So we're going to go ahead and get started. I'm Stephen Willey, one of the senior biotech analysts here at Stifel. Welcome, everyone, to our 2024 Healthcare Conference. Glad to have with us here to kick things off, Anat from Compugen. She is CEO of the company. Anat, any opening comments you want to make before we jump into Q&A? Thank you for inviting me, Stephen and Stifel, and I'm happy to discuss Compugen's pipeline programs and our path forward. OK. So maybe we can start with the triplet data that you just presented at SITC. This was in platinum-resistant ovarian cancer. So this was the second data set that you've generated in this tumor type using COM701 combined with a TIGIT and combined with an anti-PD-1. What would you highlight as kind of the key takeaways from that data? So you're correct. This is indeed the second cohort. And we confirmed the data that we observed in the prior cohort of 20 patients. We showed that it's a COM701-driven activity. The responses were durable, and the safety profile of the triplet is quite safe. The patient population that we treated is platinum-resistant ovarian cancer patients. These are patients that have no other treatment options, heavily exhausted. The patients in this study cohort had four prior lines of treatment, exactly like the other cohort. And this patient population generally has less than 10% responses to PD-1 inhibitors or to PD-1 plus TIGIT. So really, our data was pointing to about 20% overall response rate in the total group of the 40 patients, the prior 20 patients, plus the current 20 patients for which we disclosed the data. 20% overall response rate, about 45% disease control. We had one complete response in this patient population. Durability in the prior cohort, we had patients, the responders, for more than 16 months on study treatment. Here in this case, the study is still ongoing. So we had five patients that are on treatment for more than 200 days. Again, safety profile, good tolerability, grade 1 to 2 treatment-related adverse events, treatment-related discontinuations, less than 4%. And the translational data is really pointing to a COM701-driven effect. OK, so we know the history of IO-based therapy in this tumor type hasn't really been that good. I think you just referenced the less than 10% response rates that have been seen with either PD-1 or PD-1 with TIGIT. What do you think is the biological or the mechanistic hypothesis that underlies the activity that you're seeing with COM701 in the triplet regimen? So this is consistent with the data that we're showing that it's a COM701-driven effect. COM701 is an antibody targeting PVRIG. We discovered PVRIG as a new drug target through our computational discovery capabilities and unlocked the biology behind it. PVRIG pathway is working in parallel and in complement to TIGIT. And it is intersecting also with the PD-1 pathway together with TIGIT. So the triplet blockade is really about blocking PVRIG, TIGIT, and PD-1 all together. PVRIG is a very unique checkpoint. It is expressed like PD-1 and TIGIT. It is expressed on T and NK cells. And it is also expressed on T-stem-like memory cells. But it has a much more dominant expression on TSCMs as compared to PD-1 and TIGIT. And this is one of the hallmarks. It is underlying the mechanism of action. It is not only reinvigorating the exhausted T cells in the tumor microenvironment as being done with TIGIT and PD-1, but it is also having a role as it is expressed on TSCM and the ligand PVRL2 is expressed on dendritic cells. It has a role in actually generating, potentially generating additional waves of T cells to infiltrate the tumor microenvironment, and we see this data in tumor types where we treat the patients with triplet blockade. We see this data of more infiltration of T cells into the tumor in tumor types that are not responsive to PD-1, so we believe this is the mechanism of action that is turning the tumor to be more susceptible to responding to PD-1 and TIGIT. OK, so the development strategy that you just outlined a couple of weeks ago and will now be moving forward with will evaluate single-agent COM701 as maintenance therapy in the recurrent platinum-sensitive setting, so I guess my first question, why evaluate COM701 as a single agent instead of as part of the triplet for which you've generated all this data? What's your level of confidence that single-agent COM701 is active in this tumor type? And what data do you have to support that confidence? So yes, so this is exactly the plan to test first start by testing COM701 as a monotherapy in the platinum-sensitive setting. And I'll explain. First, we're taking the data that we generated in the platinum-resistant setting. These are patients with advanced disease. The more you treat these patients, they turn from platinum-sensitive to be platinum-resistant. The disease biology changes. We took the data that we generated in the platinum-resistant where we see durability and very good safety profile. And we decided to take it into a setting where the patients have less immune-compromised system. So they will be more amenable for IO treatments, more for immune checkpoint treatments. And testing and using COM701 mechanism of action basically to extend the interval in the maintenance setting of platinum-sensitive patients. Maybe I'll go first and explain the platinum-sensitive setting. Patients are being treated with platinum. And they are going through two cycles of platinum. Usually, they get in these two cycles, they get Bev or PARP. In the third setting, they usually, if they already got Bev and PARP, they do not get any maintenance. So they turn to PR, CR, and they're just sitting in maintenance with no treatment. In this patient population, we believe that COM701 mechanism of action may be advantageous because of the durability, because of the safety. And this is why we decided to test it in this setting. Also, these patients, because they were treated with chemotherapy and chemotherapy is activating TLS and TSCM, it goes back again to COM701 mechanism of action. It may generate an edge for treating these tumors when they're sensitized with chemo through COM701 mechanism of action. Also, as I said, these patients are getting no treatment. We decided to start with monotherapy and not go ahead first with triplet. The data that we have from monotherapy is also supporting this path forward. We've tested a small amount of patients with monotherapy. We had six patients that were treated. We got disease control, and out of these six patients, we had one patient with partial response that was on study treatment, actually responding as partial response for more than 18 months. This data is favoring moving forward with COM701 monotherapy. Obviously, we're not taking off the table the triplet treatment, but we'll start in this setting with these patients that are getting nothing with monotherapy first. OK. And then maybe my second question, which I think you just kind of partially answered, again, as maintenance therapy, kind of third line recurrent. How much of this decision to pursue this line of therapy specifically was driven by data biology or just the competitive landscape? Actually, all of the above. There is, as I explained on the biology front, there is a strong biological rationale. There is also a strong clinical rationale. The data that we see in advanced setting in patients that are really not responding to immunotherapy, we see durable responses. And we see good safety profile. And we believe that this could be translated to the maintenance setting. So clinically and biologically, this is very relevant. The design that we picked is a platform design. And we start with monotherapy. As I said, it will allow us also to understand the contribution of components, what's the contribution of effect of COM701 alone. And then with the additional arms, we can add additional combinations. So COM701 will serve as a backbone. And on this, we'll add additional combination studies. This will allow us also to have an approach to the regulatory authorities with COM701 as mono and potentially with combinations, and it will also serve as a basis for potential partnerships for additional combos. OK. Can you talk about the general design of the trial that you've outlined, patient numbers, endpoints, any specific patient baseline characteristics that you might need to stratify for? Sure. So as I alluded to, we're going to employ an adaptive platform trial design. We're going to start with sub-study one, which will test COM701 as monotherapy as compared to placebo. The arms will be randomized two to one. Overall, we're going to enroll 60 patients. The endpoints are going to be the primary endpoint is going to be or maybe first I'll relate to the patient population. The patient population is patients that were treated at least twice with platinum. And they were platinum-sensitive. They already got Bev and PARP. And they're not eligible. They're not candidates for Bev and PARP in the setting that we enrolled them. The primary endpoint is PFS. The secondary endpoint would be safety. And then exploratory endpoints will be further assessment of potential biomarkers. OK. So what are your assumptions for PFS in both the placebo and then also the COM701 arm? And what's your level of confidence in the placebo arm assumption? And how sensitive is that assumption to the type of clinical benefit that a patient achieves with platinum therapy? So I would imagine there's a scenario where a patient responds or a patient simply has stable disease. So do we know what the dichotomy of PFS outcomes looks like in that patient population depending upon what your initial response to platinum is? The historical data, the data in the literature, is very consistent for those patients that are not getting maintenance. This is about, in the literature, the range is between 5.4-5.6. There is only one outlier of the OCEANS study that is pointing to 8.4. In general, we're relating to the PFS, the baseline assumption that the PFS will be around six months. The expected PFS for the treatment, we're looking for three months improvement over the six months. It means nine months. The patients that we're going to enroll for the study are patients that are having CR or PR as part of the prior PARP treatment. They will be in CR or PR when they will start the monotherapy or placebo treatment. The data is very consistent in the literature. OK, so I guess given that consistency of the data in the literature, it sounds like you're pretty comfortable around limiting the placebo arm to only 20 patients. You feel like the confidence intervals around that data point are going to be sufficiently tight. Yes, so in general, you know we could go ahead with the historical data, but at the end of the day, we know that it's better to put a control arm, and this is what we've decided to do. The statistical analysis that we used is suggesting that 60 patients in the two to one randomization will be good enough in order to show the three months improvement, and that's based on the landmark studies that are out there. You've indicated this trial will start in the second quarter of next year. Correct. How quickly do you think you can complete patient enrollment? And how big of a trial site footprint do you need to accommodate that enrollment goal? So we're planning an aggressive enrollment and aggressive execution in order to, we also said that the interim analysis is going to be in H2 2026. We have the network. We already have done studies in ovarian cancer in the past, including the prior cohort. So we have the network of investigators, the key leaders. There is enthusiasm around the study itself. And we're going to use this network. And also, I'll say the competitive landscape is different than the competitive landscape in platinum-resistant ovarian cancer. And we believe that this will be in our favor when we enroll patients for this study. OK. And so you mentioned the interim data that's going to be available in the second half of 2026. Will that be interim data that gets triggered based upon some pre-specified number of progression events? How will that interim out? How does that interim analysis formally work within the design of the trial? Yes. So we will obviously monitor events as part of the study. But we're also incorporating a fixed interim analysis into the trial. So we'll do both, monitor the events and have an interim analysis. And we'll also take advantage of an independent data monitoring committee that will look periodically on the data. Okay, so maybe last COM701 question before we get to the rest of the pipeline, but how big of an addressable market opportunity is this? I think there's a fair amount of seemingly reliable data regarding how big second line recurrent platinum-sensitive is. There doesn't seem to be a lot of data out there in the public domain with respect to the third line, so what is your best guess with respect to just patient numbers? Yeah, that's a very good question. In general, the patients, the platinum-sensitive patients in the first line is about 90,000 patients globally. And out of these patients that are getting and they go through the first line, then there is a recurrence. They go through the second line. 20%-30% of the patients that are in the second line that are not eligible for maintenance are the patient population that we're addressing. I'll say that this is for the monotherapy part. I would estimate it between 7,000-10,000 patients. I'll say that this is relevant for the monotherapy. Obviously, if the data is positive, this could go into first line and second line as well. So that's just a start. OK. Maybe we can switch gears to COM503. So you announced this partnership with Gilead, I think, about a year ago. Right. It's an asset that you're now suggesting will be entering the clinic before the end of this year. Can you just kind of speak to the biological and mechanistic differentiation that underlies the enthusiasm that I know both you and Gilead have for this asset? Yeah. I think that IL-18 at this point in time pathway is getting a lot of traction and COM503 in it because of the way we're harnessing cytokine biology to treat cancer. So our discovery capabilities, I didn't mention it. But our discovery capabilities are computational discovery capabilities, which are feeding our own pipeline. Based on these capabilities, we discovered that IL-18 levels are higher in the tumor microenvironment as compared to the periphery. But what we've also identified is that it is sitting in the tumor microenvironment blocked by a natural blocker, IL-18 binding protein. So it is really ineffective in the tumor microenvironment. When we understood this, we understood that if we're going to develop a very high affinity antibody that will block this binding between IL-18 and IL-18 binding protein, we will be able to release active IL-18 in the tumor microenvironment where it is needed to act and spare its effect in the periphery that is being the hallmark of cytokine biology resulting to toxicity. So this is what we're doing with COM503. And as you stated, it was licensed to Gilead. We're in charge of taking it into phase one studies, which should start this quarter. And thereafter, Gilead will take it forward for further development and commercialization. OK. So you are leading the phase one development effort. Correct. Correct. So can you maybe just walk us through kind of what initial dose escalation looks like? Are you pre-specifying for certain tumor types? And I guess, do you think this agent will have single agent activity? Or do you think this is something that needs to be combined with some other IO-based mechanism to really drive the clinical benefit that you want to see? So first, I'll say that we will test it in monotherapy in the clinical studies, monotherapy and combination, in this case with Zim, the Gilead PD-1 drug. In the preclinical setting, we did see monotherapy activity. The question is whether it will be translated in the clinic. But we will test it. We're going to take it through dose escalation, expansion cohorts, and as I said, also in combination. Speaking about the tumor types, I'm not sure that we'll specify the exact tumor types at this point in time because we want to be data-driven. We'll look at the data, and we'll see what the data is telling us. I will say that in a paper that we published, we refer to the mechanism of action of blocking IL-18 binding protein based on the biology that we explored. And we believe that due to the mechanism of action, the tumors should have some inflammation in the tumor in order for it to be active. So we believe that the tumor types that will go after will be tumor types that have some inflammation. So it won't be the desert ones. OK. And so when does the handoff to Gilead here occur? Is it after dose expansion with monotherapy? And then I know you have a meaningful amount of economics that are tied to this program. Can you realize any of those milestone payments within kind of the early phase one-ish part of development? So we will do, as I said, the dose escalation and the expansion monotherapy and combinations. And following the phase 1, it will move to Gilead. In terms of financials, I'll remind that we already got the upfront payment of $60 million and the milestone payment for the IND acceptance for $30 million. We're still eligible for more than $750 million under the collaboration. Obviously, I cannot specify exactly the timing and the size of the milestones. And we're also eligible for single digit to low double digit tiered royalties. OK. You have another partnership with AstraZeneca, rilvegostomig. This is a TIGIT PD-1 bispecific. I think Astra now has this in five phase three trials. Correct. I think they also slapped a $5 billion peak sales guidance sticker on it as well. So TIGIT has been, I think, a kind of disappointing narrative for a lot of folks. We really haven't seen a lot of phase one two data sets translate to phase three success. So kind of what gives you and, I guess, AstraZeneca the confidence that this drug has the capacity to change that narrative? Yeah. So I'll start by saying that, indeed, as you said, we licensed the rights to develop bispecific antibodies for our TIGIT antibody, COM902, to AstraZeneca. And AstraZeneca developed this TIGIT PD-1 bispecific, which they take broadly around across indications and combinations and stages of treatment. I think that you're correct. There is a lot of skepticism in the field for TIGIT. But I will say the following. What makes us encouraged is the fact that there are five phase two randomized studies that were showing benefit of TIGIT plus PD-1 over PD-1. I think that this is beyond being random at this point in time. Recently, at SITC, there was the ARC-10 study results, which were showing some overall survival data. It's a study that is in the midway. But still, there was some OS data. I think that at the end of the day, there will be a critical mass of data for us out there in order really to see whether the TIGIT phase 2 data is going to be translated to OS data that will be meaningful. I think the field is suffering from, and by the way, there will be obviously the AstraZeneca data. Up until now, AstraZeneca was showing encouraging efficacy and very tolerable safety profile, and it looks good. I think that what happened in the field is really the failures that were out there, but the failures need to understand, need to be judged with the study design, with the relevance of the control arm. Is it relevant to the disease setting or not? With the patient population that is being selected, is it an inflamed tumor type? What's the level of PD-L1 expression? And also, as we were speaking for a long time now, the Fc region of the antibody. It seems like the Fc active region has a very narrow therapeutic window. And while the risk-benefit is maybe better in advanced setting, the benefit is incremental. So you can afford the risk in advanced setting. But we can start to see with the data out there that in early disease setting, it becomes more challenging. And the Fc silent version, Fc inactive version, like ours, like Arcus, like AstraZeneca, that picked specifically an IgG1 and mutated it in order to become Fc inactive, it offers a better safety profile for advanced setting and also, by the way, for combination with chemo. So I think the jury is still out. Hopefully, when there will be critical mass of phase three studies that are being done in the inflamed setting with the right control, with the right PD-L1 level of expression, right Fc, I hope that it will be translated to positive data. All right. Maybe the last question. We have to be quicker. So you talked about the computational platform. I mean, you were first with TIGIT, first with PVRIG, first with IL-18 binding protein. How big of an effort do you still have ongoing there? And then how do you think about the balance between capitalizing on BD opportunities that emerge off that platform like you did with 503 and then also expanding the whole pipeline? So we have an ongoing investment in our early stage pipeline. This is our way to feed our own pipeline. We're currently incorporating new technologies into our infrastructure. We're developing new discovery engines. And we have multiple programs that are ongoing. And this will be our next program to preclinical and clinical setting. BD-wise, we tailor collaborations to our needs. Our goal is to continue to feed our own pipeline and generate a sustainable clinical pipeline. So it is important for us to have programs that are internal and that we progress forward. On the other hand, we use collaborations in order to generate revenue stream for the company. So hence the Gilead collaboration and the AZ collaboration. All right. Very good. If there's no other questions out there, I'm not. Thank you for the time. Always good to catch up. Thank you very much. Have a good day. Thank you.