non-small cell lung cancer combinations?

Go ahead. I was just going to emphasize again what you were saying, Anat, because when we look across the indications that we've presented data in, we definitely do see an effect driven by COM701. So I think that there are opportunities even within other indications like endometrial, breast where we've presented data before and we are considering a lot of different options to have a more robust sort of strategy moving forward.

And I think at this point in time, we're focusing on the pure IO. We have strong data from preclinical to clinical. This is really strong immune-modulating regime that has an excellent safety profile. It's chemo-free, it's really attractive, and the data we've seen and are now in ovarian and some of the other indications really pushes us to continue and explore this IO pure combination. But again, doing other combinations if we need, or maybe in some indication in which we'll need it is definitely an approach and there's a rationale for that. I mean, the unique biology of PVRIG, the ability to prime new T cells is there is a rationale to combine with ADCs of chemotherapy with the enhanced immunogenicity that we see. There's rationale to combine with BEV with the effects of T cell infiltration. So moving forward, we definitely consider the data, the indication, and other rational-based indications that we may consider in the future.

Great. Thanks.

The next question is from Tony Butler of Rodman & Renshaw. Please go ahead.

Good morning and thank you. Anat, with respect to the ovarian cancer data set that's forthcoming, will data also include patients who are actually segmented by positivity with PVRL2? That's part A of that question. Number two is, you mentioned a biomarker strategy, I believe, for moving forward with a larger potentially registrational trial. Have you settled on, and this may be for Eran, have you settled on an H score, as I recall, those individuals who had clinical benefit had H scores that were, I guess, relatively high, 300 or so? And then the third point is, while I assume all ovarian cancer patients will have had BEV, is there a reason why they would not want to stay on BEV, even if in fact it has marginal activity certainly of single agent? Thank you very much. And one last point. Is 20% the hurdle rate that we should be looking toward or forward toward the fourth quarter for that data set? Thanks.

Thank you, Tony. So I'll let Michelle answer the question on BEV. I'll start with what you asked about the biomarker and let Eran relate to the H score. First, I'll say that in terms of the data, yes, we present data that relates to the activity, to the efficacy, the durability, translational, the data that we'll have in hand. We also anticipate to share PVRL2 or biomarker data, obviously pending on data, the work in progress now and with the data that we have in hand, we present what we have in hand. I will say before I let Eran relate to the H score, I will say that we will look at the data and different bars of data will allow us to make a decision, do we go with or without the biomarker? We're not limiting ourselves to a biomarker. This is an enrichment strategy that may help. It will depend on the data that we have in hand, but we are not really going to study that will not be biomarker. Reason, maybe a study that will still continue to assess the biomarker findings. It really depends on the data that we have in hand. And Eran, do you want to take the H-score one?

Yes, so yes, Tony, remember it correctly. This is a very important observation from our previous study in which we showed that the patient who responded had clinical benefit from the treatment of the COM701 combination had a higher H score of PVRL2, and this opened the door for a potential biomarker, yes, to enrich for this patient to have long, durable responses and then, of course, to move the registration faster and all the benefits of having a biomarker. So this work is ongoing also in this study. To define the cutoff, obviously, we need to show also in this study that the phenomena repeats itself. We need to really define looking, and now we have much more patients combining the studies together. We can really look at the totality of the data, the response rate, the correlation to the ACE score and then to define the actual cutoff if and when we will move forward with a biomarker-selected study. So this is ongoing. Yes.

Do you want me to comment on the BEV?

Yeah, Michelle, go ahead.

Yeah, so in the initial lines of treatment in these patients, they do get bevacizumab together with platinum. Platinums are basically the mainstay of therapy in the ovarian cancer population. Generally, if a patient does relapse following a full regimen, which includes bevacizumab maintenance, they may get put onto the PARP inhibitors as second line, or sometimes they will do it the other way around. They generally are not repeated. They might repeat BEV, but it's really more repeating the platinum agents until the patient becomes resistant. So that's defined by a platinum-free interval of six months or less. And the patients that have been enrolled in our studies so far are the platinum-resistant patient population.

Thank you very much.

This concludes the Q&A session and Compugen's investor conference call. Thank you for your participation. You may go ahead and disconnect.