Compugen Ltd Investor update

Eran, please go ahead. Good morning, everyone, and thank you for joining us.

I'm Eran Ophir, President and CEO of Compugen. Today, we'll provide a brief overview of Compugen's key value drivers, discuss the clinical opportunity for COM701, our first-in-class anti-PVRIG antibody being studied as maintenance therapy in second and third-line platinum-sensitive ovarian cancer, and share an update on the continued evolution of Unigen, our AI-powered discovery platform. Dr. Oladapo Yeku, the lead investigator on our MAIA-ovarian adaptive platform trial from Harvard and Massachusetts General Hospital, will share his perspective on the evolving treatment landscape in ovarian cancer, setting the stage for the interim analysis of the MAIA study with PFS readout that is expected to be reported by Q1 2027. Later on, Dr. Sharon Kredo-Russo, our Senior Vice President of Research and Discovery, will discuss how we're expanding Unigen's capabilities to support Compugen's next generation of immune oncology discovery.

While we will not be disclosing any new targets today, we believe it is important to keep you updated on the capabilities we're building in this area of high unmet needs. Following presentations from Dr. Yeku and Dr. Kredo-Russo, Dr. Michel Mahler, our Chief Medical Officer, will join us for the Q&A session. Let's get started. This slide highlights Compugen's main value drivers today, all rooted in our discovery capabilities and derived from our AI-powered computational target discovery engine called Unigen. First is COM701, our wholly-owned potential first-in-class anti-PVRIG antibody, currently being evaluated as maintenance monotherapy in second and third-line platinum-sensitive ovarian cancer in the MAIA-ovarian adaptive platform trial, which Dr. Yeku will focus on. Second is COM902, the TIGIT antibody discovered following our computational identification of TIGIT in 2009.

COM902 became the TIGIT component of AstraZeneca's bispecific antibody, rilvegostomig, that AZ is currently evaluating in 12 phase III trials. Compugen is eligible for up to $195 million in regulatory and commercial-based milestones and up to mid-single-digit royalties on rilvegostomig, which AstraZeneca has previously projected to have peak year non-risk-adjusted revenue of over $5 billion. Third, we're advancing GS-0321, formerly COM503, which was licensed to Gilead in 2023. This program also originated from our computational discovery platform, Unigen. GS-0321 targets the IL-18 binding protein and represents a novel approach to harness cytokine biology for the treatment of cancer. To date, we have received $90 million from Gilead, $60 million upfront and $30 million upon IND acceptance, and remain eligible for up to an additional $758 million in development, regulatory, and commercial milestones, and single to low double-digit royalties on worldwide future net sales.

Altogether, these programs and partnerships validate Unigen as an engine for identifying novel immune oncology drug targets. Unigen discovered targets currently make up our undisclosed research pipeline, and through our expanded capabilities, we are working to continue to bring more innovative molecules into areas of unmet need for patients with cancer. With that broader context in mind, let me focus on COM701, our most advanced wholly-owned program, and why we believe PVRIG inhibition is relevant in ovarian cancer. In this slide, we summarize this biological rationale, including the unique dominant expression of PVRIG on stem-like memory T cells, which is different from other checkpoints like PD-1 and TIGIT. Therefore, by blocking PVRIG, COM701 is designed to alter the tumor microenvironment, including in less inflamed tumors such as ovarian cancer.

Accordingly, we have observed anti-tumor activity of COM701 in patient populations typically less responsive to conventional checkpoint blockers like PD-L1 negative ovarian cancer. As is typical for new drugs, we began our COM701 clinical trials in heavily pretreated platinum-resistant ovarian cancer patients. In these early trials, COM701 in monotherapy and combinations induced clinical benefit and durable responses regardless of PD-L1 status. As you can see here in these turquoise bars, that represents clinical benefit in patients with PD-L1 negative disease. Importantly, PD-L1 negative platinum-resistant ovarian cancer patients historically showed zero overall response rate even when PD-1 and TIGIT blockade were tested in combination, highlighting COM701's unique mechanism of action.

In addition, we identified retrospectively that patients without liver metastases appeared more likely, as you see here in this slide, almost 40% to benefit clinically from COM701 even if informed the MAIA-ovarian design, where we decided to enrich for patients more likely to respond to COM701 by going earlier in the treatment algorithm from the very right slide of this graph, heavily pre-treated platinum-resistant ovarian cancer patient into the second and third-line maintenance settings. We select patients with no liver metastases. Their immune system is less compromised by multiple rounds of chemo, and they have low tumor burden as we select only patients that responded to the last line platinum chemotherapy. These patients have an unmet need for a drug with strong safety and durable antitumor activity to prevent or delay tumor recurrence following response to platinum-based chemotherapy.

The MAIA-ovarian is designed to evaluate COM701 monotherapy against placebo in these defined maintenance settings with 40 patients randomized to COM701 and 20 to placebo. The goal is to determine whether COM701 can extend the period of platinum sensitivity, delay progression to platinum-resistant disease, and help preserve future treatment options while maintaining a tolerable safety profile for patients in the maintenance settings. As mentioned, data from this trial is expected to be reported by Q1 2027. With that context, I am pleased to turn the call over to Dr. Yeku from Harvard University and Massachusetts General Hospital. Dr. Yeku will share his perspective on the evolving treatment landscape in ovarian cancer and the rationale for evaluating COM701 in these maintenance settings. Dr. Yeku, the floor is yours.

Hello, everyone. Thanks for this opportunity to share some of my thoughts about the evolving landscape, in the management of ovarian cancer. Next slide, please. When we think about ovarian cancer, it is helpful to understand the patient journey. Basically, thinking about how patients move through, and how we think about the goal of therapy at each setting. Generally speaking, when our patients present with advanced disease on diagnosis, we use a combination of chemotherapy and surgery either before or after each other, whether we use a neoadjuvant version or an adjuvant version. Depending on a patient's genetic findings, they may be eligible for maintenance therapy. Our goal in this initial treatment strategy is to cure the majority of patients.

Unfortunately, some of our patients will recur with disease, and depending on their histology or stage, at least in ovarian cancer, it is something that happens more often than we would like. This period of remission is defined by the time of platinum sensitivity, which I will talk about in a minute. The longer it takes for the cancer to come back, the better. However, the bottom line is that for the majority of patients, they will have relapsed disease. Understanding and developing therapies that are both efficacious and also preserve quality of life in this setting is what is most important. Next slide, please. As I mentioned before, the way we delineate or distinguish recurrence or relapse is by platinum sensitivity. The current definition of this is the time from their last carboplatin or cisplatin exposure.

If it is greater than six months, that is the PFI, the platinum-free interval, then they are thought to be platinum sensitive. If it is less than that, they are thought to be platinum resistant. Eventually, most patients who develop platinum-sensitive disease will eventually develop platinum resistance. You can imagine that a patient is treated. About a year later, their disease recurs. That is platinum sensitive. They get another platinum doublet combination. That may work for a time. If it works for greater than six months, then they are still platinum sensitive. Unfortunately, over time, that platinum sensitive free interval will decrease, and all patients who are platinum sensitive will become platinum resistant. Even though this timing seems particularly arbitrary as it is timed to the carboplatin exposure, it does have biological significance.

We know that patients who are in the platinum sensitive stage of their disease or platinum sensitive state of the disease have more options. Their survival is longer. Patients who have platinum-resistant disease now have multiply treated cancers that are continuously evolving. In those particular settings, the mortality is higher. Again, it is on a continuum, if you will. We have more options for platinum sensitivity or platinum-sensitive disease. There are fewer options for platinum-resistant disease. For a long time in ovarian cancer, there has been a lot of work into understanding why there is a dichotomy in patient outcomes for these and what strategies we can use to extend platinum sensitivity, both biologically and also clinically. Many of our efforts so far have not been successful in the past. We would use chemotherapy, pazopanib, all sorts of things, but we have not been successful.

Constantly highlighting that this is a goal. There is one medication that we often use in this platinum-sensitive setting, and that's bevacizumab. The goal of bevacizumab is where we combine it with the platinum doublet. We can then continue it as maintenance, providing an option for patients that's reasonably tolerated, even though it has some side effects that I will talk about later. But in some patients, it extends that platinum sensitive window, so they do not become platinum resistant and have to deal with all of the sequelae that comes with that. Next slide, please. One of the key goals of patients who have recurred from a solid tumor perspective is that we know that these patients are no longer curable. Treatment selection, including maintenance options, becomes a balance of both toxicity and efficacy. We want to control the disease.