Good morning, everyone, and thank you for joining us at the first day of the Needham and Company Healthcare Conference. It is my pleasure to have with me this morning, Eran Ophir, the CEO of CompuGen. Eran, please go ahead and start your presentation.

Thank you, Yeri. So I'm delighted to share some of the advances CompuGen is making, utilizing our AI-based computational engine to identify new drug targets to activate the immune system against cancer. And maybe we'll start with a few words about the history of CompuGEN. So actually, we were established in the 90s. Initially, it's a hardware company, really trying to deal with the vast amount of biological data that started to accumulate these days. Later on, we listed the NASDAQ in 2000 and we moved to employ more software and doing collaboration with pharma companies and using our computational capabilities. But the CompuGene that we know today is the CompuGene world who realized that to make the most of the value out of our computational engine, the best thing would be to take the computational discoveries, the new drug targets that we identified, but to develop the drugs themselves and take it to the clinic ourselves. so around a decade ago we started to employ this strategy really not only doing the discoveries but also developing the drugs and taking to the clinic and after around a decade of this strategy i think this is a very exciting time to talk about Compugen because we both have a whole pipeline derived this computational engine and hopefully in the near future we're going to have our first drug derived from our computational discovery to be approved, as we have one of our partner drugs now in 11-page street trials ongoing by AstraZeneca. So we're active in the field of immune oncology, meaning to activate immune system against cancer. The poster child of this approach is Keytruda, the best-selling drug in 24 and 25 in general. But Keytruda and other PD-1 blockers and other oncology drugs doesn't work for all patients, and certain patients and patient population really do not respond to Keytruda and similar drugs. And immuno-oncology and oncology in general are trying to employ different combinations, new mode of actions, and really to eventually bring immuno-oncology to a larger fraction of the patient. And this is exactly where Comprogen fits in. We're using our validated computational engine, Unigen, to identify new mode of actions, novel biology, to really expand and improve treatment option for cancer patients. And I'm saying that NGEN is validated because using this NGEN, we've shown again and again, we can bring new drug targets to clinical testing with clinical signals. And most importantly, the platform is validated by the partnerships on the drug targets and drugs we developed with AstraZeneca and Gilead. So we have two fully owned programs in our pipeline, clinical programs in our pipeline. COM701, which is a potential first-in-class antibody checkpoint blocker against PBRG, a target that we identified. And COM702, potential best-in-class anti-digit antibody. We also license to AstraZeneca the right to use COM902 at part of their PD-1 TIGG bispecific antibody with vagostamine. And this antibody is now moving in 11-phase free trials, hopefully toward registration from 28 and on. Now, the field of TIGGIT, and we identified the target in parallel to Genentech in the past, and the field has it definitely ups and downs for those who follow. But we truly believe that rilvogostomy can be successful in places where other tissues have failed. And I will explain in the following slide why do we believe so. In addition, we licensed to Gilead more recently, a potential first-in-class anti-ILT-embodied protein antibody. The tablet was licensed to Gilead, and we are now moving this tablet into phase one. And we also have an additional early-stage pipeline, multiple undisclosed assets, all derived from our validated computational discovery engine, Unigen. So Compugen in 26 is uniquely positioned with a rich clinical pipeline and with validated partnerships with potential more than 5 billion in milestones plus royalties. We also ended 25, with a very solid cash balance of more than 145 million. And this should allow us to continue to run all our operations, clinical, pre-clinical, without any further potential milestones that could arrive into 29. So let's start with our pipeline. First is our COM7-1 antibody, anti-PVRAG antibody. This study is now moving in the Mayo-Varren trial. It's a randomized adaptive trial study, and the sub-trial one is a randomized study of com-7-1 monotherapy versus placebo, and we expect results in 2.1.27 for this study. Then, rilvogostomy is driven by AstraZeneca now, PD-1-digit by specific, across 11 phase three trials, and 14 phase one or two trials across multiple indications with multiple combinations. The GS0321 part of the program is run by us in the phase one study that was initiated at the beginning. The first patient was dozed at the beginning of 25, and again, the early-stage pipeline of undisclosed assets, all derived from unigend to computational engine. So let's talk about COM7-1. COM701 is targeting PVRIG, a checkpoint that was not known to the scientific community when we identified computationally, so moving forward with the first mover advantage, the first to enter the clinic to show clinical results. And what is unique about PVRIG is that the biology is very, very different from TIGIT. It's very different from most of the other checkpoints in general. And this unique biology, and we will not go through all the details today, but has the potential to really drive T-cells into less inflamed indications, which are typically not responsive to checkpoints. And specifically, the pathway is very high in ovarian cancer, which again is an indication which typically is responding less well to checkpoints. And ovarian cancer was a target indication for us before we even started. And then we started the clinical trials, and this is definitely an indication when we treated last-line button-resistant ovarian cancer patients, patients who failed every treatment option, we saw clinical results with COM7-1 in monotherapy and in combination. The patients who did respond have very durable responses with excellent safety. So what we decided, taking these signals in the last line of patients, and to take them where we thought, along with the QOLs we discussed with, would fit the most to this type of drug, and this is the platinum-sensitive settings. We talk about patients, for the second or third line, they receive four to six cycles of chemotherapy. This is early reliant to what we've seen before, meaning they have a more potent immune system, less compromised by repeated cycles of treatment. We take only patients who responded to the chemotherapy so they have low tumor burden and this we believe makes it a better situation for the COM7-1 to really induce its effects. And the goal of this study and that's why we call it the maintenance settings is to prolong the PFS to really prolong the time the patients are following responses to chemotherapy to prolong the time before the relapse. And the subtrial one is randomizing 60 patients after responding to hemotherapy. They're randomized to COM7-1 versus placebo. There's no standard of care for this patient population. And the readout is expected in Q1-27. Following successful readout, clearly showing that COM7-1 has monotherapy activity this patient population, then we can definitely think about past registration as monotherapy. We can think about a backbone for combinations, for example with ADCs, and obviously following positive results with clear monotherapy signal, we can think about going earlier in ovarian cancer, later in ovarian cancer, and also other indications in which we saw signals for COM7-01. Then revogostomy. Why do we think revogostomy can succeed where other digits have failed? So first is the antibody formants. What AstraZeneca did is they took Co9O2, our antibody, and put it in the spout of the PD-1 digit by a specific antibody. One arm binds PD-1, like intruder, and the second arm binds digits. So the antibody binds two targets. And what AstraZeneca have shown in a very translational ex vivo system, meaning taking tumors directly from patients and testing them with the different drugs, and this system was shown to correlate very nicely with actual clinical activity, they showed that this specific formative regostomy through its cooperative binding is not only more active than PD-1 in this system, But it's even more active in PD-1-digit to drug combination that was tested thus far by others. So the biospecific could be more effective than PD-1-digit combination. This is one. But then looking at the whole clinical strategy of AstraZeneca, and I'm not speaking on their behalf, but really looking at what seems to be a very comprehensive plan, that they use refugostomy in a way trying to replace PD-1, PD-L1, IO backbone across different indications, across different combinations, notably I would say the ADC combinations and HERTO, DATRAWAY that was not tested by others, and also the clinical trial design that they employ. In some cases it seems, again looking from the side, they learn from the mistakes of others and are basing the clinical design based on the mistakes of others. So we believe Virgostomy could fail where other TIGIT players failed due to the antibody formats, the combination strategy, and the clinical trial strategy. From this collaboration, we received today $95 million. We're eligible for additional $195 million in milestones. And most importantly, with this extensive clinical strategy, and AstraZeneca previously predicted more than $5 billion annual sales for hypogastomy were being eligible for up to mid-single-digit to the royalties from this potential bloodbusters drug could really drive the future financial stability for Compogen in a very meaningful way. It will allow us to continue to bring more assets using this financing. While the phase three studies are ongoing, and the results will be after 27, meaning 28 and on, there are multiple other trials ongoing, each of them showing different results. And next week in ACR, actually there are five presentations, both research and clinical, that I believe could shed additional light on why us two are so excited for milvogostomy. Then COM503, called today GS0321, Another demonstration of our computational capability, this program which targets IL-10 binding protein, which is an inhibitor of a cytokine, really a first-in-class program, but also a first-in-class approach. Nobody ever tested such an approach that has the potential to really overcome a lot of the challenges that others had, trying for years to engineer cytokines to make these potent immune stimulants into drugs. And while there are some approved cytokines in the clinic, most of the attempts to reduce toxicity while maintaining a good therapeutic windows have failed to date. And we believe this program has the potential to really make a difference. And Gilead thought so as well. And we licensed the program to Gilead. We received to date $90 million for this program that was licensed in the preclinical stage. We're eligible for additional $758 million in milestones and up to low double-digit dualities. CompuGEN is responsible for the ongoing phase one trial that started at the first session with those in the beginning of 25, and Gilead will take it then to the later stage trials and hopefully to commercialization. So to summarize, I think that CompuGEN is really well positioned today with It's a solid financial stability, and then also the computational engine, a validated computational engine that could use this financial stability to bring more assets to continue and build our own pipeline, where in parallel, the validating partnerships are ongoing, hopefully with an approval on the near horizon. So I would like to thank you for your attention, and if you have any questions, please don't hesitate to send us.

Thank you, Eran. At this stage, we will open the floor up for questions, but while we pull for additional questions, maybe a couple from us, maybe I'll start with something a bit fundamental. So, you know, investor disappointment in this space has been driven by the fact that all these new IO agents, and I'm speaking broadly in the last decade, haven't really reached this sort of breadth of activity that we've seen in PD-1s in general. Is there like an underlying biological reason why the PD-1 axis seems more amenable?

Yeah, it's a great question. And I think that overall, there are specific types of patients who respond to PD-1. These are specific indications, specific patients who have probably normally some baseline inflammation in tumor environments, some baseline T-cells. And this patient profile, either they respond to PD-1, or to date, when added other IO agents, if they didn't respond, meaning the tumor microenvironment was not prone to respond to IO in general, and they didn't respond also to the combination. So this is, I think, one of the reasons that, and PD-1 obviously is very dominant. So all the IO agents arrived afterwards had, for example, TIGIT. TIGIT did show activity in randomized studies. It just was not sufficient to achieve a phase 3 success. LAG-3, by the way, at Notru is much more active, and it did, with the properly designed trial, did eventually, it was approved in Melanova. So, if we talk about, and take this into the two assets, I would say that the two checkpoints that we work on, PVRG and Digit, so on the one hand, PVRG, first of all, did show some monotropic activity, and that is something that was missing for many, from some of the other IO agents who failed. We didn't test many patients, but we did see monotherapy activity. And in general, the biology and the signals that we're showing in other indications, less inflamed indications, is very unique. And we'll have to see how it plays now in a randomized study in the ovarian study. Then for levogostomy. So yes, I think it's quite clear it is active. Definitely not as active as PD-1 monotherapy compared to chemotherapies and disease-like medications. TIGIT is active in places where it is adding in places where it is active. And now I think it's really the game of having the right format, having the right combination, and also design to try properly and understanding the magnitude of effect that TIGIT can bring.

So maybe as a lead on there, do you think that other programs just didn't design the correct study?

I think it's, first of all, most of the other programs who failed have an FC active digit, which I really think that even though the initial result of the FC active looked good, eventually they had more safety, they had high discontinuation rate, they took the activity of the digit, which is not huge, in a way and arose it with the safety and maybe a bit less efficacy. So this is one. And so I think having the right drug format is one thing, which is important. And then, yes, also having the right combination and the right trial design definitely is pretty important and I think along the 11 phase three trials of AstraZeneca you can really see some of them are comparing head to head versus Keytruda for example but they are I think were rightly powered with selection of PD-L1 which is important that not everybody did and then also some of the trials are really doing this combination also the costumic plus ADC and they just use it as an IO backbone, they don't even really compare But this is a bit of a different story. Some of these rats don't really measure digit activity directly. And because it's a bispecific, it's a bit of a different story also for AstraZeneca in this case.

So maybe switching gears here a little bit, a bit on the rationale of moving forward in platinum sensitive versus platinum resistant, not the most common path forward.

So the rationale was that after we saw quite clearly, again, not many patients, but we saw the signals in the last line, especially, for example, PD-1 or PD-1 even plus digit in the past showed zero response rates in PD-1 negative. And we saw responses in PD-1 negative ovarian cancer, again, last line, platinum-resistant, WISCOM-701 in one patient, in few stabilization of disease, and in combination. So we're quite sure that we have a signal there. And the patient who did respond, the response was very terrible. But in the last line of patients, when you have such highly progressive tumors, some of them never even had a chance to respond to IO. Few, and this is what we tried, IO-only treatment. And we had, I think, two options. One was what Merck did recently, to combine with chemotherapy, to provide some kind of debulking, to add it to the IO. But we decided not only to use debulking, but also to go earlier, to go into patients in the second, third line, platinum-sensitive. They had less rounds of treatment, so their immune system is less compromised. We took only patients who are responding, so they have debulked tumors to begin with because we take patients to respond. And then we really give the opportunity to come 7-1 with its excellent safety and durability of response to prolong the response with the chemotherapy.

So if I'm to rephrase this, you're basically looking at patients with higher T cell quality as it relates to MAPA, basically like consolidation. So if the chemo is debulked, there's less target cells to go after, basically.

Yeah, and I think that for, And I think this concept was shown also by others, for example, by AstraZeneca and their strategy in IO going earlier into maintenance, adjuvant, neoadjuvant. We didn't invent the concept of going earlier. And I think really immunocology has better potential to work in earlier settings with less compromised immune system again and also with low tumor burden. So I think this is what exactly we did. And, yeah, it's really interesting to see the results.

Okay, that all makes sense. Why bispecific instead of just using both agents at the same time for real-world gossip?

Yes, it's an excellent question. So first of all, as I showed in the presentation, when you use the bispecific, you have this kind of cooperative binding. And not as for Zeneca, I've shown that you have induced games of affinities. So you are first talking with the high affinity antibody that is derived from Com9O2 or antibody, and then co-blockade of PD-1 and DIGIT on the same cells. This cooperative binding eventually, and this is what they showed in this ex vivo system, is more active in PD-1 DIGIT combination. So I think this is one aspect that the biospecific seems to have, and we eventually see it in the clinical settings obviously, but seems to have the potential with its unique cooperative binding to deliver more activity than just pd1 plus digit combination but then going into the clinical combination strategy when you have a bispecific in some cases you don't really have to prove contribution of components because nobody can ask you to take out digit and show it's active and since the drug is using also the fc reduced approach that we utilize in contrast to most of the competitors so the safety is excellent so now we have a drug which is safety that until now seems quite similar to pd1 blockers alone which enhance activity and now testing it in the trials again in some of the trials for example entropion lung 10 they're comparing rilvergostomy plus idc versus intruder they don't really have to prove and they use rilvergostomy is the IO backbone, if you may, a better type of PD-1 and combining with ADCs and compare it to Keytruda and other trials with Inherto, for example, plus ribagostomy versus PEMBO plus L-septin. So overall, I think that the strategy gives potentially more active drug, but also much easier combination strategy and clinical path forward in clinical trials.

Great. And maybe as a last question on your Gilead program, can you walk us again through the differences on your IL-18 strategy? Why do you think it would be more effective than just providing IL-18 or is this all a safety profile question?

It's a matter of therapeutic window. I mean, eventually cytokines, if you put T-cells in a tissue culture plate, you put IL-18 or any other cytokines on them, they are exploding with activity. But typically what people are doing, and actually IL-2 isn't a proof drug, right? But you put it into veins of the patients. And then you have systemic side effects because the first thing that the T-cells in the blood will see is the IL-18 or IL-2 or any other cytokine. and then sometimes some of it can reach sufficient level to the tumor to induce the actual activity you want to see. What we are doing, we are utilizing the fact that in a tumor environment, naturally, there is a high level of IL-18 blocked by IL-18 binding protein and it's very low in the blood because it's induced by inflammation. And then we use a blocker antibody. We're not using a cytokine. We're using a blocker antibody and again, it's a first-in-class approach. The concept itself was never shown by others. and we are inhibiting the inhibitor. And what we have shown preclinically that we're modulating only the tumor and not the periphery. And this is a conceptual difference in the approach. So we are utilizing the potency of the cytokine, which is naturally a tumor-like environment. And by that, the terapotic window, again, at least preclinical, is completely different from all the attempts of the cytokines using recombinant cytokines with others of trials.

I don't currently see any further questions from the audience. So, Eran, I would like to thank you for attending today.