Good morning, everyone, and welcome to Compugen's COM701 in Ovarian Cancer and Unigen Platform Update event. At this time, all participants are in a listen-only mode, and a question and answer session will follow the formal presentation. To our analysts joining us live, please use the raise hand feature at the bottom of your Zoom under the reactions button to indicate you have a question. Before handing the call over to the company, please review the forward-looking statements on this slide.
I'd now like to introduce Dr. Eran Ophir, President and Chief Executive Officer of Compugen. 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. Michelle 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. We want to prevent progression of the disease. At the same time, we want to make sure patients preserve their quality of life. I just mentioned the role of bevacizumab being one of the agents that we use in this platinum sensitive and even in the platinum resistant setting. But there are many patients who are ineligible for bevacizumab. For example, some patients may have received it with their upfront treatment, and their cancers progressed while they were on it. Many patients have absolute contraindications. They might have fistulas, or they might have high blood pressure. There's a long list of medical reasons why bevacizumab might not be suitable for a patient. In addition, there are quality-of-life side effects that we see with this drug, such that some patients elect to not take bevacizumab and undergo observation.
Again, with the understanding that their cancer will progress at a certain time, but they value their quality of life in the current moment, so they go that route. For patients who are eligible for bevacizumab, it's something we discuss, and we offer as maintenance. We give it with the chemo and then following the chemotherapy. But for some patients, observation is the way to go because, again, it preserves that quality of life. The way we follow these patients is with periodic or regular clinical exams. We do scans about every three months or so of disease progression once patients have suffered a relapse. Next slide, please.
To fill this space, knowing that bevacizumab might not be appropriate for some patients and knowing that even patient preference might skew you away from bevacizumab and knowing that the idea of observation is something that patients might need to default to, we've continued to do research into trying to understand what other therapeutic modalities we can incorporate into this platinum-sensitive space to prolong, again, that platinum-free interval or decrease the time it takes for the disease to progress. And one drug category that's moving into this space are antibody-drug conjugates, either as monotherapy maintenance or in combination with bevacizumab. There is no doubt that antibody drug conjugates are effective. We have lots of efficacy data in the platinum-resistant setting. This is where these drugs are, and they've really reshaped the way we think about chemotherapy and therapeutic sequencing in this space.
T hat same logic, that if they work in the platinum-resistant setting, we need to move them up to the platinum-sensitive setting, either with chemo and/or as maintenance, is something that is actively being pursued in clinical trials. The results are too early to tell. We've had at least one study that showed no real difference in terms of progression-free survival, but this was using a different type of ADC. There are newer ones that are being tested, and those results will be seen soon. The one thing we do know is that adding an antibody drug conjugate, either with bevacizumab or by itself, increases side effects. That is the one guarantee we have. And we know this because these drugs have a well-defined toxicity profile that we've learned from the platinum-resistant setting.
For patients who are still trying to avoid a toxic option as maintenance, they're still going to have the same problem. We will buy some efficacy because ADCs work similarly to chemotherapy, but that will come at a cost of increased adverse events. Another issue is that the vast majority of our ADCs have a topoisomerase-1 payload. And currently, there's a debate in the field that because most of the ADCs we have are topoisomerase-1 inhibitors, if we use them in the platinum-sensitive setting or as maintenance and the patients progress or relapse, now they are coming in with increased toxicity burdens, maybe platinum-resistant disease. And the best treatment we had, which are the topo-1 ADCs, have now been expended as maintenance, which some people feel is perhaps not the best way to deploy or utilize this medication.
Now, that said, there's research going on on both sides of the fence to better understand this. There are pros and cons or certainly some notable reasons for why antibody drug conjugates may not be the appropriate choice for all patients as a maintenance treatment, especially in the platinum-sensitive setting. Next slide, please. Before we go into why COM701 might be an option in this setting, it is also worth mentioning that some of the other maintenance treatments that we've tried in the past, including PARP inhibitors, have since been withdrawn for this use by the FDA, the second-line setting. But in case some people were not familiar with that, in the past, we used to do or give PARP inhibitors as maintenance with or without bevacizumab. Most of the time, without. And this was because these drugs have their own toxicities.
And what we found was that even though initially they appeared to be helping, when we looked at overall survival, and we looked at the burdens of toxicity from these drugs, they ended up becoming detrimental in some cases and ineffectual in many cases. And that has since been withdrawn. Currently, anti-angiogenics like bevacizumab are what we have. Antibody drug conjugates have pros and cons with the most recent data we have showing that they're not efficacious as maintenance therapy. We need new options. One of the advantages of COM701 as an immune checkpoint inhibitor is its tolerability profile. We have some data in the platinum-resistant setting about its preliminary efficacy, and there will hopefully be a public reporter manuscript to this effect soon.
But one of the highlights of this drug was that we found that there was a subset of patients who, based on the mechanism of action of this drug, were having responses and durable responses without toxicity. As I mentioned before, the absence of toxicity is a highly prized asset in patients who are looking for maintenance therapy because they've had chemo. The chemotherapy has debulked the disease, and what they're looking for is something that can extend that benefit, that is also compatible with their quality of life. A key advantage of COM701 is that we know very well that it's very well-tolerated, and we know that it can provide a long progression-free survival in select patients. These characteristics make it a suitable candidate to be evaluated as maintenance therapy.
Because we're using it earlier on in a patient's journey before they become platinum resistant, all of our data currently with COM701 is in the platinum-resistant setting. We know that these patients are fitter, both clinically and also immunologically. There's a lot of data in ovarian cancer and other solid tumors that the more chemotherapy we expose to our patients, that physical frailty that we see in the clinic and that decline, there's also an immunologic reflection of this as well. For several reasons, and the ones I highlighted, looking at an immune checkpoint inhibitor like COM701 in a platinum-sensitive setting becomes something worth pursuing. Next slide, please.
The question then becomes, to what end? Immune checkpoint inhibitors have been studied extensively for GYN cancers with mixed benefits, and it wasn't until recently that we got our first approval in the platinum-resistant setting with chemotherapy, for platinum-resistant ovarian cancer. The key goal in the second or third-line platinum-sensitive recurrent setting is to maintain that platinum sensitivity. Because if we have a drug or a therapeutic that's reasonably tolerated, low side effects, is not chemo like an ADC or chemo-like like an ADC, and extends a patient's platinum-free interval, then we've kept them in that box that I showed you a few slides ago, in that platinum-sensitive setting. This allows them, in the future, if they progress, to be rechallenged with a platinum agent, a platinum doublet, and these patients can stay in that physiologic or biological, clinically defined box.
Providing a drug or a treatment that has low toxicity is important. Providing a drug that maintains platinum sensitivity is important. Inevitably, the longer a patient stays in the platinum-sensitive box, the longer it takes them to progress or evolve into the platinum-resistant box, the more we can perhaps benefit our patients in the long run. To briefly recap, the goal of COM701 studied as a maintenance after platinum doublet therapy in patients with second or third-line relapsed platinum-sensitive ovarian cancer, is to provide a clinically meaningful, well-tolerated option for patients who might not be eligible or intolerant to bevacizumab, which is the current treatment, with the hopes that this agent will prolong their platinum-free interval, keep them in that platinum-sensitive state, and also provide them adequate quality of life at a time when their immune system can be meaningfully engaged.
Thank you, Dr. Yeku. As a reminder, Dr. Yeku will join company management for the Q&A portion of our call. At this time, I'd like to introduce Compugen's Senior Vice President of Research and Discovery, Dr. Sharon Kredo-Russo. Please go ahead.
Good morning, everyone. Thank you for joining us today. My name is Dr. Sharon Kredo-Russo, and I'm the Senior Vice President of Research and Discovery at Compugen. I'm excited to share today an important capability we have built based on our established discovery engine. We believe this capability has the potential to bring value to areas with high unmet needs. As discussed earlier today, over the years, Compugen's discovery platform has generated multiple assets. Some programs are in early stages of discovery, some are in clinical developments, and several are being advanced through strategic partnerships. What is the engine behind all these discoveries? Behind all these discoveries stands Unigen, our AI-powered discovery engine, continuously connecting computation, biological validation, and clinical learning.
At the center of Compugen approach is our proprietary knowledge base. This is a computational engine, which is actually a collection of specialized AI-powered computational approaches and algorithms that are designed to study very complex biological systems. These algorithms prioritize hypotheses based on their therapeutic potential and select the right tools that are then applied across multiple data types. The discovery engine's output are potential novel immune oncology targets that are experimentally validated, resulting in the therapeutic drug candidates that have, over the years, entered the clinic. Clinical trial data then generates an additional layer of information that feeds back into our database and supports all our future and ongoing discovery efforts. It is this established engine that we are now expanding into a new opportunity space called the tumor-associated antigens.
Tumor-associated antigens provide a tumor address to the target therapies, directing the drug activity or delivery specifically to cancer cells while sparing the healthy ones. A bispecific antibody is engineered with one binding arm to the tumor antigen, while the other arm brings the modality. TAA plays a central role in many of today's promising cancer therapy modalities. For T-cell engager, the TAA brings the T-cells into direct contact with the tumor cells. For other targeted immune activation approaches, it may mean the tumor selective activation of immune pathway. Beyond immune engagers, for other targeted modalities such as ADCs, the TAA enables the local delivery of the therapeutic drug directly to the tumor cell sites. Across all these modalities, the target determines where the therapy goes and where the biological activity happens.
As a result, the TAA quality can directly influence both efficacy and safety. That is exactly where one of the larger unmet needs lies in the field today, the need for novel and selective TAAs. Focusing now on T-cell engagers, which have emerged as one of the most exciting modalities in oncology. Proximity in space to the tumor cells, resulting in their direct killing. This powerful modality has attracted substantial industry investments and growing market opportunities in recent years. However, the power of this high immune activation modality also highlights a fundamental challenge. A T-cell engager can only be as selective as the antigen directing it, and only few TAAs have the right profile of tumor specificity, low healthy tissue exposure, and high tumor coverage.
As of today, 12 T-cell engager drugs have been approved, validating this therapeutic modality, and yet only two in solid tumors where target quality is still a critical constraint. The figure below shows how we look at target profile signal across healthy tissues, where red means high level in the healthy tissue and green means low level.
One example of a clean target is DLL3. The approval of tarlatamab in small cell lung cancer targeting this antigen demonstrates how a favorable clean target profile can help to unlock the potential of the therapeutic modality. You can see how DLL3 is exceptionally clean with no red tissues at all, meaning it is mostly absent from the normal healthy tissues and expressed almost only on the tumor cells. On the other hand, mesothelin is an example of a different type of target. You can see here that the target is quite clean beside the red. That means high expression level in the healthy lung cells. As a result, the development encountered those limiting toxicity of on target off-tumor, meaning activity outside of the tumor in the healthy lung that indeed associated with its normal high lung expression of the TAA.
Actually, many targets display extensive normal tissue expression, as shown here, while others display different restricted pattern, and the TAA selection for the right indication has became a challenging task. As we believe that the powerful therapy is only as good as its target, we have expanded our established capabilities in target discoveries to build UniGenX , a dedicated engine for TAA discovery. We built upon our proven foundation of Compugen's knowledge base and combining biology, computational, and clinical validation. We start with the knowledge base and the upfront definition of the target's desired profile. Then, specialized AI-focused discovery tools integrate multiple layers of biological data simultaneously, spanning different omic types. Moving to the output, the platform first generate explainable target scoring. This prediction then undergo extensive TAA-specific experimental validation, including immunohistochemistry, normal tissue exposure, functional toxicity assessment, resulting in the drug candidates.
Ultimately, the output delivers differentiated opportunity, novel TAA, novel drug candidates, and patient selection matching the targeted therapies with the right patient population based on biomarker and target expression. But how do we find the right TAAs? As said, finding the right TAAs is a major challenge. Our approach is differentiated in several ways. First, it is a multidimensional approach. A target is evaluated broadly and deeply using genomic data, bulk RNA sequencing, single cell transcriptomics, proteomics, and spatial biology, and is assessed based on multiple parameters together. This is a versatile discovery platform. We match the defined TAA criteria to the desired specific modalities and the analytical approach to the biological questions, which opens opportunity across targeted modalities.
This deep biological understanding and explainability allow us to identify opportunities that may remain invisible or when viewed through a single data set, enabling us to uncover novel targets with the aim of translating them into clinical-stage therapeutics. How is our multidimensional multi-omics approach allowing us to achieve this specificity and understanding in novel discoveries? First, we start with search broadly. This means giving our algorithm access to a very rich biological landscape. The platform integrates information for more than 100 million single cells across multiple cancer subtypes, over thousands of tumor and normal proteomic samples, and a proprietary normal cell atlases composed of multiple tissues and over 100 healthy cell types. We believe that the data scale, however, is not enough, and understanding deeply means creating a multiparameter target profile for every target candidate.
We assess tumor specificity, patient coverage, normal tissue exposure, heterogeneity, and then calculate the potential therapeutic index. That integrated assessment is a defining element of UGenX used for an informed TAA selection. We integrate these multiple biological layers into explainable target scores. The graph shows two major scores the platform produces, predicted efficacy or activity on the Y-axis, and predicted safety or toxicity on the X-axis, with each dot representing a potential TAA, in this case, in colorectal cancer. Zooming in now on a specific target A that we have discovered with very high scores in efficacy and safety. The figure divided into different features that originate from the different omics data types, allowing us a deep understanding of the biological profile of each potential target relative to benchmark TAAs. This allows us to adapt each scoring system to the desired modality and its requirement.
Importantly, it enables stronger hypothesis and the ability to identify targets with potentially better profile than benchmark. But deep understanding is not only the scoring system, as we perform deep validation on every feature, and here is how the data look like. Evaluating multiple parameters such as RNA expression profile, the cellular resolution of the different cell types, and the protein membrane level in both normal and tumor tissues. Importantly, we experimentally validate each target localization through immunohistochemistry to identify tumor specificity across patient cohorts. Individually, we believe looking at each layer separately gives only partial information. But together, we believe that they build a confidence in the target differentiated biological profile. Indeed, we have several target candidates that have been prioritized for further experimental validation in our early pipeline. But what if we could expand the TAA discovery space beyond a single TAA?
We believe the target pairs can expand the TAA discovery opportunity. It is important because some therapeutic challenges may be addressed more effectively through a paired targeted approach. In an AND gated strategy, two targets, A and B, must be present together on the same cancer cell. The goal is to improve selectivity and sparing the healthy tissue. Therefore, the T- cells will only kill in the presence of both targets on the tumor cell and will not kill the healthy cells expressing only one of the targets. In an OR-gated strategy, either target C or target D can support killing activity of the tumor cells. The goal here is to broader tumor cell coverage within the patient and overcoming potential resistance mechanisms of down-regulating or mutating a single TAA. On the graphs below, light blue represent the tumor cells, while dark blue represents the healthy cells.
The top two rows show the expression of each individual target A on the top and target B in the middle, while the bottom row shows their combinations. As shown, upon dual targeting of target A and target B in an AND gated approach, tumor selectivity is improved, sparing the healthy tissue. The example on the right represents an OR gated approach from prostate cancer, demonstrating how combining target C on the top, target D in the middle, and either target C or target D in the bottom improves the coverage of tumor cells within the patients. We believe these approaches could significantly expand the discovery space from individual targets to rational target combinations that may create opportunities that cannot be addressed by conventional single target discovery approaches.
To summarize what we have discussed today, we started with Compugen's validated discovery foundation, Unigen, with a track record of identifying novel immune oncology targets, as discussed earlier today, and translating them into the clinic. On the right is UniGen X expansion of this foundation into new and broadly valuable space that include novel TAA discoveries to create differentiated opportunities for multiple targeted modalities such as T-cell engagers. Ultimately, our goal is to make a meaningful difference for cancer patients. First, we believe that a scalable discovery engine has a potential to generate multiple TAA-driven opportunities across solid tumor indications and modalities. We believe these discoveries could support future potential partnerships.
Finally, discoveries from our platform can potentially be combined with our current ongoing early programs. To conclude, we have created an expanded target discovery engine across IO field to support the next generation of targeted therapies, with the aim of achieving clinical meaningful therapeutic effect for unmet cancer indications. Thank you very much for your attention.
With that, I will hand back the call over to our operator, who will take us to the Q&A portion of our event.
Great. Thank you, Sharon. Yes, at this time, we will be conducting a question and answer session with our speakers. As a reminder to our analysts who are joining us live, please use the raise hand feature to indicate you have a question. We are going to begin with two questions we received over the webcast. The first one is, what is your platform's differentiation versus competitors, other companies looking for new TAAs?
Sharon, do you want to take this one?
Sure. Thank you, Tara. As discussed today, we are taking a broad, multidimensional, and multi-omics-based approach, together with a very deep biological rational understanding. We are not looking into a single layer of data sets, but we are looking on multi-parameter, multidimensional understanding of the tumor and the biology. Another aspect is that we built upon Unigen foundation in the IO field and the vast data sets that we have investigated and digested over the years at Compugen.
Great. Thank you, Sharon. The next question, what would be your first modality to focus on, and why?
As mentioned earlier, we can use the TAA discoveries for any desired targeted modalities. For example, an antibody-drug conjugate that brings the drug immune activation, as we believe in the power of immune activity that can be directed specifically to cancer cells, assuming we have the right TAA to select or the combination.
Great. Thank you, Sharon. Our next question will come from Stephen Willey at Stifel. Please go ahead.
Yeah, can you guys hear me okay?
Yes, we can.
Perfect. Maybe a question for Dr. Yeku. I know that we've seen some attempt at leveraging immunotherapy within platinum sensitive maintenance, I think with some differing results. How do you think the mechanism of COM701 has the potential to change the narrative around the use of maintenance immunotherapy? Maybe a question for the company. Just curious how you plan to leverage this discovery effort into TAAs, and is this something that you would look to build out your own internal pipeline, or do you see this more as an opportunity for various collaborative partnerships? Thanks.
Yeah, for sure. I can tackle the first part of that question. I think a lot of our efforts so far with immune checkpoint inhibitors as maintenance therapy for ovarian cancer, much of that stems from our understanding of the role of PD-L1 as a biomarker, and this was way back when. I think now it's better understood that this marker is not the most reliable one that we have because it's very dynamic. Many of these trials involve a combination of immune checkpoint plus chemotherapy, followed by immunotherapy or immune checkpoint inhibitors by themselves. Again, our understanding in terms of the effects of chemotherapy or concurrent chemotherapy with steroids and everything else, and the potential kind of opposite effect that that might have leading into maintenance, I think is becoming better understood.
There are a lot of trials now that are separating both of those things. I think the prior studies, one, because we weren't using an appropriate biomarker, two, because they were chemo plus IO followed by IO, which is a different strategy here. Those are the two first reasons. The third, and perhaps most important reason is that COM701 works very differently than a PD-1 checkpoint inhibitor of various, PD-1 or PD-L1. The PVRIG pathway has been shown to be specifically important in ovarian cancer, just in terms of the way it works via dendritic cells and, further down the line, cytotoxic T- cells, that I think a more disease-specific mechanism exists for COM701 that doesn't necessarily or hasn't necessarily existed for immune checkpoint inhibitors targeting the PD-1, PD-L1 axis.
Because we've separated out the cytotoxic debulking phase of our plan from the maintenance phase, again, all of the issues that we'll be concerned about regarding the myelosuppression or immunosuppression we get from chemotherapy and steroids, that's already behind us without necessarily jeopardizing the debulking effect that we're getting with chemotherapy. I think for those reasons, at least for me, it's reasonable to expect a different result than some of the other studies that we've done in the past.
Thank you, Dr. Yeku. I will take the second question about the utilization of the platform, either for internal pipeline or collaboration. I think that eventually the way we always handle it was right for our older assets. Some of them are in our pipeline, some of them are being partnered, and it's the same for Unigen and UniGenX partners. It really depends on what is right for the program. If we think that for the program, we can move it ourself and bring value and take it to cancer patients at the right settings and bring it in the right pace and eventually bring value to our shareholders, we'll take it ourself. If we think that there is a good reason why to partner it, and for different programs, it could be in different stages, then we could also partner.
I think overall, I would say that what you saw from us in the past is also the plan for our next asset. Sometimes we can partner, sometimes we can move it ourself.
Great. Thanks for the question, Stephen. Our next question comes from Bill Ling at Leerink. Please go ahead, Bill.
Hey, morning, everyone. Got Bill on for Daina. Just one from me. I am just curious, what is the path forward for COM701 now that there are several ADC trials ongoing in the maintenance setting? Do you have to run a phase III against those ADCs?
Maybe I can start, or maybe Michelle can start, and then Dr. Yeku can give his perspective. Michelle, you want to take it?
Sure. Happy to. Hi. Thanks. Firstly, in order to set up a pivotal trial, we would need to have the ADC already become part of standard of care to be able to compare. While the ADCs are all being studied in earlier lines of treatment as well as in platinum-sensitive maintenance, they've yet to actually be approved in that setting. At this point in time, for the patient population that we're currently studying COM701 in, the most appropriate standard of care would be bevacizumab, and that is one of the options that we would consider as part of a path forward. I think one of the other advantages we have with COM701 is because it's well-tolerated, it does allow us to combine it with other agents.
Let me pause. Maybe Dr. Yeku would like to also put in his thoughts around this as well.
Correct. Everything Dr. Mahler said is correct. In fact, we were deliberate when we were designing this study to avoid that particular question. These are drugs that are in different therapeutic classes answering completely different questions. Inevitably, there will be patients who will need an ADC maintenance strategy as part of their disease characteristics, et cetera. But we're looking for a population of patients who cannot tolerate the side effect burden of ADCs or who might be better served by receiving their ADCs in the subsequent line, either as a platinum-resistant therapy or someplace else. The reason looking at ADCs as a maintenance strategy and how combination trials in the future might be very challenging is because by the time the data that we're expecting for ADC maintenance comes out, everyone would've been looking at antibody drug conjugates in first-line maintenance. Newly diagnosed first-line maintenance.
All of the data that people are looking at for platinum-sensitive maintenance becomes irrelevant. The data that we get from [audio distortion] this study is above that frame because we're looking at a different population answering a different question. Whether or not two or three years from now the standard of care is to get an ADC in first-line newly diagnosed disease, it doesn't matter, as long as you're platinum-sensitive and you've received bevacizumab. Looking at COM701 as a maintenance treatment, if the results are positive, will be an option for you. If ADCs are approved as maintenance in the platinum-sensitive setting, a patient will have to sit with their doctor and decide, do you want to go through all the toxicity, get the benefits and et cetera with an ADC?
Or if you've had it in the first line or someplace else, do you want to use a different strategy, such as COM701? Looking at this from multiple different angles, I don't see a scenario where we would be forced or required to randomize against an antibody drug conjugate arm as a registrational strategy.
Great. Thanks, Dr. Yeku.
Great. Our next question comes from Leland Gershell at Oppenheimer. Please go ahead, Leland.
Oh, yeah. Great. Thanks very much for hosting this terrific event. Just a question for Dr. Yeku. Just wondering, you had mentioned bevacizumab being an option, yet there are many patients who either poorly tolerate it or are ineligible. Could you just tell us, in your experience, of those patients who respond to platinum, so therefore would be eligible in the maintenance setting, what fraction do you think that 701 would really be a preferred alternative to bev, looking at those for whom bev would not be a good option? I have a follow-up. Thank you.
Absolutely. I would say at least in our practice, it is as high as 40%. If you look at other non-U.S. sites where the use of bevacizumab is more strictly regulated, either to a platinum-resistant setting or first-line setting, or even certain parts of the United States, like the Midwest, some of the sites there actually reserve bevacizumab for either stage IV up front when patients have ascites and pleural effusions where they think it might be helpful, or in the platinum-resistant setting. In those particular settings, the proportion of patients who either because they cannot get bev or require something different is much higher than the 40%, and I would say as much as 60%.
Also recall that some of our patients, at least the way we have designed this study, they may have been previously platinum sensitive. They may have even received bevacizumab in a previous platinum-sensitive setting. And as long as they're platinum sensitive again, for a lot of those folks, the cumulative [audio distortion] report in their section has to decide, do I continue to bear with the bevacizumab, or do I undergo, I would say anywhere from 40%-60% of patients would be eligible for this kind of study, just looking at the population at risk.
Okay, thanks. The connection was a bit choppy, but I think we got the key message. Then just to follow up, with the ADCs sort of also being studied in the maintenance setting, it sounds like there's also some drawbacks there in terms of tox. Do you see kind of an efficacy bar, in which the ADCs could be preferred no matter what? Or do you think that because of the safety advantages, tolerability advantages of 701, that would still be an option that would have uptake irrespective of what ADCs are able to show? How does that calculus kind of play out in your mind?
ADCs are like chemotherapy. There are going to be some patients that even after six rounds of chemotherapy, they're still going to have a high burden of disease. They might have liver metastases, a population we have excluded in our study. Some of these patients might be on the verge of progression, and you want to give them more chemo. We think about ADCs as giving more chemo with slightly less side effects than conventional cytotoxics. Those are the patients we'll give, that will be continually eligible to get more chemo, and doctors will continue to give them ADCs. I think for the patients who's had a good response, so you've had your six cycles, you have no evidence of disease left, maybe you've even undergone a secondary subtle reduction, and you have no evidence of disease.
For those patients, an ADC, which is like more chemo, is overkill, right? You need tumor cells to be dividing to uptake the ADCs, and that's why the risks are justifiable. For those patients, a maintenance option that's very well-tolerated when you have no evidence of disease, I think clinically is going to be the choice. I envision a clinical scenario where if both are available and both have efficacy data, it's going to come down to individual patient characteristics and both can exist together. They just serve two different and distinct patient populations.
Understood. Thank you very much.
Thank you for the questions, Leland. Our next question comes from Chad Messer at Lake Street. Please go ahead, Chad.
Great. Thanks for taking my question and thanks for putting together this presentation today. Two great topics. On UniGen X, the data you showed on those targets A through D, very impressive. Appreciate you took the time to do all that. You got four validated candidates with qualified expression profiles, colorectal, prostate cancer. Is it possible to give us a sense of how many candidates have gone through this process so far to date? Maybe just an idea of what the next milestone we should look for from you guys is on the platform.
As we said, and Sharon said along the call, there are few that passed the computational part into validation. What we have shown is not necessarily yet validated. For us to really say that an asset is validated, there is a long way of validation and going through animal studies and ex vivo studies, et cetera. We put ourself a very high bar before we move it further. Yes, quite a few targets have passed through a few stages maybe, or definitely from the computational platform and out. There are still stages to go. First-in-class assets are always complicated. Definitely when an asset will be de-risked enough for us to communicate and to take commitments also with our investor community, then we will disclose exact timelines and number of assets moving forward. In this stage, there are few assets moving in validation, yes.
All right. Great. Thank you.
Thank you for the questions, Chad. We have another question that came over the webcast from Charles Wallace at H.C. Wainwright. For Dr. Yeku, what size of PFS gain would you change your practice here in PSOC? Does keeping a patient platinum sensitive matter beyond the PFS number itself?
Yeah. I'll answer those questions in reverse order. Yes, keeping a patient in a platinum sensitive setting is very important. I think, as I had mentioned before, during the pre-recorded or the previous discussion section, that serves two purposes. We think and we're refining our understanding, but patients who are platinum sensitive have a different biology of disease than those who are platinum resistant. We know this because many of our trials that we've gone from moving from platinum resistant to platinum sensitive, response rates goes up, PFS goes up. Everything gets better when you move upstream. We know there's something about the biology, something about the host, something about the resistance mechanism that makes these two different kind of buckets.
Of course, molecular testing will refine that in the near future, but for now, it's a very good rough surrogate that anybody can wrap their mind around that this group, platinum sensitive, it's upstream of platinum resistant. They tend to do better with almost any therapeutic as you go upward. There is intrinsic value in keeping patients there. From a practical point of view, patients who are platinum sensitive, regardless, you don't want it to be five days and strikes midnight, and it's exactly six months. But patients who are truly platinum sensitive, they're eligible to receive carboplatin Taxol again, or carbo-Doxil or a different platinum combination. They can then go on to another platinum doublet. With an ADC, they can do lots of things that a patient who's now transitioned into the platinum-resistant setting cannot do.
If you look at most guidelines all over the world, international and U.S., the recommendation for those folks outside of a clinical trial is single-agent chemotherapy. Whereas in the platinum-sensitive portion, we're still encouraged to use platinum doublets if you can because people feel there's value with that kind of dose intensification. Yes, there is intrinsic value to the physician and to the patient to remaining in the platinum-sensitive setting. Now, to answer the first question, which is: Is there a number that I would like to see? I don't have any specific one in mind. I think in oncology, we have certain numbers that are multiples of each other that make us feel comfortable. It's three, six, 12, 18. I don't think they mean all that much. Of course, the longer the PFS is relative to the observation, I would like that.
But if you're asking for, oh, would I feel more comfortable if COM701 maintenance gave me a 12-month PFS versus a seven-month PFS? That's a much tougher question to answer because I want to see, first of all, are they remaining in the platinum-sensitive setting? If yes, then for how much longer? I think all of us who've done Kaplan-Meier or looked at these distributions before, they're going to be on both sides. There are going to be some who are going to be on for a very long time, and we know this from our platinum-resistant COM701 data. Some of our patients end up doing very well for surprisingly long periods of time.
Of course, there are going to be some that are just going to be at the margin. But I don't have any magical number in mind. But I want a comfortable buffer between the observation cohort and the active treatment cohort or the maintenance cohort.
Thank you, Dr. Yeku. Then a follow-up to Charles's question. Beyond PFS, which endpoints matter most to you in terms of maintenance, time to next therapy, response to the next platinum, quality of life, and how much side effect burden will patients accept?
Quality of life is not an accepted, for better or worse, an accepted endpoint for our studies. I would argue that it should be, especially for me. Again, we were very deliberate when we designed this study to decouple the cytoreductive chemotherapy that patients were getting from maintenance. Unfortunately, people don't really do that. Most trials combine both of them together. You get both drugs, or they're one unit. This one is separated for that reason because the goal of maintenance therapy, if you think about it, is to maximize the benefit from the preceding debulking chemotherapy and also to maximize quality of life. What is the appropriate dial between both of those? Because of course, I can give you 20 cycles of chemotherapy and get a longer PFS. But the side effects, at some point, those burdens will become overbearing.
I think that will be a key distinction between drugs that work like COM701 or have a similar toxicity profile and anything else. Recall that in the past, we've looked at other drugs for maintenance for ovarian cancer. We've looked at weekly Taxol as maintenance. As ridiculous as that sounds in retrospect, we tried it. The PFS was longer, but a lot of the patients had permanent crippling peripheral neuropathy. We've tried other small molecule inhibitors like pazopanib, which we thought maybe not so bad, but these patients had appetite issues, weight loss. They had rashes, things that made it not suitable as a maintenance treatment. Even though I'm an oncologist and I like hardcore endpoints, in a maintenance setting, quality of life is important if you can show that it is truly active and not a placebo.
Again, that's why we decided to do the hard thing and study this as a placebo-controlled trial. Now, outside of that, we want receives or has a break, quote unquote, with maintenance therapy of eight, 12 months, valuable thing before they go back on chemo, go back on Taxol. Time to next therapy is important. The response to next therapy is important. We know that if we give certain PARPs in the platinum-sensitive setting, people's PFS, too, might be shortened. Their overall survival might be shortened. By giving them certain kinds of maintenance therapy, we can make problems downstream for the patient[audio distortion].
I would want to see time to next therapy. I would want to see PFS, too, on the next therapy. Because we're doing this in the platinum, we know they can just go back to another platinum doublet, and I can expect them to do well. We will not expect the same thing with PARP inhibitors. We've seen that from the PICCOLO study, and we may not see that from ADCs, and we've seen that from some of the recent data presented at ASCO.
Great. Thank you, Dr. Yeku. This concludes our Q&A session and the event today. We thank everyone for joining, and you may now disconnect.