AGEN | Agenus Inc. | earnings call 2026-09-15
Verbatim transcript (source: faster-whisper-small.en)

Good afternoon, everyone, and thank you for joining us today. My name is Stephanie Nkarr, I'm Chief Communications Officer here at Agenis, and want to welcome you to our September Stakeholder Webcast. Joining me today are Garo Armin, our Chairman and Chief Executive Officer, along with Dr. Stephen O'Day, our Chief Medical Officer, and we'll also hear from Dr. Benjamin Schlechter of Dana-Farber Cancer Institute. Our discussion today will focus on the progress made since our July webcast, including implementation of the Robin Phase III Neo-Adjutant Program, continued physician interest in our access pathways to Bot Bow, and recent clinical and investigator-led activity that is helping inform the acceleration of the Bot Bow program into earlier disease settings. Following the prepared discussion, Agenis leadership, including Dr. O'Day, as well as Robin Taylor, our Chief Commercial Officer, will join Garo for a live Q&A. Questions may be submitted anytime during the webcast using the Q&A function at the bottom of the Zoom event. Before we begin, just a brief reminder that today's discussion includes forward-looking statements. Please refer to our SEC filings for additional details, which can also be found on our corporate website. With that, I'm pleased to introduce our founder, chairman, and CEO, Garo Armin. Garo? Thank you very much, Stephanie, and thank you everyone for joining us today. When we had this session back in July, we spoke about the financing that was announced then, and we also spoke about the strategic shift into the new adjuvant setting in terms of our approval strategy. At that time, of course, the concern was before that announcement, the concern was our path forward. I think very few people were questioning the high activity of our product or combination, but people were more interested in how were we going to take this to the finish line. And certainly, the financing played a major role in addressing that question. And since then, our stock has reacted favorably by all standards, and we believe that some of the critically important risks associated with financing the company's future were at least removed for the time being. Now, we're not going to repeat that discussion today, but what matters now, and you're going to hear about this from Dr. Oday, and if there are any questions, of course, Dr. Taylor, how are we doing since then? What are we doing to execute towards that strategic goal of initiating and completing our new adjuvant trial? Now, over the last few weeks, there were two important bodies of bot-bile clinical evidence that moved into peer-reviewed journals for clinical cancer research, which is the prestigious journal of the American Association of Cancer Research. And the longer-term phase 1B study, which is in the refractory MSS metastatic colorectal setting, published, shows longer-term follow-up and durability, and you'll hear about this also from Dr. Oday, durability of responses in patients that respond. These are, of course, important studies for us. The next one is the NEST new adjuvant study, and that also talked about how we haven't had any recurrences since this study began. Now, we're also seeing increased investigator interest in studying bot-bile in the earlier disease setting. Of course, shifting to the new adjuvant setting for our approval strategy helped, but we're seeing also additional investigator-sponsored proposals and studies for new adjuvant. You're going to hear more about them, including the rectify-1 study led by Dr. Ben Schlechter, and Dr. Schlechter is going to be joining us in just a bit. We interviewed him two days ago because of his patient schedule, and we're delighted that he had the time to discuss some very important points with us. Now, all of this is important because it gives patients the opportunity to be able to benefit from bot-bile. It doesn't change our course with the Robin study, that is the strategic focus of the study, both for a financial allocation of resources and people allocation of resources, but it also reflects the broader clinical interest in asking what bot-bile may do before surgery and creates additional clinical trial access to patients. At the same time, physician interest in accessing bot-bile outside of clinical trials also continues. We've had geographic reach, and our access programs have expanded. We're seeing repeat interest coming from physicians. As you know, we have the French AAC program, and then outside of that, we have the paid name patient program, and those requests are coming in, and that demand is growing. Now, at Agenis, our development priority, as I said before, remains very clearly advancing Robin, our new adjuvant CRC study in the colon cancer setting, forward. Steven will update you on how this program is moving forward. We've had some very exciting initial interactions. Well, they're not initial interactions anymore because I think we've covered the majority of the sites that will participate in this trial already. We'll also discuss what we're seeing through our access programs in addition to what I mentioned before. So, as I said, you'll hear from Ben Schlechter, Dr. Ben Schlechter of Dana-Farber, why the timing of immunotherapy may matter in colorectal cancer for the first time, why MSS disease has historically resisted first-generation immunotherapy while we're seeing responses in bot bowel patients, even in the late-state setting where there's really no treatment options left for them. So that's where I'd like to stop and turn this over to Stephanie to take the program forward. Great. Thank you so much, Gero. And with that, Steven, let's actually start on a conversation here together and kind of take up where Gero left off. So, when we announced the Robin Phase III Neo-Adjutant Study back in July, we had done a lot of work, you in particular, to define the study, the components that we received FDA feedback on, on those key elements of this program to move forward and really establish the resources to move forward, including the financing that Gero just alluded to. So I know it's only been about two months, but there's obviously been a tremendous amount of work and activity from you and the team and the organization towards opening up this global study. Can you share a little bit about what has changed operationally since July and where the team is focused today? Well, thank you, Gero and Stephanie. And boy, has it been a busy couple months. Really unprecedented in my experience with excitement and enthusiasm. We obviously have a deep network of thought leaders and principal investigators around this very mature Bot Bow program. But in July, we were focusing primarily on the design of brahmana, aligning with the FDA, rationale for moving Bot and Bow into the Neo-Adjutant Study, a very important pivot that really optimizes the signal that we're getting with Bot Bow with an intact tumor and draining primary lymph nodes. But since then, our focus in the last two months has been really increasingly and almost exclusively a shift to implementation and startup of this very important Robin Global Study. This includes building and continuing to expand our global investigator and site network, advancing the regulatory and ethics work required in the countries where we intend to conduct the study, establishing pathology and translational infrastructure, and aligning our clinical, operational, and drug supply functions around the study initiation. There are a lot of individual work streams in the company right now involved with opening this Global Phase III trial. And we are moving in parallel with rapidity and efficiency and excellence. And our goal continues to be enrolling the first patient in quarter one, 2027. Well, that seems to be a huge undertaking, but very confident, particularly even, you are no novice to clinical studies being an investigator yourself before coming here to a genus. So give us a little bit of a sense of the scale of that effort, Stephen. How large of a clinical network are you building for Robin? And what can you tell us about the geographic footprint, particularly? I know we haven't really shared much about that as of yet. So this is a Phase III global trial of approximately 850 patients. It will involve North America, Europe, South America, and Asia. We are extremely mindful, and I am in control with my team, of selecting high volume and high quality sites. And this is particularly important with a neoadjuvant study. It's really very different than studies in the late stage metastatic setting. It's important these sites see the patients which are high risk stage two and three cancer. As you know, there's an epidemic worldwide. So these cancers are prevalent, particularly in the MS stable, 90% of all colon cancer. And most importantly, though, that neoadjuvant studies require multidisciplinary teams to identify these patients become aligned around neoadjuvant treatment. Now this involves the medical oncologist clearly. But what's different here is we need alignment and leadership from our surgical colleagues, but also our radiology colleagues, our pathology colleagues, our gastroenterologist, and our research teams. And this is no small chore, but our deep networks, my experience across 30 years in the clinic and networking with KOLs around the world has definitely been very helpful. But the data itself is what is most helpful and is really exciting people to participate in the trial. Most of the sites are major academic centers, but we're also selecting high performing, high quality community based centers and networks, as long as they're integrated in terms of the multidisciplinary neoadjuvant setting. Interacting with medical oncologist alone is simply not enough. In order to be successful, we need to align and the enthusiasm from these multiple stakeholders. Thanks for that, Steven. Question. So you just talked a little bit about the broad scope in your personal involvement in site selection as well, likely because of all of the relationships that are out there and the experience. Are these sites and some of the investigators, primarily investigators that are already familiar with BAPBAL, are you seeing that Robin is also bringing in new investigators and institutions that don't have prior involvement or haven't really been connected much more broadly with the program previously? So it's a combination, but I will say with almost more than 1200 patients treated in our agenda sponsored trials as well as our investigator initiated trials across the globe, we have an extensive network of investigators and thought leaders. But what's interesting is there's also thought leaders and investigators that have been more concentrated in the neoadjuvant space and we're leveraging this. So we are bringing in additional new thought leaders and investigators with a particular experience in neoadjuvant setting. And as you know, in MSI colon cancer, there is now an evolving experience in this neoadjuvant setting for GI oncologists. And so we're really piggybacking and really driving that experience. And so the short answer is it's a combination of our existing, but a whole new group of investigators are seeing this data, have done neoadjuvant trials and want into this large global trial. Yeah. I think that we'll get to this a little bit later, but even more so recently, a lot more neoadjuvant investigator sponsored studies are launching as well. In our July webcast, we had Dr. Pashtun Kossi with the NEST3 study and Dr. Benjamin Schlechter today who started the rectify one study at Dana-Farber. And then there's other neoadjuvant studies as well going on at MSK and then also in the Netherlands. So a lot of interest in the neoadjuvant setting, which I'm sure is a part of a lot of the excitement too around Robin. Earlier, just getting back to something that you had mentioned though, Stephen, about the multidisciplinary nature of these sites. You started to allude to this a little bit, but what is operationally a bit different about a neoadjuvant study like Robin compared to a traditional later line study? And why is that experience so important as we think about appropriately and efficiently getting Robin off and opening it and rolling and that consistency that you alluded to earlier across all these different global sites? Can you talk a little bit about that? Yeah. So let me build on, I've obviously talked about the multidisciplinary alignment that's really critical. What people are very excited about is that this could be a paradigm shifting study that will not only reduce recurrences and improve survival, but deescalate chemotherapy in this very early stage setting. So that's really important. But there are other issues here. In addition to aligning the medical team, you're dealing with patients that are newly diagnosed, they're in healthcare systems expecting potential standard of care surgery and adjuvant chemo. Patients want more than that. Doctors want more than that. And Robin trial inserts a defined treatment period before the surgery so that part of the process must fit within this established clinical pathway. I think patients are more than willing to delay their surgery a short period of time given the data that we've shown that none of these patients have progressed during this period of time. And the opportunity to improve survival and reduce chemo is a win-win for doctors, surgeons, medical oncologists, and everyone involved. But you do have to identify the patient, you have to stage them, you have to identify their MS status, which is now routinely done in all colon cancer. And then you move forward in a relatively short interval and you need the teams to be ready and teed up. And that's what we're spending a lot of time talking to the teams and really being sure that they're set up for success. Success will require that patients be present, but also that the teams really function at a high level to get the treatment in and the surgery and the adjuvant therapy. Yeah. So that's a lot of coordination across the different parties at the different sites. You also mentioned pathology and the importance of that particular expertise within the multidisciplinary function because it's also a very important feature of how we're going to begin learning about the impact of BotBAL within the Robin study. Can you share with us a little bit about what needs to be in place to ensure that the pathologic response, the assessments, right? We know that this is a huge milestone for us, are consistent and rigorous across how it's going to be assessed across this large global study. Yeah. So I think what's important is we're not starting from scratch here. The neoadjuvant setting with immune therapy has been established in melanoma. It's also prevalent in breast cancer now and lung cancer in terms of neoadjuvant perioperative. So things are in place in terms of leveraging that history. But what's really exciting for everyone is that even though time to distant recurrence or metastasis from the cancer is the primary endpoint of the study, we will get an early readout after the first eight weeks or so of treatment on the depth of this pathologic response. And more important than ever in immune mediated therapy, more so than chemotherapy or targeted therapy. The depth of these responses are so highly predictive of eventual metastasis. So we will be looking at complete and near complete responses and that will give us a lot of confidence as we go through. And this will be centrally reviewed by the trial that we are consistent with our phase two data and highly set up to succeed in terms of the primary endpoint of the study. Now this does require that we coordinate this and we have leading centers around the world that have a lot of experience with pathologic response. And we're leveraging and identifying these centers to help us coordinate and make sure that this is a rigorous process of pathologic assessment. We're also collecting CT DNA and other biomarkers that will also be very helpful, not in real time in this study, but as important supplementary information as we wait for additional primary endpoint time to event. Great. Thank you, Steven. And certainly once the sites begin opening and enrolling, that's really where I think the attention naturally will be like, how quickly are we actually enrolling patients? What do you see from your perspective and your role, what will determine how efficiently Robin moves from all of this builds up to the site activation into actual patient enrollment? Yeah, as Garo and I often discuss, it's not, I mean, the first patient's very important and we're on target, but we want to get really a crew quickly and I think we're setting this up. It's not the number of sites ultimately, although we're well set up with a global trial, but it's the quality of these sites and their enthusiasm and alignment around identifying and treating the patient. You know, colon cancer is common, but Robin is enrolling a defined population of stage high-risk two and three patients. So ideally, we look forward to, in parallel, opening a number of early sites and then obviously as quickly as possible due to regulatory timelines continue to open sites in early 2027. Great. Okay. So I have one last question for you, Steven, before the live Q&A at the end. For all of our listeners and the stakeholders that are following Robin, what are the most meaningful indicators of progress between now and that first patient in that you just alluded to and then as the study begins enrolling more so? What are you looking for? So the first thing is the work we've done the last two months and we'll do in the next two months is really rigorously identify sites that will succeed and produce rapid accrual and high quality data. So that's number one. And then driving enrollment and we have a plan for very active connection and really staying very close to these centers as they ramp up. So I think in terms of Robin, I think it's best to think of this in three stages. You build and activate the network. We're doing that with wholehearted enthusiasm, both from our team and our investigators around the world. You then drive enrollment and as these responses become apparent, it will only increase the enthusiasm of the sites. And then obviously getting a readout of the surgical pathology results will be also very, very important. We are on track to first patient enroll in the first quarter of next year and getting some pathologic data in the second half of next year as we've outlined previously. But ultimately it's all about can we through bottom bow and surgery, can we reduce recurrences and improve survival and at the same time reduce the need for chemotherapy in a curative and tense setting. And this will be the paradigm shifting feature of the study. Great. Thank you so much, Steven. Thank you for your time and walking us through that today. So, Garo, I'm going to come back to something you mentioned earlier at the beginning of the call because this is another area where the team is really focused and also seeing some meaningful activity since our last discussion in July. Robin, as you mentioned, is clearly the company's development priority and our focus. But at the same time, as you've mentioned before, our kind of moral obligation that there are patients who need treatment today and physicians who continue to approach yourself and Janice seeking access to Bot Bow. Can you give us an update on what has changed across the access program since we last spoke in July? So, just to be clear, we have, as you know, two access programs in addition to any trials that are ongoing that allow a patient to have Bot Bow treatment. One clearly stated is the program that was approved in France and we have not disclosed the number of patients treated. However, we have disclosed the reimbursement revenue that we get from the French government every quarter and we will be talking more about the progress that we're making there. So that's a very important program and French patients have been privileged enough to have access to this and have the government reimbursement. Now, in addition to that, we also have the Paid Name Patient Program and that's a program that allows a patient whose physician is seeing it appropriate to refer that patient to a country and a center where the treatment can take place. And these include, of course, as we've talked about before, the UK, Switzerland, France can treat patients with Paid Name Patient Programs that are willing to pay out of pocket in addition to reimbursing their own patients, Belgium, Spain, Brazil, Argentina, and a number of countries are growing. Now, under this program, a patient can request or the doctor can request to be treated for any indication that they seem to be fit for the patient. It doesn't have to be restricted by the AC program communications or anything else. As long as there is data, and as you know, we have data on over nine different kinds of cancers where we have shown consistent activity. In fact, at last year's ESMO in Berlin, there was an oral presentation where we showed the consistency of response rates in late stage patients that have exhausted all other treatment options. So this is quite exciting actually. It's exciting because we're seeing the momentum develop and in terms of the Name Patient Programs, for example, we have US physicians referring patients to any country or any center where they can be treated with Paid Name Patient Programs. And as long as their physician sees it appropriate for the patient to undergo such a treatment, they can get it. Now, the unfortunate reality is that can you imagine a patient struck with cancer? They may not be in the best of health. They may not be in the best of shape to travel. But unfortunately, the US patient has to travel to some other country willing to pay out of pocket and be treated. And we hope that that reality will change sometime soon. But that's the reality right now. But one of the things that I wanted to also mention is that, as you know, Europe shuts down in the month of August and in fact, increasingly, US is also shutting down in the month of August. And we expected a slowdown in demand by doctors for August. In fact, we've seen a growth, not a slowdown, but a growth. And so those are very indicative of the fact that there is substantial enthusiasm by physicians and by patients to be treated with BotBAL because it can offer them a hope and a reality of survival for an extended period of time. Dr. Ode always says the durability of responses in immuno-oncology combinations is really very notable. And so that's what we're seeing. And we're very excited that the roster of physicians who are familiar with the data and are willing to treat patients is growing. Great. Thank you. And I know that the team anticipates this share more specifics during our Q3 earnings update. But again, very, you know, positive that the interest still continues to grow even over these periods where we were expecting and anticipating maybe some malevoline. But you've mentioned in the past, Gero, too, that, you know, not just the expansion of additional countries and making the access to BotBAL available for their patients, but you're starting to see physicians, repeat physicians, treating multiple patients at their centers. What do you think is driving the physicians to come back and seek access for additional patients after they've initiated treatment? I mean, it's definitely, this is a very important point, of course. One very important aspect of this, and we've heard this from physicians that most recently have shown very high enthusiasm in participating in our trials, particularly the Rabin trial. One very notable reason is that, as I talked about a little while ago, for example, in the last few weeks, we had two publications discussing long-term outcomes for patients, one in the late-stage disease and one in the new adjuvant setting. We expect more to come between now and the end of the year, of course. These are very important drivers, the credibility of the data and their own personal experience. So if you treat one patient and you see something happening, you want to treat another patient. That doesn't mean that every single patient is going to respond, particularly in the late-line setting, that's not going to happen. But it's encouraging because it's the last hope for patients. And hope is a very important element here, very important element because, you know, how could you tell a patient that we've exhausted all treatments and there's nothing else we can do for you? So we offer that last hope for the patients who have exhausted all treatments, and that's clear based on the data that's been published and presented. And we also hope for patients in the new adjuvant setting to be treated less, I should say, less in a punishing way, more in a sustainable benefit. Dr. Odey explained this beautifully. It's a very important point for patients. And in some cases, what we hope is that patients will be able to benefit from lesser surgery, lesser surgery, meaning some of these surgeries are quite radical, debilitating for the patient. For example, if you have rectal cancer or colon cancer that's near the rectum, you have a life-changing surgery. We have some patients, including relatives of our colleagues, where they have been treated with radical surgery, and life is never the same for them. And what we hope to do with the Robin trial is to change that reality for patients. I think.