Joining today from Agenus are Garo Armen, Founder, Chairman, and Chief Executive Officer, Dr. Steven O'Day, our Chief Medical Officer, Robin Taylor, our Chief Commercial Officer, and Zack Armen, VP Corporate Development and Investor Relations. We also have the pleasure of having two globally renowned thought leaders in the space of neoadjuvant colon cancer treatment and research. Also joining today is Professor Myriam Chalabi of the Netherlands Cancer Institute, a Globally Recognized Leader in Gastrointestinal Oncology, S cientific Co-Chair of the ESMO Congress, the pioneering investigator behind the landmark NICHE studies in neoadjuvant immunotherapy for colon cancer, and the 2026 Innovators in Science Award recipient, and a ROBBIN investigator.
Also with us is Dr. Pashtoon Kasi, the Rad Family Chair in Gastrointestinal Oncology and Medical Director of GI Medical Oncology at City of Hope Orange County, whose leadership of the landmark NEST trial has helped establish neoadjuvant botensilimab plus balstilimab as one of the most promising new immunotherapy approaches for patients with MSS colorectal cancer. Both are investigators in the upcoming ROBBIN trial. The following webcast contains forward-looking statements regarding Agenus's businesses that are made pursuant to the safe harbor provisions of the Federal Securities laws. Please reference these full forward-looking statements in our statement shown now, which can be also found on our website in this webcast presentation, along with our company overview presentation.
With that, I will turn the call over to Garo.
Thank you very much, Stefanie, and thank you, our guests, Professor Chalabi and Dr. Kasi, as well as all of you for joining us this morning. Today's announcement marks an important development for Agenus. At its core, it represents Agenus 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 BOT/BAL in MSS colon cancer. For those of you that may not recognize that term, MSS colon cancer accounts for approximately 85% of all colon cancers, as well as it is the most difficult to treat colon cancer and unresponsive to immunotherapy until BOT/BAL.
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 ROBBIN trial, our phase III registration-enabling study of neoadjuvant BOT/BAL in high-risk Stage 2 and Stage 3 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 NEST and UNICORN, and with the input of some of the most prominent clinicians, two of whom have joined us today. The data from NEST and UNICORN, along with Dr. Chalabi's NEOASIS trial, are consistent across more than a dozen clinical centers in the U.S. and Europe.
Importantly, we have discussed the ROBBIN trial with the FDA and received feedback supporting it as a registrational pathway for BOT+BAL in this prevalent treatment setting with no newly approved therapies in the last two 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's mission, to move next-generation immunotherapy agents to the settings where it can have the greatest impact. The financing announced today lets us pursue that path. The $85 million upfront is expected to remove near-term financing pressure, and with full warrant exercise, the structural objective for this is to fund the ROBBIN 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 Zack on the transaction, Robin on the strategic rationale, Professor Chalabi and Dr. Kasi on the clinical foundation, and Steven on the ROBBIN design. 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 Zack.
Thank you, Garo. Earlier this morning, we announced a private placement of up to $340 million led by Commodore Capital with participation from RA Capital Management, TCGX, Invus, and Ligand Pharmaceuticals. This transaction includes $85 million of upfront gross proceeds and two warrant tranches totaling potential additional gross proceeds of $255 million. Each of the three 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 ROBBIN trial timeline and our path toward full approval. Our conviction is that the ROBBIN trial will unlock BOT+BAL'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, Zack. 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 instability-high, which are candidates for immunotherapy. About 85% of resectable colon cancers are microsatellite stable, which are immunologically cold and refractory to conventional immunotherapy. That is where BOT and BAL comes in. botensilimab 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 cm mass in a 40-year-old woman. On the right, the same colon seven weeks later after just one dose of BOT and two of BAL immediately prior to surgery, and this was subsequently confirmed as a pathologic complete response. One of many across the BOT and BAL neoadjuvant studies. This example clearly demonstrates what BOT, an 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 in late-line metastatic tumors, including MSS colorectal cancer. The benefit we can deliver in the neoadjuvant curative-intent setting, the high-risk Stage 2 and Stage 3 MSS colon cancer dwarfs the impact of metastatic disease for a population with no major therapeutic advance in over 20 years since oxaliplatin was approved.
Our strategic pivot rests on four points. First, the population is larger, roughly 38,000 high-risk Stage 2 and 3 MSS patients treated annually in the U.S. Second, the impact for patients and for payers is greater in a curative-intent setting. Third, two phase II studies demonstrated deep, rapid pathologic responses and support a high probability of success in phase III. Fourth, ROBBIN'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 are most aligned. In NEST and UNICORN, neoadjuvant BOT/BAL produced consistent results with respect to pathologic response.
A 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 ROBBIN 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 two 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 FOXTROT, 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 PCR rate observed in the NEST and UNICORN phase II trials meaningfully exceeds that target. Replicating the 30% PCR rate would correspond with an estimate hazard ratio of about 0.5.
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 already 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 2 and Stage 3 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 years 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 Myriam Chalabi, whose work has helped shape the field of neoadjuvant immunotherapy in colorectal 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. 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. First of all, it's good to set the stage on how do we treat patients with 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, 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. Everybody gets the same treatment, usually when they have a high-risk Stage 2 tumor when it comes to MSS colon cancers, or when they have a Stage 3 tumor, meaning that they have lymph node-positive disease. Despite this treatment with surgery followed by chemotherapy, there's still a very high recurrence rate for these patients who receive up to six months of adjuvant chemotherapy sometimes and the surgery, 20%-40% of these patients can still recur.
We still need a better treatment option for these patients and to 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, there's definitely room for improvement in both outcomes, but also in side effects that we incur based on our treatments. Next slide, please. The FOXTROT 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 FOXTROT study. The FOXTROT study was actually the very first study in which patients with colon cancer were treated with neoadjuvant chemotherapy. These were patients that were treated, randomized to either perioperative chemotherapy, either neoadjuvant plus adjuvant chemotherapy or adjuvant chemotherapy alone, and this was based on clinical staging.
Patients were selected based on their T stages and 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 it was safe, that the rate of complications was not higher compared to adjuvant chemotherapy. Also there seemed to be ultimately an improvement in outcome for patients who received neoadjuvant chemotherapy. There's definitely a subset of patients that might benefit from neoadjuvant treatment.
This actually set 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%-25% if you consider other trials as well. 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. 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.
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. There's definitely a need for improvement for that patient population. Next slide, please. What we did in the new 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 non-metastatic disease.
What we set out to do in the NICHE trial, and this was the very first trial to look at the neoadjuvant 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 BOT and BAL and before the next generation CTLA-4. That was with ipi/nivo, in this case. Patients with metastatic disease were not responding to immunotherapy. We had this 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 immunogenic and can respond.
We treated 31 patients in this trial with neoadjuvant ipilimumab and nivolumab, just two cycles of nivolumab, one cycle of ipilimumab, and that was the whole treatment, and patients went to surgery within six weeks thereafter. Very much according to our hypothesis, we found that a subgroup of patients did respond, and this was not just a little bit of response. These were patients that had deep pathologic responses, including PCRs, within 4.5 weeks from the first dose of immunotherapy to surgery. There's a 26% response rate that we saw in this study with just two 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.
Ultimately, you will want to compare this to the standard of care, which is adjuvant chemotherapy in this case. 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 MSI colon cancers as well. This being a small group of patients, of course, and that has to be kept in mind. 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. That was my last slide.
I think now I will pass it on to Dr. Pashtoon Kasi, who will be talking about his experience with the NEST and UNICORN with the neoadjuvant BOT and BAL.
Thanks so much, Dr. Chalabi. I'm glad to be here as a clinician and investigator of the neoadjuvant studies, the so-called NEST group of studies. I'll also be talking about the UNICORN study as well. NEST and UNICORN both matter because they're exactly evaluating the combination of BOT and BAL in the setting where ROBBIN trial is going to happen, which is before surgery, when the tumor is still present and a timeline that fits into a surgical schedule. As mentioned earlier a few times already, the neoadjuvant setting is attractive because the primary tumor is still in place. The draining lymph nodes are in place. The tumor can serve as a source of antigen, and as Dr. Chalabi also 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 neoadjuvant setting is the ability to get tissue. We're not talking about responses on scans, we're talking about pathologic responses of resected tissue and also the opportunity to assess the biology in real time. As shown here in the schema, the NEST group of studies, the NEST-1 and NEST-2, looked at two schedules. Essentially, we looked at if the longer time to let the immunotherapy brew. Initially, when we proposed the NEST-1 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. We had a very short window of opportunity to not to delay curative treatment.
Patients, on average, went for surgery within three to four weeks, as early as 20 days from the first dose of BOT, 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 BOT, but a couple of extra doses of BAL, but more importantly, a higher time to let the surgery happen at about approximately eight weeks. UNICORN study, as shown on the right side of the schema, is a very similar design but done independently. The average time of surgery was a median of about five weeks. If we can go to the next slide.
Summarized here is the NEST group of data. We had a few MSI-High patients treated as part of the initial design to provide proof of principle. Most of the data is focusing on MSS tumors. In the MSS tumor, approximately, if we look by the definition of at least 50% tumor regression, this was nearly about 59%. If you look at least 90% of the tumor being dead, it was about 41%, and completely pathologic response or no tumor viable at the time of surgery was about a third. Again, I want to reemphasize this was pathologic responses on tissue, not simply imaging changes. That is the big distinction when we talk about neoadjuvant setting. I'll show more data, but again, one important thing to highlight is there have been no recurrences reported across these three different studies to date. If we can go to the next slide.
Our Italian group of investigators, the UNICORN trial. Why is it important? It provides independent corroboration. While you can argue one center, one investigator, here, it's a similar design. BOT/ BAL. One key distinction was this group also looked at monotherapy with BOT, so the question of contribution of components and what does BOT monotherapy add? It at least helps us understand the contribution in both MSS and MSI-High tissue. As 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.
If we go to the next slide, and now across the multiple patients, approximately 38, treated with MSS with the BOT/BAL combination, there have been no recurrences reported to date. Again, this follow-up is a little early. I've treated my first patient on March 17th, 2023. We'll have updated data coming out soon. What is very heartening across these studies is no recurrences to date, 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 neoadjuvant setting, is potentially more cures. Next slide. If we look at another variable and an area of interest for me, in particular, is the value of circulating tumor DNA, these liquid biopsies.
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%-94% chance of being cancer-free, disease-free survival at two to three years of follow-up. As you have more ctDNA negativity, the sensitivity increases further. 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 remained cleared, which equates to the 100% disease-free survival down the line, but also the rapidity with which this happened when we were checking it on the second dose of the BAL, which was within two weeks.
We saw rapid ctDNA 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 paramount importance. 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 a third of these patients, if not more, are not unfortunately cured with surgery and chemotherapy, it's still the standard. You cannot do anything that would compromise the standard. That part is in terms of safety, toxicity, surgical feasibility. That actually was the primary goal of the NEST-1 group of studies was showing that it was feasible and that was a non-negotiable 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 was delayed by 10 days. 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 BOT/ BAL setting. This is also to echo Dr. Chalabi's note. One is, of course, the goal is to reduce recurrence. That's the most important thing. In colon cancer, surgery can still happen. Again, it's also potentially 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 was standard of care and they elected to refuse that. That was not part of the study. Despite many patients refusing chemotherapy, which was not the intent, they still achieved 100% disease survival. Why has this approach earned a phase III additional 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 the broader precedent, laying the foundations for investigators like us for moving immunotherapy earlier in the disease course.
Thank you, Pashtoon and Myriam, for the excellent contextualization of the data. Myriam for setting up sort of the standard landscape of these high-risk colon cancer patients who undergo surgery and then three to six months of chemotherapy and still have a 20%-40% risk of distant recurrence and death, and with toxicities that can be chronic from the chemotherapy. Then setting up the neoadjuvant field first with chemotherapy and then with first-generation immunotherapy through her NICHE trials. Then, of course, Pashtoon really showing us this compelling and exciting BOT/ BAL data that appears to be differentiated from first generation. I want to put this all in context by going back to melanoma, which lays the foundation and really further supports our plans with ROBBIN. Along with my melanoma colleagues, I have been at the forefront of cancer immunotherapy throughout my entire 30-year career.
Over the past eight years, I've focused intentionally on BOT/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 BOT monotherapy or BOT/BAL combination therapy across multiple poorly immunogenic tumors and IO-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/BAL, and also established the contribution of BOT/BAL components, both in the metastatic setting and, as you saw from the UNICORN trial, in the neoadjuvant setting. This forms the basis of registration-enabling studies.
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 BOT/BAL. 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 two years, and importantly, were 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.
After this extraordinary success in late line disease, we moved PD-1 agents into the adjuvant post-surgical setting. This is not a neoadjuvant. This is after surgery where the tumor has been removed but has not recurred yet. We showed remarkable clinical benefit, substantially reducing distant recurrence of metastatic melanoma. It was really the last several years that two seminal trials have transformed the melanoma field even further, and these were two practice-changing trials, one SWOG 1801 , and then, of course, the NADINA study with Christian Blank, Myriam's colleague at the Netherlands Cancer Institute, which was presented as a plenary presentation at ASCO two years ago.
These two trials in Stage 3 melanoma clearly demonstrate a substantial decrease in the development of metastatic disease with immunotherapy in a pre-surgical setting, where others have reminded you have an intact primary tumor with its draining regional lymph nodes. This intact tumor and these lymph nodes leverage the power, adaptability, priming, and memory of the immune system. These principles are highly relevant here and now with BOT and BAL. The neoadjuvant data you've seen from NEST, UNICORN, and Myriam's experience with NEOASIS, a pan-tumor setting, are compelling but not surprising based on the neoadjuvant melanoma experience, and further bolstered by neoadjuvant success in breast cancer and lung cancer, leading to recent regulatory approvals in these diseases.
Now let's focus on the all-important ROBBIN study. The ROBBIN 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 2 and Stage 3 MSS colon cancer. The treatment arms will compare six-eight weeks of neoadjuvant botensilimab plus balstilimab, followed by surgery, which is standard of care, compared to immediate surgery within the first four weeks. Both arms of the trial will receive standard adjuvant chemotherapy, but it will be based on the surgical pathologic staging. The primary endpoint of this study is event-free survival. For those of you who may not be as familiar with 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 Robin 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. 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 ROBBIN trial by the first quarter of 2027. 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. O'Day. Thank you for the rest of our Agenus team, and particular thanks to Dr. Chalabi and Dr. Pashtoon, not only for participating on today's call, but for their pioneering work with BOT/BAL in the neoadjuvant setting. What you've heard from our speakers today speak to the why and the 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. You've heard the rationale for it, as well as the data that supports initiating it. The NEST and the UNICORN data, of course, provide the clinical foundation for all of this.
The financing provides the capital path. 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. The trial is designed for this purpose. BOT/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 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.
Hey, everybody. Thank you so much for all of your questions. Just as a reminder, you could use the Q&A functionality of the Zoom call to initiate questions, and we'll begin answering those now. If you don't hear your specific question answered as is, just know that we're trying to consolidate the questions so we can get as many answered as possible. To start off with, Professor Chalabi, there was a question here, just to put things into context, 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 are 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 will be really practice-changing if the ROBBIN phase III 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. 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. When we already, based on the tumor characteristics at baseline, think that this patient will probably need adjuvant chemotherapy, then you might as well give it in the neoadjuvant setting to also decrease the tumor size.
Still, that is a very small proportion of patients that are getting neoadjuvant treatment. 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 neoadjuvant. We've seen that with MSI-High tumors. 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. I think if you show that this is better with neoadjuvant immunotherapy than the standard of care adjuvant chemo, it's going to become much easier to treat a much larger population with neoadjuvant immunotherapy.
Great. Thank you so much for that, Professor Chalabi. There's also a question, too. We have a lot of our investors as well as the public that follows along quite closely with all of our clinical studies. 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 ROBBIN study, maybe you could share a little bit about how they actually complement one another.
Exactly. That was exactly my comment. As of two weeks ago, we actually dosed our first patient. Registrational studies like this, it's not a competition with investigator-initiated trials, things that Dr. Chalabi will continue to do on the NEOASIS or investigator-initiated trials like NEST-1, 2, and now 3, and ongoing work by the Italian 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 of standard care, there is a deeper understanding that you can learn from translational studies, other aspects that go in tandem with some of these investigator-initiated trials that are not always possible in a phase III setting.
That is actually officially open and enrolling, and I would imagine that the other investigator-initiated trials will continue as well and will continue to complement and support each other.
Great. Thank you for that, 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 thinks that we could provide the most value to patients in the neoadjuvant setting based off 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 BATTMAN study, and what do we anticipate to do with the French AAC, as well as the named patient programs that are helping to provide access in the later line setting. Can you comment on that, please?
Certainly. Thank you. First of all, with regard to patients on the current BATTMAN study, CCTG is a great organization. Their intent to address the needs of late-stage patients is a very noble one. When we were proposed this study, we embraced it because of the great patient need and because of the fact that CCTG was subsidizing, through their own network, a good chunk of the financial needs of the study. All along, as we did this, dating back to the earlier parts of this year, we knew that the neoadjuvant setting, and thanks to the works done by Professor Chalabi and Dr. Kasi and Dr. Filippo in Italy and others, that this would address a significantly greater need for patients. When the financing became a reality, we decided to focus on this. Now, back to the patients on the existing BATTMAN study.
We certainly will meet all of our obligations to those patients in terms of providing study drug. With regard to other late-stage programs that we're undertaking right now in France, the French authorities had a review done for the dire need for these patients in the late-stage setting. The French government, as you know, is paying for these patients, and that will continue. There is a very important need. Unfortunately, it's only for French nationals. We have instituted a paid named patient program whereby patients from anywhere can travel to locations such as the U.K., Switzerland, France, Belgium, Spain, Argentina, and Brazil, and get treatment with pay out of pocket. Unfortunately, this is for patients that can afford to do this, but we hope that that number is going to be growing, number one, because there is a great need for these patients' treatment.
We've also had some proposals from some noble patients to potentially fund through a philanthropic effort for patients that cannot afford to do this out of pocket. The bottom line for us is to really exercise our judgment based on our resources to bring BOT/BAL to the finish line as soon as possible, and that is the intent of the company.
Thank you, Garo. There's another follow-up question. There's been some questions in here, I think it would be helpful just to clarify why the actual shift from the BATTMAN study over to the ROBBIN. We went through that, Robin Taylor shared a little bit about the commercial opportunity as well as the clinical potential for patients. There's some questions here related to, was there any outside circumstances related to data or FDA feedback that really perpetuated our development decision? I know this has been a developmental internal strategic discussion for quite some time, but maybe you could reinforce and clarify that a bit more.
The answer is no. There were no exogenous reasons for our shift to the ROBBIN study. As you know, we started enrolling this at the end of March or early April. It's impossible to gather data in such a short period of time to suggest that the study is going one way or another. The answer is absolutely not that the FDA and the absence of data were the triggers for this. Dr. Taylor, I think, articulated this very well. It is an important consideration for us to help greater numbers of patients in a setting where the impact is significant.
The impact, as you heard from Dr. Kasi, is significant in the sense that, and Dr. Chalabi also mentioned this, that you're seeing an effect in a very short period of time with a limited number of drug administrations, and that is a very big impact for patients. The answer is very simple for us. Strategic patient impact, greater number of patients affected, and in the future, of course, we will do what is in the best interest of the overall patient population.
Thank you, Garo. Another question here. Perhaps, Garo, you could start off, and then if any of the other members of the executive team want to join in. There are some questions related to accelerated approval and whether or not we might be able to still consider that for the late-line disease, and does our current strategy, neoadjuvant, enable a potential for accelerated approval as well?
Okay. The question of accelerated approval, of course, is an open question. It is going to be a function of several things for us. Number one, our resources, and I don't mean just financial resources, but also overall people resources. We're a small company. We cannot focus on very many programs simultaneously, like large companies can. With regard to accelerated approval, I think we have a substantial amount of data generated. We don't plan on having additional data generated other than the programs that I spoke about, the French AAC program and the paid named patient program. The decision on whether or not we pursue accelerated approval is going to be driven by three things. The FDA's input, because we're unwilling to go on a wild goose chase, so to speak, and hope and pray that the FDA will proceed with our accelerated approval strategy.
That's number one. French authorities certainly have put money into supporting this setting. That's one. Number two is the strategic considerations for the company. Dr. Taylor is a major driver of this consideration. There are many factors that we haven't discussed. For confidentiality reasons, we will not discuss publicly. The third thing, as I said, is the financial resources and people resources that will drive this decision. Stay tuned. We will be very transparent, as we have always been, on our path forward based on all of these considerations as the time unfolds.
Thank you, Garo. I just have two other quick questions before we close the call. This one is for you, Robin Taylor. There was a question, given all the timelines and the study, can you share and reiterate the loss of exclusivity and the patent life for BOT and for BAL, if that's something that you're able to share?
I saw the question asking, I think basically the question's asking, are we going to be able to complete the study, get to market. Still with a good window in terms of the loss of exclusivity? The answer is yes. We have public information on sort of the patent term. There's always patent term extensions, coming up with an exact number is not something that I would venture. Certainly, there is a good runway for the product.
Great. Thanks for that, Robin. Dr. O'Day, there was a question here. We briefly mentioned that NEST and UNICORN, those studies had data presented at ASCO GI back in 2025. With the information that you have and can share, when would we anticipate having updated data on that? Dr. Kasi could probably reply to that as well.
Thank you for the question. As you know, we showed you data that was publicly presented about a year ago for both of these trials. Obviously, the trials have continued to mature and are both under active manuscript review, and we expect some data very soon on hopefully publications that will be very, very meaningful, not only for the clinical results, but the translational results that will really help clarify the mechanism of action of BOT and BAL and how cold tumors turn hot. Stay tuned. This is going to be very exciting data.
Great. I think one just last question, then we'll close before the top of the 9:30 A.M. mark here, is related to the French AAC program. Dr. O'Day, can you maybe just clarify whether or not we're still collecting data from that program, how that will be continued to be utilized?
It's a good question. This is a very rigorous program through the French government that, number one, they looked at the data very carefully before making decisions to reimburse. There are data collection and outcome data, not as rigorous as a clinical trial, but real-world outcome data that we are collecting under their guidance as part of this program. There will be data on these patients also.
Well, thank you very much for our special guest, Professor Chalabi and Dr. Kasi, for the rest of the executive team, for this call this morning, for those attending globally this afternoon. We will have a replay of the actual event, the webcast, up on our website shortly, along with the presentation from today, there will be follow-up engagements in certainly the coming number of weeks as we look to our next earnings as well for additional questions and answers. Thank you all for your participation and engagement, have a great day.