Agenus Inc. (AGEN) Earnings Call Transcript & Summary

[ May ] (sic) [ December ] '25 Stakeholder Webcast where we bring together scientific leaders, clinicians and patient voices to discuss the progress and global momentum surrounding the BOT/BAL immunotherapy program. Before we begin, a quick reminder that today's discussion will include forward-looking statements. These are subject to risks and uncertainties that could cause actual results to differ. Please refer to our SEC filings for more detail. Today's session brings together 3 distinguished guest offering scientific depth, clinical insight and lived experiences in colorectal cancer. First, we'll hear from Dr. Christopher Lieu, Professor of Medicine at the University of Colorado Cancer Center, where he'll discuss the evolving role of immuno-oncology in colorectal cancer, particularly in MSS disease. And he'll also share a remarkable case from this practice that demonstrates the potential of deep and durable responses. Then we'll have Dr. Jonathan Loree, medical oncologist, Associate Professor at the University of British Columbia and the senior investigator with the Canadian Cancer Trials Group. He will provide an operational update on the global Phase III BATTMAN trial, including rapid site engagement, broad international enthusiasm and key drivers on trial momentum heading into 2026. And finally, Dr. Benny Johnson, Senior Medical Director at Agenus and former GI oncologist at MD Anderson Cancer Center will share his family's personal experience navigating early onset colorectal cancer, a journey that shapes this dual perspective as both the clinician and the caregiver. Following these discussions, Agenus leadership, including Dr. David -- excuse me, Dr. Steven O’Day, our Chief Medical Officer; and Dr. Richard Goldberg, Chief Development Officer; along Benny Johnson, Senior Medical Director will join Garo for a live Q&A. As there were some pre-submitted questions related to biomarker development, Dhan Chand, our VP of Research, will also join for the Q&A as well. Questions may be submitted at any time to the e-mail [email protected]. 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, all of you for joining us today. Based on our previous experience, we have patients, caregivers, advocates, clinicians, regulators, policy leaders as well as investors and everyone else who is committed to advancing the future of cancer care. Now we've decided to have these sessions with some frequency for 2 very clear purposes. Number one, we want to make sure that we keep you abreast of the latest developments concerning BOT/BAL, particularly, but also concerning the company. And secondly, we would like you to hear the points of views of a broad range of experts in the field. And that's what we've done in the last 3 sessions. And that's what we will continue to do with frequency in the future. And so these are not quarterly meetings, but these are meetings that will be presented to you with a higher level of frequency. In 2025, the BOT/BAL program reached a number of important inflection points. Clinical data now spend more than 1,200 patients treated across 9 tumor types from the most refractory settings to earlier localized disease. These findings continue to reinforce the fact that a clear trend is emerging in a significant number of patients. Immunotherapy may hold far more potential, including particularly cold tumors than previously believed and this has surprised a number of experts, but the data is clear. MSS colorectal cancer is among the clearest examples of this. For years, this disease was considered largely unresponsive to immunotherapy. By the way, when we talk about MSS colorectal cancer, this accounts for well over 90% of colorectal cancer patients in the U.S. and across the world. So this is the substantial chunk of colorectal cancer patients. But this past year has brought forward new signals with our experience, certainly, in both refractory and earlier stage settings, as I mentioned before. We're seeing meaningful responses, and these are durable responses, and we're seeing them consistently across multiple centers around the world. And of course, one of the concerns is that if your data is only from 1 or 2 centers perhaps there's the risk of cherry picking. But we are not talking about dozens of centers in 3 different continents. These findings clearly challenge the long-held assumption and that opens the door to new possibilities for patients with chemo-free treatment options. For all of us at Agenus, this work is deeply personal. As you'll hear from the interview with Benny Johnson, who is also here live today. Every patient and family navigating this disease reminds us that why progress must continue with a high sense of urgency. Today, you'll hear from 3 leaders, as Stefanie talked about, who reflect the scientific, operational and human dimensions of this work. Dr. Lieu, will share how expectations for immunotherapy in CRC are evolving. Now these expectations were nonexistent other than for MSI-high tumors, which account for about 5% of all CRC patients. He's going to share a case from his practice with a hepatocellular carcinoma patients. And I'll let him, of course, describe his experience with this, which is a remarkable outcome. Dr. Loree will describe the extraordinary global mobilization behind the Phase III BATTMAN trial. This is our Phase III potentially approvable trial, a level of alignment driven by strength of early-stage clinical signals and the urgency felt by investigators worldwide. And of course, Dr. Johnson, our very own Dr. Johnson will offer a deeply personal perspective as both a physician and a caregiver, reminding us that behind every data point is a family, a patient whose life is shaped by the options available to them. And we're very proud of the fact that we're expanding those options, particularly chemo-free options for them. As we move into 2026, our priorities are clear. We will expand patient access to BOT/BAL, including through French's reimbursed AAC pathway and Agenus paid name patient program available in approximately 30 countries that allow self-pay or pay with special insurance that has a patient's ability to access and none yet approved treatment. Number two, we will advance the BATTMAN global Phase III program with speed and rigor. And number three, expand our neoadjuvant studies that are now beyond CRC, where the potential for [ Pure ] is the greatest. These efforts are essential if we are to bring meaningful innovation to patients in years. And I hope, in some cases, it will be in days and months, but not decades. I want to thank you, Dr. Lieu, Dr. Loree and Dr. Johnson for joining us today and for your commitment to patients. So let's begin our program. Andy? [Presentation]

I've been in the oncology space for 31 years, formerly [indiscernible], but we did not get to know you until BOT/BAL. And so you are a very accomplished physician with varied interests and you've been at MD Anderson for your fellowship, I believe. And now you're at [indiscernible] now. When I look at your institutions background, ensure it lifts everything under the sun for the treatment of cancer. And I'm not talking about your research interest, of course, by the institution, but it doesn't talk about immunotherapy because -- partly because, of course, it's understandable immunotherapy is relatively new. Why do you think that is? And what is it going to take for us to get around the historical barriers to embrace new treatments? What do you think is the issue with MSS colorectal cancer, which constitutes about 90%, 95% of the patients today?

That's right. MSI-high colorectal cases have gotten a ton of press, which is phenomenal, right? I mean like for that 4% or 5% of patients that are MSI-high to be able to offer them single-agent immunotherapy or, in some cases, double immunotherapy and to have -- I mean, what I think are outstanding outcomes, I mean, that is exciting, right? We see that in the metastatic setting. We see that in the neoadjuvant setting, into curative setting, particularly with locally advanced rectal cancers. But just like you said, 95% to 96% of our patients with metastatic colorectal cancer will be micro-satellite stable. And of course, the issue there is that when we've done studies with [ pembrolizumab or nivolumab ] or even [ nivolumab and ipilimumab ] in this subset of patients, the 96% of patients that are micro-satellite stable, we know that the responses have been virtually 0, right, for lack of a better term. It's just really not been effective. And the reason why is because when you look at MSI high cancers, I mean the T cells are there, you can even look inside the tumor and their lymphocytes, right, that are infiltrating into the tumor. But when you look at micro-satellites stable colorectal cancer, it is the perfect definition of an immune desert. There are no T cells. It seems like there's very little upfront immune activation. And so the way I describe it is that for micro-satellite stable colorectal cancers like having a dance floor, but nobody is on the dance floor, right? You're turning up the music louder and louder, but there's nobody dance because there's nobody there. To use the same analogy in MSI-high colorectal cancer, it's like you have the dance floor, and there are a ton of people already there. You just got to start the music. And it really just shows you there's a very, very distinct difference in the tumor microenvironment between the majority of our patients, micro-satellite stable and are patients that have MSI-high colorectal cancer.

What you're seeing in the small group of patients who have MSI-high colorectal cancer is nothing short of America, right? So then how do we repeat that miracle?

Yes. I think we were very fortunate at the University of Colorado to be able to be involved early in drug development for BOT/BAL. And I think that when we initially started the Phase I. I think there was some healthy skepticism in terms of what we may or may not see. Just based off of the mechanism of action, we just kind of wanted to see, okay, well, what are some of the responses that we're seeing with this combination. And I think one of the things that really just impressed not only me but our entire team, our entire Phase I unit or some of the responses that we're seeing and what we are talking about are really kind of 2 things. Whenever patients have really refractory cancers you really want to focus on response rates because that's a very, very early endpoint. But our patients just feel better, right, when they have less tumor burden. And so when we are seeing dramatic responses, that's always exciting. Patients are excited. They're feeling better, CT scans are looking better, and you can show them right, the difference before and after, and we were seeing that with BOT/BAL. And then the second thing is the durability of response. It's no fun at all for any patient or any provider to have a response that lasts for 2 months. because 8 weeks after you start treatment, you're super excited and then like literally 16 weeks after you started treatment, everybody's super, super upset and sad, right? And so it's response and it's the durability of that response because if you see great response to a treatment, and it goes on for a really long time. I mean that's the way, right? And so when we started seeing that early, early, right, in the drug development of BOT/BAL, it was unbelievably exciting. I had a patient with severely refractory hepatocellular carcinoma liver cancer and immunotherapy is actually used upfront for the treatment of metastatic liver cancer, [ HCC ]. And so this patient was started on [ atezolizumab and bevacizumab ], she didn't respond at all. She started on a second-generation tyrosine kinase inhibitor that targets VEGF, we tried [ lenvatinib ], that didn't work. And by that time, she had this mass that was in her abdomen that literally you could feel and with each subsequent therapy, the immunotherapy, the targeted therapy, even the other Phase I clinical trial, we saw continued growth of this tumor. It was causing a ton of pain. So she reported kind of continuous 7 out of 10 pain that's really unacceptable. And we also knew that -- I mean if this thing is going to continue to grow, eventually, it's going to block the bowel or I mean, even potentially [ petrude ] out of the skin. And so usually, in that case, as oncologists, we're going to recommend hospice because we expect in the next couple of months that maybe there would be a really, really unfortunate or bad outcome. And I think my patient kind of understood that as well. But she was eligible for BOT/BAL. We put her on the Phase I. And really, I mean, this is the last Hail Mary attempt. We knew if this didn't work, we were absolutely going to send this patient to hospice where the life expectancy really would be measured in months. And just after a couple of doses, you can actually feel this thing in her abdomen her pain went from a 7 out of 10 after like literally 4 weeks it went to 0 out of 10. It was unbelievable. Her AFP, alpha-fetoprotein, which is a tumor marker that we measure in the blood, it was literally 200,000, right? Normal, you don't want that thing to be above single digits, right? And that had completely normalized after 2 months. One of the most dramatic responses I've ever seen in my entire life. And the thing that was so gratifying about it says the patient just her pain was gone, right? When you look at the imaging, all that was left was like the shell, right? Kind of what I assume is just byproduct or scar tissue. The amazing thing about this patient is that she was going to hospice, 2 years later after being on the BOT/BAL study, she came off study because that's protocol, and she hasn't required treatment for her cancer now in over 2 years. And this really kind of shows you, number one, exactly what we're talking about, response. Patients feel better. Number two, the durability of response. And for all intents and purposes, with a normal AFP, a normal scan, no treatment in 1.5 years to 2 years, when we're effectively talking about cure of a disease that would have probably given her only a couple more months to live. Really just one of those things that you'll never forget as a physician, and it's just an honor to be part of it, a life saved and literally a life cured. And there are stories like this across all investigators that have had experience with BOT/BAL.

Wow. Now that is a wow. It is nothing short of a medical to see something like that. And yet when you talk to individual patient case studies with regulators and regulatory experts. The typical response is that it's an anecdotal case with traditional treatments like chemotherapy, not only often do you require continuous therapy for the patient in order for the response to persist. But you also have to deal with the toxicities associated with traditional treatments. More is sometimes resulting in more responses, but more is also resulting in a lot more toxicity.

When you think about chemotherapy side effects, especially if you say like, okay, well, chemotherapy is going to decrease white blood cells. You imagine when you stop chemotherapy that there will be at least somewhat of a recovery, right, of those accounts because you're taking that kind of poisonous toxicity off the table. One of the things with immunotherapy is that when you activate somebody's immune system, you obviously hope it attacks the tumor by golly, it really did, right, in this patient. But you also have immune activation in other areas as well that can cause side effects. For this patient, she actually developed adrenal efficiency, right? And that is a known side effect of immunotherapy. So that requires her to take a daily small amount of steroid and she'll tell you, right, time over time that you would trade that a million times over for the cure that she's received. But the toxicity balancing that toxicity and the efficacy of the drug is something that we all do as investigators as physicians. And here, I would say the trade-off is pretty clear, right? You're cured, you do have to take this medicine. But it's kind of one of those things where is it worth it? For her, she was tell you that she's living her best life, right? And so I don't think that she really has too many long-lasting toxicities besides the fact that she does have to take the medicine.

So how does a physician like you who has also served on ODAC, FDA's oncology advisory committee reconcile all of these anecdotal cases that are miracles for patients?

Well, I think from a regulatory standpoint, it's difficult, right? I mean what we -- the paradigm of how we traditionally look at progression-free survival curves and overall survival curves is really changing in the setting of immunotherapy. And I think that the FDA is really trying to maneuver this change from what we typically see with chemotherapy and even targeted therapies with some of the long-lasting impacts that we see with immunotherapy. And so -- and it's not an easy job because whenever you look at these curves, we know that there are some patients that are just not going to respond at all to these drugs. And then on the flip side, there are going to be patients like my patient that -- where that curve is just going to keep going, right, kind of forever. What we call the tail of the curve. And really what that means for people who aren't familiar with looking at some of these kind of survival curves is we have to keep in mind that whenever a survival curve drops, I mean those are patients that are passing away from their cancer. And there should be -- that should be a sobering thing whenever we look at it. But at the same time, when you look at these curves, and the drop-off stops and then there becomes this tail of the curve where people are just continuing to live and live and live, which again suggests either 2 things that the disease is under incredible control or that there's a cure. We, as physicians, as investigators, as patients, even as regulators are going to have to really determine where that tail of the curve is and what that means for our patients. So do approvals start to happen because we see that like, say, what if 20% of the patients that enroll onto a study are essentially either have durable responses are cured? Well, that's something that needs to be considered. And there have been treatments that have been approved based off of this long continuous either cure rate or continuous response curve or durability of response.

How do patients react or even embrace when you explain the prospects of being treated with immunotherapy versus the traditional treatment?

I think that there's always a lot of excitement from our patients whenever they're offered anything other than chemotherapy, right? And I think that there is a knowledge that immunotherapy isn't going to work for everybody, but it's the idea that there's a chance of a durable response that I think really gets everybody excited. Again, it's up to us to make sure that we provide access. Number two, make sure that we provide the right clinical setting. But number three, one of the most important things is to really just find out who those amazing responders are and offer those patients the drug to make sure that if they do experience any side effects as well worth it because the responses are going to be so much higher, we have to identify the patients that are going to have that durable response. And I think that, that's a lot of the work that's coming up for all of us.

Well, thank you very much. You probably always do that for your patients, but for your extra time that you've devoted to us this morning, and we will see you soon.

Absolutely. Thank you for this opportunity.

So we thank Dr. Lieu for his very insightful discussion, which you experienced with Dr. Lieu having served on the FDA Advisory Committee, he has a substantial amount of regulatory experience and the ability to decipher data in ways that other investigators may not have. And Dr. Lieu is new to you. We haven't featured them. And we expect that many others in the next months will be here talking about their experience with BOT/BAL. His remarks underscore a meaningful shift underway in oncology. As clinicians observed responses in diseases like MSS colorectal cancer, typically unresponsive to not just immunotherapy but poorly responsive to other treatments, particularly in the metastatic setting. And the fact that we have to move very quickly with a high level of urgency. This sentiment is growing. It's increasingly clear that immunotherapy will play a role in this and other disease settings. The question now is how quickly can we bring these advances to patients? So few people have had a closer view of this momentum than Dr. Jonathan Loree. Dr. Jonathan Loree is one of the lead investigators for our CCTG trial that has gotten underway actually, working with the Canadian Cancer Trials Group, that is the full name for CCTG, and partners across Canada France, Australia and New Zealand where the trial is going to be conducted, and the patient recruitment is going to take place. He has helped drive one of the fastest-moving global trial efforts we've seen. His prospective reveals not only the scientific promise but also the operational readiness and enthusiasm from investigators around the world. And let's turn now to that discussion. [Presentation]

Hello, Jon. Dr. Loree. Thank you very much for being with us today. The first time we met, I believe, was almost 3 years ago at ASCO. You and Chris had come to meet with us with our team. And you made a very, very strong case as to why CCTG, along with the interest of your colleagues in Canada and elsewhere would be the best candidates to enroll patients in this trial.

Yes. The Canadian Cancer Trial Group had recently finished at the time, a clinical trial evaluating different immunotherapy compounds, [ durvalumab and tremelimumab ] in a trial called CO26. This was a Phase II trial, and it was weekly positive, but it wasn't something that moved to a Phase III trial. And we thought that this is a population that really there is an opportunity for there to be benefit for immunotherapy. But then when we saw the data with botensilimab and balstilimab, it really stood out as something that was exceptional and different. And when we thought about the Phase III trial and something that should move forward in the same population, they really stood out as the agents that would be ideal. We had a strong track record in Canada for that trial, the CO26 trial, and we worked very closely with collaborators in Australia, New Zealand and France in a number of trials across our cooperative groups. And so we've got a strong track record in shared history. And so we knew that this was something that we were excited about the science, cited about the possibility of progress for our patients. We have the capacity across our networks and a shared history that we can really do this trial efficiently and do it at a level that was going to be important to move this as something that would evaluate it properly for moving into the clinic.

Typically in colon cancer, you don't really look at immunotherapy as an option. Jon, what is the sentiment from the field. Your core circle of hospitals and investigators. What are they thinking? And what's the level of early receptivity?

There's been a sense of awe really seeing what immunotherapy can do in micro-satellite instability high colorectal cancer. We've seen just how dramatic that effect can be when we see patients in clinic, who don't have micro-satellite instability high, we felt a little bit like we're failing them. People are excited about the possibility of doing that in the 95% of colorectal cancers that are not micro-satellite instability high. And so that's led to a lot of hope and enthusiasm for this to be something that is a new option for patients and not just an option that's an incremental step, but something that can really make a big impact for our patients.

Jon, patients are looking for a an option that is different than the traditional toxic options.

The field is excited about this, and the preliminary data looks really good. I'm excited about the BATTMAN trial being something that we're doing in a way that is going to give us the data showing that this combination improves overall survival. And one of the key priorities when working with the Canadian Cancer Trial Group is we're designing this trial also to make sure that not just is it positive from a regulatory perspective, but the went gets to a health technology assessment that payers across every country are going to have the data that they need to make their decisions on reimbursement. And I think that's really important. We need to plan for not just the trial now, but also planning to make sure that we have all the data elements that are there and required to make it so it's something that can move into the clinic. You mentioned the cytotoxic component, and that's really important. Patients when they're at the point that they would enroll on BAL and they've been on cytotoxic chemotherapy for a couple of years. And they're getting tired. They've had a lot of the psychotoxic side effects, they build up over time. And having something different, it's a world of difference for what their quality of life means. And it gives them a chance to spend the quality time with their loved ones and doing the things that they want to do. And so I think that's also really important, having that different mechanisms, so that way they can recover from what they've been through.

And not only do you have to address their needs to had a longer life, but you said a better quality of life.

Yes. That's a major thing that patients tell me in clinic is that they want to live longer with their cancer, and they want to live well and they want to be able to do the things that they used to do before their cancer diagnosis. And having that long curve. That's amazing and super exciting, but also being able to see patients in clinic and have it be a good visit, a visit that's about kind of the successes that have happened and less about the toxicity, I think that's a really impactful opportunity with something that has not those cytotoxic side effects, as you mentioned.

Now what about the prospects of having patients be treated with BOT/BAL, for example, for a reasonably short period of time, and having results without necessarily the need for chronic continuous treatment because, as we know, with traditional cytotoxics, if you stop treatment, often the disease comes back very quickly. So you have to continue on treatment. And of course, there is the cumulative toxicity of that treatment.

Yes, that's what really excites me in clinic to have that as something that's a possibility for the patient sitting in front of me, and it excites them as well. And those -- that time off therapy is a really important metric because that's the time that people can travel, they can -- they're not tied to coming into see me continuously. It lets them prioritize the things that they want to do. So I think you highlighted are really impactful benefit of something that if patients have a durable response that they can enjoy those other aspects of their life and not be tied to the chemo center. I love those appointments when somebody comes back and tells me about the trip that they just had and this amazing thing that they did in the grandchild that they got to hold because they were able to travel to someone because they didn't have to be here for everything continuously. Another thing that my patients tell me that they want is they want quality of life. And many of our surgeries and our treatments lead to impaired quality of life for bowel function, sexual function, overall health. Thinking about the surgeries that are required, sometimes requiring a lifelong stoma. And so the opportunity for organ preservation and for cancers to either disappear to a point where there -- it's a different surgery that might provide a better quality of life or maybe a nonoperative management is a possibility. And I think as people gain experience and understand kind of the effect of something that works on a typically cold tumor, they're going to be really excited about that, both patients and providers.

And are you seeing early signs of this amongst the exploration of your expansion to beyond your center in Canada, France, Australia, New Zealand?

Yes. I hear from investigators all over the world where are things at. We're excited about this. Can we be part of this. And so I think that the momentum is incredible. And that's quite an exciting thing to be a part of. And I'm very grateful also at the things that have helped make that momentum possible. There's great collaboration, both with the clinical development team at Agenus. But with our clinical colleagues across these cooperative groups. We have this shared history that's really rich over the past 20, 30 years where we've done lots of trials together.

It's wonderful to hear, actually. So when we started the trial efforts [indiscernible]. We said, well, how quickly can we gear up to get this thing started? And if you can give us a sense of what has really driven the speed with which we have arrived to where we are and the level of excitement that has driven the speed and how quickly your organization has geared up to put all the elements in so that the first patient in can be accomplished as quickly as possible?

You highlighted a really key word, and that's enthusiasm. I think there's a lot of enthusiasm amongst sites and the central offices and our patients because of the data that they've seen to date and because this is a group that really needs something new. We see so many patients who are still well and they run out of treatment options. And they need more things in our toolbox and they need different things. We've talked a little bit about potential side effects that can happen from chemotherapy. This is a different drug that affects patients differently. It's durable. That's really exciting to providers. They've seen how good immunotherapy works in micro-satellite instability high colorectal cancer and the opportunity for that in the 95% of patients that don't have micro-satellite instability, that's huge. That gets people really excited. And when you combine that with the Canadian Cancer Trials Group's experience running large trials working together with our collaborators at the Australasian gastrointestinal trial group, AGITG and [ Uni Cancer ] in France. There's this shared history where we work together. We know each other's policies. We know the things that are important for each site. We know the protocol kind of the key important pieces that need to happen to put a trial together that's successful, and we know each other and those relationships are really important. It's not just receiving an e-mail from someone that you don't know. It's someone that you've known for years, you've worked together, you have a shared history, and that's really important. So you say, I've got this really exciting opportunity for us and people get excited about it. And it's really it's infectious, and that's been exciting. We've done a lot of groundwork. And so that groundwork has been important for getting our sites excited. There's one thing of all the operationalization that happens at a central office between institutions in different countries, but getting sites excited about them and telling them we've got a trial. It's going to be for your patients. These are the compounds. This is the exciting part. That's really important for kind of getting the system ready and priming the pump. So that way things are ready to go. And when you combine all that together, that groundwork the excitement, that shared history, it's really led to something remarkable as far as how fast things have gone. We've gone over a period of about 4 months from contract signing to protocol development, regulatory approvals in multiple regions to now as having sites asking, let's go, we're ready to activate. And that's really exciting. So we are moving very quickly.

That's powerful. That's very powerful. Thank you very much for that. And all of this obviously catalyzes a process by which we can achieve enrollment quickly and collect the data on the important end points. We appreciate your being a major driver of the BATTMAN trial, and we are very excited about working side by side with you to make sure that we complete enrollment quickly and that we also get the readout from the trial as quickly as possible for the benefit of our patients. Thank you.

Thank you.

So we thank Dr. Loree. His remarks highlight a critical reality. And as he said and others have said, patients around the world are looking for treatments that extend life, but also importantly, allow them to live without the burden of traditional treatments like chemotherapy, which could have lifelong impact on the quality of life. The momentum behind the Phase III program reflects the need and the possibility of investigators around the world in their belief in such an outcome, and that is now within reach. Now it's also important to remember why we do all this work. Every data point represents a person, a family whose life is shaped by the options available to them. What stands out most in our work with CCTG and our global partners is the level of enthusiasm that is building, and that's very tangible. The kind that accelerates timelines removes barriers and aligns teams across many continents behind the shared purpose. Improving the lives of patients with colorectal cancer and many other types of cancers, which were the subject of our ESMO presentation in Berlin about a month ago. And this, of course, brings this to our next segment. [Presentation]

Our next session is with Benny Johnson. Benny Johnson joined us a little over 2 years ago from one of the world's most renowned cancer centers, MD Anderson Cancer Center in Houston, Texas. And shortly after he joined the company, his wife was diagnosed with Stage II colorectal cancer. And here is Benny to tell us about his experience in having joined Agenus as well as his experience going through that process with his wife. It's been a delight to have you at Agenus as a colleague. And before Agenus, if you can give us a little bit of a synopsis of what you did, more importantly, how did your daily life look every day, taking care of patients?

Yes. Before joining Agenus, Garo, I was actually an assistant professor in GI Medical Oncology at MD Anderson Cancer Center in Houston. So my focus was primarily colorectal cancer patients and anal cancer patients. As my career evolved at MD Anderson, I took on a particular interest in young onset patients and work towards developing that program at Anderson. And so my clinic really became a clinic full of peers, if you will, depending on the day. So about 2 days of clinic, 2, 3 days about with research trying to work towards clinical trial design and investigator-initiated studies.

Your decision to join Agenus, and how did your knowledge of BOT/BAL materialize even before you joined the Agenus. What was the critical driver for you?

Yes. As I mentioned earlier, a good amount of my time was thinking about investigator-initiated studies, but also finding the right collaborators, right sponsors to work with because when you see really exciting data we want to partner with those companies early because we want to not only help them run meaningful trials for our patients to offer new therapies. This is the way that we move the needle forward for metastatic colorectal cancer. And so the way that Agenus came to me was very interesting, one of my mentors, [ Dr. Michael Overman ] sent me an e-mail and said, "Hey, there's a Phase II trial being proposed in colorectal cancer, and I really want you to lead this program and increase our interaction with this company." And that was really the excitement around that, as you know, and now that I know was the data from the Phase I study that was showing in refractory colorectal cancer patients, MSS which is 95% of our patients. We were seeing response rates with an immunotherapy combination, BOT/BAL that we never really saw before in MSS colon, never seen it over 20% and then having durable responses. And the percentage of patients enjoying that and even potentially being cured, right? So I had the opportunity to be the Phase II PI. And then in my interactions with some of the clinical development team just in that space, there was an opportunity here at Agenus, and I really felt that it was continuing the same mission that I had to move the needle forward for the majority of metastatic colorectal cancer patients. And so I jumped on it. I think it was really just an amazing opportunity to be a part of this team.

So it wasn't just a job at another company that there was a greater purpose in all of this.

100%. I think we all want to find meeting in what we do. And the experiences that I had at MD Anderson were really formative for me. And then having the opportunity to then take a really powerful combination and think critically and work with a really talented team here at Agenus to push the boundaries and bring it to more patients sooner was really an opportunity that I wanted to dive into to have to have that experience to help many patients with colon cancer, not just the few that I see in my clinic but a global need and being a part of that.

So you joined Agenus and then you get hit with a personal challenge. And of course, you come from a medically sophisticated family, including your wife. How does that factor into your decision-making to deal with that challenge?

I would say about 4 months after joining the company, this is when we found out that my wife was diagnosed with sigmoid colon cancer. And leading up to that point when we actually receive the diagnosis, we both knew something wasn't right. Her -- she had some symptoms of just GI symptoms that were new, change in bowel habits that were new, periodic bleeding. And we just -- we both -- without saying it to each other, we knew there was some urgency in getting to the bottom of this. And so actually, Garo, for many weeks, the 2 of us actually never said what we were thinking allowed to each other. And I think that's because, as you mentioned, just having -- obviously, me having my background but even my wife, who saw -- who has a tremendous amount of background in primary care, understands these red flag symptoms. And one of the things about young onset colon cancer is primary care physicians still are learning that a young patient less than 50 years old, a 30-year-old, 40-year-old patient can actually have colon cancer. That's really not something that is on the top of their mind or their differential. And so we saw that even as 2 health care providers, we saw this delay in diagnosis. We were told when she was found to have an anemia, we were told to just take iron bills for a couple of months and come back and reassess. When we told an OB/GYN, she was having this unusual pelvic discomfort she was told, "Well, now you're over 40, you just have different symptoms now." It was just -- it was really sad and surprising to me that, that still happens to patients we advocated for ourselves because we kind of understand that no, something is not right. But for the layperson, I think they would just believe their doctor and say, okay, I'll just do what you say, and I'll come back 6 months from now. And unfortunately, for some patients, that may result in advanced disease. So all that to say that we were able to move forward and she was diagnosed with [ Sigma ] colon cancer. And our lives changed immediately, immediately, you could imagine.

And you have children, of course, and that makes it challenging. So what factored into your decision to -- for your life to be treated with BOT/BAL?

As you mentioned, I knew I knew what was on the table, right? For a patient that has what we call clinical stage 3 disease. Standard of care is to move to upfront resection, followed by anywhere from 3 to 6 months of adjuvant FOLFOX or [ C-box ]. So we're talking about 2 chemotherapies that have some side effects. But what was in the back of my mind was I've treated many patients just like that. And unfortunately, even with our best treatments, anywhere from 22% to 30% of patients will still recur within 2 to 3 years. And that statistic was in the back of my mind. And I wanted something more and what was available. And you mentioned earlier, just the timing of it all to kind of have experience with BOT/BAL as a PI in the Phase II CRC programming for advanced disease, but still nonetheless, seeing the responses there. And then joining the company to see some of the early published data that was available in the [ NEST ] clinical trial, a neoadjuvant trial of BOT/BAL for patients with resectable colon cancer. So how do you take that mindset of, hey, there's this trial that's an option for you? And also kind of knowing the standard of care and then present it to not only my wife, but my wife comes from a very educated family. I had to convince them too. Explain to them the novelty here, and the fact that we have one chance. We have one chance to do our very best. And at that moment, I think we felt it was the right decision for us. And ultimately, she decided that she was willing to do whatever it takes.

What happened? She gets treated. How many treatments did you have?

Yes. So we received 1 dose of BOT, 2 doses of BAL very operatively. And then she went for kind of evaluation endoscopically. And we saw within 7 weeks that a very large sigmoid tumor had complete resolution endoscopically. So what we call kind of a clinical complete response. In that moment, her surgeon, we still decided as part of the protocol and standard of care to move on with surgery, and we were then able to confirm a complete 100% pathologic response. And so this was just an amazing news for us. I think [indiscernible] often says that I really wasn't breathing when she started the clinical trial. And up until that endoscopy is kind of when I was able to exhale because I feel as though I was holding my breath for months. And so that was a really powerful moment for her, for me. And then it allowed so many things that I think she benefited from I mentioned earlier that most patients would go on to get anywhere from 3 to 6 months. And young patients, there's this idea that we kind of need to give them everything. So she may have very well have received 6 months of adjuvant chemotherapy, but at the very least, 3 months, but it was -- it would have been 2 drugs. But the fact that she had this amazing response, this 100% clinical complete response or pathologic response we were able to de-escalate her adjuvant chemotherapy to a single agent. So we look at it as an unbelievable win for our family that she was able to have this opportunity be a part of a really novel immunotherapy combination that I think will eventually change the entire landscape for localized colon and rectal cancers. And then to be able to de-escalate our adjuvant chemotherapy is huge. These treatments come with a lot of long-term side effects. And for someone like her who's a runner, young kids, an 8-year-old and a 3-year old at home peripheral neuropathy would have been crippling for her.

Here you are a colorectal cancer specialists. You join a company that has a remarkable treatment. Your wife comes down with cancer shortly thereafter, gets treated, you witnessed the outcome firsthand. How does all of this factor into your thoughts? [indiscernible] as you're building a career?

Right. I think the lesson here is this is not just an old person disease, right? Colorectal cancer is impacting -- can impact any of us. And the rising incidents in young people, it just brings it to the forefront to really see how close to home it hit. It was -- it really was one of the most challenging times of our lives, as you can imagine. Because even though I was taking care of these patients and walking with them and just how this huge admiration for what patients and families, especially our young patients were going through. Now I had a front row seat, and I got to admit, I didn't really want to have that viewpoint but I did. God decided for us to have that viewpoint. And I think where it leaves me now is I'm just so thankful, as I mentioned before, I've been able to see BOT/BAL on all sides of the development, if you will, as an investigator now here at the company and developing it further. But [ Liga ] story is one of many other stories as we see the mature NEST data that will be published soon. This is an amazing story that's not just impacted her as a one-off. It's a powerful regimen that is impacting many other patients with very similar results. And so I think moving this it drives me to move it for an available therapy for all of our patients, right, to really change where localized colon cancer is going, right? Currently, we're still using the same therapies we've been using for over 20 years, and I think it's time to move that needle. And so watching -- having this front row seat has provided a real passion for me to do whatever it takes to move it forward and to innovate, right, to innovate therapies for our patients. Because honestly, Garo, if you have Stage 3 disease, and you're doing everything you can at the best centers with the best oncologists, the best surgeons, and we're still having a 22% to 30% recurrence rate, it's just not enough, right? Because that percentage impacts one family, right?

So as you said, it's not just one patient. It's now scores of patients that have experienced some remarkable responses. And if you were to explain to a patient knowing what you have gone through, this optionality, how would you paraphrase the advantages of having BOT/BAL?

I really say we want to do everything we can to train your immune system to fight your cancer. And if we have drugs now that are able to do that, that is the change, right? It's not just a matter of giving therapies early, right? So for instance, there's data now that if you give your standard chemotherapies like FOLFOX, like [ HPOX ], before surgery, the response rates are still very low. It's not what we're seeing when you give novel immunotherapies like BOT/BAL before surgery. So it's a significant difference. It's to give them their best shot and also to use their immune system to their advantage to fight the cancer in a way that will really result in lasting change and cure.

If your wife looks back at her experience. How does she tell her own story in terms of on experience versus, for example, what you would have expected when she was first diagnosed?

But I think looking at it now, as you mentioned, an abbreviated course of therapy, having her surgery and then being able to de-escalate chemotherapy to a single agent drug for about 3 months. The benefits of that, I think, have been so impactful for her because now she's not thankfully having to deal with chronic chemotherapy toxicities or having a risk of developing peripheral neuropathy from [indiscernible] Platinum because she was able to avoid the drug altogether. And that's been huge for her because now she's kind of back at what she was doing before looking for a new job, look getting back to running, which she loved, being fully available at the kids' school and being able to take care of both of our children. And so doing all the things that she loves again, and I think being able to avoid some of these therapies played a role in that for sure. And so she's thankful. She's very thankful. And then both of us as I mentioned before, last year was kind of a year where we just needed to survive. And this has been -- and this year has been one where we were kind of, wow, last year really happened, and we're unpacking it. And one of the things she said is I'm just so thankful that I was able to receive this therapy and now be done with therapy a lot sooner on the back end. And she has no long-term side effect profile, which is really, really unique. And I think just something we are so happy for her to have that opportunity.

And based on your experience, certainly as an important member of our clinical team. We've treated over 1,200 patients across 9 different types of cancers treated patients in the last line setting as well as in the earlier stage like the case of life. And it's a chemo-free option. And so the question is young patients want something a little bit more innovative and luckily, for your wife that innovation was available for her setting in time to benefit what's the chances of all of this happening you joining the company 4 months later, your wife comes down with it. By then, we have generated data that has convinced not just you and your wife, but your family to allow her to participate in this trial. And here we are, a beautiful outcome. And that's what we really want to have for all patients as soon as possible.

We are doing tremendous work in with really some amazing investigators all across the globe. And the excitement from oncologists here in the United States, but also globally just kind of speaks to the data and speaks to the novelty and the potential to really transform solid tumor cancers, right? And so yes, it's a miracle. I think about just the fact that I'm here, like you said, it's not a coincidence. And I get to be a part of this wild ride and work with an amazing team that is focused and dedicated. Even though we're a small team, each of us has these stories and has the patient in the back of their mind or the family member that's been impacted. And we realize the current standard of care is just not enough. So what can we do? So Agenus has this amazing pipeline. This amazing drug in BOT/BAL that we will bring to the finish line. And I think that's our goal. And then patients benefit. And so that's where we're here, and I'm truly excited to be part of the team.

Thank you very much for that, Benny, and we're delighted to see that your wife is -- had such a phenomenal outcome. Thank you, Benny. Benny is with us today, along with members of our technical, medical and commercial team to field questions. But we appreciate your transparency Benny and sharing such a deeply personal journey with us. Your family's experience reminds us of the importance of the urgency as you stated, of patient access to a treatment option like BOT/BAL. Taken together today's discussion reaffirms the importance of our mission. Number one, patients need better options. Two, the path forward is becoming increasingly clear. With that, we'll now turn to your questions and continue the conversation with our leadership team. Stefanie take it away from here.

Great. Thank you so much, Garo, and welcome to our Chief Medical Officer, Dr. Steven O’Day, he is with us as well as Chief Development Officer, Dr. Richard Goldberg, and welcoming back Benny, Dr. Benny Johnson. And we also have other members of our team that we added based off of the questions that we were receiving. Dr. Dhan Chand is with us as well, our VP of Research. And I believe that we were able to get our Chief Commercial Officer, Robin Taylor, I think he was trying to come back through travel. So thank you all for joining us today. With that, I'm going to jump right in because I'm noticing the time, but we did have some questions that were submitted from our call in October that we didn't get to. And I'm going to give these questions to Dhan. Some of these questions are related to our partnership and our collaboration with [ Noetix ]. So we announced that quite a couple of months ago and there were some questions related to, is there anything that has come out of that? Or can you share with the status of that work that's being done with [ Novec ] and their AI platform?

Yes. Thank you, Stefanie Nacar. So this is Dhan Chand, I'm the Head of Research at Agenus. So our collaboration with [ Noelic ] is focused on identifying biomarkers that can predict response to blood pile. And while these studies are still ongoing, I'm very excited by the early results that we're seeing because now we can distinguish are starting to distinguish at the molecular level responders from nonresponders. And if you can imagine, as this data matures, it will empower us for patients that are most likely to benefit from BOT/BAL. Now we do expect to share these findings with the broader scientific community as the data matures. So stay tuned. We're hoping to have that share as early as next year.

Thank you, Dhan. And while you're on the line, there was another question that I think would be appropriate for you to answer as well is that, is there any plans in looking at other specific biomarkers that may come out? Particularly, there was a specific question about c-MET inhibitors or potentially eGFR. Can you comment on any specific biomarkers or work related to that as well?

Great question. We're definitely exploring a range of biomarkers to help -- they're most likely to benefit from BOT/BAL. But what's been really interesting is that we're seeing clinical activity independent of your traditional biomarkers, which fits BOTs unique mechanism of action. Now regarding cMET and EGFR, specifically, these are well-established biomarkers in lung cancer, but it's less well known for its role in response immunotherapy in colorectal cancer. So while our focus right now is on colorectal cancer and prioritizing biomarkers for that patient population, we'll absolutely continue to explore other biomarkers as the development of BOT/BAL and other indications mature.

Great. Thank you so much for that, Dhan. So let's switch gears a little bit here. There was a question that was submitted related to the priority voucher program. And Dr. Goldberg perhaps you could answer this question. So of course, we can't comment necessarily on what colorectal cancer sits in the priority list for the FDA. We don't have specifically those insights per se. We know that colorectal cancer has been something that has been top of mind in a lot of communications coming out of the administration and the FDA. But can you share with the audience just what our plans are for submitting a voucher and with the status and if we've actually tried to take part in that program or not.

Sure, I'd be happy to. So when we heard about the Directors voucher program. We were very excited about it. He came out with statements that he hoped to shorten the time to getting drugs that satisfy an unmet need into the hands of oncologists and patients as well as other physicians as quickly as possible. And so we immediately submitted an application to be considered for the voucher program for BOT/BAL. Unfortunately, we weren't 1 of the 10 drugs that were chosen but then we were heartened again when an announcement for a second group of drugs and applications to be examined. And so we immediately again, submitted our application for the voucher program. The [indiscernible] process is actually a very brief 2-page application process. So I also sent an e-mail to [ Martin McCarrey ], the FDA and Director, adding a few details about what we've been explaining to you today. We haven't heard back. I don't think anyone's heard back about the second tier of applications, but we're waiting with bidded breadth.

Great. Thank you so much for that, Richard. And I have a question here that's just been submitted for Garo. Let's see if we can get Garo back on camera. The question is related to Zydus and CFIUS review. And -- but if we could comment on how operationally the ownership transition of the manufacturing facility is progressing? And also, there's a question here about on the BOT/BAL supply and if we have that secured for the Phase III trial?

Sure. So with regard to CFIUS and Zydus transaction, as you know, we had a number of unforeseen events, amongst them was the government shutdown for a period of time that basically put some of the key workers at government in various departments in hibernation, but we've come out of that. And we're hopeful that a decision by CFIUS will be made very soon. Now with regard to the Zydus team, we have been working very collaboratively with the Zydus team all along. In fact, as you know, they extended a $10 million loan to us to make sure that their commitment is very clear and it continues. We continue to work collaboratively with them. We will continue to work collaboratively with them post the closure of the transaction. By the way, once CFIUS clears the transaction, we expect in less than a year -- I'm sorry, there was a big slip. In less than a week from the CFIUS clearance, we'll be able to close the transaction. We're geared up for it with a meeting with the team yesterday actually, to make sure that everything is lined up so that we can advance it to an expeditious closure. And as you know, after the transaction, we will be a very big beneficiary of the collective resources of the Agenus team that's in existence as well as the Zydus team that's coming into place. Now with regard to supply, we have a substantial amount of but supply in the form of drug substance. And that truck substance could be converted to drug product very, very quickly. However, we have separate from this drug substance, which could be enough to treat tens of thousands of patients, and you can extrapolate from that what the potential revenue is upon approval of BOT/BAL. But aside from that, we have ample supply to conduct the BATTMAN trial in the form of drug product that is undergoing right now labeling and packaging. So that portion of it is secure. In fact, we have shipped the first batch of product to Canadian pharmacies where we expect the first enrollment to take place prior to France, Australia and New Zealand.

Thank you for that very thorough answer, Garo. The next question here, there's actually been a lot of questions that are coming in. So thank you all and please continue to send them in to [email protected]. If we don't get to them today because I'm already looking at the time, we'll certainly be able to get to them at future webcast. But the next question here, I'm going to share this question with Dr. O’Day, kind of 2 questions here. One is that we have a number of really important investigator-sponsored trials that are running. This particular question is which ones do we think that we should be watching the most closely in terms of new incremental data set? Those that have a really high unmet need, particularly those that might be beyond colorectal cancer because we know that we've been focusing a lot on colorectal cancer, but we have some neoadjuvant studies as well as some other data from our Phase Ib study as an other. So can you share a little bit from your perspective on any of those ISTs that we should be watching closely. Steven, I think you're still on mute perhaps, can you double check? Thank you.

Can you hear me now?

We can. Thank you so much.

Okay. So we have 4 major ISTs at major centers around the world. The NEST in the [ unicorn ] ISTs that our colorectal based and then a pan-tumor IST and with [ Myriad Shalby ] at the Netherlands and then a new rectal dedicated IST at Memorial Sloan Kettering with [ Andrea Surat ]. These are compelling...

Maybe Dr. Goldberg, you can continue on this.

Right. So I can take off where Steven left off. So these 4 studies are looking at the use of BOT/BAL in the neoadjuvant setting. So similar to the setting that Benny's wife received the drug for it. And what we're seeing in initial studies are broad activity across our colon and rectal cancers as well as other cancers where adjuvant and neoadjuvant treatment is commonly given. So we're excited about data coming from the Netherlands in triple-negative breast cancer. And as a consequence of this, we're putting together future potential indication granting studies, Phase III studies particularly in colon cancer. We also had a meeting with the FDA previously in August for rectal cancer. And it makes sense that the real power of these immune activating agents is going to be in patients with lymph nodes intact because the source of immune cells in many cases, is the lymph nodes and lower tumor burden. So we're really bullish on the potential to make a real difference here. And that follows in the pathway that Dr. [indiscernible] blazed with her initial trial in MSI-high rectal cancers where 100% of her patients had complete responses in the MSI-high setting. But of course, we're treating mostly patients in the MSS setting here, although some patients have been treated with MSI-high tumors, and we've seen similar dramatic activity to what she's reported in her initial trial. So stay tuned. We're very hopeful that this will change the paradigm in the management of colon cancer and potentially other cancers.

Thank you so much for following up on that, Richard, and it looks like we have Steven back. A follow-up question. So perhaps I don't know, Richard, if you have the insight of this, there were some questions specifically the neoadjuvant or early line studies. Is there any update or any indication when we might be anticipating having any of that data shared in publications or at upcoming congresses in 2026?

So at this point, that data is maturing. We did have an update last spring that was in the public domain. The trial at Sloan Kettering is accruing very quickly, but the data has to mature and patients have to complete their treatment before we have more knowledge of that. The data in the Netherlands Cancer Institute Group is expanding as they're accruing more patients across the various indications. So it probably will not be until ASCO of next year that we would have an update on these data. So stay tuned.

Great. And we'll be sure to keep everybody posted when we do have a better idea of those abstracts or that data being available either through manuscripts or through congress presentations. Given the time, I want to be really respectful of everybody's time, I'm actually going to turn it back over to Garo to close out the call. We do have a number of submitted questions that we didn't get to, but just like what we did this time, we will keep them together and make sure that we do address them at their next opportunity, our next webcast or earnings call. So with that, I am going to turn it back over to Garo to close out our call and thank you all for joining us today.

Thank you very much, Stefanie. And I also want to especially thank our participating clinicians as well as our team and all of you who have joined us today. What we've heard through this session from Dr. Lieu, Dr. Loree, Dr. Johnson and members of our team points to a profound shift which is underway in not just colorectal cancer, but in all cold, warm or hot cancers. This scientific insight that immunotherapy can work in those types of cancers, has very important global implications in the way we manage patients. We've discussed the personal stories patients who have experienced this, their patients, family members. And all of this reinforces the fact that there is an unmistakable truth, patients urgently need better options. And we are closer than ever to delivering them. I mean, who after all, would not want to have a chemotherapy a debilitating treatment-free, mutilating surgery-free option. And potentially, this is what we're heading towards. This year, we've seen encouraging signs across multiple fronts. Consistent clinical activity across refractory and earlier stage settings and that story is growing. Our global Phase III trial has been launched with unprecedented collaboration and speed with one of the leading organizations, CCTG and the principles, including Dr. Loree, who you heard from today. Stories of real patients and families whose lives have been changed by across this by access to this innovative therapy. And these are not abstract accomplishments. They are reminders of what is at stake and what is possible. As we enter 2026, we're committed as a company and as a team to continuing to advance the BOT/BAL program with the highest sense of urgency, as an organization with a highly dedicated team and the highest priority for us is to make sure that we provide every single patient who can benefit from BOT/BAL, the opportunity to be treated through either a government paid program like the French AAC or through a self-pay program or through private insurance paid program. And of course, we will engage closely with regulators with a near-term emphasis on ex U.S. regulators in pursuant of approval. To all of you, patients, clinicians, advocates, partners and shareholders, we thank you. Your engagement strengthens our ability to success and our ability to make sure that patients and their families have access to less toxic treatments and patients, of course, would desperately need less toxic and more effective treatments. We look forward to our future sessions, updating you on the progress that we're making in months ahead. Thank you very much. We wish you and your families a healthy, happy and joyful holiday season.