Rodman & Renshaw Fireside Chat | November 2026 - AGENUS INC

many more patients starting when we do our first enrollment for the Robin trial, which we anticipate in the next few months. Great. And I'm Robin Taylor. I'm the chief commercial officer. I've been with the Gen S for a little over three years. Spent the bulk of my career actually at Genentech and Roche and had my start actually with colorectal cancer with the launch of Avastin over 20 years ago. So the last four years I spent at Genentech. I'm old enough to remember Herb Hurwitz's presentation and his standing ovation that he got at ASCO. Indeed, indeed. Yeah, it was a momentous occasion. Still a foundational therapy, at least in metastatic disease. Yep. And then the last 4 years I spend at Genetech and Roche, I led the immuno-oncology franchise, not only the late-stage development with Ducentric, but also working very closely with both the Roche and Genentech research groups. So immuno-oncology is very close to my heart. When I saw the data over three years ago coming out of Agenis, I was surprised. I was amazed to see this level of activity of an immunotherapy in a cold tumor, MSS colon cancer, and that's what brought me to the company. So looking forward to talking more about that today. And, obviously, I share that excitement because I recall that, I forget what year it was, since he in Boston, but, you know, a very compelling response rate as well as, you know, very long tail on the event-free and overall survival curve. So, that was great. But, excuse me, I don't know how many people know about the history of Agenis, but you know, the company has quite a bit of expertise and experience with first-generation CTLA-4 xalofrelumab, and, you know—botoncelumab is the, you know, successor to that. So, maybe you can talk a little bit about the science there, and what kind of scientific hypothesis were you trying to show there, and what does the FC enhancement change about how the drug works? Great. Zach, we're still seeing the presenter mode here. Presenter mode. There you go. Perfect. So if we go to the, yeah, here, the schema of the antibody, the secret sauce in bodoncillumab is a couple of point mutations in the FC region. What this does is it enhances the binding of the antibody to the FC receptor, the FC gamma R3A receptor. and that has a couple of effects one is the binding to antigen presenting cells and so it provides an opportunity to create a tighter synapse with those antigen-presenting cells and that allows basically bodensilumab to help the immune system to identify these weaker neoantigens so we see expansion of that actually we've saw it you know pre-clinically but we actually see it now in the clinic from the nice data we have from the neoadjuvant studies in colon cancer with both nest and unicorn. And what you see here is the visual example of that. Basically, we're turning a cold tumor hot. You can see there are these CD4, CD8 positive T cells in the periphery of this tumor on the left. That's pre-treatment with bot val. Then after treatment, you see this flood of purple and green. Those are the CD4, CD8 positive T cells, and you don't see any red anymore, and the red were the T regulatory cells that have disappeared, and this is just one example of a number of the analysis that was done in both NEST and also in the UNICORN study. Robin, can you say what aspects of the cells you're staining here? Are these the, you know, surface receptors? Are These, you know internal you know proteins or what what are you actually measuring here in the slides on the right yeah so we're measuring in green is cd4 purple cd8 fox p3 is the red that's measuring the t-regs right and then the tumor is which you don't want right and like this is an actual biopsy of a patient who was in the nest trial who had mss colon cancer so very similar profile of the patients we will be enrolling in the Robin Phase 3. And as Robin Taylor just mentioned, you can see on the left, pre-Bot-Bal, the tumor is excluding that immune system. So, you know, these cold tumors are broken down into just low immunogenicity. There's also tumor exclusion and tumor evasion. There are different sort of ways in which the tumor seems to be disallowing the immune system to to do what it's naturally programmed to do right and then and then bot battle essentially unlocks or ignites that immune response and helps proliferate the army of killer cells which you want to be entering the micro environment and then is kicking out the regulatory cells which we need so that a cut that we get doesn't turn into a massive bleed out but in the case of fighting a tumor we don't want those regulatory cells to be around to dampen that immune response. Yeah and do you know I don't want to put you on the spot here but do you know sort of the case history of this patient was this you know third line plus kind of patient just trying to get a sense of go ahead. Yeah no this is a patient with de novo colon cancer. De novo okay. This is from the neoadjuvant study so this patient had not had any treatment for their disease previously. Okay would you expect this kind of result if you were looking at a metastatic patient that had, you know, multiple prior rounds or would it be, you know, less compelling? You may see something like this. It's there is a little bit more complexity because the health of the immune system is a factor. Right. So, you know, I think one of the reasons that we see potentially more robust results in early stage disease is that individuals typically have healthier immune systems. You know, the the wear and tear of multiple rounds of chemotherapy and other treatments can kind of wear down people's immune system in late-line metastatic disease. Right, right. But, I mean, I still think from, you know, like your metastatics setting, the C800 study, you still had really good response rates. Yeah, exactly. So over 20% response rate. And, you Know, and response didn't tell the whole response, But you see there's quite a large group that have stable disease here. You see that in the spider plot. And you can see some of those going out quite a long way. So you've got patients out, you know, 120 weeks with stable disease. Yeah, no, it's, yeah, that's the part of the compelling story that I like here. Yeah, and that translated in the phase 1b to a median OS of 17 months. but, you know, at two years, you still see 39% of patients alive, which is pretty remarkable for this late-line treatment setting in these patients. Right, right, and we'll get to the rationale why that, you Know, the flip to the front line, the neoadjuvant setting. Well, let me, let me just table that for a second. I just wanted to also, I don't know if you have the slide here, but I don' t know if You had, You know, your translational work has shown that BOT lowers regulatory T-cells inside the tumor, and even in patients who had stopped responding to earlier checkpoint drugs, but maybe you can tell us why that matters for cold tumors like MS-stable colorectal, and what does BAL add to that, that BOT, you know, alone doesn't generate? Yeah, well, you Know, one of the challenges with immunotherapy is that, you know, we've seen either PD-1 or CTLA-4 plus PD-2 explored across almost every tumor you can imagine to try to see where the signal is, and the signal's been in hot tumors. It's been where there's been typically enough or sufficient immune response already that you're able to unmask it with the addition of a PD-1. Cold tumors are more challenging because you need something to ignite the immune response. And that's why bodensilumab has this ability now to be able to broaden the range of immunotherapy to cold tumors. The classic being colorectal cancer. Zach, if you go to the next one. you know here's the example from from the the phase 1b just looking at the 123 patients being enrolled with colorectal cancer without active liver mats but what you see is a 21 response rate you know and three-year survival of 33 in this patient population so you know a clear benefit and you know along this is sort of the conditioning that you want with the immune system, right? You want the immune system to continue this surveillance, be able to keep the tumor at bay or ideally eliminate it. Right, right. Go ahead. Should we move on, Robin? We also have the ovarian cohort, Mike, that was just presented at the ICGS conference. Let me just hold on one second because I just want to, you know, the one thing that I do want to point out to people is that I think this kind of compelling data has sort of generated a bit of a renaissance in CTLA-4 you know, assets in clinical trials. Now, you know you've got some, you know, fast followers that are, that are you know putting activated FC CTLA-4 antibodies or masked CTLA you know CTLA for I'm sorry FC active CTLA for antibodies into the clinic. So you know while we would like to have as little competition as possible, I like the fact that the scientific validation is coming along behind this, and obviously you guys have a substantial clinical lead, but I won't name any of those companies. I'm happy to talk to people about them privately, but there's some significant developments in CTLA-4 antibody space, which had gone kind of fallow for a while after the launch of Yervoy. So anyway, go ahead, Zach. Why don't you show the ovarian data? Yeah, and here's the data that we recently presented, an update of our ovarian data from the phase 1b. You can see a nice response right here, but more impressively, what you see is these continuing responses, so very consistent with what we see in colorectal cancer. Interestingly, one patient who had stable disease, and then, you know, at 18 months, you see a response. It's really quite interesting sometimes how, you know, the effect of CTLA-4 can suddenly flip a switch with the immune system and you actually get these late responses. Right. And, yeah, ovarian is typically seen as a cold tumor. Yeah. And we see, you Know, and what, you know, what's really impressive is you see this plateau in terms of the overall survival. So these long-term patients. We don't see any, you see this long plateau with about half of the patients alive at two years here. Yeah. No, it's interesting to me. P-ROC has gotten a lot of attention lately. There seems to be a flood of ADCs that are coming to the space. And I know you guys are pretty, you know, kind of limited on what you can do right now with the development of BotBell, but it definitely begs the question about what, you know, what kind of benefit patients could get, P-ROC patients, or then, of course, earlier as well, with, you know, ovarian combining BotBELL and an ADC. Yeah, I mean, expansion is certainly in our future plans, Mike. Just what this data is also showing, which I think is important, and we see this consistently in other cold tumor types, MSS-CRC being obviously our largest data set, where patients who had a number of prior lines of therapy, whether it be one or two or greater than four, as we're showing in the right, or whether they had platinum resistance or sensitivity, those patients all had a similar survival benefit, regardless of how many prior lines they had. And this is important, we think, obviously, because when you're going later in the metastatic treatment lines, patients are losing options that are going to help extend their lives. And to have something that's going to benefit those patients as much as it benefits those earlier stage patients is really a great thing. But it also speaks to the robustness of Bot-Bal, where it's able to drive this durable response, even in those sickest of sick patients, at the same level of efficacy as those patients who are less sick and have had less courses of prior cytotoxic therapy. Right, right. Yeah, it also brings up the intriguing possibility of maintenance therapy, but we don't need to go there right now. But I think it's a good pivot, Zach, to go and talk about neoadjuvant and why untreated, resectable colorectal cancer is the ideal place, at least initially, for Bot-Bal versus the metastatic disease, despite the consistency of benefit. Maybe you can cover some of the immune system aspects of that and tell us about the pivot to Robin. Yeah, no, I'm happy to. The reason we went to phase three in the neoadjuvant setting is because of the data that came out of two key studies, the NEST study run at Cornell and the UNICORN study run by an Italian cooperative group, the GONO group. And here's an example of what we saw. This is a patient with an eight-centimeter mass, 40-year-old patient, lymph node positive. One dose of BOT, two doses of PAL, and seven weeks later, you can see that the tumor is not there. And this patient, after this scope, went to surgery and pathologic complete response. And it's one of several pathologic-complete responses we observed across both studies. So what this really demonstrates is that CTLA-4 in particular, when you have an intact tumor, and this has been seen not just in our data, but also with first-gen CTLA4 and melanoma and hot tumors, you can see that you're providing the immune system with all of the neoantigens of the tumor at a stage when the disease has not spread. And that's the most powerful thing you can do because now you're educating the immune system, you're creating that surveillance. And what we're doing here with neoadjuvant Bot-Bal is, in a sense, we're, you know, why do you use adjuvant chemo? You use adjudant chemo because you're trying to get rid of any remaining, you knows, residual disease. Well, now if you train the immune systems to do that, you now, we may actually be able to dispense with chemo. And, you know, we won't be able to completely eliminate chemo in our phase three study, but we expect that actually we're going to see a de-escalation of some of the use of chemotherapy, which is also a patient benefit. Right. If you go to the next slide, I think we can, you now, show you that part of the reason for our pivot, because we were studying, you kno, Bot-Bal in the metastatic setting, is really the size of the population here. you know, we're looking at a very large patient population with MSS colon cancer. About 85% of patients are microsatellite stable as opposed to MSI high. Obviously MSI-high are very responsive to immunotherapy. And so, you know. But for those MSS patients, there really be no advances in the last 20 years. The current treatment is surgery followed by adjuvant chemo if the patients are high risk. So about half of these patients in the early stage disease setting are what we'd call high risk, these are high risk stage two, which is a large tumor, or stage three, which is lymph node positive. And in terms of our, you know, how we assess the addressable market here, you know we're looking at what we think would make sense in terms of a cost for course of therapy of about $200,000 in the U.S., which is comparable to existing perioperative treatments. You know, for example, Keytruda in triple negative breast cancer is in that range. So that gets you to a total U. S addressable market of over 7 billion, a very large market opportunity. Yeah, I don't think anybody would dispute the commercial potential for MS stable colon. I just want to ask, just take one quick step back and sort of amplifying the point that Zach made earlier about the consistency of effect. You know, both nest and unicorn had sort of remarkably similar PCR and MRR rates. And so what did it tell you? Because I know you guys had explored or your investigators had explored different doses, different regimens. Maybe, I don't know if you have a slide on that, but I just wonder what you could tell us about the different doses of bot that you looked at and then the you know two doses of bowel versus four doses of bow and kind of what the learnings were from from those studies yeah so that's the two different studies nest at cornell shown on the left here initially the nest study looked at about four weeks to surgery it was a short window of opportunity you know the surgeons wanted to make sure that they weren't seeing any progressions. But once they saw the results with a single dose of BOT, two doses of BAL, then they were encouraged and Pastor Nkasi was able to convince them to expand the study to eight weeks to surgery. And with the additional time, we'll show you the results. You can see that, in fact, you see you're allowing more time for the immune system to really act on the tumor. The unicorn study was similar in some ways, which was it was about five weeks to surgery. But in UNICORN, this was a platform study, they looked at both bot monotherapy as well as the addition of BAL. So we get a nice look at the contribution of adding PD-1 to CTLA-4 in this setting, both in MSS and in MSI-high. So I'll show you the NEST results first. Here what you see, you know, this on the left, NEST-1 is the four weeks to surgery, we do see a pathologic complete response, but it's really obvious that when you go to the longer time to surgery and potentially more additional doses of Val, you're seeing more depth of response, more pathologic complete responses. And so that's the basis actually for why in the Robin study, we're going eight weeks between the initial dose and surgery. You also see, you know, great responses in the MSI high, but that's what you expect. You see that with first-gen CTLA-4. But, I mean, it's, I know Catrude has approved or not in the setting, but you just wonder if you, you know, again, we're talking blue sky here, but eventually, you know, if you want to think about it as sort of like PD-1, you know, first generation, then VEGF plus PD- 1, that's taken the therapeutic benefit higher, you know, maybe eventually you guys could get into the, you know, the MSI high tumor setting given these kind of compelling results and really step up the magnitude of the benefit in those. Particularly given the rapidity of the response and actually the next slide, it shows the unicorn data. I'll start on the right here this time. What you see in the MSCI high cohort, you can see that, But, you know, here we're seeing also what the addition of BAL to BOT does. So BOT, we actually see monotherapy activity in MSI-high. We think this may be potentially the first monotherapy data people have seen with MSI high in colon cancer with BOT or with a CTLA-4. But clearly the addition OFPD-1 here, you get almost all pathologic complete response. These 100% major path response in a very short period of time, you know, within five weeks, you're seeing this result. So you think about how quickly the immune system is eliminating the tumor there. And then on the left, you see in a cold tumor, in MSS, again, the contribution of PD-1 to CTLA-4. So the BOT-BAL combination, you know, we see a 30% pathologic complete response rate and 70% of these patients with over 50% tumor reduction. So very consistent with the NEST study. In fact, in some ways a little bit better given the short time window to surgery. The Unicorn investigators are actually running an additional cohort now where they're expanding to eight weeks to surgery, encouraged, of course, by the NEST results. But very consistent results between these two studies. And importantly, what we see of every patient who was treated with the combination, none of them have recurred. So, you know, Bot-Val together in both MSI-High and in MSS, you know remarkably, we're seeing this median follow-up of anywhere from 19 to 32 months with no recurrences. Well, yeah, and that's what's important about this. Zach, do you mind just flipping back to the previous slide real quick? Because I want to stay on this for a minute. Again, you know, a lot of the questions that typically come up with any drug in the oncology space, whether it's IO or, you known, precision oncology, whatever, is, you knows, the durability. And, you known, the follow-up here is substantial, which means that these are durable responses in both instances. The other question or another point I want you to just drill down on is, you know it looks like bot on its own is uh you know is quite active but it clearly you know does a hell of a lot better when you add val to the equation so um i mean i think that's the you know the strongest argument for why this is uh the pair that uh yeah the combo that needs to be yeah exactly um also so um another question i had um and it relates to the next slide doesn't really matter but if you didn't uh achieve a pcr an mmr are you include are you included in these survival plots or this is only this is all the patients okay this is my regardless of response this is every patient that received botanical who had an mss tumor yeah and that's pretty you know what you expect to see in this patient population if they're treated with surgery and chemo is, you know, somewhere between 20 to 25% of patients would relapse by three years. By two years, you'd expect to see about 20% relapse rate. And we did see in unicorn and in the bot monotherapy treated, there were some relapses. So, you Know, this is a patient population and has a risk of relapse. So you know and the key thing here I think is that it's again, it's sort of cta4 conditioning the immune system for surveillance uh and that's how you can get rid of residual disease in a different manner to the treatment with adjuvant chemo right right so you know you know i mean you never say never uh need need sort of a top-up uh eventually but you would think that uh at these numbers yeah and we get questions mike from some investors about um and we're going to get to the Robin trial, of course, but just one item that relates to this point on adjuvant chemo. We get questions from some folks that say, well, because your adjunant chemo will be tumor-stage guided, are you concerned that because patients in the control arm will get more chemo than patients in about bowel arm, that that may harm your efficacy numbers and your recurrence rates. And our response is, well, no, we know how the control arm will likely perform based on all the previously reported data. And we want patients to get less chemo in the Bot-Bell arm. That's a huge metric of QOL and what we know is going to matter to patients. And we're confident that Bot-Dell will deliver a better recurrence rate with less of that chemo. That's part of the value proposition of our therapy. Right, right, exactly. Okay. And I know I don't want to, you know, I know we're spending quite a bit of time on sort of the setup for Robin, but do you want to just take a quick look at NeoASIS? Because, you Know, it's another sort of confirmatory, if you want to call it that, study that gives you very high NPR rates and where you, I think, got a better sense of the bot dose that you need to, that you're going to use in Robin. Yep. We have that next mic, but we do think it's important to address safety um you know in this population safety is is really imperative and and you know i think i think the the tolerability profile that we're demonstrating here is going to be sufficient and we're you know we're obviously really focused on um the the treatment protocols for the phase three being such that we'RE going to be able to show a similarly strong safety yeah and i would also point out that these are substantially below what you saw in c800 because you've got patients with much more robust immune systems. Yeah, and I also think that the other point here is that it's one dose of BOT as opposed to two to four, which was typical in the metastatic setting. So, yeah. Yeah, okay. Should we take a quick look at neoasis? Yeah, so neoasis is actually a fairly large neoadjuvant study looking at multiple different tumor types. This is being run by Miriam Chalabi at the Netherlands Cancer Institute. She's well known for the Niche study, which examined ipi-nevo in both MSI-high and in MSS patients. They expanded, you know, Niche was expanded in the MSI high population, showing very nice data, and they recently showed very long-term follow-up in that study that's very impressive. So it shows the power of the immune system in a responsive tumor. But what's interesting here is that here we're looking at MSS tumor type. Look at two different doses. She was dose escalating 25 to 50 to evaluate safety. They're small cohorts, so, you know, 5 at 25 milligram. Those are the striped. 5 at 50 milligram are the solid bar. What's interesting here is we see activity across a range of tumors. We see sarcoma, which is consistent with what we see in the metastatic setting. We see very nice responses in sarcomA. But also triple negative breast cancer, both NDE or positive breast cancer here. And then the MCC is one Merkel cell carcinoma, which has a warm tumor. So you kind of expect that to be a little bit more positive. But was that an MCC that was previously treated with Keytruda? Because that's indicated. so well this is uh no these are de novo so this is untreated yeah okay yeah and i wistfully look at the uh sarcoma patient because i remember brie wilkie's presentation a few years ago and the remarkable results she got there again another cold tumor yeah and we continue to have uh a lot of interest in sarcomа as well and maybe just a little digression on the metastatic setting you We have an access program in France. The three approved indications there are metastatic colorectal cancer, ovarian cancer, and sarcoma. So the ANSM, the French Regulatory Authority, recognized that there's an unmet need for those patients and that BODPAL has data that makes sense to provide them access. So we're quite happy the French government is providing access to those patients in France, Do you find when you talk to investors, Zach, that people are aware of that? That there's, you know, there are docs out there, they're getting real-world experience using BotValve? When you study it, whether they prioritize it is really up to them. Whether they process it or not is another question? Okay. Yeah. All right. So, and then recently at ESMO this year, just a few weeks ago, Miriam Chalabi presented the DMMR colon cancer cohort from the NEOWASIS study. And here you see some nice results. You know, they're, you know, 83% major path response rate here. um you know i think that you know be nice to see sort of you know pushing the dose a little higher she's at 50 i think 75 would probably be yeah you know maybe get a little bit better response in a couple of these patients yeah very nice okay um let's move on to i think this you know was a good point then to transition to the discussion about Robin. So, you know, it's your phase three trial, 850 patients, randomized one-to-one, event-free survival is the primary endpoint. Talk a little bit about how FDA feedback shaped the design, including a control arm, standard care, and then also the inclusion of high-risk stage two and three disease. Yeah, so we modeled this study actually on a precedent, which was the Foxtrot study, which looked at neoadjuvant full FOX in the same population, high-risk stage 2 and stage 3 patients. And, you know, here you're staging clinically. You're using CT scan to stage the patients to be able to try to find the appropriate high-risk population. So we discussed with the FDA the patient population, the study design where we would evaluate BOT, BELL versus basically standard of care. And standard ofcare here is going to surgery followed by adjuvant chemotherapy. One of the discussion points with the FTA was what adjuant chemotherapy are patients going to get after surgery? and um what what they what we agreed to with them was that the staging at surgery would determine what adjuvant chemo they would get and that would be based on nccn guidelines and so that uh was was consistent with what the fda was looking for they wanted basically investigators to have some guidance on how they would treat patients but what it means is that if we see a pathologic complete response and lymph node negative at the time of surgery in the neoadjuvant arm, then those patients would go to observation. So they wouldn't get any chemo, which is consistent with what patients with a stage one tumor would get as a standard of care. And so here we hope that we're going to see some de-escalation of chemo particularly oxaliplatin because oxaliplatin carries with it significant neurotoxicity. And additionally, of course, the primary endpoint is important here because the primary viewpoint is event-free survival. This is the standard in terms of neoadjuvant perioperative adjuvant studies. So there was no debate over the endpoint. And the target hazard ratio of 0.65 was viewed as a significant benefit in this patient population. And just for the record, Robin, the standard chemo, the adjuvant chemos can be full FOX, full FURI, can it be just 5-FU-leucovorin? Yeah, the standard adjuvant treatment is either 5-FU, if it's a smaller tumor, or CAPOX or FOLFOX for larger tumors or lymph node positive disease. Typically, the staging will determine whether it's three or six months of treatment with CAPO X or Folfox. Folfuria is not used typically in this setting. Okay. And you're also trying to measure the oxaliplatin neuropathy as part of the benefit, correct? That's right, yeah. Okay. And how you quantify that is just... It's one of the quality of life measures. Okay. Yeah. And that's the, what, the QL36 or... It's not the QO36. There's a specific tool. Colorectal. We didn't list it specifically here, but there is a specific tool that kind of addresses that neuropathy associated with xyliplatin. I'm just curious, so what you'll be looking for, event-free survival on an intent-to-treat basis? Correct, and so what we expect in the control arm is that at basically three years, you'd expect about a 25% relapse rate. So, EFS would be 75%, you know, who are event-free at three years in the control arm. And we're looking to improve that by, you know risk reduction of 35%, so we'd be up, you know this an absolute basis, a significant improvement for these patients. And that's if we hit the target hazard ratio, if we go better than the target has a ratio, which if you look at other studies of neoadjuvant CTLA-4, we've actually seen, you know, even more impressive results. In Nadina, for example, which was ipilimumab in stage 3 resectable melanoma, you know ipinivo neoadjuvant versus adjuvant nevo had a hazard ratio well below 0.5. It was like 0.35, I think. so so yeah and then you know if you think about the uh triple negative breast cancer uh setting as well you know it's uh like some of the studies that were done by i spy with uh you know neoadjuvant uh pembro followed by either chemo or sac sac g you know you've seen those pcr rates um correlate really beautifully with event-free survival and overall survival. Yeah, and actually we took a look at that, looking at the delta in terms of pathologic complete response rates to see how well it correlates with event free survival. And you see actually a pretty good correlation in terms this improvement in pathologic complete response rate, you know, if you hit sort of where we saw in Nest and Unicorn at a 30% PCR rate delta, it would predict a hazard ratio of around 0.5. You know, for our target hazard ratio, 0.65, you know that would correlate with about a PCR of 17%. So we think that would be reassuring. We don't think it's going to tell the whole story because I think that, you now, when you look at the niche data, for example, and our own data, well, it's hard to correlate our own data because 100% of patients are recurrence-free with Bott and Bell, so that would be great to see. But in niche, in the MSS cohort, this is ipinebo here, you can see that any patient who had at least a 50% tumor reduction was recurrence. Yeah, no, it's a beautiful thing. All right, well, maybe this might be a good time to talk about kind of the event horizon, if you want to call it that, Zach, if we want to maybe walk through sort of the, yeah, here you go. So why don't you walk us through sort of the near term milestones that people should be mindful of, and then what's going to come, you know, with, with time? Sure. And why don't I start, Mike, and I'll frame this timeline in the context of the transaction that we did back in July, because I think that the timeline that we have for the Robin trial is very much aligned with that transaction. So just to remind everyone, the transaction we are referring to, we closed on July 13th of this year. It was a pipe, it was a private placement, which was oversubscribed for up to $340 million of financing, $85 million of which was done up front at the time of closing, and the remaining $255 million of potential proceeds are part of two warrant tranches, the Series A warrant tranche and the Series B warrant tranache, and we'll talk through the mechanics of those as well. All three tranches, the upfront, the Series A warrants, and the Series B warrants were priced at premiums to the then market price, which was $335 on the date of closing. And so we're obviously focused and investors are focused on the sort of economic value of those warrants. But also the critical milestones that relate to those warrents are part of the Robin trial. So just to go through it, the Series A warrants will have an expiration date that is 30 days after we publicly disclose that 60 patients have been enrolled in the Robin Phase 3 trial. We expect that event to occur in Q2 of 2027. As we've alluded to before, our anticipated first patient enrolled is expected for Q1 of this year, and based upon the sort of expectation of enrollment ramp, that's how we get to those time points. And we can obviously talk a little bit about the excitement that we're feeling among the oncology community and the sites that we've been engaging with for the trial. We did talk a bit about that in our earnings announcement earlier today. But just to stick to the timeline, so the Series A warrants would result in $85 million of gross proceeds into the company if all of those warrants are exercised. Those warrants aren't priced at $4.02 per share. And so once we trigger those warrants, and if those proceeds come into the company, that obviously extends our cash runway, and we project that to be a cash runway extension through Q1 of 2029. The next big inflection point is the interim readout on pathologic response rate in the first 100 patients enrolled in the trial, 50 on the bot bowel arm, and 50 on the control arm. That we expect to happen in Q4 of this year, or of next year rather, and that will trigger the 30-day expiration of the Series B warrants, which if all are exercised would result in an additional $170 million dollars of proceeds into our balance sheet and those are priced at five dollars and three cents per share um an important mechanic which uh i'm not sure people appreciate but it is part of the the filed um terms of the transaction is that if series a warrants are not exercised by investors they will lose their series b warrant right and so there is an expectation that these warrants will be exercised uh we of course know that investors will be looking to the response rate data as part of that series B tranche as a true clinical de-risking outcome. And as Robin alluded to earlier, we know that pathologic complete response rate is an important correlate, but we also believe strongly that major path response is an importante correlate as well to long-term EFS benefit. And we'll be announcing both of those metrics along with just the pathologic response rate, which is anything above 50% tumor shrinkage. We anticipate LPI in the trial to be second half of 28. And so that would then lead to our projected timelines for the readouts for the primary endpoint of EFS, the interim analysis in the second half is 29. That's at a 75% information fraction, meaning 75% of the EFS events are anticipated to have occurred at the time of that data cutoff for that interim readout. And then the full readout, which is, of course, 100% of the anticipated EFS events would occur roughly one year thereafter in second half of 2030. And will you be following people, patients ultimately for OS or once they... Yeah, OS is a key secondary endpoint. Okay. And Zach, can you talk about operationally in the early part of the study for the first 60? Is the site initiation ramp um going to be gated in any way or are you going to basically just start ramping as if you know assuming that the the warrants are exercised and you're just going to you know you're going to plow forward with the target number of sites does that make sense yeah no i understand your question no we don't we don'T have any gating we're anticipating that um you know we're basically trying to activate every site we can as quickly as we can we expect you know u.s south america australia potentially to be the earliest sites to be open and then europe takes a little bit longer in terms of the clinical trial application we expect them to come in at you know not too much later you know about a quarter later maybe and then asia as well we're opening the study um so it's you know it takes time around the world but we definitely expect to have um the full study open uh by mid-year next year how many sites uh robin we um we haven't said specifically but uh and we're still sort of in that phrase where we're kind of um validating a number of sites so we'll we'll hold off on on saying that for the moment but well we're focused on high volume sites because we and we're doing something unusual which is that typically you know a lot of times you'll work with a CRO CRO will recommend a bunch of sites and you end up with you know 300 sites but a third of them never enroll anyone here we're do something different which is we're actually getting on a meeting with every single site that we're going to include in this study we're having a discussion with them we're understanding if you know they're going have any challenges uh and we're selecting and so we're being very selective about who can participate in this trying to be trying to get be part of it or no we're evaluating china uh can't say for certain yet but it's certainly all the major markets mike will be a part of the trial well the thing about china i mean you just can enroll you know so many patients it's just they're incredible um and operationally i think they're as good as anything you get elsewhere but yeah no we've been speaking with words in your mouth either with some key sites in china and yeah no you're right the the volume of patients they see is is uh dwarfs anything we see anywhere else yeah it's remarkable what i mean in terms of volume um is there any qualification that the surgeons need to have as far as how many patients per year you know they they see or their experience with the surgery etc yeah no definitely um you know adequate volume uh in terms of the number of surgeries that a site sees is is part of the the screener that we have um also it's a you know it's plus if the surgeons have had experience with uh other neoadjuvant colon studies. So there's, you know, the MSI high is the obvious ones. Some of the Azure studies, for example, I think that's where we're seeing there are some surgeons who already have experience and so they're kind of used to it. And very much, I think the standard now across the world is that sites are, you know, evaluating first whether a tumor is DMMR or PMMR prior to deciding whether to go to surgery or not. Right. Okay. I think, you know, we're coming up, you know, on time fairly soon. I just was curious, you know, here are the Robin, you know, timelines. I'm just curious, are we going to see any further updates, little gumdrops, little breadcrumbs that your investigators might drop on, like, NeoASIS? Is, you know, Miriam Chalabi going to, you know, be, I know you can't speak for her, but would you imagine that there would be data drops throughout the course of 2027 and so investors can get comfort yeah you know yeah for sure you know we have a number of uh ists that are ongoing uh miriam's neoasis study is obviously one of the key ones and we are anticipating that she is going to present data next year we also have a number of rectal cancer studies that are outgoing um andrea serchak and memorial sloan kettering is running a study with Bott and Bale. Rectal is really interesting. Yeah. Yeah, especially if you can, you know, increase a level of syncter preservation. Organ preservation. Because you had that in... For sure is a key one. And ability to de-escalate radiation in particular, but also chemo and radiation. I mean, there's such a bigger need in that setting, Mike. Not to compare need. I mean every patient has a need, but it's very clear in rectal that there's a sense of urgency among oncologists and among regulators to find a better solution for these de novo patients. And to Robin's point, we do have multiple ongoing ISTs in that neoadjuvant MSS rectal disease area. We do believe that there will be some data from those coming out next year. We can't speak to specifics on that, but that is certainly our sort of second focus beyond the Robin Phase 3 when it makes good sense for our company to potentially start to think about sponsored trial expansion, that is very likely where we will go. Yeah. Yeah, okay. Well, look, I'm looking in the chat, and I'm working on my email. I don't have questions here, so I don' know if you want to wrap up with anything before we give you back your time? You know, I' m just going to wrap up with uh the fact that you know i'm super excited that we're evaluating bought and bail in the curative intent setting when you look at mss colon cancer there'd be no improvements in the treatment of these patients in over 20 years i mean the last therapy to come into this space was oxaliplatin and that was in 2004 yeah yeah remarkable and i'll just frame it mike a little bit in the sort of uh investor frame, which is, we think we've presented now a very clear pathway of how we get this therapy to its first full approval. And we've established what we think are the fair market metrics to understand what that means from a value creation perspective. And, we've also sort of solidified, at least for the time being, our capital needs through this pipe transaction and how many shares will be out there. So for investors who are taking a first principles approach to valuing our business and establishing a view on whether the price is undervalued or overvalued, I think we've given them all of the key parameters to do that. We, of course, are always looking to help investors and refine that. And we do a lot of that through our sell side analysts like you and your team. But we do think that that story has very much crystallized over the last few months. And obviously, our view is that there's a whole lot more value in our, you know, stock price. And then what our stock price is reflecting today, our jobs are to continue to execute. But for those out there who are looking for a fundamentally oriented deep value story, we think that we represent that. Yeah. And if you're looking for a validated mechanism of action and de-risked assets, I don't know how you can get much better than BotBal. So anyway. All right. Well, listen, I want to thank you guys for joining me here today. It was a pleasure. We'll keep our close watch on your progress. I want thank everybody for joining us here today and enjoy the rest of your day. Yeah. Thank you. Thank you, Mike. Thanks, guys. Appreciate it.