Agenus Inc. (AGEN) Earnings Call Transcript & Summary

Good afternoon, everyone, and thank you for joining us today. I'm Stefanie Nacar, Chief Communications Officer at Agenus, and welcome to our first stakeholder webcast of 2026. Today's discussion comes at a meaningful moment for our company, one shaped by important progress across patient access clinical development and operational readiness as we enter a pivotal year for Agenus and for the patients we serve. Before we begin, a brief reminder that today's discussion will include forward-looking statements. These are subject to risks and uncertainties that could cause actual results to differ. So please refer to our SEC filings for additional detail. Today's program is designed to reflect the full arc of momentum we are seeing globally for manufacturing and execution to expanded patient access to the clinical evidence needed to support regulatory pathways. You'll hear perspectives from leaders who are directly shaping this progress. Garo and I will discuss recently closed Zydus collaboration and what enables operationally for Agenus, an expert clinical perspective on the expansion of France's reimbursed AAC program, including its relevance for sarcomas and insight into how growing physician and patient interest is reshaping our medical affairs infrastructure to support access responsibly and at scale. Following these discussions, Agenus' leadership, including Dr. Steven O’Day, our Chief Medical Officer; Jose Iglesias, our Chief Medical Affairs Officer; and Robin Taylor, our Chief Commercial Officer, will join Garo for a live Q&A session. Questions may be submitted at any time during the call to ask at agenusbio.com. So thank you again for joining us today. And with that, I'm pleased to introduce our Founder, Chairman and CEO; Dr. Garo Armen. Garo?

Thank you very much, Stefanie, and thank you, everyone, for joining us today. We've had patients and families, physicians, researchers, partners and shareholders, of course, all of them are our stakeholders. We appreciate your time and your continued engagement with Agenus. And all because the Agenus is on a very important mission, and we'll be talking about the details of that during the course of our session today. As we enter 2026, we're doing so with a greater clarity. And that means clarity means lack of uncertainty. Certainly, some of the uncertainty that we experienced in the second half of last year with delayed closing of one of our important transactions. So with the recent closing of our collaboration transaction, which involved the sale of our facility in Emeryville, as well as our sale of equity at a significant premium to market price. With Zydus Life Sciences, Agenus has strengthened our ability to go about our business. This collaboration secures long-term U.S. best biologics manufacturing capacity for us because it's the facility that we built and it's the team that helped build that facility and operationalize some of the wonderful capabilities of that facility. That will allow us to supply clinical and authorized access programs and support future commercialization, all with the same expert team, as I said, that we built. And just as importantly, it provides the capital that we need in order to be able to have a level of resilience to be able to execute our strategy with a high level of discipline and focus. And we've already started doing that in the first weeks of this year. As you know, we've talked about this, and I don't think the constituency that looks at us understands the full power of our accelerating momentum for patient access. This started in last September, with a surprise to the world of France's reimbursed AAC program. This is a program where every French citizen who is eligible for access to BOT/BAL can have access to it with the French government providing full reimbursement for it. And what began with colorectal cancer in this program has now in the last few weeks, expanded to include sarcoma and ovarian cancer. Even though colorectal cancer is the largest indication, sarcoma and ovarian cancer patients who have exhausted other means have a very significant potential benefit from BOT/BAL. And we, of course, published and presented this data in a major setting in at ESMO GI in -- I'm sorry, ESMO in Berlin. It wasn't ESMO GI. It was a big ESMO conference in Berlin, Germany. It was an important plenary recession presented by Michael Gordon, who was one of the participants in our previous webcast program. These decisions namely patient access, reflect more than regulatory flexibility. They reflect urgency and a recognition that innovation must reach patients who are in need, while the confirmatory trials continue. They're very important consideration because as you know, confirmatory trials can take a long time. And while we're pursuing those as well, access to patients before based on the data that we have generated significant data for that matter, is very important. So the urgency that we feel, the urgency that patients feel is well founded. When we speak about historically resistant cancers, we're talking about very specifically microsatellite stable tumors. And microsatellite stable tumors are in the form of many different types of cancers, and they represent more than 80% of all solid tumors. And importantly, more than approximately 95% of colorectal cancers. I just want to note that, for example, with colorectal cancer, you may have heard in the headlines that there are products such as PD-1s and PD-L1s that have shown some very impressive activity in colorectal cancer patients. But remember, those are less than 5% of the patients, the other 95% of patients targeted by our BOT/BAL are the kinds of cancers that don't respond to these other currently approved products. So at the same time of all of this, the societal burden of colorectal cancer is accelerating. Just last week, many of you may have heard that American Cancer Society and Journal of American Medical Association, JAMA, reported at CRC, unfortunately, is now the leading cause of cancer-related deaths in people under 50. We were expecting this to happen by 2030, but unfortunately for patients, and for the overall population, reaching this milestone is now 4 years ahead of expectations. This is not just a medical challenge, it's a societal crisis. In some countries, including France, are recognizing both the urgency and the potential value of immunotherapy and responding to it. And lastly, we have the BATTMAN randomized trial. It's an important trial for us, of course. And this is a trial that is going to be launched very, very soon. It is a trial rigorously designed for a global Phase III study in the MSS, metastatic colorectal cancer. Population, as we talked about, long considered beyond the reach of currently approved immunotherapies. Of course, the level of engagement we're seeing from investigators and cooperative groups reflects a shared understanding that we're very hopeful about the quick enrollment of the randomized trial. The early efficacy from a large Phase I and Phase II trials is driving this. When I talk about large Phase I and Phase II trials, we're talking about close to 500 patients worth of data that has been generated and now this will be tested in a randomized setting, which is next on the roster for us. Now looking ahead, taken together, these developments shape our priorities for 2026. Expanding appropriate patient access through authorized pathways, a very important initiative. You're going to hear a lot more about that during the course of the session and beyond, preparing for global regulatory filings informed by both clinical trials and real-world evidence. Now previously, as you know, we've had our challenges with the U.S. FDA in terms of filing for accelerated approval in the U.S. Well, there are also changes in the regulatory environment in the U.S. So we're going to diligently pursue filing in the U.S. for accelerated approval once again. And in Europe, things have been a bit more optimistic, of course, with the progressive way of thinking in Europe. We've had meetings with the European regulators, and they have been a lot more receptive for conditional approval possibility than historically what we have faced in the U.S. Advancing BATTMAN with urgency and rigor is a very, very important priority as well. And to be able to accomplish all of this, we're scaling up, as we speak, our medical affairs capabilities. And this is going to support growing physician and patient interest and responsibility. Our medical affairs team is represented by Dr. Jose Iglesias today, and you're going to hear from him, both during the webcast session as well as during our Q&A. So unquestionably, the role of immunotherapy is expanding. There's no question about it because chemotherapy and some of the other toxic therapies are archaic treatments, and we're confident that they will be either displaced completely by the new generation of treatments like immunotherapies or they're going to be used as adjunctive treatments to immunotherapy in the future, which is fine. And our responsibility to patients must expand with the expanding immunotherapy usage. And with that, let's begin.

Well, Garo, welcome. I'm very excited to actually be on this side of the fence talking to you today about a very exciting closure that we just had a few weeks ago with Zydus Life Sciences. We originally announced that deal back in early June of 2025. And finally, we went through a long process of getting that deal closed. Can you say a few words about that?

Well, this is a location that will allow us to have a definition on the next steps for our company, our treatment, our partners. And as you know, transactions take a long time. People don't realize that. They think that we come to an agreement, shake hands, the agreements are drafted, and here we go. It doesn't happen that way. Of course, there's extensive negotiation. And as you said, with Zydus, we really started negotiating well, well over a year ago. And then we came to a point of announcement last June. And of course, our expectation was that after the announcement would come to an expeditious closure, usually, transactions between 2 companies are governed by Hart-Scott Rodino Act, which is an antitrust regulatory act. In this particular case, it was added to that with the national [indiscernible] clarity that needed to be explored. And regrettably, that took about 6 months more.

I think we're going to get to talk a little bit more specifically about CFIUS, what you just mentioned and what that means. But maybe let's take a step back first, for those of our audience members that may not be as familiar with the deal or just joining us recently. But as you mentioned, you -- and the organization started conversations with Zydus Life Sciences approximately about a year ago, and certainly manufacturing is the heart of this transaction and this collaboration tell us a little bit about why Zydus Life Sciences and why this transaction of this collaboration is so important right now at this time of Agenus evolution?

Their needs and our needs had to really match up. This is a company that has a culture, it has the absolute right intentions for the people that they're serving, which includes, of course, their patients and their employees. Zydus is basically a company that has made its fortune in the generics business. It's a $10 billion company in terms of market value. A lot of their operations on the generic side of things is in the U.S., but they didn't have a manufacturing facility in the U.S. No biologics manufacturing and as you know, a number of high value-added biologics, particularly in the oncology field, are coming of age now in the biosimilar area, meaning [indiscernible] we're on very high value-added biologics are going to now be introduced as biosimilars in the U.S., of course. And to do that, you need to have a U.S. manufacturing facility. And so this is what it provides sides with. Our pipeline is, of course, driven by biologics and in our case, our lead programs, BOT/BAL, are two antibodies that we aspire to manufacture in our West Coast facilities. And the beauty of this transaction progress is that it will provide us with the capital that we need right now. And it will also give us a luxury of being able to use this facility for manufacturing with the team that was also the key players in manufacturing of our product.

As we have been testing BOT/BAL across more than 9 different tumor types across different settings of disease, both in the earlier settings through some of our investigator-sponsored trials as those as well that are in the later-stage disease, like the BATTMAN study that we'll be enrolling patients shortly. Your vision was to have a fully integrated operation in which we could serve patients faster, more quickly, control costs, housing manufacturing really from the beginning part of drug substance to supply to fill and finish and labeling all underneath 1 controlled setting. Manufacturing tends to be 1 of the most challenging aspects when you launch a drug to make sure you understand demand that you have enough inventory in place. Can you share with us a little bit about your vision for Agenus West and what you and the team were able to foster and build which was really the interest mark from Zydus Life Sciences to really utilize those facilities as their flagship locations for their CDMO business in the U.S.

You have a treatment that may be in high demand upon approval. You want to make sure that you don't find yourself of not having appropriate supplies of the product, that is the cornerstone of this treatment. And I've learned this lesson from many years ago with my affiliation with Immunex when for [indiscernible] arthritis product that was introduced, they couldn't produce enough and so they had to put patients on a lottery. So that has been impregnated into my head. And so many years ago, I thought that we wouldn't really want to find ourselves in such a predicament should our product be improved quickly and the demand for it should skyrocket. And that's why we want to have our own manufacturing. And so the Emeryville, which is a commercial facility, who fills that dream for everything is under [indiscernible]. And so with this transaction, we'll be able to meet our needs and meet the demand down the road with a partner who has the same vision that we do. There are honorable people that are in the business of serving the patients, and they have retained our entire team. This is a superstar team they were key in designing the facility, bring the facility up to where it is today, and they will be continuing with the leadership of our Chief Manufacturing Officer, [ Al Dadson ], who will be now a Zydus executive serving both Zydus and Agenus. So it meets our capital requirements and our operational manufacturing requirements. So it's the best of all worlds really.

I'm not sure if many people outside of the immediate industry understand that even for large pharmaceutical organizations, many times, the drug substance that you need to create the treatment is produced in one location, 1 continent and then get shipped to another facility and another continent for actually making the treatments themselves. And in other cases, it's been shipped to a third location for fill and finishing and labeling before it even gets sent to the different pharmacies around the world. So that is a lot of exchange of hands, a lot of transportation, a lot of operations. And for you to have the foresight to think about doing this within the U.S. on U.S. soil, particular given where the industry is now with tariffs of exporting pharmaceuticals. Share with us a little bit more about the confidence that provides and the element of the deal in which Zydus is going to be manufacturer for BOT and BAL throughout for clinical trials as well as for our French AAC program, which now is covering reimbursement for 3 different tumor types as well as our paid named patient program.

These are critically important questions, and we foresee those things many years ago because as you said, we had drug substance being produced in Seattle. It was being shipped to [indiscernible] Germany and then being shipped back to the U.S. and then back to a warehouse, every time this happens, it affects costs. There are risks associated with shipment. And it also affects timelines. Imagine our product visiting multiple continents if it can be made in 1 location efficiently. And that was the reason -- fundamental reason why we built the Emeryville facility.

You spoke about your visit right out to India during this process, and it was upon presenting some of our data to the KOLs in the region that the partnership actually expanded. This collaboration expanded to now include the ability for Zydus Life Sciences to develop and commercialize bot and Bow in India and Sri Lanka because of the data that they had seen and so that took a little bit of an additional component, which was a wonderful, I think, recognition of the data that we had presented previously. Tell our folks here on the line today a little bit more about that from Zydus Life Sciences perspective because they may only be thinking of them as a CDMO, but they actually have hospitals, clinical trial operations within that region of the world that could help also enable additional development of BOT/BAL. Can you share a little bit about that with us as well.

You mentioned they have hospitals. In fact, they have oncology hospitals as well. In fact, they have a hospital that also provides patients with free treatment. And so this is a very normal company. It's a very normal company, and we're delighted that they have these capabilities in India, that you spoke about, hospital capabilities as well as clinical research organizations that can streamline the development of a product or generation of clinical data. We visited with their Seattle. We visited with their hospitals -- several hospitals. And we also visited with the company. Over a dozen physicians, oncologists came from all over India, to Ahmedabad to meet with us. things got done in 1.5 days without any bureaucracy, and this is what we need to implement in our country.

When you and the team were out in India, a lot of the bureaucracy was kind of put to the wayside and real conversations were able to be had and alignment and an understanding was had in days time. Then upon returning closure and the announcement and the final closure of the deal seemed to take a very long time. So earlier, you had mentioned this point about CFIUS. Can you describe a little bit about what CFIUS means? And why this became relevant for this collaboration at this time and why now it's so important that we're able to move forward.

So over my career, I had always heard about it's got [indiscernible] [ HAHSR ] and that's very well known. Of course, the government is in the business of making sure that there is no monopoly, and that clearance for us took literally 30 days because there was no issue. I've never heard of CFIUS, but CFIUS has been in existence for a long time. It's a government agency that is sort of supervised overseen by the Department of Treasury, Department of Defense now is Department of War and also the Department of Commerce. And it's expressed purpose is to make sure that when a transaction takes place between a U.S. company and a foreign company that, that transaction doesn't pose a national security trend. A very important consideration, but the government is not really a specialist in health care per se. And so when this review got started, similar to [indiscernible], we thought it was going to be a relatively straightforward thing.

And then the government shutdown for 40 days within that time frame as well, right?

There was a perfect storm. So we had CFIUS officials very good people doing their due diligence, and it's a back and forth educational process of course because you don't expect these officials to know much about Agenus or much about Zydus. So there's an education that goes on about both companies. But to the credit of CFIUS officials. These people worked through Thanksgiving through some of the shutdown, through Christmas and through New Year's. All of this resulted in an expedited closure and expedited closure meaning it could have extended more.

So wonderful news that the closure came, and now we're able to move forward with many of the plans that we had set out for 2026. So tell us, as we look ahead into 2026, Garo, can you tell us about how that -- this collaboration and the closure enables us to effectively move forward with the execution of those priorities in 2026.

It's not a secret, Stefanie, that we came through a 6-month period where our financials were very challenging. No question about it, very challenging in spite of the fact that we have a treatment like no other in our industry. I'm a CEO that has worked for no cash compensation for an extended period of time. It is done because of a high sense of responsibility to the patients. Now we have more financial needs to attend to our priorities, given the data that we've generated data that has been presented at major conferences. It's been published amongst the most prestigious journals. Priorities for 2026 are very clear. Number one, we've seen a growing interest I must say substantially growing interest in our name patient programs, namely the paid name patient programs [indiscernible] France and outside of France. It is our more responsible is to make sure that, that demand is at honorably and with compliance. Number two priority of the company in the next 6 to 12 months is to make sure that we're on a path to file both in the U.S. and in Europe, for the registration of our product, even though the old FDA oncology division has not been helpful in endorsing a accelerated approval filing. We just heard from another company today that they are revisiting this, and they're going to go ahead and file for approval even though the FDA -- the previous FDA oncology did not. And the third priority, of course, is to do our randomized trial.

Thank you, Garo, and thank you for your time. I know that we're on to many other interesting conversations today talking about the French AAC expansion and the sarcoma data as well as later on talking more specifically about the need to expand our medical affairs infrastructure because of the incoming interest from both physicians and patients for utilization of BOT/BAL and the appropriate pathways. Thank you.

Thank you very much, Stefanie. Well, as we heard, the Zydus collaboration represents far more than a completed transaction for us, it reflects a year of deliberate -- even with the delays, a very deliberate planning to ensure that when scientific momentum accelerates, execution does not become a constraint, and that's what we've done. And so -- it must be also matched by clinical insights and responsible access, particularly for patients facing cancers, as we talked about, where options have been historically very limited. And that brings us to France's reimbursement AAC program. And of course, that expansion includes sarcoma. Sarcoma represents a very challenging cancer, one of the most complex and underserved areas in oncology. It is biologically heterogeneous often aggressive and has limited benefit from first-generation immunotherapies, and to help us understand why recent AAC expansion decision matters and what the emerging data may mean for patients. I'm pleased to speak with Dr. Robin Jones. Dr. Jones is a leading sarcoma specialist globally and an independent clinical investigators. And I'd like to now turn it over to that discussion. Thank you very much for joining us, Dr. Robin Jones. I was remarking before you join that you are not only a brilliant physician, but you're a physician who cares about patients, which is a very special attribute in today's environment where physicians are so busy and patients perhaps don't get as much attention and love. And as we know, one of the areas of greatest unmet need in oncology today, sarcoma. Dr. Jones is a specialist in sarcoma. He has been a leading sarcoma specialist at Royal Marsden Hospital in the U.K. and is widely respected for his work advancing new treatment approaches for patients with rare and difficult-to-treat cancers. Of course, sarcoma is amongst the top of that list. And sarcomas represent a very big unmet need in oncology. They are rare, they're biologically complex, where treatment options become extremely limited once patients progress and where immunotherapy has historically been of little impact. He has closely reviewed the BOT/BAL sarcoma data and was an author of the peer review manuscript published last year in the Journal of Clinical Oncology as well as a broader pan tumor Phase I data presented at ESMO 2025 just a few months ago, which included patients with sarcoma as well as 6 other tumors. Given his frontline experience treating these patients and his independent perspective on the data, we felt that Dr. Jones was uniquely positioned to help us understand what these results may mean for patients? And why recent decisions to expand reimbursed early access in France are so important because they include sarcoma. So Robin, thank you very much again for joining us. If I may start with some opening questions. Many people aren't as familiar with sarcoma. It is other tumor types. Everybody knows what breast cancer is lung cancer, it is kidney cancer, it is colon cancer now. Can you tell us what sarcoma is and why it remains one of the most complex and difficult cancers to treat.

Well, thank you so much for the invitation and Garo, and it's a real pleasure to be with you today. So to start with sarcomas are tumors of connective tissue, so the bits that joined the body together. So that includes bone, cartilage, muscle, fat, et cetera. And the word sarcoma is derived from the Greek word sarco, so saw flesh or fleshy substance. And because of this, because their tumors have connected tissue, the first point to make is that they can occur anywhere in the body. And this makes them very difficult to diagnose and you've already alluded to 2 other major challenges in terms of diagnosing and treating sarcomas. And the second is that sort of rarity, i.e. that they account for about 1% of adult cancers and then the third point is that they're very heterogeneous. So there are over 80 different types of sarcoma each with its own different biology and clinical behavior. So those 3 things together, the fact that they can occur anywhere in the body, the fact that they're rare and the fact that they are very heterogeneous and lots of different subtypes makes them extremely challenging to diagnose and treat. And superimposed on this is the fact that they can affect anybody from the age of -- from infants to people in their 90s, make them incredibly challenging to treat and diagnose.

Many years ago, Robin, we were told that certain sarcomas can respond to immunotherapy because they may be ideally suited to do that. But the first-generation immunotherapies have not really done a very good job with that. But what does the current treatment paradigm look like for sarcoma.

Gary, in terms of the majority of soft tissue sarcomas, the current treatment paradigm for local disease, so localized tumors consists of complete surgical reception with or without radiation. The role of pre and postoperative chemotherapy remains under discussion, although that over the last 10 years, there has been a shift towards using more preoperative chemotherapy in particular. But in many ways, the sort of major unmet need remains the treatment of metastatic disease. And for a lot of soft tissue sarcoma subtypes, this really hasn't changed, it's still a one-size-fits-all approach for most patients with multifocal metastatic disease where we use chemotherapy, older chemotherapy drugs such as doxorubicin and [indiscernible]. There are salvage -- schedule salvage treatments that are effective. But as I say, it's still very much a one size fits all for many soft tissue sarcoma subtypes. And there's a huge unmet need. As you mentioned, the first-generation checkpoint inhibitor trials have been, to a certain extent, disappointing for most sarcoma subtypes, apart from notable exceptions such as [indiscernible] soft part sarcoma, potentially undifferentiated pleamorphic sarcoma and cutaneous angiosarcoma as well.

So just the fact that you're citing all of these different sarcomas is confusing enough. And if I heard you properly, you said, even though there are standards of care, one size fits all. There's a wide variability in terms of outcomes. And of course, once patients recur or the disease becomes metastatic, I'm assuming that the treatment can be all over the place. Why is there a high level of interest in, for example, all in the treatment of resistant or recurrent or metastatic sarcomas.

So you're absolutely right. For patients with symptomatic multifocal metastatic disease, the current treatment options are extremely limited. As I mentioned, the deem therapy options can help some patients, but there remains a huge unmet need for well-tolerated treatments that drive durable benefit. And I think the -- as we discussed at the ESMO meeting in Berlin, the data from the early stage BOT/BAL trial, the sarcoma specific data, very promising in that respect both in terms of the safety of the combination, but also the provisional efficacy data. So I think that's got a lot of sarcoma experts interested and keen to explore this combination in sarcomas and particularly in angiosarcoma.

BOT is a CTLA-4 targeting anybody, but it does a lot more than just targeting CTLA-4. Can you also tell us a little bit more about why do you think BOT is showing the kind of activity that hasn't been seen before in a challenging tumor like sarcoma.

I think the major point regarding the publication, the data published in the JCO is that the activity of BOT, I think, is probably superior to the other agents out there. And the fact that it seems to improve the efficacy of immune checkpoint inhibition, particularly in immune cold tumors such as sarcomas. And the majority of sarcomas are particularly immune cold. And I think it's that activity of BOT in these immune cold tumors that is a crucial factor in the success that we've seen so far with the combination, particularly in [indiscernible] sarcoma.

And that's a type of a sarcoma that really doesn't respond to much of anything, particularly immunotherapy. And so when you see these kinds of responses in a very difficult sarcoma and the durability of these responses, once there is a response with an immunotherapy agent, that response is more likely to be durable. So how much of you and your colleagues sense of the data is driven by that durability phenomenon, the tail of the curve that shows any responses that you see can be long lasting. So how do you interpret all of that in the context of your experience?

My experience with the combination has been very favorable. I've had patients derive durable benefit from this treatment. And I think as you've pointed out, the context is really important. Many of the other treatments that we have to treat. Sarcomas can actually result in a response or stabilization of disease. But again, crucially, it's that durability that is an issue in terms of the treatments can work for a period of time, but the nondurable and when we had the trial opened in the U.K., I was impressed, as I mentioned, with the -- not only the efficacy and the durability of benefit with the combination, but also the exceptional tolerability of this particular combinations.

Now most recently, the French authorities granted BOT/BAL, a reimbursed use in CRC, colorectal cancer. And we all know the colorectal cancer is a major problem today. And in fact, I spoke to 3 patients over the weekend, and we're getting these unsolicited inquiries, and these inquiries are translating now an increasing number of reimbursed patient treatments in France, French authorities are quite sophisticated when it comes to oncology. They're also very sophisticated based on our previous experience when it comes to immunotherapy. So how does it affect you and your colleagues in sarcoma. To have the French authorities provide government reimbursed allowance for sarcoma now after CRC, we have sarcoma and ovarian cancer. What does it say in terms of your confidence that even the regulatory authorities are making a move in the right direction with these small steps.

Yes. I think this is great news and great news for patients. I have very frequent e-mails, letters from oncologist. So all over the U.K. asking about access to bottom Bell either through a trial or expanded access programs. And I think for French patients, this is fantastic news. And opens the door to another treatment option effective treatment options. So I think it's really, really good news. And I hope that other regulatory agencies. Other countries will follow suit in time, we'll be able to access the combination in the U.K. as well. But the bottom line is, I think this is absolutely great news.

What can we expect that would be the best outcome for patients and their physicians, particularly in your field?

That's a fantastic question. I think in the sarcoma community, we're all very excited about the activity of BOT/BAL, and we hope that we can proceed with a registrational clinical trials so that more patients around the world will be able to access this combination. As you and I have discussed as such an unmet medical need. And I'm really, really optimistic that we can collaborate and develop this clinical trial and lead to registrational approval for the combination.

Thank you very much, Dr. John. As you said, expanding access is not simply about availability. It's a sense of responsibility, sense of duty to patients. And as reimbursed and authorized access expense, particularly across multiple tumor tags, it brings with it a responsibility to ensure that patients are treated thoughtfully, physicians are appropriately supported and real-world data are captured in the process. This is especially critical as an interest grows well beyond friends. As we said, we're getting inquiries now and we're treating patients in real time with out of pocket reimbursement driven by physicians seeking options for patients who have few remaining alternatives. And some of these patients, unfortunately, are desperate, many of them are. Meeting that demand requires an appropriately structured infrastructure, a disciplined approach, and of course, clinical leadership that is dedicated for this purpose. And to discuss how Agenus is scaling its medical affairs organization to support this growing interest while maintaining scientific integrity and patient safety. I'm pleased to be joined by Dr. Jose Iglesias, our Chief Medical Affairs Officer. Jose?

[indiscernible].

Welcome to our forum. We have been doing. As you know, we have been doing these webcast, discussion sessions. I think this is our fourth or fifth time, but they're very informative, and I am delighted that you're joining us because you're a newcomer to the company, but you have 30 years of global experience in oncology. You're a physician yourself and you've also been involved in immuno-oncology drug development. And most recently, you had senior positions at a number of smaller companies. But prior to that, your Chief Medical Officer, at Abraxis. You're also a Vice President of Clinical Development at Celgene. And so -- you've also offered, I believe, more than 70 peer-reviewed oncology publications. So that's no small feat, and you've earned your medical degree in Uruguay, then you've done a fellowship at the Weitzman Institute, the famous Weitzman Institute in Israel. You've been at Duke University, and University of Toronto. After this career, what brought you to Agenus. Why did you decide to come to Agenus?

Well, where do I start? I mean there are several factors, Garo. First of all, the innovation and the science. I mean I was always attracted a science was actually what drove my career all along. When I discovered the developments that Agenus was conducting in immuno-oncology, that really caught my attention. And when I dug into the science, all of a sudden [ I was like ] I was not too familiar with it. I was really impressed. The world of immuno-oncology is dominated by a number of immune checkpoint inhibitors. But when I discovered the uniqueness of botensilimab or BOT for short, as we all know it, it really opened my eyes to a very new domain. I mean the activities are shown in tumors that normally do not respond to immuno-oncology. That was a very powerful magnet for me. I'm thinking of the implications that it could have, many patients have tumors that are without the reach of immuno-oncology. So providing a solution and a hope to these people is extremely important.

Thank you. Now to get more specific, I had the pleasure of listening to your presentation to a group of doctors recently. What is the most compelling nature of the data that you cite from a physician's perspective as well as a patient's perspective.

We have a large database of patients, as you know, more than 1,200 patients receive this innovative therapy and the results have been striking, not only in metastatic disease, which is with the bulk of their work started, but in new areas like [indiscernible] therapy or treatment prior to surgery. And every physician I talked to or have discussed the data with have shown a lot, a lot of interest. I actually get statement I'd say, "Oh, I can't wait to get my chance how soon can I treat my patients with this" because it is a significant advancement in immuno-oncology. I mean for a time, [indiscernible] inhibitors have been around for several years, but none to this time has presented this degree of innovation and promise like botensilimab has.

So if you can give us some sense of what you're heading up at Agenus. And some of the ways with which patients and doctors can be treated with BOT/BAL with existing programs.

In France is the authorization of compassionate access. And this is an initiative that is fully reimbursed by the French government. In addition to that program, there is the opportunity for patients who live outside of France and are not eligible for not being French citizens to participate in the program through cross-country health care arrangements like the existing Europe is reimbursed by insurance companies in their country of origin or if that's not possible, they can also provide self-pay for the program. So the therapy is not denied to people who need it. And I think that's a very important spirit to exert in a program like this. And not having just 1 way to access a drug but several routes to make the streaming available. Medical affairs is supporting all this, of course.

France government is paying reimbursing for the use of the product for French citizens. And there are other countries you said where the product can be made available with special insurance or out-of-pocket pay and are you seeing traction since you joined us in terms of at least tangibly going through the process of governments reimbursing and patients paying for product through other means. And beyond France, where are we seeing activity, if you will.

Well, let me tell a little bit about France at this moment. We have 60 total inquiries from physicians. But side of France, we have several countries in Europe and also in Latin America, providing access to these patients to the named patient program. And again, this can only increase with time as the knowledge increases. Publications and conferences have divulged a lot of knowledge that have actually generated all this interest. So we are actually receiving comments and requests from physicians from several countries. France is, of course, the main one because the program started there. but we are hearing from other parts of the world, as I mentioned, Latin America and other countries of Europe as well. So we're very pleased with hearing this interest and as a result of that, we are beefing up our medical affairs division to cope with this increased interest from physicians.

So tell us, now you've started building a medical affairs department.

Well, as you know quite well, we are already quite emerged into the process of building medical affairs. I mean this increased demand and interest has to be met with resources because otherwise, everybody loses. I mean the patients that are waiting and the physicians are also waiting to start this treatment as soon as possible. So we have hired a Vice President of Medical Affairs who is based in Europe, is based in Switzerland but is French and with strong connections to the environment. He's an oncology. So in the process of hiring right now, medical scientific liaisons, or MSLs, for short. Some other people call them regional medical liaisons, or RMLs. But they are professionals with PhDs and MDs that actually have participated in this kind of activities of Leasing between companies and sites and patients before. And they are the direct conduits for all kinds of requests and initiatives that originate insights to actually maintain a constant dialogue with them. And that is ensured not only just to know what's going on at the sites, but to make sure that every request for compassionate access is properly assessed evaluated and authorized. There are some eligibility criteria, some selection criteria that need to be met. And this criteria are very strict and also about the request of the French government we need to observe what happens with these patients, collect data and reported, which is of great importance because the data that comes from clinical trials, like the ones we have embarked in the large Phase III BATTMAN study. Those are very selective populations very strictly chosen from the patient that comes through the door every day. So they are not representative of the general population. This program, the compassionate access program provides what is called the real world experience. This data is absolutely invaluable. Regulatory agencies, including the FDA and the European Medicines Agency is increasingly looking at the value of this real-world data and for that to happen, as you can imagine, there has to be compliance from the sites. There has to be vigilance from our side, not only in terms of data compliance and data entry, but pharmacovigilance. I mean we need to know how these patients are doing, safety-wise, we need to know how they are doing efficacy-wise, and that information will be supplementary to whatever we file with regulatory agencies in every part of the world. One of the other reasons that we are expanding the medical affairs division because as people may have known recently the European agency, the French agency authorized reimbursement for 2 other indications that were not the original ones. The original one was colorectal cancer, and the 2 new ones are ovarian cancer and sarcomas. So there is an increased number of patients beyond colorectal cancer that now have the opportunity to receive this innovative treatment. And again, we're very happy at the vision of the French government to have increased access for the French population. So all this translates into a lot of work for us, and we need to have a good and robust medical affairs division to actually face this program and make it work.

Thank you for that. So it's our responsibility. It's our privilege actually to make sure that patients are served, what is the best outcome from a patient's perspective.

So our hope and desire is that patients with late disease who have exhausted all available therapies as the program requires can have prolonged time of symptoms, not free of disease, but free of disease progression. So increasing the time of progression and ultimately increasing survival. When you are a cancer patient and not at this stage, every minute counts. So prolongation of life is important to meet milestones and at the same time, with the quality of life. There's no point in increasing life if you have to suffer the pain of chemotherapy complications or radiotherapy. BOT/BAL is chemotherapy and radiotherapy free treatment, which you can imagine after patients have been bombarded with multiple things during the journey of the disease, arriving at a point where that suffering could be at least helped or remote in addition to prolonging enough time to be with their families and at the same time, not suffering from the tumors that they carry. That's a satisfactory outcome for us and for any physician that cares of oncology patients. There are more than Kaplan curves. They are more than confident in terms they are more than p-values. These are things that are important in terms of science, but they are very measurable in terms of human outcomes.

What do you see Dr. Iglesias as the medical affairs will in making sure that what is available in France for patients also becomes available throughout the world for patients that need it. You cannot treat a patient in the U.S. either with government pay, like the AAC program in France or out-of-pocket. And so patients are not allowed to make a choice. If a patient in the U.S. wants to be treated with BOT/BAL, they have to travel to a different geography. Can you imagine a patient that is suffering from cancer, you're going to have to travel to the U.K., Switzerland, France or South America to get treatment. I mean it is unconscionable. So what can we do, besides formal approval -- of course, we're going for formal approval. That's a very important part of our agenda. But as soon as possible, how do we make treatment available to patients as expeditiously as possible without enduring any additional hardship. How does medical affairs play a role.

That's an excellent question, Garo because there are 2 prongs to this. One of them is what we can do, and there is what the countries individually can do. talking about the latter, I would wish that more countries follow the example of France that they have the illuminated challenge in order to recognize the value of the data and act accordingly by the French city -- the French government has done for their citizens. Now from our side of medical affairs, education and physician contract is absolutely key. And that can be delivered in many ways. I mean, in France through the America Scientific liaisons and ourselves, as we mentioned, and in other places, we take advantage of course of conferences and meetings, they are lectures, they are invited symposia where data can be shared and discussed with physicians. New data always needs discussion.

I'm hopeful that the new professionals, leaders of the health care system in the U.S. now may be much more patient-centric. So I'm hopeful that perhaps these changes may happen quickly because cancer cannot wait cancer doesn't wait, doesn't take a day off in its efforts to grow. So this will be critically important for us. Any final comments from you?

My enthusiasm is being fueled every day.

That's a consistent theme: Scientific momentum, patient urgency and operational readiness, of course, are converging, and they must move forward together. Expanded access programs provide immediate for patient in need, Clinical trials like BATTMAN provide the evidence required for lasting change even with bureaucratic regulatory organizations and medical affairs ensures that both are executed responsibly, ethically and with patients at the center. Taken together, these efforts reinforce why 2026 is such an important year for patients and for Agenus. And why the work ahead matters so deeply for everybody? With that, let's turn to your questions and continue the conversation. Stefanie, back to you.

Great. Thank you so much, Garo. And thank you for all of those that are still staying with us on the line for some of the live Q&A. And thank you again to our doctors, Steven O'Day, Dr. Iglesias and Dr. Robin Taylor for joining us for the Q&A. So without further ado, let's jump in and get started. I actually have received a number of questions via [email protected], so please keep sending them forward. And I do have some questions as well that we didn't get the opportunity to answer during our last webcast. So if they don't get answered today, we will be sure to address them as soon as we can. So the first question here is actually going to be for Dr. Steven O'Day, so the first question for you, we've commented a number of times that BOT and BAL have been studied in over 1,200 patients either bought alone or in combination with BAL in over 9 different tumor types, collectively from studies that Agenus has sponsored or investigator-sponsored trials across different stages of disease. The question that came in was how broad can BOT/BAL be applied? And can you maybe share some just high-level overview of the tumor types that we have studied BOT/BAL. Obviously, there's a lot of specifics related to biomarkers and diseases tend to be a number of diseases 1 tumor type. So this is a very general question, but this particular person unfortunately, has had a lot of experience with family and friends with a lot of different tumor types. So I was very curious just about the expansiveness of our development program with BOT/BAL.

So thank you, Stefanie. It's a great question. So why is BOT/BAL impacting so many tumor types. With traditional oncology where you're attacking the tumor specifically through targeted therapy or chemotherapy, it's much more specific for disease. Here, with the immune system, we're actually not targeting the cancer specifically. We're targeting T-cells and activation to these very important primal checkpoints, CTLA-4 and PD-1. And botensilimab, which is the next-generation CTLA-4 is really the magic of the combination that is driving these T cells to recognize tumors more broadly, even tumors that stay hidden to the immune system historically. And this is the large proportion of solid tumors. So it's not surprising to me that when you have an effective CTLA-4 like botensilimab and a PD-1 that is its companion and you're activating and expanding these T cells against multiple neoantigen targets that were not restricted in tumor types. And I think our data in our large Phase I data, particularly the more than 400 patients that we presented in a plenary session at ESMO this year really speaks to the consistency of the data across these tumor types and the French government, as Garo and Jose have recently just talked about, is really recognized not just MS-stable colorectal, but sarcoma and ovarian, 2 other of the 9 different disease types that we're showing these consistent.

Yes, I think that's really important, and it's a very helpful description and a way to take a look at it because I think everyone historically is not very specifically about treatments targeting certain tumors themselves, and this is really activating the immune system to combat the cancer. So for those of you that are more interested, there's publications that are listed on our website, if you want to take a look more about that across a number of different tumor types as Steven just described. I think our Phase I included colorectal cancer, ovarian cancer, hepatocellular lung. There's been investigation in sarcoma as well as melanoma and in some of the ISTs, there's even been triple-negative breast cancer others. So we're very excited about the breadth. And with the data that Dr. O'Day has referred to previously at ESMO that phase 1 showed a lot of consistency across many tumor types supports the explanation that he just shared. So thank you for that explanation, Dr. O'Day. The next question here that I've received, I'm going to pitch this over to Garo first. And then if others on our panel want to join in, it has to do with our named patient program. And the international access programs are expanding. We've heard about the additional tumor types that France is now included in their protocol. Can you share as well what signals this might be providing to Agenus in validating this as a potential global pathway or expansion pathway to other countries? And are there other countries that are enabling the similar pathway, either through a paid name patient program or a specific pathway like France, which is uniquely reimbursing that from a government perspective.

Thank you, Stefanie. By the way, you mentioned the -- our website being a resource just for everybody's benefit, we have a wonderful, brand-new website. which is very patient-centric. So we welcome everyone to visit our website and see the is with which information has been available now since the launch of this website, which is only about 2 weeks ago, I think, and that it is improving with additional comments coming in. But more directly addressing your question, as I mentioned earlier, France happens to be a very sophisticated regulatory agency, they have been sophisticated in oncology reviews. They've been also very sophisticated in understanding of immunology. And we're very grateful that they consider this an important treatment for patients and that they have not only allowed access but also providing reimbursement for patients, which is a very significant commitment. Now beyond France, there are other countries such as the U.K., Switzerland, some of the South American countries like Brazil and Argentina that allow for out of pocket pay or pay through special insurance that patients may have. Now we're -- with the expanded medical affairs team, we're attempting to expand those geographies where not only patient access may happen, but possibly reimbursement by governments may happen as well. And those include some of the Middle Eastern countries as well as some of the Asian countries. And since Dr. Iglesias has arrived at Agenus, those are being pursued with rigor and all with a very high sense of responsibility for patient's sake. It is an important consideration for us to make sure that patients who need treatment and badly needed treatment like BOT/BAL, either for end stage patients that don't have any other alternatives or even, in some cases, for earlier-stage patients that they have a path forward. And so that's something very important for us to expand.

Thank you, Garo. And I don't know if we had a follow-up question that it relates to specifically the French AAC program. And now with the expansion of the 3 different tumor types, is there a number that we expect to treat. I'm not sure that we can answer that specifically, but we know that interest continues to come in. Maybe very broadly, you could just comment on that and talk to the preparations that the organization has to be able to fulfill requests as they come in.

A couple of thoughts on this. Number one, when we were interviewing -- I mean, taping for this show, which was less than 2 weeks ago, Jose mentioned in his tape clip that we've had 60 inquiries. Now I just want to caution everybody to understanding that not every inquiry translates to treatment and reimbursement. However, in France, a reasonable proportion of these inquiries are translating to reimbursement and treatment. So he mentioned 6 inquiries have come in. Now the total number of inquiries that we've had are more than double that. So this is happening in real time. And just to make sure that there may be concern out there, we're expanding in medical affairs, and we're expanding in a way where it costs us money. One of the reasons we terminated unpaid name patient or compassionate use programs is because we're a small company. We have already spent billions since inception 31 years ago. And it's not really feasible for us to provide product for free going forward. That's the reason why we converted our compassionate use programs to paid name patient programs or government reimbursed programs like the one in France. So with that in mind and with the ramping up of our medical affairs team, based on the current trend, I expect that our expenses associated with medical affairs will be many times covered by the revenues that we get from paid reimbursement programs. So I just want to make sure that, that is a clear understanding by the viewers. And that's not because we're a greedy company and clearly, we're not going to become a highly, highly profitable company like the major pharma companies. But this will go some ways in terms of reducing our burden, if you will, financial burden.

Thank you, Garo. Let's see, I'm looking at the question that we had received last time, but we were unable to answer. I think this is probably one of the closing questions. So post Zydus. We had mentioned a couple of times in 2025 what our annual cash burn target was going to be and what we were trying to do to enable a real focus on our investments and our financing to be focused on enabling broader access and registration for the company. So can you maybe share a little bit of guidance now that the Zydus deal has closed and a lot of overhead related to manufacturing facilities in California, what is our cap rating burn rate anticipated now for 2026?

So just once again, for everyone's understanding, we have reduced our cash burn, operating burn very significantly in the past 2 years to the point where our current operating cash burn, not counting revenues coming in from, for example, the paid access programs, not counting those in because it would be premature for us to plan for that. Our operating cash burn is approximately 50,000 -- I'm sorry, I wish it was -- $50 million a year. I wish it was $50,000, but it isn't. So it's $50 million a year operating cash burn. Now at the closure of the Zydus transaction, we filed this -- our cash position was a little over $60 million. So the question may be from shareholders, how do you get from $91 million to a little over $60 million in cash on the balance sheet. At the close of the year, we had essentially no cash. I mean it was down to the bone, as they say. And with the Zydus transaction, there are a number of obligations that we have had to meet simultaneously with the closure of the transaction. They included, for example, purchasing the equipment from the leasing company that goes along with the manufacturing facility, it included some of the closing costs. It included some of the monies that we owed third parties. And so -- and it also included an escrow, $7.5 million of the proceeds received went into escrow for a period of time. So net-net, we ended up with over $60 million. And with an operating cash burn of $50 million with potentially revenues coming in, not counted in that projection, we think we'll be able to manage our affairs with our operating burn for the balance of this year and perhaps into next year.

Great. Thank you for that clarification. And Robin, this last question is going to be for you. And this might be a little bit harder to quantify. But the question is given all the tumor types that we've investigated BOT/BAL and one of the questions here is -- how big is the potential slice of the pie, so to say, here from BOT/BAL and I know that's going to be really hard, right, because we're in so many different tumor types, and there's lots of different ways to take a look at this. But I think perhaps maybe how we could describe this or maybe that you could address, particularly looking at the example of colorectal cancer and how much MSS disease is in colorectal cancer versus how it's being addressed today and how prevalent MSS is in solid tumors, just to give an idea of the potential application, if it were to work in different tumor types, really how broadly MSS disease is cross-sell tumors.

Thank you, Stefanie. Well, let's start with colorectal cancer because in colorectal cancer, there is a small proportion of colorectal cancers that are hyper mutated. They're called microsatellite instability high. It's about 5% of the metastatic setting, and it's about 15% in early-stage disease. So for those patients, immunotherapy is very active because there are lots of mutations is like melanoma or lung cancer. But for 95% of the patients with metastatic colorectal cancer, they don't have that -- those high mutation burden. And to date, immunotherapy is not being particularly active. PD-1s are clearly inactive. First [indiscernible] 4 has had some level of activity, but not to the extent that botensilimab does. And so we have this opportunity beginning with the Phase III in the late-line setting to be able to provide patients with really the first really active immunotherapy in this setting, that's 1 setting. But within colorectal cancer, we already have data now generated in combination with FOLFOX and Avastin, which is the first-line standard of care. We have a study ongoing at Duke University, looking at BOT/BAL alone prior to chemotherapy. And then finally, we have remarkable data in early-stage disease from 2 different investigator-sponsored studies in colorectal cancer, both demonstrating that one dose of BOT and 2 to 4 doses of balstilimab can generate pathologic complete responses those patients, in the data that was reported last year at ASCO GI. There would be no recurrences of any of the patients who had been treated with the combination. So colorectal cancer is a very large tumor type. Just within colorectal cancer, this is a multibillion-dollar opportunity just talking about the late line setting and that early stage neoadjuvant setting. Adding in the frontline setting as well, where there's a big possibility expands that even further. And then you started the question by talking about, okay, where else outside colorectal cancer is their potential. And we've already seen this in our Phase Ib. We've seen that there is significant activity in other tumor types, ovarian, hepatocellular carcinoma lung cancer. And so there is this potential to expand into many other tumor types. If you think about where immunotherapy has been active. It's been in tumors that are more mutated they're classified as warm tumors. That only constitutes essentially about 1/3 to 40% of tumors. The rest have not been particularly responsive to immunotherapy, and that's a wide open space that we certainly like to explore. So where is the potential for botencilumab? It's very hard to estimate because it is so broad.

Thank you for that. I know that, that was going to be a little bit challenging question to quantify, but I think you did a fantastic job in describing MSS tumors and where we are. So lots of development opportunity. Right now, we're being very focused and prioritized, but lots of interest out there as well. So with that, I wanted to thank everybody for staying a little bit longer. We know that it's important to be able to answer some of the questions live. So with that, I'm just going to turn it back over to Garo just for some closing comments before we close out this webcast for the first of the year in 2026. Thank you all.

Thank you, Stefanie, and I want to thank our colleagues for joining us today and everyone else who joined us today on the call. As my colleague said, it's remarkable to see this consistency of data across different tumors across different continents for clinical trials have been conducted different types of studies and of course, different stages of disease. And that's what is so revolutionary about BOT/BAL and it is so encouraging that now regulatory agencies such as France, are having not only a patient-centric attitude, but also putting a significant amount of money to reimburse for treatment. And what we've discussed, of course, reflects a shift in how we think about cancers. And how long have we've considered beyond the reach of immunotherapy, particularly in MSS disease as Robin and Dr. O'Day and Jose made references to. Patients, there's no question. Patients are asking for better options. They're asking for potentially curative options and options that are not [indiscernible] with poisonous traditional treatments like chemotherapy. Physicians are seeking responsible pathway to treat these patients. And some countries, as we said, friends are demonstrating the urgency to act. As we move through 2026, we remain committed to advancing BOT/BAL with rigor, expanding appropriate access with discipline and working with regulators, clinicians and partners to bring meaningful innovation to patients who deserve them. We appreciate your continued engagement and look forward to sharing updates as the year progresses with these conversational very interactive programs. Thank you very much.