Agenus Inc. 12th Annual Cantor Fitzgerald Global Healthcare Conference

Sure. Thanks, Alexa. Agenus has been a company that has been approaching leveraging the human immune system to deliver curative outcomes in cancer for the last 32 years. We were founded back in 1994, and the mission of the company has always been the same through many different chapters of our history. What we're really excited about today, and what we're going to spend our time on today, is to talk about our lead asset, which is the combination therapy of botensilimab and balstilimab, or as we call it, BOT/BAL, which we've now treated over 1,300 patients in both the metastatic setting and the locally advanced settings across prevalent solid tumor cancers like colon and rectal cancer, lung, ovarian, sarcoma, melanoma.

What we've seen are unprecedented results in what are called cold tumors, or the MSS population, which are typically the most prevalent portions of the population of these solid tumor cancers. That's what's given us not only the excitement for the potential of this therapy, but has also attracted investment. We'll talk a little bit about the transaction that we just closed two months ago. Just to explain what you're seeing here, this is an example of a patient who was actually in one of our neoadjuvant BOT/BAL in colon cancer trials, which was held at Weill Cornell Medicine in New York City. On the left side, you're seeing an 8 centimeter colon tumor that a patient was diagnosed with through a colonoscopy.

After treatment only with our drug, no concurrent therapies, no prior therapies, after seven weeks, you see when they went back in for their surgery, there was no tumor. This looks like a miraculous case. It's not necessarily miraculous in our mind. It's what we expect this therapy to do. It's what the translational data has all shown is what's happening with this drug, which is a proliferation of immune cells, both to detect, kill, and remember the tumor, which is how the drug was designed by our research team. We've seen this now, similar responsiveness now in dozens of patients in this setting. It's the basis for which we are moving into a phase III registrational trial in the stage 2, stage 3 MSS colon cancer setting.

We have a line on that phase III trial design with the FDA, and that trial formed the basis for the transaction that we closed back in July. That was a $340 million PIPE financing. $85 million of those dollars were in upfront proceeds. Another $255 million are divided into two warrant tranches, the first of which is what we call a Series A tranche, priced at $4.02 per share. That will be triggered based upon our disclosure of the 60th patient enrolled in that trial, which we expect to occur in the second quarter of next year. The second Series B warrant tranche will be triggered by our public disclosure of the pathologic response rate data from that phase III trial, which we call the ROBBIN Trial. Not named after my colleague here.

Similar sounding. That path response rate data would be in the first 100 patients enrolled in the trial, 50 in the BOT/BAL arm, 50 in the control arm, and that we expect to be a Q4 2027 event. If both warrant tranches are triggered, we will have enough cash proceeds to get through end of year 2031. As you'll see from the timeline slide here, which we'll get more into.

Alexa, we are planning to have EFS readouts on an interim basis in the second half of 2029 and on a full analysis basis in the second half of 2030. The transaction was important for us because it obviously gave us the capital to go and start the trial, but we also think it's really valuable that it gives us the capital to fulfill the full needs of the trial, along with our company expenses through what we hope to be a full approval outcome.

That's a good question. I will focus on the capital market side and I will let Robin Taylor chime in on more of the scientific and medical side. I do think that there's clearly an appreciation for the strategic rationale to move into this earlier stage setting. It's a bigger opportunity. It's a chance for us to really deliver curative outcomes in patients who are starting their treatment journey, and we think that impact could be in a larger population of patients that unfortunately are diagnosed in this setting every year. We think that maybe there's a bit of a lack of understanding of the size of the opportunity. That comes down, obviously, to the number of patients, the pricing that we can garner, and the penetration rate that one would expect if we are able to deliver the clinical benefit that we expect to. We think that's part of it.

We also think maybe the actual timelines and the catalysts that we have forthcoming in the trial, maybe there's a belief that those are not yet de-risked or there's a high degree of risk associated with some of those milestones. We don't know what the future will hold, but our team is heavily focused on executing this trial. It's the focus of all of our senior leadership and our operational teams. So we feel very strongly that we're going to deliver the trial with a high degree of precision and success.

So let's talk about each individually. BOT is a next-generation CTLA-4. The modifications to this antibody were based on observations that tighter binding to basically the Fc receptor create this tighter synapse, stimulating immune responses. BOT's been engineered with two-point mutations in the Fc region that create this tighter binding, and also one mutation that was engineered in that abrogates complement binding to improve the safety. That's actually an observation that some of the more long-term toxicities observed were first-gen CTLA-4. You could potentially eliminate those by eliminating the complement binding, and that's actually what we see. We see a much lower rate of some of these more difficult-to-manage toxicities like hypophysitis that you see with the first-gen CTLA-4. So BOT is a next-gen CTLA-4. BAL is a PD-1 that is comparable to other PD-1s, comparable to Pembrolizumab or Nivolumab. It was engineered that way.

Together, what we're seeing is that you have BOT to stimulate the immune system, create this priming, generate T-cell response, and generate T-cell memory. We're also seeing that BOT is causing a depletion of Tregs. So we're seeing both aspects. One is that you are amplifying the immune response. You're also taking away this immunosuppressive Treg environment. We see that not only in pre-clinical, in the clinic, but we're also seeing it now in these neoadjuvant studies where we can look at pre- and post-treatment biopsies. The first example of that was just reported in Clinical Cancer Research.