Agenus Inc. Investor update

Joining me today are Garo Armen, our Chairman and Chief Executive Officer, Dr. Steven O'Day, our Chief Medical Officer, and we will also hear from Dr. Benjamin Schlechter of the Dana-Farber Cancer Institute. Our discussion today will focus on the progress that we have made since our July webcast, including implementation of the ROBBIN Phase III neoadjuvant program, continued physician interest in the access to botensilimab/balstilimab, and recent clinical and investigator-led activity that is helping inform the acceleration of botensilimab/balstilimab into the earlier disease settings. Following the prepared discussion, Agenus leadership, including Dr. O'Day, as well as Robin Taylor, Chief Commercial Officer, will join Garo for a live Q&A. Questions may be submitted at any time during the webcast using the Q&A function of the Zoom event below.

Before we begin, just a brief reminder that today's discussion includes forward-looking statements, so please be sure to refer to our SEC filings for additional details also available on our website. With that, I am pleased to introduce our Founder, Chairman, and CEO, Garo Armen.

Thank you very much, Stefanie, 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 neoadjuvant 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. Certainly, the financing played a major role in addressing that question. 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 are not going to repeat that discussion today, but what matters now, and you are going to hear about this from Dr. O'Day, 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 neoadjuvant trial? Over the last few weeks, there were two important bodies of botensilimab/balstilimab clinical evidence that moved into peer-reviewed journals for Clinical Cancer Research, which is the prestigious journal of the American Association for Cancer Research. The longer term for Phase Ib study, which is in the refractory MSS metastatic colorectal setting, published shows longer-term follow-up and durability, and you will hear about this also from Dr. O'Day, durability of responses in patients that responded. These are, of course, important studies for us.

The next one is the NEST neoadjuvant study, and that also talked about how we haven't had any recurrences since the study began. Now, we're also seeing increased investigator interest in studying botensilimab/balstilimab in the earlier disease setting. Of course, shifting to the neoadjuvant setting for our approval strategy helped, but we're seeing also additional investigator-sponsored proposals and studies for neoadjuvant. 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 2 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 botensilimab/balstilimab. It doesn't change our course with the ROBBIN study.

That is the strategic focus of the company, both from a financial allocation of resources and people allocation of resources. But it also reflects the broader clinical interest in asking what botensilimab/balstilimab may do before surgery and creates additional clinical trial access to patients. At the same time, physician interest in accessing botensilimab/balstilimab outside of clinical trials also continues. We've had geographic reach, and our access programs have expanded. We're seeing repeated interest coming from physicians. As you know, we have the French AAC program, and then outside of that, we have the paid Named Patient Program, and those requests are coming in, and that demand is growing. Now, at Agenus, our development priority, as I said before, remains very clearly advancing ROBBIN, our neoadjuvant 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 Dr. Ben Schlechter of Dana-Farber Cancer Institute, 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 botensilimab/balstilimab patients, even in the late stage 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 Stefanie to take the program forward.

Great. Thank you so much, Garo. Steven, let's actually start on a conversation here together and take up where Garo left off. So when we announced the ROBBIN Phase III neoadjuvant 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 those key elements of this program to move forward and really establish the resources to move forward, including the financing that Garo just alluded to. So I know it's only been about 2 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, Garo and Stefanie. Boy, has it been a busy couple of 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 botensilimab/balstilimab program. In July, we were focusing primarily on the design of ROBBIN, aligning with the FDA rationale for moving botensilimab and balstilimab into the neoadjuvant setting, a very important pivot that really optimizes the signal that we're getting with botensilimab/balstilimab with an intact tumor and draining primary lymph nodes. Since then, our focus in the last 2 months has been really increasingly and almost exclusively a shift to implementation and startup of this very important ROBBIN 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 1 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 Agenus. Give us a little bit of a sense of the scale of that effort, Steven. How large of a clinical network are you building for ROBBIN, and what can you tell us about the geographic footprint particularly? I know we haven't Yeah really shared much about that as of yet.

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. This is particularly important with a neoadjuvant study. It is really very different than studies in the late-stage metastatic setting. It is important these sites see the patients, which are high-risk stage II and III cancer. As you know, there is an epidemic worldwide, so these cancers are prevalent, particularly in the MSS, 90% of all colon cancer. Most importantly, though, neoadjuvant studies require multidisciplinary teams to identify these patients, become aligned around neoadjuvant treatment. This involves a medical oncologist, clearly.

What is different here is we need alignment and leadership from our surgical colleagues, but also our radiology colleagues, our pathology colleagues, our gastroenterologists, and our research teams. 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. 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 are also selecting high-performing, high-quality community-based centers and networks, as long as they are integrated in terms of the multidisciplinary neoadjuvant setting. Interacting with medical oncologists 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. You just talked a little bit about the broad scope and 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 botensilimab/balstilimab, or are you seeing that ROBBIN is also bringing in new investigators and institutions that do not have prior involvement or have not really been connected much more broadly with the program previously?