Agenus Inc. (AGEN) Earnings Call Transcript & Summary

Reporting communications Officer at Agenus. Thank you for joining today's webcast [indiscernible] earlier this morning. Joining today from Agenus, Garo Armen, Founder, Chairman and Chief Executive Officer; Dr. Steven O'Day, our Chief Medical Officer; Robin Taylor, our Chief Commercial Officer; and Dec Arnon, VP, Corporate Development and Investor Relations. We also have the pleasure of having 2 globally renowned thought leaders in the space of neoadjuvant colon cancer treatment and research, also joining today is Professor Miriam Clay at the Netherlands Cancer Institute, a globally recognized leader in gastrointestinal oncology, Scientific Co-Chair of the ESMO Congress the pioneering investigator behind the landmark niche studies in neoadjuvant immunotherapy for colon cancer in the 2026 Innovation & Science Award for Cipient and a Robin investigator. Also with us is Dr. Pastan Kashi, the RAG Family Chair in Gastrointestinal Oncology and Medical Director of DI Medical Oncology at City of Hope Orange County, whose leadership at the landmark NES trial has helped establish neoadjuvant Botensilimab and balstilimab as one of the most promising new immunotherapy approaches for patients with MSS colorectal cancer. Both are investigators in the upcoming Robin trial. The following webcast contains forward-looking statements regarding agenesis businesses that are made pursuant to the safe harbor provisions of the federal security laws. Please reference this full forward-looking statements in our statements shown now, which can be also found on our website in this webcast presentation, along with our company overview presentation. So with that, I will turn the call over to Garo.

Thank you very much, Stefanie, and thank you, our guests, Professor Shalabi, and Dr. Kase, as well as all of you for joining us this morning. Today's announcement marks an important development for Jens. At its core, it represents a genius focusing on a program which can be life-changing for patients and create unprecedented value for Agenus stakeholders. It also signifies a deliberate decision by the company to concentrate our resources behind what we believe is our highest impact and highest value opportunity that is neoadjuvant but ball in MSS colon cancer. And for those of you that may not recognize that term, MSS colon cancer accounts for approximately 85% of all colon cancers, well as it is the most difficult to treat colon cancer and unresponsive to immunotherapy until backbone. And with this additional infusion of cash, it will provide us with the opportunity to execute that strategy from a position of financial strength. We made this decision to pursue the Robin trial our Phase III registration-enabling study of neoadjuvant pupil in high-risk Stage I and Stage II MSS colon cancer. We designed this study based on data generated in multiple ongoing ISTs, and you'll hear more about them from our guests, highlighted by Neste unicorn. And with the input of some of the most prominent clinicians 2 of whom have joined us today. The data from Nest and Unicorn, along with Dr. Trilabs NeOASIS trial, are consistent across more than a dozen clinical centers in the U.S. and Europe. Importantly, we have discussed the Robin trial with the FDA and and received feedback supporting it as a registrational pathway for but plus bar in this prevalent treatment setting with non newly approved therapies in the last 2 decades. This is the setting where we believe the biology of BOT+BAL, the clinical need and the patient impact and the value creation opportunity come together, converge basically most powerfully. While we have generated exciting and for some patients, life-saving clinical data, in late-line metastatic disease. Patients with advanced disease are generally very sick, heavily pretreated and often have limited time in the neoadjuvant setting on the other hand. We are treating patients earlier where the treatment setting is most appropriate. While the primary tumor is still present, while the immune system is more competent, and while the intent is to cure patients, this has always been central to Agenus mission to move next-generation immunotherapy agents to the settings where it can have the greatest impact. The financial -- or the financing announced today, lets us pursue that path. The $85 million upfront is expected to renew near-term financing pressure -- and with full warrant exercise, the structure objective for this is to fund the Robin trial and Agenus operations through the year-end 2031, carrying us through several key value inflection points of this registrational program. You will hear more from Zach on the transaction, Robin on the strategic rationale Befesa Colaba and Dr. Kate on the Clinical Foundation and Stephen under Robin design. And I'd lastly like to thank our new distinguished investors for having done the significant amount of work to make this decision. With that, I will turn it to Zach.

Thank you, Garo. Earlier this morning, we announced a private placement of up to $340 million, led by Commador Capital with participation from RA Capital Management, TCGX, Invis and Ligand Pharmaceuticals. This transaction includes $85 million of upfront gross proceeds and 2 or in tranches totaling potential additional gross proceeds of $255 million. Each of the 3 funding tranches, including the $85 million upfront, were priced at a premium to the market closing price as of last Friday, July 10. This structure aligns capital with key value inflection points within the Robin trial time line and our path toward full approval. Our conviction is that the Robin trial will unlock Bots Ball's promise to deliver significant patient benefit and shareholder value. And this financing provides us with the resources needed to execute on that promise. We are excited for the path forward and thank all of you for joining us on today's webcast. We are fielding Q&A questions now if you would like to submit through the Zoom webcast application. I will now turn the call over to Robin Taylor, our Chief Commercial Officer, to frame the unmet need and strategic rationale.

Thank you, Zach. Let me start with the unmet need. Colorectal cancer is now the leading cause of cancer-related death among Americans under 50. Across all ages, the overall disease incidence is 155,000 cases every year in the U.S. About 70% of these tumors are colon cancer and about 15% of early-stage tumors are microsatellite high, which are candidates for immunotherapy, but about 85% of resectable colon cancers are microsatellite stable, which are immunologically cold and refractory to conventional immunotherapy. That is where BAT and BALL comes in. Botensilumab is a next-generation Fc-enhanced anti-CTLA-4 antibody designed to work with balstilimab, our anti-PD-1, to turn cold tumors hot driving broad immune activation and T cell memory. Go to the next slide, please. There we go. These images are from a patient with MSS colon cancer treated in the neoadjuvant setting from the NEST study. On the left, an 8-centimeter mass in a 40-year-old woman, on the right, the same colon 7 weeks later after just one dose of BAT and 2 of Ball immediately prior to surgery, and this was subsequently confirmed as a pathologic complete response. One of many across the bat and ball neoadjuvant studies. This example clearly demonstrates what BAT and FC enhanced CTLA-4 can do when the primary tumor with its full repertoire of neoantigens is still in place. We have shown broad activity of BOT and BAL ell in late-line metastatic tumors, including MSS colorectal cancer -- but the benefit we can deliver in the neoadjuvant curative-intent setting, the high-risk Stage I and Stage II MSS colon cancer dwarfs the impact in metastatic disease, for a population with no major therapeutic advance in over 20 years since Oxaliplan was approved. Our strategic pivot rests on 4 points. First, the population is larger. -- roughly 38,000 high-risk Stage I and II MSS patients treated annually in the U.S. Second, the impact for patients and for payers is greater in a curative intent setting. Third, 2 Phase II studies demonstrated deep, rapid pathologic responses and support a high probability of success in Phase III. And fourth, Robin's design is aligned with FDA feedback and backed by financing through the program's major value inflection points. In short, we are focusing BOT and BAL, where the rationale, the need, the data and the value were most aligned. In Nest and Unicorn, neoadjuvant bought ball produced consistent results with respect to pathologic response. The key measure used for pathologic response is the pathologic complete response rate or PCR, for short, which is defined by the finding of no viable invasive cancer cells in the resected specimen after neoadjuvant therapy as determined by a pathologist after surgery. For event-free survival, the benefit is measured as a hazard ratio, which is a statistical measure of the relative treatment effect on a time-to-event outcome. The ROBBIN Phase III study is targeted to a hazard ratio of 0.65 or a 35% reduction in the risk of recurrence or death. To understand the effect of the PCR rate on the potential hazard ratio of the ROBIN study, we analyzed 21 neoadjuvant and perioperative trials, examining the relationship between the PCR rate delta between the experimental and control arms, and the event-free survival hazard ratio. As you can see, there is a strong correlation between the 2 measures in the plot on the left. The table on the right shows the projected hazard ratios at different PCR deltas. We expect a PCR rate of 0% in the control arm, as was seen in prior studies such as FOX Tri, NeoCol and optical for patients who went straight to surgery without neoadjuvant treatment. A PCR rate delta of 17% in the ROBBIN study would be projected to achieve a hazard ratio of 0.65. The target hazard ratio for the ROBIN study -- the PCR rate observed in the NEST and Unicorn in Phase II trials meaningfully exceeds that target, replicating the 30% PCR rate would correspond with an estimated hazard ratio of about 0.5. Now let's consider the market opportunity. Approximately 85,000 people are diagnosed with Stage 1, 2 or 3 colon cancer in the U.S. each year. About 15% of these patients have MSI-high tumors and are RRD candidates for currently approved immunotherapies -- the remaining 85% of patients with MSS tumors equals about 68,000 stage 1 to stage 3 patients. Of this group, ROBBIN focuses on the high-risk Stage I and Stage II MSS population which is about 38,000 eligible patients annually. At an illustrative $200,000 course of neoadjuvant treatment, the addressable market opportunity translates to greater than $7 billion market opportunity. This is why the ROBBIN study is commercially and clinically different from a late-line metastatic program. The patient population is larger -- the clinical goal is tied to preventing recurrence and preserving long-term survival and has a greater impact on life year saved and the endpoints are aligned with the goal of changing clinical practice. To put this into clinical context, I will now turn to Professor Miriam Telavi whose work has helped shape the field of neoadjuvant immunotherapy in colorental cancer.

Good morning, everyone. It's great to be here to discuss the exciting avenue of neoadjuvant immunotherapy in colorectal cancer, something that I think over 10 years ago, we didn't think was possible, especially not for MSS colon cancer. So I'll be discussing some of the data on where we stand in terms of treatment of colorectal cancer in general as well as what we have on neoadjuvant immunotherapy in colorectal cancers, both MSI and MSS colorectal cancers. So first of all, it's good to set the stage on how do we treat patients with colorectal colon cancers I would say, at this time. And this hasn't changed over the past 20 years. we treat patients with direct surgery usually unless there's a real need for neoadjuvant therapy, which is not the standard of care. We treat them with surgery, and then we decide based on the pathologic assessment, whether there's adjuvant chemotherapy needed yes or no. All patients are treated mostly with the same type of chemotherapy regardless of whether they have an MSI or MSS tumor. We don't look at molecular subtypes or anything like that at this time yet. So everybody gets the same treatment usually have a high-risk stage 2 tumor when it comes to MSS colon cancers or when they have a stage III tumor, meaning that they have lymphnode positive disease. There is -- despite this treatment with surgery, followed by chemotherapy, there's still a very high recurrence rate for these patients who receive up to 6 months of adjuvant chemotherapy sometimes and the surgery 20% to 40% of these patients can still recur. So we still need a better treatment option for these patients. And ultimately improve their long-term outcomes and decrease toxicities, of course, because chemotherapy is not without side effects -- many patients suffer from polyneuropathy also in the long term. And there's definitely room for improvement in both outcomes but also in side effects that we incur based on our treatments. Next slide, please. So the FOX Rove study, what I mentioned before is that neoadjuvant therapy is not a standard of care. It's becoming standard of care more and more. And this is also thanks to the [ FOX THAT ] study. FOX START study was actually the very first study in which patients with colon cancer were treated with neoadjuvant chemotherapy. And these were patients that were treated randomized to either very operative chemotherapy, so either neoadjuvant plus adjuvant chemotherapy or adjuvant chemotherapy alone, and this was based on clinical staging. So patients were selected based on on their T stages in their tumor, such as will be the case for the ROBBIN trial. In this study, there was no specific requirement of having an MSS or an MSI tumor. And that was because back then, we did not know what these data were going to show us in terms of the differences in responses between MSI and MSS tumors. What this study showed is that neoadjuvant chemotherapy was feasible because we didn't have a large trial showing us that that it was safe, that the rate of complications was not higher compared to adjuvant chemotherapy. Also, there seems to be ultimately an improvement in outcome for patients who received neoadjuvant chemotherapy. So there's definitely a subset of patients that might benefit from neoadjuvant treatment. This actually sets the stage for the possibility of neoadjuvant treatment, be it chemotherapy or immunotherapy in that sense to be given prior to surgery in patients with colon cancer. What this study also showed is that if you look at the pathologic responses, pathologic responses in MSS colon cancers where this chemotherapy is the standard of care, of course, also in the metastatic disease setting still. The response rate to neoadjuvant chemotherapy is about 20% to 25% if you consider other trials as well. So that is kind of what we're looking at in terms of the standard of care and how that performs in the neoadjuvant chemotherapy setting. And that is something to keep in mind when discussing what we're looking for in terms of responses and ultimately also improvement in outcome when considering neoadjuvant immunotherapy because MSI tumors respond exceptionally well to neoadjuvant immunotherapy, and that's almost 100% of patients that may respond, but that's a completely different biology. And that's a small subset of patients with colon cancer. While the 85% of patients still have their chemotherapy as the standard of care, and that's all we have. Actually, other chemotherapies have been tried and that hasn't worked. So there's definitely a need for improvement for that patient population. Next slide, please. So what we did in the NET study, and this is a large platform study where we have treated patients with MSI colon cancers. And as I mentioned before, immunotherapy works exceptionally well for that group, but that's not the group that we're talking about here. We're talking about the patients with MSS colon cancer that encompass most of the patients with early stage nonmetastatic disease. What we set out to do in the NICE trial, and this was the very first trial to look at the neoagifan immunotherapy in a group of patients with MSS colon cancers. We had the hypothesis that if you treat patients with early-stage disease that there was a higher chance of them responding to immunotherapy compared to the data that we had back then, that was before BAT and BAL and before the next-generation CTLA-4 that was with ipinivo in this case, patients with metastatic disease were not responding to immunotherapy. But we have the hypothesis that treating earlier such as is the case also for other tumor types, leads to better responses. -- also for colon cancer, where we know that a subset of MSS colon cancers can be immune and can respond. So we treated 31 patients in this trial with neoadjuvant, ipilimumab and nivolumab, just 2 cycles of nivolumab, 1 cycle of ipilimumab. And that was the whole treatment of patients went to surgery within 6 weeks thereafter. And very much according to our hypothesis, we found that a subgroup of patients did respond, and this was just not just a little bit of response. These were patients that had deep pathologic responses, including PCR, within 4.5 weeks from first dose of immunotherapy to surgery. So there's 26% response rate that we saw in this study with just 2 cycles of neoadjuvant immunotherapy, meaning that if you have an even better treatment including a better anti-CTLA-4, hopefully, that will lead to more responses in this patient group when you look at a very large data set in a randomized trial. And ultimately, you will want to compare this to the standard of care, which is adjuvant chemotherapy in this case and compare that, of course, also to what we're seeing with neoadjuvant chemotherapy from the FOxTROT trial. We also saw that when patients respond to immunotherapy that they don't have any recurrences and this is something that has been shown in melanoma trials. This has been shown in McClean cancers as well. and this being a small group of patients, of course, and that has to be kept in mind. But we also see here that patients who do have a pathologic response to that very short duration of treatment have an excellent long-term outcome without recurrences, while patients who don't respond are at significantly higher risk of recurring. Next slide, please. And that was my last slide. So I think now I will pass it on to Dr. Pashu Kaz. You will be talking about his experience with Neste Unicorn with the neo adjuvant BAT and BAL.

Thanks so much Chelavi. I'm glad to be here as a conation, an investigator of the new adjuvant studies, the so-called NES Grupo studies. And also we're talking about the unicorn study as well in Nestinutocon, both matter because they're exactly evaluating the combination of bar and bowel in the setting where Robin trial is going to happen, which is before surgery, where the tumor is still present and a time line that fits into a surgical schedule. Now as mentioned earlier, a few times already, the new adjuvant setting is attractive because the priming tumor is still in place, the draining lymph nodes are in place, the tumor can serve as a source of antigen. And as Dr. Slabialso mentioned, there are reasons why the same setting can be more conducive to immunotherapy in this case, checkpoint blockade. The other thing that's also very powerful in the agent setting is the ability to get tissue. So we're not talking about responses on scans. We're talking about pathologic responses, resected tissue and also the opportunity to assess the biology in real time. As shown here in the schema, the next group of studies, the Nest 1 as I looked at schedules, essentially, we looked at if the longer time to let the immunotherapy grew. Initially, when we proposed an X1 study, the standard of care is you get to surgery as soon as possible, whether that's next week or in the next couple of weeks. So we had a very short window of opportunity to -- not to delay curative treatment. So patients on average went for surgery within 3 to 4 weeks as early as days from the first dose of bought, we had patients going for surgery. Once we had more data on the first set of patients showing deep pathologic responses and no safety issues, the Nest 2 was looking at the same single dose of bought, but a couple of extra doses about, but more importantly, a higher time to let the surgery happen at about approximately 8 weeks. Unicorn study is shown on the right side of the schema. It's a very similar design that done independently, and the average time of surgery was a median of about 5 weeks. Now if we can go to the next slide. The summarized here is the next group of data. Again, we had a few MSI high patients treated as part of the initial design to provide proof of principle, but most of the data is focusing on MSS tumors. In the MSS tumor approximately, if we look at by the definition of at least 50% tumor regression, this was nearly about 59%. Now if you look at at least 90% of the tumor being dead, it was about 41% and completely pathologic response or no tumor viable at the time of surge was about. Now again, I want to reemphasize this was pathologic responses on tissue, not imaging changes. And that is the big distinction when we talk about new adjuvant setting. I'll show more data, but again, one important thing to highlight is there have been no recurrences reported across these 3 different studies to date. If we can go to the next slide. Now our Italian group of investigators, the unicorn trial, why is it important, it provides independent corroboration. So while you can argue 1 center 1 investigator here. It's a similar design. Again, BAT and BAL. One key distinction was this group also looked at monotherapy with BAT so the question of contribution of components and what does BAT monotherapy adds? It at least helps us understand the contribution in both MSS and MSA high tissue. And you can see you do need the combination as highlighted in the schema showing deeper pathologic responses, both in MSS and MSI high setting for a similar patient population. So if we go to the next slide, now multiple patients, approximately 38 treated with MSS with the BAT and BAL combination. There have been no recurrences reported to date. Now in this follow-up is a little early. We -- I've treated my first patient on March 17, 2023. We'll have updated data coming out soon. But what is very heartening across these studies is no recurrences to data and that's of paramount importance, which highlights that an immunotherapy responder, even if it's not necessarily the arbitrary cutoff of 90% or 100% or 50% is a very different kind of biology and what it might entail, which is in the new adjuant setting is potentially more cures. Next slide. If we look at another variable and the area of interest for me in particular, is the value of circulating tumor DNA, these liquid biopsies and we knew in some respect, if we look at the 100% disease free survival that, that was going to be a very likely possibility is because if you look at some of the CTDNA data, a person who is ctDNA-negative, is likely to have over 90% to 94% chance of being cancer-free disease survival at 2 to 3 years of follow-up. And as you have more CTDNA negativity, the sensitivity increases further. So this is a very important early surrogate and it's an important part of the foundation provided here because we saw, number one, not only that the CTDNA cleared and remain cleared, which equates to the 100% DC survival down the line. but also the rapidity with which this happened when we were checking it on cycle -- the second dose of the bowel, which was within 2 weeks, we saw rapid CTT clearance, which is exactly what we want to do for patients undergoing surgery with the intent to cure where the goal here is to eliminate the micrometastatic disease. Finally, a quick word on safety, which is of Panama and potent. And again, in a curative intent setting, the last thing you want to do is to cause any issue from a safety standpoint, regardless of the fact that at least 1/3 of these patients, if not more, are not unfortunately cured with surgery and chemotherapy. It's still the standard. -- and you cannot do anything that would compromise the standard. So that part is in terms of safety, toxicity, surgical feasibility. And that actually was the primary goal of the next group of studies was showing that it was feasible and that was a nonnegotiable factor in this setting. What is heartening to note is no surgery was delayed. There was only one patient in the Unicorn group of investigator that had a period of hyperthyroidism that patient still got surgery, but it was delayed by 10 days. But -- so across over 52 patients, we have manageable expected immune-related adverse events that we know how to manage from experience from checkpoint blockade and toxicity over decades and now with hundreds of patients in the bad valeting -- and this is also to echo Dr. Slavis note. One is, of course, the goal is to reduce the current. That's the most important thing. In colon cancer surgery can still happen. But again, it's also potentially causing sparing chemotherapy-related toxicity, the polyneuropathy I mentioned earlier as well as protect recovery and quality of life. Many patients in both these studies, chemotherapy with standard of care and the elected to refuse that, that was not part of the study, but despite many patients if using chemotherapy, which was not the intent, they still achieved the 100% disease survival. So why is this approach in a Phase III Acision trial? I think these signals are multiple across multiple studies and are hard to ignore. The ROBBIN trial is the right next step to not only assess this in a formal randomized setting, but looking at pathologic response, CTDNA clearance recurrence-free survival so that we can benefit a larger group of population with the intent to cure. I'll now call Dr. Steven O'Day to walk us through the ROBBIN trial design and then the broader precedent, laying the foundations for investigators like us for moving immunotherapy earlier in the disease course.

Thank you, Pashtoon and Mariam for the excellent contextualization of the data, Mariam for setting up sort of the standard landscape of these high-risk a colon cancer patients who undergo surgery and then 3 to 6 months of chemotherapy and still have a 20% to 40% risk of distant recurrence and death and with toxicities that can be chronic from the chemotherapy and then setting up the neoadjuvant field first with chemotherapy and then with first-generation immunotherapy through her niche trials. And then, of course, Pashtoon really showing us this compelling and exciting bought out data that appears to be differentiated. -- from first generation. So I want to put this all in context by going back to melanoma, which lays the foundation and really further supports our plans with Robin. Along with my melanoma colleagues, I have been at the forefront of cancer immunotherapy throughout my entire 30-year career. Over the past 8 years, I've focused intentionally on BAT and BAL from first-in-human studies to late-line trials and now to these exciting neoadjuvant trial results. We have treated more than 1,300 patients with bought monotherapy or bot bow combination therapy across multiple poorly immunogenic tumors and I/O-resistant solid tumors. This is predominantly in the metastatic setting. This allows us to clearly see the differentiation of BOT from first-generation CTLA-4 antibodies. Importantly, the body of this extensive work and data establishes a selected dose of bot bol and also establish the contribution of BAT and BAL components, both in the metastatic setting and as you saw from the unicorn trial, in the neoadjuancy setting. And this forms the basis of registration-enabling studies. But now let's go to the arc of the melanoma story that is particularly close to my heart. And the lessons learned from the late stage to early stage, which is particularly informative today as we focus on the registration path of Bob. If you remember, in melanoma, CTLA-4 monotherapy and then the combination of CTLA-4 with PD-1. -- first demonstrated this long-term survival in late line, not early line disease. This long-term survival was characterized by extraordinary survival plateaus that had never been seen before in solid tumors that began after 2 years and importantly, we're accompanied by treatment-free survival, meaning patients were living with no additional therapy. This was transformative and continued beyond 10 years and now beyond 15 years in these initial studies. Combination PD-1 and CTLA-4 therapy now cure more than 50% of patients with widespread melanoma. This is extraordinary. And after this extraordinary success in late-line disease, we moved PD-1 agents into the adjuvant postsurgical setting. Now this is not a neoadjuvant. This is after surgery where the tumor has been removed, but has not recurred yet. And we showed remarkable clinical benefit. Substantially reducing distant recurrence of metastatic melanoma. But it was really the last several years that seminal trials have Trent formed the melanoma field even further. And these were 2 practice-changing trials1801 swag and then, of course, the Adena study with Christian Blank, Miriam's colleague at the Nashville Cancer Institute of the Netherlands, which was presented as a plenary presentation at ASCO 2 years ago. These 2 trials in Stage 3 melanoma clearly demonstrate a substantial decrease in the development of metastatic disease with immunotherapy in a presurgical setting, where others have reminded you, you have an intact primary tumor with is straining regional lymph nodes. This intact tumor in these lymph nodes leverage the power, adaptability, priming and memory of the immune system. Now these principles are highly relevant here and now with BAT and BAL. The neoadjuvant data you've seen from Nest, unicorn and Marion's experience with neoasis, a pan-tumor setting are compelling, but not surprising based on the neoadjuvant melanoma experience and further bolster by neoadjuvant's success in breast cancer and lung cancer, leading to a recent regulatory approvals in these diseases. Okay. Now let's focus on the all-important ROBBIN study. The ROBIN study is designed as a registration-enabling trial. It's global. It's a Phase III, it's randomized. Approximately 850 patients. It's in the group, we've talked about all morning, the high-risk Stage I and Stage II MS-sable colon cancer. The treatment arms will compare 6 to 8 weeks of neoadjuvant, botansilumab plus balstilimab, followed by surgery, which is standard of care compared to immediate surgery within the first 4 weeks. Both arms to the trial will receive standard adjuvant chemotherapy, but it will be based on the surgical pathologic staging. The primary endpoint of the study is event-free survival. And for those of you who may not be as familiar with this, this is the time after surgery and adjuvant therapy to the time to a recurrence, predominantly distant recurrent Stage 4 disease. The study is powered around, as ROBBIN said earlier, a target ratio of EFS hazard ratio of 0.65 and we will have an interim EFS analysis at 75% of events and a final analysis when 100% events have been accumulated. Now importantly, the FDA has aligned around key elements of the ROBBIN Phase III study design, including the proposed patient population, both the experimental and the control arms and, of course, the primary registrational endpoint, the EFS. We are targeting first patient enrollment on the ROBIN trial by the first quarter of 2027. And an interim top line pathologic response readout by the end of 2027, the interim EFS analysis in the second half of 2029, and the final study analysis in the second half of 2030. I will now turn it back to Garo for a short conclusion before Q&A.

Thank you very much, Dr. Day. And thank you for the rest of our Agenus team and particular thanks to Dr. Telavi and Dr. Pashtoon, not only for participating on today's call, but for their pioneering work with BAT and BAL in the new adjuvant setting. What you've heard from our speakers today speak to the why and what of the significance of this moment for patients as well as Agenus stakeholders. The ROBBIN trial is a focused FDA aligned registrational path in a large underserved curative intent microsatellite stable colon cancer population. And you've heard the rationale for it as well as the data that supports initiating it. The next and the Unicorn data, of course, provide the clinical foundation for Lotus. The financing provides the capital path and the opportunity for us is to bring next-generation immunotherapy earlier in the disease setting, where it's more appropriate for affecting a significant number of patients. And the trial is designed to for this purpose. BAT and BAL shows impressive activity quickly, as you've heard, after a brief course of treatment. Today's announcement and the transaction represent an important financing as well as a focused execution strategy. It is the realization of our Agenus mission in a setting where the biology, the patient need and the opportunity to create significant value are all aligned. We will now open it for questions, and back to Stefanie.

Thank you so much for all of your questions. [Operator Instructions]. But to start off with Prof. Telavi, there was a question here just to put things into context about you shared a lot about neoadjuvant utilization within your overview. And certainly, within the area of MSI high, there was a question specifically related to how many patients today, would you say, on average, you're actually getting treated with neoadjuvant setting that specifically have MSS disease. Is this something that is a part of the treatment algorithm today? Or is this something that be really practice changing if the RAPID trial were to succeed and show efficacy.

That's a great question. I think this has been moving a little bit ever since the FoxTrot study that we're treating patients more readily in the neoadjuvant setting, but that's with chemotherapy, of course, even for MSS. And usually, that's the case for patients who need induction treatment, where we feel that the tumor needs to become a bit smaller, to make it easier on the surgeon to remove the tumor completely or when we are already based on the tumor characteristics at baseline think that this patient will probably meet adjuvant chemotherapy, then you might as well give it in the neoadjuvant setting to also decrease the tumor size. But still, that is a very small proportion of patients that are getting neoadjuvant treatment. So in that sense, when you have a treatment that is superior to what we're doing in the adjuvant setting, that will shift to the new. We've seen that with MSI-high tumors, right? MSI High tumors, we showed exceptional responses in the neoadjuvant setting and that has been shifting. Even though it's not even standard of care everywhere, it has been shifting to treating patients more and more with neoadjuvant immunotherapy because it's better than the alternative that we have had. So I think when you show -- if you show that this is better with neoadjuvant immunotherapy than the standard of care adjuvant chemo, then it's going to become much easier to treat a much larger population with neo-adjuvant immunotherapy.

Great. Professor Telavi. There's also a question too. There's -- we have a lot of our investors as well as the public that follows along quite closely with all of our clinical studies. And Dr. Kasi, there was a specific question here. about the Nest 3 study and how that's evolving with your program and how that fits in with the strategy now moving forward with the Robin study? And maybe you could share a little bit about how they actually complement 1 another.

Exactly. So that was exactly my comment. As of 2 weeks ago, we actually dosed our first patient. So registrational studies like this. It's not a competition with investigator share trials, things that Dr. Telvi will continue to do on the new basis or invest initiated trials like Nest 1, 2 and now 3 and ongoing work by the talent colleagues. These are investigator initiated efforts that will continue in parallel. They have separate goals. While the registrational study will hopefully bring this to the larger patient population in standard of care. There is a deeper understanding that you can learn from transportational studies. -- other aspects that go in tandem with some of these investigators share trials that are not always possible in a Phase III setting. So that is actually officially open and enrolling. And I would imagine that the other investigatorial trials will continue as well. And will continue to complement and support each other.

Great. Dr. Kasi. Garo, this next question, I think, would be best for you to answer. There are some questions in the chat. Certainly, this is an exciting opportunity where Agenus things that we can provide the most value to patients in the neoadjuvant setting base of everything that we heard today. There were some questions, however, related to what's going to happen to the patients that are on the current Batman study? And what do we anticipate to do with the the French AAC as well as the name patient programs that are helping to provide access in the later line setting. Can you comment on that, please?