That excitement, because I recall that— I forget what year it was, CITI in Boston, but a very compelling response rate as well as 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 Agenus. But the company has quite a bit of expertise and experience with first-generation CTLA-4, zalifrelumab. Batinzelumab is the successor to that. 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. Zack, we're still seeing presenter mode here. There you go. There you go. Perfect. So if we go to the Yeah, here, the schema of the antibody. The secret sauce in batinzelumab 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 batinzelumab to help the immune system to identify these weaker neoantigens. So we see expansion of you know, T-cell repertoire. You see priming, activation, and memory formation. And we also see activation of myeloid cells. Additionally, what we see is a reduction in regulatory T-cells, so depletion of those intratumoral Tregs. And we see that actually, we saw it preclinically, but we actually see it now in the clinic from the nice data that we have from the, the neoadjuvant studies in colon cancer with both NEST and UNICORN. And what you see here is the visual example of that, basically, where 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 pretreatment with BOTVAL. 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 are you actually measuring here in the slides on the right? Yeah, so we're measuring in green is CD4, purple CD8. FOXP3 is the red, that's measuring the Tregs. Right. And then the tumor is— which you don't want. Right. Yeah. And Mike, 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-BOTVAL, the tumor is excluding that immune system. So, you know, these cold tumors are broken down into, 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 do what it's naturally programmed to do. And then BOTVAL essentially unlocks or ignites that immune response and helps proliferate the army of killer cells, which you want. to be entering the microenvironment and then is kicking out the regulatory cells, which we need so that a cut that we get doesn't turn into a massive bleedout. 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? Go ahead, Robin. Yeah, no, this is a patient with de novo colon cancer. Okay. So 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 multiple prior rounds, or would it be less compelling? You may see something like this. There is a little bit more complexity because the health of the immune system is a factor. 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. Was this, you know, third-line-plus kind of patient? Just trying to get a sense of Right, right. But I mean, I still think from, you know, like your metastatic setting, the C800 study you had, you still had really good really good response rates. So, yeah, exactly. So over 20% response rate. And, you know, and response didn't tell the whole story in the metastatic setting because patients with stable disease had stable disease sometimes for you know, a couple of 2 to 3 years. Right. Right. You know, and that translated. So, you know, here we're showing the, you know, the overall results from our Phase 1B study. So this was over 411 patients enrolled across multiple different tumor types. These were highly refractory patients, and, you know, out of those that had efficacy-evaluable tumors, you can see that, you know, there's this really nice consistent response rate across multiple different tumors in the range of 17 to 20%. And 17% in the overall group in terms of tumor response. But you can 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 ways. So you've got patients out 120 weeks with stable disease response. Not days. Yeah. Yeah, no, it's— yeah, that's the part of the compelling story that I like here. 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 frontline, the neoadjuvant setting. But 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— 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 alone doesn't generate? Yeah, and that translated in the Phase 1B to a median OS of 17 months. But, you know, at 2 years, you still see 39% of patients alive, which is pretty remarkable for 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-1 explored across almost every tumor you can imagine to try to see where the signal is. And the signal's been in hot tumors, as being where there's been typically enough or sufficient immune response already that you're able to unmask it. With the addition of PD-1. Cold tumors are more challenging because you need something to ignite the immune response, and that's why botinumab has this ability now to be able to broaden the range of immunotherapy to cold tumors, the classic being colorectal cancer. Zack, if you go to the next one, you know, here's the example from from the Phase 1B, just looking at the 123 patients we enrolled with colorectal cancer without active liver mets. But what you see is a 21% response rate. You know, and 3-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, Zack. Should we move on, Robin? We also have the ovarian cohort, Mike, that was just presented at the ICGS conference. Sure. 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. assets in clinical trials. Now, you've got some fast followers that are putting activated Fc-CTLA-4. antibodies or masked CTLA-4— sorry, Fc-active CTLA-4 antibodies into the clinic. So 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. 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, Zack. Why don't you show the ovarian data? Yeah, and here's the data that we recently presented, uh, an update of our ovarian data from the Phase 1B. You can see a nice response rate 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 at 18 months, you see a response. It's really quite interesting sometimes how the effect of CTLA-4 can suddenly flip a switch with the immune system. 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, you know, patients, we don't see any You know, you see this, you know, long plateau with about half of the patients alive at 2 years here. Yeah. And suddenly at 3. 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 have come into 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 Bhatbal. But it definitely begs the question about what kind of benefit patients could get, P-ROC patients, or then, of course, move it earlier as well with ovarian combining Bhatbal and an ADC. Yeah, I mean, expansion is certainly in our future plans, Mike. Yeah, 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 dataset, where patients who had other— who had a number of prior lines of therapy, whether it be 1 or 2 or greater than 4, 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. 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. 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 pot bowel where it's able to mount— 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. We won't— we don't need to go there right now. But I do— I think it's a good pivot, Zack, to go and talk about neoadjuvant and why untreated resectable colorectal cancer is the ideal place, at least initially, for pot bowel. Versus the metastatic disease despite the consistency of benefit. Maybe you can cover some of the immune system aspects of that. Tell us about the pivot to Robin. Yeah, no, I'm happy to. The reason we went to phase 3 in the neoadjuvant setting is because of the data that came out of 2 2 key studies, the NEST study run at Cornell and the Unicorn study run by Italian cooperative group, the Gono Group. And here's an example of what we saw. This is a patient with an 8-centimeter mass. Uh, 40-year-old patient, you know, lymph node positive. 1 dose of BOT, 2 doses of BAL, and 7 weeks later, you can see that, uh, the tumor is not there. Uh, this patient, you know, after this scope went to surgery, 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, uh, when you have an intact tumor, and this has been seen not just in, you know, our data, but also with first-gen CTLA-4 in melanoma in 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 BOD-BAL is, in a sense, we're, you know, why do you use adjuvant chemo? You use adjuvant chemo because you're trying to get rid of Uh, metastatic, any remaining, you know, residual disease. Well, now if you train the immune system to do that, you know, we may actually be able to dispense with chemo. Uh, and, you know, we won't be able to completely eliminate chemo in our phase 3 study, but we expect that actually we're going to see, uh, a de-escalation of some of the use of chemotherapy, which is also a patient benefit. Right. So, Zack, if you go to the next slide, I think we can, you know, show you that part of the reason for our pivot, because we were studying you know, BOD-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. Uh, about 85% of patients are microsatellite stable as opposed to MSI-high. Obviously, MSI-high are very responsive to immunotherapy. Uh, and so, You know, but for those MSS patients, there really been no advances in the last 20 years. The current treatment is surgery followed by adjuvant chemo if the patients are high risk. Uh, so about half of these patients in the early stage disease setting are what we'd call high risk. These are, uh, high-risk stage 2, which is large tumor, or stage 3, which is lymph node positive. Yep. And in terms of our, you know, how we assess the addressable market here, um, you know, we're looking at what we think would make sense in terms of a cost for, for course of therapy of about $200,000 in the US, which is comparable to existing perioperative treatments. You know, for example, Keytruda in triple-negative breast cancer is in that range. So that, that gets you to a total US addressable market of over $7 billion, a very large market opportunity. Yeah, I think— I don't think anybody would dispute the commercial potential for MS stable Colin, I just want to ask, just take one quick step back and sort of amplifying the point that Zack 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 the, you know, 2 doses of BAL versus 4 doses of BAL and kind of what the learnings were from, from those studies. Yeah, so that's the, the 2 different studies. NEST at Cornell shown on the left here. Initially, the NEST study looked at about 4 weeks to surgery. It was a short window of opportunity. 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, 2 doses of BAL, then they were encouraged, and Pashtoon Kasi was able to convince them to expand the study to 8 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 5 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, we can show you the NEST results first. Here, what you see, you know, this on the left, NEST-1, is the 4 weeks to surgery. approved or not in the setting. But you just wonder if you— again, we're talking blue sky here, but eventually, if you want to think about it as sort of like PD-1, first-generation, then VEGF plus PD-1 that's taken the therapeutic benefit higher. Maybe eventually you guys could get into the Uh, we do see a pathologic complete response, but it's really obvious that when you go to the longer time to surgery and, and potentially more additional doses of BAL, you're seeing more depth of response, more pathologic complete responses. Uh, and so that's the basis actually for why in the ROBIN study, we're, we're going 8 weeks, uh, between the initial dose and surgery. You also see great responses in the MSI-high, but that's what you expect. You see that with first-gen CTLA-4. Yeah, but I mean, it's— I mean, there's a— and I know Catrude is the MSI-high tumor setting, given these compelling results, and really step up the magnitude of the benefit in those tumors. Particularly given the rapidity of the response. And actually, if you go to the next slide, it shows the unicorn data. I'll start on the right here this time. What you see in the MSI-high cohort, you can see that, you know, here we're seeing also what the addition of BAL to BOTT does. So, BOTT, 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 BOTT, where with the CTLA-4, but clearly the addition of PD-1 here, you know, you get almost all pathologic complete response. These 100% major path response. In a very short period of time, you know, within 5 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 BOTT-BAL combination. You know, we see a 30% pathologic complete response rate, and 70% of these patients with over 50% tumor reduction. Very consistent with, 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 8 weeks to surgery, encouraged, of course, by the NEST results. But very consistent results between these 2 studies. And importantly, what we see of every patient who was treated with the combination, none of them have recurred. So, you know, BOTT-BAL together in both MSI-high and in MSS, 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. Zack, 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 any drug in the oncology space, whether it's IO or precision oncology, whatever, is the durability. And the follow-up here is substantial. Which means that these are durable responses in both instances. The other question or another point I want to just drill down on is, you know, it looks like BOTT on its own is quite active, but it clearly does a hell of a lot better when you add BAL to the equation. So, I mean, I think that's the strongest argument for why this is the pair that needs to be— Yeah, exactly. Also, so Another question I had, and it relates to the next slide, doesn't really matter, but If you didn't achieve a PCR or an MMR, are you included in these survival plots, or this is only— Yeah, this is all the patients. Okay. So that's— this is regardless of response. This is every patient that received BOTT and BAL who had an MSS tumor. Yeah. Yeah. That's pretty remarkable. What you expect to see in this patient population if they're treated with surgery and chemo is somewhere between 20% to 25% of patients would relapse by 3 years. By 2 years, you'd expect to see about 20% relapse rate. We did see in UNICORN, in the BOTT monotherapy-treated, there were some relapses. This is a patient population who has a risk of relapse. So, you know, and the key thing here, I think, is that It's again, it's sort of CTLA-4 conditioning the immune system for surveillance. 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, I mean, you never say never. Need sort of a top-up eventually. But you would think that at these numbers, Yeah. And we get questions, Mike, from some investors about— 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 adjuvant chemo will be tumor-guided, tumor-stage-guided, are you concerned that that because patients in the control arm will get more chemo than patients in the BOD-BAL 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 BOD-BAL arm. That's it. That's a huge metric of QOL and what we know is going to matter to patients. And we're confident that BOD-BAL 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 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 it's another sort of confirmatory, if you want to call it that, study that gives you very high MPR rates and where you, I think, got a better sense of the BOD dose. that you need to, you know, that you're going to use in Robin? I don't know if you have that slide. We have that next, Mike, but we do think it's important to address safety. In this patient population, safety is really imperative. The tolerability profile that we're demonstrating here is going to be sufficient. And we're obviously really focused on the treatment protocols for the Yeah, yeah, okay. you know, much more robust immune systems. Yeah. And I also think that the other point here is that it's 1 dose of BOD as opposed to 2 to 4, which was typical in the metastatic setting. So Phase 3 being such that we're going to be able to show a similarly strong safety profile. Yeah, and I would also point out that these are substantially below what you saw in C800 because you've got patients with And should we take a quick look at Neoasis? There we go. Yeah. So Neoasis is actually a fairly large neoadjuvant study looking at multiple different tumor types. This is being run by Myriam Chalabi at the Netherlands Cancer Institute. She's well known for the Niche study, which examined ipi-nivo in both MSI-high and in MSS patients. The expanded 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 Uh, tumor type, uh, looking at 2 different doses. She was dose escalating 25 to 50 to evaluate safety. Uh, they're small cohorts, so You know, 5 at 25 milligrams, those are the striped, 5 at 50 milligrams 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 You know, very nice responses in sarcoma, but also triple negative breast cancer, both and ER positive breast cancer here. And then the MCC is one Merkel cell carcinoma, which is a warm tumor. So you kind of expect that to be a little bit more. But was that an MCC that was previously treated with Keytruda? Because that's indicated. So, you know, this is a— no, these are de novo. So this is untreated. Yeah. Okay. And I wistfully look at the sarcoma patient because I remember Bree Wilkie's presentation a few years ago and the remarkable results she got there. Again, another cold tumor. Yeah, and we continue to have a lot of interest in sarcoma as well. And maybe just a little digression on the metastatic setting. You know, we have an access program in France. The 3 approved indications there are colorectal, you know, metastatic colorectal cancer, ovarian cancer, and sarcoma. So, you know, The ANSM, the French regulatory authority, recognized that there's an unmet need for those patients and that BODPAL, you know, has data that makes sense to provide them access. So we're quite, quite happy the French government is providing access to those patients in France. Do you find when you talk to investors, Zack, that people are aware of that? That there's, you know, there are docs out there, they're getting real-world experience using BODPAL? Myriam Chalabi presented the DMMR colon cancer cohort from the NEOASIS study. And here you see some nice results. You know, they're, uh, you know, 83% major path response rate here. Um, you know, I think that You know, it'd be nice to see sort of, you know, pushing the dose up a little higher. She's at 50. I think 75 would probably be, you know, maybe get a little bit better response in a couple of these patients. We say it, whether they prioritize it is really up to them. Whether they process it or not is another question. Okay. Yeah. So, and then recently at ESMO this year, just a few weeks ago, Yeah, very nice. Okay, let's move on to— I think it's a good point then to transition to the discussion about Robin. So, you know, it's your phase 3 trial, 850 patients randomized 1-to-1, event-free survival as a primary endpoint. Talk a little bit about how FDA feedback shaped the design. Including the control arm as a standard of care, and then also the inclusion of high-risk stage 2 and 3 disease. Yeah, so we modeled this study actually on a precedent, which was the Foxtrot study, which looked at neoadjuvant FOLFOX in Same population, high-risk stage 2 and stage 3 patients. Um, 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. Um, so we discussed with the FDA the, you know, the patient population, uh, the study design where we would evaluate, uh, BOT-BELL. Versus basically standard of care. And standard of care here is going to surgery followed by adjuvant chemotherapy. Uh, one of the discussion points with the FDA was, you know, what adjuvant 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 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, uh, 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, you know, a stage 1 tumor would would get in as a standard of care. Right. And so You know, here we hope that we're going to see some de-escalation of chemo, particularly oxaliplatin, because oxaliplatin carries with it significant neurotoxicity. Right. Uh, and additionally, of course, the primary endpoint is important here because primary endpoint is event-free survival. Uh, this is the standard in terms of neoadjuvant perioperative adjuvant studies. Uh, so there was no, you know, debate over the, the endpoint, uh, and the target hazard ratio of 0.65, uh, was viewed as a, you know, significant benefit in this patient population. Uh, if it's a smaller tumor, uh, or CAPOX or FOLFOX for larger tumors or lymph node-positive disease, typically the staging will determine whether it's 3 or 6 months of treatment with CAPOX or FOLFOX. Uh, FOLFIRI is not used typically in this setting. Right. And just for the record, Robin, the standard chemo, the adjuvant chemos can be full FOLFOX, full FURY. Can it be just 5-FU leucovorin? Yeah, the standard adjuvant treatment is either 5-FU It's not the QL36. There's a specific tool which we didn't list it specifically here, but there is a specific tool for that kind of addresses that. Okay. Um, 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, uh, it's one of the quality of life measures. Okay. Yeah. And that's the what, the QL, uh, QL36 or basis, correct? Correct. And so what we expect in the control arm is that, you know, at basically 3 years, you'd expect about a 25% relapse rate. So EFS would be 75%, you know, who are event-free at 3 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 hazard ratio, which if you look at other studies of neoadjuvant CTLA-4, Uh, we've actually seen, you know, even more impressive results in NADINA, for example, which was ipilimumab in, um, stage 3 resectable melanoma. You know, ipi-neo, neoadjuvant versus adjuvant nevo had a hazard ratio well below 0.5. It was like 0.35, I think. So Neuropathy associated with oxaliplatin. Just curious. So what you'll be looking for, event-free survival on an intent-to-treat So yeah. And then, you know, if you think about the triple-negative breast cancer setting as well, you know, it's like some of the studies that were done by I-SPY. With, you know, neoadjuvant Pembrolizumab followed by either chemo or SacG, you know, you've seen those PCR rates 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 if, you know, how well it correlates with event-free survival. And you see actually a pretty good correlation. Uh, in terms of, you know, this improvement in pathologic complete response rate. Um, you know, if you hit sort of where we saw in NEST and UNICORN at a 30% PCR rate delta would predict a hazard ratio of around 0.5. Um, you know, for our target hazard ratio of 0.65, you know, that would correlate with about a PCR of 17%. So Um, we think that would be reassuring. We, we don't think it's going to tell the whole story because I think that, you know, when you look at the niche data, for example, and our own data, Uh, well, it's hard to, hard to correlate our own data because 100% of patients are recurrence-free with BOTTENPAL. So, right, that would be great to see. Um, but in, in, um, Um, in, in NISH, uh, in the MSS cohort, this is ipi/nivo here. You can see that any patient who had at least a 50%, uh, tumor reduction So was recurrence-free. 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, Zack, if you 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 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, you know, the timeline that we have for the Robin trial is very much aligned with that transaction. Yeah. 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 upfront at the time of closing, and the remaining $255 million of potential proceeds are part of 2 warrant tranches, the Series A warrant tranche and the Series B warrant tranche. And we'll talk through the mechanics of those as well. All 3 tranches The upfront, the Series A warrants, and the Series B warrants were priced at premiums to the then market price, which was $3.35 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 warrants 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. Based upon the expectation of enrollment ramp, that's how we get to those time points. 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 are 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-BAL 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. of proceeds into our balance sheet, and those are priced at $5.03 per share. An important mechanic which I'm not sure people appreciate, but it is part of the filed 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. 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. 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 important correlate as well. to long-term EFS benefit. 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 of '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 1 year thereafter. In second half of 2030. And will you be following people, patients ultimately for OS or once they— They will. Yeah. OS is a key secondary endpoint. Okay. And Zack, can you talk about operationally in the early part of the study for the first 60? Are you— is the site enrollment initiation ramp going to be gated in any way, or are you going to basically just start ramping as if, you know, assuming that 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 have any gating. We're anticipating that we're basically trying to activate every site that we can as quickly as we can. We expect, you know, US, 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 So it's, you know, it takes time around the world, but we definitely expect to have the full study open by mid-year next year. And ultimately, how many sites, Robin? We, we haven't said specifically, but, and we're still sort of in that phase where we're kind of validating a number of sites. So, We'll hold off on saying that for the moment. But yeah, it's going to be a big number. 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, the CRO will recommend a bunch of sites, and you end up with, you know, 300 sites, but a third of them never enroll anyway. Right. Here we're doing 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 to have any challenges, and we're selecting. And so we're being very selective about who can participate in this study. Is China going to be part of it or no? with some key sites in China. And yeah, no, you're right. The volume of patients they see dwarfs anything we see anywhere else. Yeah, it's remarkable. What I mean, in terms of volume, is there any We're evaluating China. Uh, I can't say for certain yet, but it's possible. Yeah. And certainly all the, all the major markets, Mike, will be a part of the trial. Well, the thing about China, I mean, is 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, we've been speaking 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. Adequate volume in terms of the number of surgeries that a site sees is part of the screener that we have. Also, it's a, you know, it's a plus if the surgeons have had experience with other neoadjuvant colon studies. So there's, you know, the MSI-high is, is the obvious ones. Some of the Azure studies, for example. I think that's where we're seeing, uh, 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 evaluating first whether a tumor is DMMR or PMMR prior to deciding whether to go to surgery or not. Right. Yeah. Okay. I think, and, 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, will we— are we going to see any further updates, little gumdrops, little breadcrumbs that your investigators might drop on like NeoACEs? Is Myriam Chalabi going to be— I know you can't speak for her, but would you imagine that maybe data drops throughout the course of 2027, and so investors can get comfort that things are staying consistent? Yeah, for sure. We have a number of ISTs that are ongoing. Myriam's NeoACEs study is obviously one of the key ones. We are anticipating that she is going to present data next year. We also have a number of rectal cancer studies that are ongoing. Andrea Surcek at Memorial Sloan Kettering is running a study with Botan Bale. Rectal is really interesting. Yeah. Yeah. Especially if we can, uh, uh, you know, increase a level of sphincter preservation. Organ preservation, 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. Okay. Well, look, I'm looking in the chat and I'm looking on my email. I don't have questions here. So I don't know if you want to wrap up with anything before we give you back your time. I, you know, I'm just gonna wrap up with the fact that, you know, I'm super excited that we're evaluating BOTTENVAL in the curative intent setting. When you look at MSS colon cancer, there'd been 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 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 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. Right, to do the math. Of course, we're 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, in our, you know, stock price than what our stock price is reflecting today. Our jobs are to continue to execute. Um, but for those out there who are, who are looking for a fundamentally oriented deep value story, we think that we represent that. Yeah. And, and if you, you know, if you're looking for, you know, validated mechanism of action and, uh, de-risked assets, uh, I don't know how you can get much better than, you know, than BotBao. So, uh, anyway, uh, all right, well, listen, I want to, uh, thank you guys for, uh, joining me here today. It was a pleasure. Um, We'll keep our close watch on your, on your progress. I want to thank everybody for joining us here today and enjoy the rest of your day. Yeah, thank you. Thank you, Mike. We really appreciate it. Thanks, Mike. Take care.