Earnings Call - EXSCIENTIA PLC

you you you you you you you you Thank you. Good morning, everyone, and thank you for joining Recursion's Third Quarter Earnings Call. We're hosting earnings live from the CGA IGC Annual Meeting in Denver. Today, we'll share the new FAP data that was presented yesterday at CGA by Dr. Lisa Boardman, along with updates in our oncology program RECT 1245, and progress across our partnerships. Before we get into the data, I want to start with the philosophy behind what we're building. To pioneer a new blueprint for making medicines with AI, we believe you have to tie together three core capabilities in one engine. Uncover novel biology, design differentiated molecules against challenging targets and generate clinical evidence that matters for patients. And that is what we're building at Recursion. And the higher bar we set for ourselves is repeatability. Not one target, not one molecule, or one clinical result, but the ability to do this across programs again and again. Let me show you the progress we're making. Let me start with what we see in patients. We now have positive clinical data from two first-in-class programs. With REC481 in FAP, we saw deep reductions in polyp burden that persisted off treatment. Now we're also seeing activity across the GI and reduction of larger high-risk polyps. We'll walk you through some of that data today. With Rec1245, we've seen partial responses in heavily pretreated cancer patients, two confirmed and one confirmed PR. And in that program, our AI platform guided all three decisions from biological insight on which target to pursue, how to design the molecule, and which patients to study. If you take a step back to molecule design, Sanofi recently optioned a potential first-in-class oral INI candidate. The chemistry challenge behind that was to design a single molecule that could inhibit two targets. And then when we talk about novel causal biology, we use the data that we have generated to build proprietary maps of biology and identify targets that may be driving disease. Genentech has now advanced the first neuroscience target from those maps, and we're working together on small molecules against it. That's the repeatability we're starting to see. The same engine of covering novel targets, producing new molecules, and generating evidence in patients. Behind the progress you just saw is one AI platform that connects biology, chemistry, and the clinic. We draw on more than 50 petabytes of proprietary data to make decisions about which targets to pursue, which molecules to design, and which patients to study. what makes that approach repeatable is how we learn we generate our own proprietary data which builds our models which then in turn guide the experiments we run and what we learn in the lab and in the clinic now then feeds back into those models so an insight from one program can shape what we test in the next let's start by looking a little bit more into the data from REC 4881 and REC 1245. Here, we're sharing a summary of the early clinical data from these programs. First, with REC4881 and FAP, remember there's no approved drug treatment. We previously have shown deep, durable reductions in total polyp burden. What's new is, first, we have updated this data to expand the adult population to 18 and over, and we continue to see these substantial reductions. In addition to that, we're seeing significant reduction throughout the GI tract, including the upper GI, which is a huge area of unmet need. In additional to that we're also seeing reductions in the number of larger, higher risk polyps. The safety profile remains favorable with mostly grade one or two adverse events and no additional discontinuations in this update. with rec 1245 as i mentioned we are seeing early single agent activity in heavily pre-treated patients with solid tumors vicky will walk you through the partial responses and the exploratory expansion cohort we have opened and again to say look the biological insight behind each program came from our platform and with rec 125 you can see how our use of the platform continues to evolve We're not just using it for biological insight on the target, we're also using it to design the molecule, and now it's helping us decide which patient populations to study. You can see that same evolution in our partners as well. Genentech optioned the first unexplored neuroscience target from our proprietary maps. Sanofi optioned a first development candidate from our collaboration, a potential first in class oral small molecule for INI. And each of these programs have over $300 million in milestones with high single to double-digit royalties. In total, in our partnerships, we have now achieved more than $535 million in cash inflows from our partners. What gives me confidence in the repeatability of this work is that in roughly two years, we have earned more than a hundred million across nine milestones tied to the progress in these partnerships. and i'd love to remind everybody that look underpinning all of this progress is how we use our data and the fact that we have one single engine one of the biggest rate limiting steps in science is the access to high quality relevant data and we have built a scientific data factory designed to generate this at scale our ai models draw on more than 50 petabytes of proprietary biological data to identify these novel potential causal targets. We then test those predictions experimentally and feed the results back into the models to guide the next experiment. That closed loop is how proprietary data can become a map. A map can then service a new target, and that target can ultimately become a new program that either we or our partner chooses to advance. We see also gains in productivity. Let's just take an example in designing molecules. In designing first-in-class molecules, we are now synthesizing 80 to 90% fewer compounds across our portfolio relative to industry benchmarks. In the clinic, ClinAgent can screen thousands of trial sites in minutes to help us find sites that actually see the patients we're trying to reach. We're seeing enrollment run about 30 to 60% faster than industry benchmarks. And we are advancing all of this work from a stronger financial position. We just completed our oversubscribed $200 million financing in October, bringing in leading institutional investors, and now expect our cash run rate to extend into 2029. At the same time, as previously communicated, we have lowered our 2026 cash operating expense guidance from $390 million to $375 million. And then now looking ahead for 2027, we expect that figure to come down even further to under $360 million. Before we go into a deep dive of the clinical programs, let me take you behind the scenes of a couple of our partnership programs and some of the updates to date. Let's start with the Sanofi announcement. it. We set out to design one oral small molecule that could inhibit two targets involved in inflammatory disease. Now, that's a difficult chemistry problem. Not only is it first in class, but a change that improves activity in one target could come at the expense of the other, and you still have to preserve the properties that actually allow this to be a chronically dose oral compound. For patients who may need this treatment for years, an oral option could make a meaningful difference in daily life. That's the kind of first-in-class design challenge we want to take on. Sanofi brought deep expertise in immunology and drug discovery, and our team used our AI platform to design the molecules, test them in the lab, and use what we learned to refine that next design. Sanufi has now optioned the candidate and will lead and fund as further development, with Phase 1 expected to begin in 2027. This is the first development candidate Sanofi has optioned from our collaboration and our sixth milestone across five programs together. That track record is what gives us confidence in the repeatability of our work. The option triggered a $10 million payment, bringing total upfront and milestone payments from Sanofи to be $144 million. in. Under the collaboration, each program has up to $343 million in potential milestone payments, plus double-digit royalties on net sales. Now, while with Sanofi, the challenge was to design one small molecule across two targets, with Roche, we started with a separate problem or with a different problem. We knew what cancer pathway we wanted to reach, but it had been long considered undruggable. Could our maps reveal a way in? Roche highlighted this work at its September Investor Day this year. Together, we mapped how cells responded when we altered individual genes and then exposed them to compounds. It's this gene-compound relationship that helped our biology engine to identify a new mechanism for acting on this pathway. We then advanced the most promising compounds and confirmed in vivo that they acted on that intended pathway. Much more work to come on here. And then in the neuroscience space, instead of knowing whether there was an undruggable pathway, the question was slightly different. The question was, can our maps of biology find novel causal targets that were previously unknown? This work is a great example of what deep collaboration looks like for us. We generated high-dimensional proprietary maps of geology from human neurons to uncover genes with unexpected links to disease biology. Our teams then worked side-by-side to prioritize the most compelling targets and then tested them experimentally, building that body of evidence around which ones are worth advancing. Genetic has now optioned the first target from that work, and small molecule discovery is underway that we're working on together. Importantly, the value of the collaboration doesn't stop with a single target. We are continuing to work in advance using the same reusable maps to generate and test additional hypotheses, creating the potential for multiple programs to emerge from that one shared data set. Now, what ties all these examples together is how we're using one platform across different programs and different disease areas. With Roche Genentech, we uncovered new biology that led to a novel target and more coming in neuroscience. With Roche Genentech in oncology, we found a new way to act on a pathway long considered undruggable. And with Sanofi, we designed one oral molecule to act on two targets in immunology. And in our own pipeline with REC4881 and REC1245 in rare disease and in oncologist, we're beginning to see those biological insights translate into activity in patients. now before i turn to the rec 481 data i also want to share an important board update today we announced that our board unanimously appointed fred hassan as chair fred haas repeatedly built scaled and transformed some of the most important companies in our industry including as chairman and ceo of sharing plow and pharmacy app he also brings a wealth of board perspective and experience from companies including Amgen, BridgeBio, and Prometheus. What matters to me is the perspective Fred brings at this stage of recursion. He understands firsthand what it takes to transform companies, to move companies from clinical proof through approval and launch, while building enduring businesses around them. And he also shares our conviction the data and AI are creating a new blueprint from drug discovery and development. Fred will serve as a non-executive chair, and I'm very excited to work with him as we enter the next chapter. I'm also grateful to Rob Hirschberg for his commitment to recursion and for the perspective he has brought on from many years as physician, scientist, and biotech CEO. Rob will remain on the board, and we will continue to benefit from his insights. Now let's turn to REC4801, our investigational oral MEK1-2 inhibitor for FAP. Yesterday in Denver, Dr. Lisa Boardman presented the updated tuple of results in the presidential plenary at CGA IGC. What makes this meeting particularly relevant to FAP is who's in the room. It brings together the genetic counselors who help families understand their risk, the specialized GI physicians and surgeons who take care of them, and the researchers working on new treatments. I'll share the highlights here. This update gives a broader and more complete picture of the program. It includes additional patients, where we have now expanded eligibility to adults age 18 and older. Importantly, we continue to see the depth and durability of response across and throughout the GI tract. After 12 weeks of treatment, 87% of evaluable patients had a reduction in total polyp burden. What stands out to me is the depth of the response and how quickly we're seeing these responses. About one in three patients had greater than equal to 65% total polyp burden reduction in just 12 weeks. And when we follow these patients for about 12 weeks after stopping treatment, we actually see about 85% still had a lower polyp burn than when they first started. The next thing that's really important is the activity we saw both upper and lower GI. Remember, I'd mentioned the high unmet need in upper GI polyp burden reduction. We see reduction throughout the entire GI, but median reductions of about 55% and 50% in upper and lower GI, respectively. And more importantly, that activity extended to larger, high-risk polyps. Of the eight patients who had polyps larger than 5 millimeters at baseline, six had fewer of those polyps at week 13, and four saw those counts fall by at least 80%. And when we look at safety, we see it favorable for chronic dosing with no new safety signals and no additional discontinuations in this update. Majority of the AEs that we're seeing are grade 1, 2. To put these results in context, consider what it means to live with FAP. We estimate that more than 50,000 patients across the U.S. and EU5 have been diagnosed with this disease. It's a serious, lifelong condition driven by loss of function in APC, a gene that normally helps keep cell growth in check. Patients develop precancerous polyps throughout the GI tract, hundreds to thousands, and there's no approved drug sheet FAP. Even after surgery to remove the colon, patients still face a lifetime of surveillance and life-altering surgeries. There's a psychological burden with that too. Every endoscopy brings another period of waiting for patients and their families. What will define this time? Will I need another operation? I want to spend a moment in the upper GI because this is one of the greatest unmet needs that we have heard post-colectomy from KOLs time and again. Look at the polyp on the left. It sits flat against the wall of the duodenum. That wall is thin, and removing such a broad-based polyp carries a risk of bleeding and perforation. When the disease can no longer be managed endoscopically, patients need surgery. These are life-altering surgeries to remove the duodenum, sometimes along with part of the pancreas. That's a major, major surgery with high morbidity and long recovery. And upper GI cancer remains a serious risk even after the colon has been removed. That's why we paid such close attention to whether REC-481 could reduce polyp burden in this part of the GI tract. It is that persistent and prolific disease burden that also helps the population we could ultimately serve. Our immediate focus is the estimated 37,000 patients across the U.S. and EU5 who are post-colectomy and require decades of lifelong surveillance and life-altering surgeries. We also have the potential to explore pre-colectomy patients following this immediate focus. Together, these patients and these populations underpin our estimate of a roughly 15 billion total addressable market. But ultimately, the opportunity is defined by what we can change for patients. Could a medicine, an oral medicine, meaningfully reduce this disease burden? Could it delay the need for another one of these multiple life-altering interventions or change the overall trajectory of lifelong surveillance? These are the outcomes that we're focusing on. So let's jump directly into the program. How did we get from APC loss to a MEK12 inhibitor? That was not an obvious therapeutic connection. It was an underappreciated biology that our platform surfaced. Our platform compared the changes we saw in images of APC-deficient cells with the effects of thousands of compounds to see, could they reverse the disease-associated changes to healthy? And while thousands of these compounds were screened, MEK-1,2 inhibition stood out as the top in terms of our AI model prediction, and REC-481 in particular produced one of the strongest reversals of the disease associated changes we measured. That's the unappreciated synthetic rescue we saw and what led us to license this particular molecule from Takeda to study in FAP. Now, while the platform serves as this novel insight, the biology also gave us good rationale, which is something that we're learning more about. Loss of APC is known for decades to activate beta-catenin signaling, which helps polyps form. Now, as these polyps evolve, additional mutations can also activate the MAPK pathway. What RET4801 is doing is interacting with both of those pathways. One, inhibiting the MAPPK pathway, which is downstream of the additional mutations that these polypts accumulate. In addition to that, given the crosstalk that is known between MAPPk pathway and beta-catenin, MAC1-2 can also dampen some of the growth signals driven by APC loss. It is that platform insight that led us to test a MEK1-2 inhibitor in patients with FAP for the first time. So what we see when we tested that hypothesis in patients, this tuple of updates includes additional patients, as I mentioned, and we've expanded that study eligibility to patients 18 and over. Each bar that you're seeing here represents one patient. And after 12 weeks of treatment, 13 of 15 evaluable patients, that's about 87%, had a reduction, deep, deep reduction in total polyp burden. So next, what we looked at is what happens if we follow the patients for 12 weeks on treatment, and then we take the drug off and follow them off treatment. Essentially, what you see is the rapid reduction in polyps in the first 12 weeks. And what's interesting is even when they're off drug, you see majority of the patients, about 85% or so, the polyp burn still remains below baseline. For patients living with a disease, where they may need to manage it for decades, how much time they spend on treatment matters. The possibility of dosing flexibility could therefore be quite meaningful for patients, and the persistence we're seeing off treatment gives us an important signal to explore as we think about long-term management. We also wanted to know what happens to the larger, higher-risk polyps. Here, we're counting polyps greater than 5 millimeters. As you can see, eight patients had at least one at baseline. And by week 13, six of the eight patients had fewer of these larger polyps and four, so their counts go down by 80%. The individual counts really puts that into perspective. Two patients, each went from more than 90 polyps, and when I say 90 polyp, it's 90 larger polyp to just one. Another went from five to none. In these three patients, these counts also held at week 25 when they were off treatment for 12 weeks. Now moving from the overall polyp burden, we will now break it into upper and lower GI. What we see is reduction in both the upper and low GI. And in this slide specifically, you're looking at the upper GI polyp burton reduction. Remember, this is one of the greatest areas of unmet need post-colectomy. And just after 13 weeks, we see a 92% of the patients had a reduction in their upper GI polyp burden. Well, one out of two, so about 65 equal to greater than 65% reduction in the polyp burn, and two patients had near clearance of 98% or greater. Now, let's again look at what happens to these patients when we take them off drug for 12 weeks. 11 of the 12 evaluable patients, or about 92% or so, still had upper GI polyburden reduction below baselines. That persistence matters. In the natural history that we've seen before, spontaneous regression was not something that was observed. Polyburden generally increased over time. And the fact that most of these patients remained below where they started after three months off treatment is very encouraging. These images also show what the change looked like in a patient with deep reduction. This patient had about 98% polyp burden reduction. On the left, you can see the polyps in the duodenums before treatment. On the right is the same part of the duodenum at week 13. Across the GI tract, this patient's total polyp burden measured by adding the polyp diameters fell from 1,344 millimeters to just 32 millimeters after 12 weeks of treatment. That's a 98% reduction. And of the 96 polyps that measured more than 5 mm at baseline, only one remained above that threshold. How do clinicians put this in context? One measure they use is the Spiegelman stage scoring. This grades the severity of duodenal polyps from stage 0 to stage 4, which is the most advanced. It takes into account the number of sides of the polyps, as well as what the pathologist sees under the microscope. So clinicians use that information to determine how often someone needs surveillance and also what type of intervention, including multiple types of surgery. What you see here is at week 13, six of the 12 evaluable patients, about 50%, actually downstaged on their Spiegelman score. Four went from stage 3 to 2, one went from state 4 to 2 and another went from stage 2 to stage 0. And what's even more interesting is of the six patients, four had reached their week 25 assessment after 12 weeks off treatment, and all four remained at least one Spiegelman stage below baseline. The remaining two patients had not yet reached their weak 25 assessment at the time of cutoff. And now let's finally also look at the lower GI tract. Again, these are post-colectomy patients, which means it's really focusing on the remaining rectum are the ileal pouch. 12 weeks post-treatment, we see 82% had a reduction in their lower GI polyp burden. And again, you see a few patients that had deep, deep reductions of 88% and 100%. And again when you look 12 weeks after stopping REC481, 7 of the 10 evaluable patients had lower polyp burn in the GI below their baseline. What encourages me across the totality of the data we're seeing is the consistency. We saw reductions in both the upper and lower GI tract. We see reductions in the lower polyps that are difficult to manage and are higher risk. And we see that even when these patients come back for an endoscopy three months after stopping treatment, most still had less polyp burden than they had at the start of baseline. Next, let's look at safety. At 4 milligrams QD, 21 of 26 patients, safety-evaluable patients, so that's about 81%, had grade 1 or 2 treatment-related side effects. The most common was an acne-like rash. Four patients had a grade 3 event related to treatment. Two of these are skin reactions, and two had elevations in CPK detected on blood tests. We saw no grade 4 or 5 treatment- related AEs. In terms of discontinuations, we saw four patients stop treatment because of grade 1 or 2 events. Two of these cases involved pre-existing conditions, while the other two patients had stopped for grade 1 diarrhea and grade 2 rash. Most of the discontinuations occurred early in the study. Three of the four had been reported in our first readout, and there are no additional discontinuations we see in the latest update. As the study progressed, we have refined how we work with sites to recognize and manage side effects early, including the increasing use of measures for rash. We will carry that experience into our next study. So let me bring this back together for what it means to live with FAP. Even after having their colon removed, patients face decades of surveillance and repeated and invasive procedures. Pallets in the upper GI tract can be especially difficult to remove, and patients have no approved drug to treat the disease. In Tupelo, we have expanded eligibility to adults 18 and over. After 12 weeks in oral RET481, we saw deep, deep reductions of the polyps, which are then sustained when the patients are off drug. And we're also seeing fewer of the larger, higher risk polyps. For patients, the question is whether these reductions can change the course of their care. Could an oral therapy give someone more time between not only these endoscopies, but also surgeries? Over decades of living with FAP, having an oral drug could make a meaningful difference. We're in ongoing discussions with the FDA on the design of the registrational study and based on regulatory alignment, we're targeting initiation in the second half of 2027. With that, I'm going to hand it over to Vicky. She'll bring in KOL and patient perspectives, which are especially important as we think about these data, what they could mean in the context of lifelong disease management. She'll then walk you through the REC 1245 program and the early clinical data that we're seeing there. Thank you, Nijat, and welcome everyone to our KOL panel. I am pleased to moderate today's discussion to help contextualize the new Phase II data for REC4881 presented at CGA IGC to explore its relevance to the current unmet medical needs in FAP. Joining us today are two esteemed global FAP specialists. First, we have Dr. Evelyn Decker, Head of the Expert Clinic for Familial and Hereditary Polyposis and Colorectal Cancer and Professor of Gastrointestinal Oncology at the Amsterdam University Medical Center. We are also joined by Dr. Bryson Katona, Director of the GI Cancer Genetics Program at the University of Pennsylvania Perelman School of Medicine and Tupelo Study Investigator. Dr. Decker and Dr. Katona thank you both very much for taking the time to join us And Dr. Decker, I'll start the first question with you. For those less familiar with FAP, could you walk us through the natural history of the disease, how patients are managed today, and where the greatest unmet needs are, given that there are no approved therapies? Yes. So looking at the FAP patients and their disease course, most of the patients will be diagnosed at a young age because we know family members are having FAP and they will be genetically tested. we advise around age of 12. So that will be at that time, they will come to the pediatrician and they will be scoped. They will be undergoing a full colonoscopy in our hospital. And we will look at the disease burden, which means we will see how many polyps are already present in the colorectal. From then on, they Will be checked upon regularly throughout childhood, usually two yearly depending on the burden it might be more frequent and what we will by time do is reject polyps mainly from the rectus sigmoid because taking them out from the whole colon will be difficult because it's too many polyps because they will they will by time develop hundreds to thousands colorectal polyps which might if we would not intervene develop into cancer. To be sure we can prevent colorectal cancer, we'll undergo surgery so that part of the colon will be resected. So at age 18, they are transferred to the adult gastroenterologist, usually in a transitional phase, and we will follow the patients further. Again, if they're not operated yet, which might well be the case, we will check upon the full colon. If not, we will do the end of the colon and and approximately from age 25 we will also make sure we um we evaluate the stomach and the duodenum because not only in the colorectum but also in the um in the duodenium and then later also inthe stomach they might also develop precancerous lesions so so again polyps. So lifelong checkups, necessary polypectomies or other interventions, maybe even surgery to make sure they have a long life. Thank you. And you did speak about the early management of the disease in the colon and the need for colectomies, as well as how that shifts to more of an upper GI disease burden as well as in the retained rectum. Can you also tell us why does upper GI disease become such an important clinical challenge post-colectomy and why is it more difficult to manage in some cases relative to the colonic disease? So yes, patients have an increased risk for duodenal cancer and gastric cancer and that is quite a challenge for us as gastroenterologists to battle that because pre-neoplastic lesions, so adenomas, develop in the small bowel, but generally they are more difficult to resect endoscopically, and also endoscopic resection comes with more risks for complications. So we try to, however, to do that endoscópically, because otherwise they might need surgery to prevent cancer, And duodenal surgery really is big surgery with major risks for both morbidity, but also in the end mortality. The problem also is that after surgery, the risk in the small bowel remains. And it might be also more difficult to inspect the new area at risk properly. So yes, there's definitely a challenge in the duodenum, specifically with the morbidity of the operation is more difficult. Thank you. Dr. Katona, turning to the REC 4881 Tupelo data, we saw reductions in upper GI polyp burden in 92% of evaluable patients. And about half of those patients had deep reductions of about 65% or more and rapid reduction within that 12-week treatment window. From a clinician's perspective, how meaningful is the magnitude of polyp burden reduction like this, and how might that affect decisions about patient care? Thanks, Vicky, for the great question and for the opportunity to discuss this data. You know, when we think about reduction in polyp burn and what that means clinically, you know, I think oftentimes what it means clinically is a little bit different from what people want to see from a regulatory standpoint. And unfortunately, you know, that polyp burden is not a regulatory endpoint that's typically used. But from the clinician's standpoint, it's incredibly meaningful. Most of the decisions that we make for patients with FAP are related to the polyp burden. And so like when we're determining when someone will go for surgery, how soon they have to come back for another, you know, upper endoscopy or colonoscopy is typically dependent on what type of polyp burden we're seeing on the exam. So, clinically, I think, you know, the polyp burn and seeing reductions in the polyps burn can have a major impact for patients. So just to give you an example, so say somebody who is getting upper endoscopies because of duodenal polyposis. You know, if the number of polyps that you're seeing in the duodenum starts to reduce, they're starting to get smaller. I think a lot of clinicians may feel comfortable, you know, potentially extending out the interval at which an individual would undergo an upper endoscopy. So I think from the clinical side, the polyp burden and reductions in polyp burden, especially large reductions in polyp burdens, you know, do lead to meaningful clinical changes for our FAP patients. Great. Thank you for that. One particularly interesting finding was that 92% of evaluable patients with upper GI polyp-burden reductions remain below baseline after 12 weeks off treatment. How do you interpret that durability or sustained effect of the drug? And how does durability affect how you might approach management of this lifelong disease with patients? It's a great question. I think that the, you know, the durability of a reduction in polyp burden is, you Know, an important metric to understand for any type of chemo preventive agent in FAP. You know, from my perspective, clinically, you seeing a durable response is always very encouraging. I think the dream chemopreventive agent for FAP is one that somebody doesn't have to take lifelong and potentially could be taken for a shorter amount of time or maybe potentially with intermittent dosing patterns so that individuals could see a response, have durability of that response. But I think it is very encouraging first sign for this drug. Thanks, Dr. Katona. I'd like to move on to the safety data. Dr. Katona, the safety date has showed that most patients, about 80%, had treatment-related AEs of only grade 1 or 2, and those included adverse events such as rash, including acneiform dermatitis, diarrhea, and left ventricular ejection fraction changes. Four patients had grade three events, and there were no events above grade three that were treatment-related. Given your experience managing patients with FAP, how do you think about the benefit-risk profile for REC4881 in this setting? Yeah, it's a great question and an important question to think about the risk-benefit profile and how any side effects would be tolerated by patients. I think a patient's willingness to tolerate side effects is a very personalized decision based on the patient, but then also based on how advanced or at what stage their FAP is at. So just to give you an example scenario, if you have a patient who maybe has a very attenuated FAP phenotype, they're having a couple polyps that form in their colon every year and they're getting their colonoscopy with complete polyp clearance, that individual may have a low threshold to tolerate any side effects from a medication since their polyps are being completely managed by colonoscopy. But if you go to the other side, if you go to somebody who has, you know, very severe FAP with, you know, advanced stage duodenal polyposis, say, for example, Spiegelman stage 4 duodenopolyposis and, you know, they're getting upper endoscopies every three to six months and, you know. They're right on the cusp of, you know, potentially needing a, as Evelyn mentioned earlier, a major duodenum surgery for resection. You know, I think that individual is going to have a much higher tolerance for side effects. One, to potentially avoid a potentially morbid and life-altering large surgery, but then also potentially to have to cut down on such a high burden of endoscopic monitoring. One other important point to think about side effects and patient tolerance is, are we developing strategies where patients can, you know, essentially manage these side effects or take proactive steps to prevent them. And so I think that's the other important thing to think about for side effects, especially when you know what the side effects are, and especially if it's kind of a narrow window of side effects where you potentially could either prevent or kind of aggressively treat them to reduce their impact. Thank you for that. I think it's a really important point and speaks to the need for educating both the patients themselves as well as the physicians who are treating them as you bring new therapies into the market. My next question is for both of you. I'll start with you, Dr. Katona, and then you, Mr. Decker. As people learn about this space, they often ask whether there is a threshold of polyp burden reduction that would be clinically meaningful. For example, if you have a reduction, but you still have residual polyps, would that change how you treat the disease? What are your thoughts about that in clinical practice? I guess I would say that, you know, any reduction in polyps is a good thing in our mind. And, you Know, I think that, You know, the fact that polyps don't go away is also okay as well. Those of us that take care of FAP patients, you Now, we know they're going to have polyps there. And essentially, you know, we follow them to basically make sure that these polyps don't progress to cancer down the road. But I think when you're thinking about reduction in polyp, I don't think you need to think about it as all polyps have to be eliminated. But then also to get to your point about threshold, you Know, I don' think that there's a specific threshold that we expect. Because again, I think that often is a personalized thing as well. So if you have, for example, somebody who has two polyps in their, in their rectum and those polyps decreased by 80%, you know, that's, that'S great. But, you know I would be more excited if I had somebody with a hundred polyps and their rectums that all decreased by 50% in, in size. And so I think it's, you know any polyp reduction is, is, you a good thing to see, but I don't, I think it's very difficult to put like a specific number. Cause I think a very personalized scenario based on the patient. Great. Thank you for that. And Dr. Decker? Yes, I would like to add that I agree about the personalized checkups we do. It's not a one-size-fits-all. We scope everyone one yearly and see what happens. So if the polyp burden reduces, usually that means that we can prolong intervals at which we scope. And maybe even there could be not only a regression of the polyps present, but also less growth of new polyps, because we know during the life of those FAP patients, new polyps keep coming, right? So if that would be a combination, reduction of the size of any present polyps and less new polypts, that would translate into, I think, a lot of benefits for the patients. Great. Thank you, Dr. Decker. This question is also for both of you, and this time I'll start with Dr.Decker. To recap, we talked about the intensity of surveillance to decisions about polyp removal in major surgery, which is driven by the extent and severity of polyp disease. In closing, how significant is the unmet need for medical therapy and FAP for post-colectomy patients, especially patients with upper GI disease? Oh, it's absolutely a huge unmet need for these patients, for these FAP patients to have medication as a potential treatment because they suffer a lot from the big burden of surveillance as well as the risk for having cancer, both in the retained rectum or maybe in the pouch as well as upper because the consequences upper might be even larger if we we get to the stage where um preventive polypectomies are not possible anymore and they need surgery and again more checkups after it never stops during their life thank you very much dr katona yeah i can't can't agree more um i think evelyn's uh you know use of it's a huge need is uh you Know that is spot on People have been doing research in the chemo prevention space in FAP for decades. And we still don't, at least in the United States, we still don't have an agent that is FDA approved. And so we're FAP patients, we're diagnosing them. Our numbers of FAP patience are increasing. We're still having to send these patients for major surgeries. We're doing a ton of scopes on these patients. And so the need, yeah, the need is very large, and it's only going to increase over time as numbers of FAP patients continue to increase. Thank you. I'll close this out by asking if there's anything else that either of you wanted to mention that we haven't yet covered. And I'll just add on that, you know, I think that, this preliminary or early data is, you know, very exciting and promising. And I'm definitely, you know, very intrigued to see how the rest of the results from this study turn out. And, you Know, I know the FAP community has their fingers crossed and are very interested and hopeful as well. Well, Dr. Decker, Dr Katona, thank you both for sharing your invaluable clinical perspectives on the management of FAP and helping us to contextualize the Tupelo data for REC4881. one. We truly appreciate your time and expertise today. Having heard the clinical and scientific perspective, it is now important to hear directly from individuals navigating the daily realities of FAP. We will now move on to our patient panel. I am looking forward to guiding today's conversation. This panel offers a special opportunity to step back from clinical data and hear directly from individuals living with FAP, allowing us to listen, learn, and better understand their daily experiences. Joining us today are Laura and Jesse Laster, who navigate FAP as a family. Jesse was diagnosed as a teenager and underwent a colectomy shortly afterward. To manage his ongoing cancer risk, he later required a complex Whipple procedure. Today, Laura and Jesse are raising two children who also inherited the condition, and they are here to emphasize the need for continuous, lifelong care. We are also joined by Lindsay Huff. Lindsay grew up knowing FAP would shape her life, as she and her sister inherited the condition from their father. After undergoing a colectomy in her teens, Lindsay faced significant surgical complications as did her sister, who now requires a Whipple procedure. Lindsay is here to share her journey and show younger individuals that FAP does not have to hold their back. Thank all of you for being here today. The first question is for all of vous, but Jesse, let's start with you. FAP has been part of each of your lives and families for a long time. Can you walk us through your experience from when FAP first entered your life through your colectomy? Well, my journey with FAP started around the time I was eight years old. I wasn't diagnosed at that time, but that's when I started really seeing my sister go through her journey or through her surgeries related to FAP. And then it was mainly thinking about thinking to the future when I would have to kind of go through similar situations. So as you mentioned before, I was diagnosed at 15. I had my own colectomy in J pouch, 16 years old. And that's really kind of the first part of my journey was FAP. Thank you. Lindsay, maybe we'll move to you and then Laura, I'll circle back to you. Sure. So my experience with FAP has been lifelong. Started when I was born. My parents knew that it was likely that I would have FAP, but I know I believe it was either before or shortly after birth, I was genetically tested and found out I had the gene mutation for FAP. And my journey started around age 10 with getting my first colonoscopy and finding out that my polyp burden was significant enough that I would ultimately need my colectomy at age 10. Wow. Thank you. Thank You, Lindsay. And then, Laura, as a family member who's had to navigate this, can you tell tell us what that experience has looked like for you? Yes. So what the experience with FAP has looked like for me has really started when Jesse and I met in college and explained that he had this condition and a little bit about it. But it was kind of seemed like I had this done and then we were good. Now I am healthy. But actually, very quickly after we met, within a few months, actually, he had a bowel obstruction. And I don't know, maybe that was my first clue that, you know, really the whole life with FAP is not just one and done thing after somebody has the colectomy procedure. Thank you. And so maybe we'll talk a little bit more about that now in life after colectome. Jesse, I'll start with you again. And then, Lindsay, many people assume that when someone has a colectomy, FAP is largely taken care of. I think, Laura, as you were just saying. What has been your experience, Jesse, in the years since colectome? And how has your disease been managed over the years? I'd like to start to kind of back up to before the colectomies. Whenever I did, or when I found out that I had FAP, it was very much the thought was that you just, you get diagnosed with FAP. You have a colectomy and then that takes care of everything. I remember maybe in the following years after my colectomies, bowel obstructions became an issue due to scar tissue from the surgery. But even beyond that, I had such a high polyp burden in my stomach that doctors started getting concerned with that. And then some of the polyps in my small intestine and especially the duodenum, that became more of an issue. As mentioned before, I've had a Whipple procedure because I had one polyp in particular that had what they call high-grade dysplasia or cancer in situ, they call it. They're just cancer located down to that one polyp. So I've since learned it's an ongoing maintenance for FAP. Ongoing management throughout your life. Thanks, Jesse. And Lindsay? My experience after my colectomy at age 10, our doctor had told us that every case of FAP is a little different that sometimes FAP just sticks to the colon and sometimes other families have had concerns with it going to the upper GI. Um, and so our management was doing upper and lower endoscopies every year. So after my colectomy, um, ultimately had another surgery at age 14 to have a J-pouch placed, and then ultimately had some complications from those surgeries that resulted in a small bowel obstruction. Thanks, Lindsay. I'll start this next question with you. How has monitoring or treatment of the upper GI tract factored into your experience with FAP? And how has that shaped the way that you think about your long-term health? sure um for me um i would say monitoring has been fairly stable with my upper gi i do have a significant amount of polyps but they're not staging anywhere super significant where there's concern at this time for any further surgical management my sister has had a pretty significant upper GI burden. She's had multiple duodenum polyps. And at our last scope that we had in August of this year, they found five large duodenal polyps that they staged at stage four. So ultimately, she's getting a duodenectomy, which has been described to us as a pancreas sparing Whipple procedure. And she'll be having that within the next week. you've mentioned that your sister um has an upcoming whipple procedure and over time you know as she's been scoped as the upper gi has been scoked did you or she see this coming i'm wondering did she have time to sort of mentally prepare herself or was it kind of a more sudden i i guess i'll start with she didn't really have a lot of time to prepare for this being a possibility. Last year, she had a upper endoscopy done, and it was found that she had a pretty large duodenal polyp. They didn't say whether it would come back or not, but they ended up doing a procedure to remove that polyp and place a stent. Fast forward to this year, she's got five polyps that are long and kind of branchy, and there's risk of obstruction. They ended up staging them, and they were looking like stage 4 polyps, which is about the worst you can get before they're officially cancerous. And basically, the only thing presented to her was this procedure. Thank you. And then, Jessie, perhaps answering the same question, how has the experience of having SAP and the upper GI disease as well, How has that shaped how you think about your health over the long term? I guess the way that I see managing my health with FAP has changed over the years. Like I mentioned before, from going from, you know, it's taken care of and don't need to worry so much about it. Having scopes every few years was kind of thought to be the way to manage it. Um, it went to having scopes every six months. Uh, so a lot more complicated. Um, certainly having, uh, the Whipple procedure and having, and having the cancer diagnosis, um, definitely changed the way I see that. Um. I talked to my doctor about, you know, what are the next options if I get cancer again? And I, you Know, was curious about, You know, can the Whipple be done a second time? And he said, No. So there's a lot of concerns with ongoing management. So. Thanks, Jesse. For this next question, Jesse, I'll start with you again, then Lindsay, and then back to you, Laura, as well. Jesse, when high-grade dysplasia was found and a Whipple procedure was suggested, what were your considerations in terms of making the decision to move forward? I think specifically for the Whipple's procedure decision, there didn't appear to be much of a decision. um the the the polyp that was found with high grade dysplasia uh it was presented to me as the only way to take it out was to take out the duodenum and the whipple procedure was the procedure to do for that um there were other decisions that i had to make in my journey um you know i've had doctors tell me that i needed to have a permanent ileostomy or even revisit my J-pouch. And even more recently, I had a doctor suggest that I may have to have my stomach removed. There's been a lot of decisions to make in my journey. And it's been a struggle, I guess, to manage quality of life and what is the best choice to make to manage my FAP. And then, Lindsay, you've had some significant complications from some of your surgical procedures. Are you able to share some of those experiences? And then how does that influence how you think about any additional procedures when they're recommended? Some of the serious complications, the major one that I've had is from my colectomy and my surgery to get a J pouch. I had that temporary ileostomy and had it reversed. In 2016, I was a freshman in college and I had adhesions from those previous surgeries. I was in my dorm room shower and I bent over to grab soap and my bowel flipped. And so that caused a small bowel obstruction. I was emergently ambulanced to a local hospital. We didn't know whether they would know anything about FAP or anything going on with my health. and ultimately had 70 centimeters of my small bowel removed. I had another temporary ileostomy placed from October of 2016 to May of 2017 when I finished my freshman year and ultimately have that reversed again. Ongoing complications, I don't really have much bowel left at all. So there's a lot of issues with malnutrition, absorbing nutrients from the food that I'm eating. um and you know continued concerns for adhesions and potentially you know looking to avoid another bowel obstruction that could happen um and ultimately there's not enough bowel to reverse that in the future and i would have a permanent ileostomy for the rest of my life so um you know thinking about knowing that complications are a possibility because they've already happened um you know if there was another procedure recommended i believe it would be an emergent procedure and there really wouldn't be much decision it would just be basically life sparing for me thank you for sharing that this one's for all of you again um thinking about your own experience and your family's future, what would a medicine for FAP need to do to make a meaningful difference in your life? And when you think about the future of FAP care, what would meaningfully change your daily life? I think as far as my medical care goes, I would see a medication that reduced the amount of procedures that I had to do would definitely help with my care, you know, reducing polyp burden and especially the polyps that are concerning to my care team. That would be a great advantage, I think, to my medical care. An extension of that would be, you Know, for my own two children, they're still early on in their journey. They haven't had to have any surgeries yet. I would see a great benefit to, you on their medical care, even to be able to reduce all of burden and eliminate all of burden potentially for them and then reduce or eliminate the need for surgery for them. So kind of an echo of my care needs would be on them too. Thank you. Laura, anything you'd want to add to that? Yeah, I mean, just looking at a medicine that could contribute to less polyp burden, as Jesse said, less procedures having to happen. And I mean, where we live, we're driving four hours one way to do this. It's expensive hospital that we go to. It doesn't accept all insurances. And so there has been just life considerations and having to do less ongoing procedure maintenance. Besides, of course, I, you know, what, what you're around long time. Also, just like a expense issue, too. I mean, it is something we need to do, but it's just something we have to plan for as a family. So if there were less requirement of monitoring and avoiding so many procedures, all of which come with risks, that would be fantastic. Thanks, Laura. Lindsay? I have to echo a lot of what Jesse and Laura said. I think a medication that could reduce polyp burden or potentially eliminate polyp burden would be beneficial to prevent any future complications for myself or my family. Thinking to the future, my wife and I have started thinking about starting a family and what does that look like? I would love for my children to not have to go through the same experiences that I've had to go though. And echoing again what Jesse and Laura talked about with the financial burden that comes with that. You know, we my family flies across the country to go and receive specialized care. There's a significant amount not only for travel expenses, but the procedures that we're having to have done. I think that would lift a lot of the financial burden that we have to think about when we're Having medical care done as well. And I think a medication that could, you know, potentially lessen the amount of monitoring that we have to have could really help as well. Along with the issues with insurance, you know, we've talked about facilities take a lot of different insurances, but they don't always take all insurance. And so this year specifically, I am in South Dakota and I have my healthcare company's insurance plan even though my insurance was going to be accepted as in-network because they didn't accept the insurance my insurance normally they take 50 of what you're going to ultimately owe to the medical facility up front which for me the total that they were estimating was around $15,000. And as a 28 year old, I don't have $15000, let alone much more under that available to give up front. There's a lot of financial hoops that you have to navigate and jump through and advocate for yourself for, especially when you need that specialized care. Lindsay, Laura and Jesse, thank you so much for sharing your stories and giving us a window into the daily realities of living with FAP. Hearing your experiences firsthand brings such important perspective to our discussions and reminds us exactly why this work matters so much. We truly appreciate your time today. I will now move on to talking about our REC 1245 program in solid tumors. REC1245 is an investigational, orally administered, and potentially first-in-class molecular glue degrader of RBM39, a master splicing regulator. Degradation of RPM39 disrupts the splicing of stress response and DNA repair genes that cancer cells depend on for growth. The molecule and the initial insight came from our engine. Our phenomics found that RBM 39 degradation phenocopies CDK12 loss while sparing the CDK13-associated liabilities that have made that biology so difficult to drug. We screened 204 compounds to achieve a development candidate in 18 months, compared to an industry benchmark for small molecules of roughly 2,500 compounds over four years. In dose escalation, we are seeing evidence of clinical activity. Three partial responses, two confirmed responses in endometrial cancer, and one unconfirmed response in hepatocellular carcinoma. Disease control rate at eight weeks was 91.7%, 11 of 12 patients, at doses of 45 milligrams and above. We've now selected 45 milligrams once daily for expansion, a dose with no serious treatment-related adverse events and no dose reductions reported. it. Let's look at how recursion's engine got us here. The heat map on the left is an actual platform output. RBM39 clusters phenotypically with CDK12 and not with CDk13. That's the insight. CDK 12 loss has been understood as a vulnerability in genomically unstable cancers for a long time, but CDK12 inhibitors have struggled because they hit CDK13 too. RBM39 gave us a way into this pathway that others hadn't seen. In the middle, RBM 39 ensures proper splicing of critical stress response and DNA repair genes. In non-clinical models, RPM39 degradation leads to disrupted mRNA splicing and impaired DNA damage repair and cancer cell death. REC1245 is highly selective and orally bioavailable and drives rapid RBM39 degradation in human PBMCs within 24 hours, with significant tumor regression seen across multiple xenograft models driven by replication stress. The potential opportunity is broad, with more than 100,000 addressable patients a year across the US and EU5, spanning hard-to-treat tumors like endometrial, HCC, and ovarian, and transcriptionally driven cancers, including pediatric tumors like Ewing sarcoma and neuroblastoma. We see two complementary development strategies, monotherapy in tumors that are intrinsically primed and vulnerable, which is where we are today in dose escalation and now expansion, and combination where REC-1245 could create vulnerabilities alongside standard of care and potentially move into earlier lines of treatment. Our phase one dose escalation enrolled patients with unresectable or metastatic solid tumors or relapsed refractory lymphoma who've progressed on available therapies. Six cohorts were enrolled on continuous daily dosing. The primary objectives are PK and safety. Antitumor activity is a secondary objective. Based on the results of the dose escalation, we have selected 45 mg daily for our expansion cohorts and are currently enrolling these, including one in endometrial cancer. I'll walk through safety data and evidence of antitumOR activity on subsequent slides. In terms of safety, REC-1245 was well-tolerated at doses up to 45 mg daily. The 65 mg daily dose exceeded the maximum tolerated dose, with 3 of 4 patients enrolled on that cohort experiencing dose-limiting toxicities, including stomatitis, neutropenia, febrile neutropena, and anemia. The most frequently reported treatment-related adverse events across all doses were fatigue and anemia at 30% each, followed by nausea, thrombocytopenia, and stomatitis. About 27% had a grade 3 or higher treatment- related event, with the most frequent being anemia. At the 45 milligram dose, which was selected for expansion cohorts, the most common treatment- to fatigue, anemia, and nausea. We saw no dose-limiting toxicities and no serious treatment-related adverse events. The two grade 3 events of that dose were elevated creatinine and hypokalemia. Turning to activity, this is a heavily pretreated patient population with patients having received between two and eight prior lines of treatment. There was no evidence of antitumor activity at doses below 45 milligrams. Across the 12 responsive valuable patients who started at 45 or 65 milligrams, 11 of 12 had evidence of disease control defined as an initial response of SD or better at eight weeks. Four of the 12 remain on treatment. Among these 12 patients, there were three partial responses seen here on the right. Two confirmed responses in endometrial cancer at 38.2% and 48.9% reduction, and one unconfirmed response in hepatocellular carcinoma at 55.9%. The two patients with endometrio cancer who have responses continue on treatment while the HCC patient has discontinued. I'll now walk through case studies of the two confirmed responses. First, a 70-year-old woman with recurrent progressive stage 4 high-grade serous carcinoma of the endometrium, which is p53 mutant, HER2 non-amplified, and microsatellite stable. She's had four prior lines of therapy, including platinum chemotherapy, a TKI, immunotherapy, and an antibody drug conjugate. She started at 65 milligrams, interrupted for grade 2 oral and abdominal pain, and restarted at 45 milligrams. She has tolerated the 45 milligram dose well and abdominal pain resolved. At the week 9 CT scan shown on the right, we saw a partial response with 32% reduction in target lesions in the lung, liver, and pelvis. The response was confirmed at week 17 with a 49% reduction. She's currently asymptomatic from her disease and remains on therapy. Next is a 54-year-old woman with recurrent progressive stage 4 endometrioid carcinoma, which is p53 mutant, HER2 amplified, ER positive, and MMR proficient. She had received seven prior lines of therapy, including platinum and taxane chemotherapy, a VEGF inhibitor, her two-targeted therapy, immune checkpoint inhibitor, a tyrosine kinase inhibitor and antibody drug conjugate, and investigational CAR-T therapy. She started REC-1245 at 45 milligrams. At her week 9 radiographic assessment shown on the right, she had a partial response with a 33.9% overall decrease in target lesions, including periportal and mediastinal lymph nodes. At week 13, that response was confirmed with a 38.2% reduction in target lesions. She has tolerated the drug well with predominantly grade 1 and 2 GI adverse events and laboratory abnormalities, and she remains on treatment. As I mentioned earlier, we are currently enrolling an expansion cohort of patients with endometrial cancer who have disease progression following available therapies. Endometrial cancer is the fourth most common cancer in women in the U.S., with roughly 68,000 new cases expected this year, and treatment options are limited in the metastatic setting after first-line therapy, especially for the roughly three-quarters of patients who do not have HER2 amplifications and are therefore ineligible for a HER2-targeted ADC. Five-year relative survival with distant stage disease is around 20%. Based on the mechanism of action and the activity seen to date with REC-1245, we see opportunities for 1245 as a monotherapy, including potentially in the post-ADC setting and potentially in combination with existing treatments for endometrial cancer, including immunotherapies. These are hypotheses to be tested, and REC 1245 is investigational. We expect preliminary data from this cohort in the second half of 2027, and we're also exploring additional tumor types in dose expansion. I'll now pass it to Ben Taylor for further business updates. Thank you. Earlier this month, we completed an oversubscribed follow-on offering with $200 million in gross proceeds. Over 90% of the financing came from healthcare-dedicated specialists and mutual funds. that did not own recursion prior to the financing. We were able to access this new pool of knowledgeable, long-term focused investors based on the strength of our pipeline data, demonstrated repeatability of the AI engine, and continued operational discipline, including the net proceeds from the offering. We had $749 million in pro forma cash and equivalents as of September 30th, which does not include the recent $10 million milestone from Sanofi. We have extended our runway into 2029 through not only financing, but also continuing to concentrate capital on the highest value operations. As I've said in the past, we want to continuously increase the impact of every dollar we spend. In this quarter, we are in a stronger position to do that than ever before. Our 2026 full-year cash operating expense guidance of less than $375 million, excluding partnership inflows and one-time expenses, represents a nearly 40% reduction from comparable 2024 pro forma expenses. We are going to continue our year-over-year efficiency gains. In 2027, we expect cash operating expenses to be less than 360 million. We fundamentally believe that a dollar invested next year should achieve more than a dollar today. Through adoption of technology and disciplined, data-driven management, we expect to keep lowering OPEX while aggressively investing in the best of our pipeline, partnerships, and AI engine. We are concentrating our investment where we see the clearest path to value. In our pipeline, that means prioritizing highly differentiated, wholly-owned programs, and also knowing that we shouldn't try and do everything ourselves. Since 2024, our partnerships with Roche and Sanofi have produced more than $100 million from nine progress-based milestones, bringing the total proceeds from partners to over $535 million. Internally, we build and test our AI models on real pipeline programs so that we can efficiently identify which technology investments are likely to have real-world impact. Our in-house supercomputer allows us to move quickly while still controlling compute expense. Finally, our investment over the last decade to create more than 50 petabytes of multimodal proprietary data gives us a large and reusable asset that creates unique insights beyond what is publicly available. With a stronger balance sheet and lower cost base, we believe we have the time and resources to deliver multiple important milestones across our pipeline and partnerships. And with that, I'll turn it back over to Najat. Thanks, Ben. Now let me bring it all together. The financial strength you just heard about from Ben gives us the ability to keep investing behind programs and capabilities where the evidence is the strongest. And this slide shows just what that means across the engine that we talked about at the beginning of the call, discover, design, and deliver. We now have delivered tangible proofs across all three. In discovery, Roche Genentech advanced the first unexplored target in neuroscience from our maps. In design, Sanofi optioned our first-in-class development candidate, which is an oral molecule in INI. And in the clinic, REC481 and REC1245 are generating encouraging evidence in patients. Now, the focus is to do it again. In discovery, we're working towards additional targets with our partners and expanding our proprietary maps of biology across additional disease areas. In design, the candidate that Sanofi just optioned is expected to enter phase one in 2027 with potential for additional partner milestones in 2027. And in the clinic, we expect to update our FDA conversations for REC 4881, generate additional phase two data, and of course, depending on regulatory alignment, initiate a registrational study in the second half of 2027, we also expect preliminary REC 1245 examinations to expansion data, and additional clinical readouts from the rest of our portfolio. This is the bar that we've set for recursion. Again, as I mentioned before, not one target, not one molecule, or not one clinical result, but the ability to move repeatedly from novel biology to differentiated molecules to evidence in patients, all from one connected AI-native engine. We have the capital to execute. We are concentrated in our focus set of priorities and a series of meaningful catalysts ahead. We're excited about what's to come next. With that, we will now move on to Q&A. All right. Thank you, everyone. With that, now let's go to some questions. We have quite a few questions from REC 481. So I'll start with a question from Alec from Bank of America. On REC481, what does the activity in larger high-risk polyps. Tell us about the drug's ability to change standard of care. Vicky, I'll have you take that question first. Thanks, Nijat. So patients with FAP, as we've spoken about and as you've just heard, face a lifetime of surveillance and procedures, interventions such as surgeries and excisions. And the standard of care currently, there are no approved drugs in FAP that can alter the disease progression, right? So over time, polyps continue to grow both in the lower as well as the upper GI tract. Patients have routine surveillance. The surveillance frequency is somewhat determined by the extent of polyposis, including, you know, the size of the polyps. And there's nothing out there that can, you know, approve, that can alter the course of the disease and, you know, modify the need for these procedures. So in terms of what we're seeing with the Tupelo data, we've seen substantial reductions in polyp burden overall, as well as in both the upper and lower GI tracts. And we've seeing an effect on larger polyps of five millimeters or greater. And as the polyps get larger, this drives the need for increased surveillance frequency. It drives the need for additional procedures, including excisions, as well as potentially additional major surgeries down the line. And so what we've heard is that, you know, KOLs are really impressed with the data. So we're here in Denver right now at the CGA IGC conference. We've been meeting over the last 24 hours or so with many of these KOLs. And they're really impressed both by the extent of polyp burden reduction, as well as the durability of that reduction. And so how we're thinking about this is REC 4881 could potentially be an adjunct to routine surveillance. And, you know, the phase three will determine whether that reduction, that impressive polyp burden reduction that we're seeing can actually translate into benefit that's meaningful for patients in terms of reduction in the outcomes that are important, such as, you know, such as cancer development, high-grade dysplasia, and also need for these surgical procedures. Thank you, Vicky. I'll just take the next question. This is from Steve from KeyBank. If this drug reaches commercialization, what percentage of the addressable patient population do you think will continue to go the surgery route? You know, I would say, Steve, I mean, similar to and building on what Vicky mentioned, these patients go through a series of interventions and a lot of them is driven by polyp burden, but definitely the size of the polyp, as well as also dysplasia and other factors. So we do think the fact that we are seeing a reduction in the large polyps, reduction in polyp. So I think that's a really good point. I think it's a good point in the polypt burden overall. And the addressable population is pretty large, right? About 37,000 patients that are post-colectomy, we do think that there's potential for a pretty significant impact in terms of either avoiding or delaying these kind of life-altering interventions that are done. You heard on the patient panel, I mean, duodectomy where you're either sparing the pancreas or even removing the pancreates, Wickel procedures, but also just ampulectomy or tectomy. There's so many procedures that these patients go through. So we're excited and we'll learn more in the coming months. Next question. How are you thinking about chronic dosing for RAC481? Commercially, do you expect patients would require scheduled drug holidays, 13 weeks off pattern using the clinical trial, or regular treatment breaks? I'm going to hand this over to Vicky, but I will say we're both here in Denver at the CGA conference, and one thing that we've heard time and time again, is that at the end of the day, these patients are so young, they're in their 20s post-colectomy or even younger, that having flexibility in terms of the dosing regimen, and this is a question from Priyanka at JPL, so thank you, Priyanko, is a really, really big need and something that they haven't really had even an optionality before. But Vicky, I'll hand it over to you. Yeah, thanks, Najat. You know, we are hearing a lot of excitement around the data, a lot of excitement around the durability in that treatment break, and that allows flexibility for patients too in terms of dosing, in terms of life events. So having the flexibility to be able to take a break from treatment is really meaningful for both patients and physicians. So I think that durability of effect is really important. Ultimately, how this will play out, I think ultimately will depend on the phase three data in terms of the chronic dosing, but having that opportunity to have a drug that both shows significant polyp burden reduction that may reduce, ultimately be proved in the phase three, may improve these events that are important for patients, and then the flexibility to be able to stop dosing and have an opportunity to take a treatment holiday or a treatment break. Thank you so much, Vicky. Okay, now we'll move on to the next set of questions. This is from Gail from Needham and also Alec from Bank of America. Given large AI labs are increasingly leaning into applications in healthcare, how are you positioning Recursion to compete? Does unique data win the day here or maybe something else? I'll take that question. I think it's great to see the interest in terms of the convergence of AI and healthcare, which Recursion really pioneered for many, many years. Here's what I'll say. I always say there's three areas of moat for the company. One, yes, the data aspect, the Data Factory, the 50 petabytes of data, but not just the volume of data. The quality of data to build models and close the loop to find novel targets is critical. We pioneered in that a long time ago. We've built on that. Some of the examples with Roche Genentech, Sanofi, et cetera, that you see really build on not just data matters, especially in a space, as we've seen with LLMs, you know, a lot of the human history of text and data exists, but you don't have that in science. So being able to create that data and then actually leverage it to find novel targets, design novel molecules, and ultimately show data in the clinic we think is critical. But the next step that's even beyond that is, look, I said that at the beginning of the earnings call today, we firmly believe in order to actually make differentiated medicines with AI, you need to tie together those three capabilities. Novel targets, designing molecules for those novel targets, and then actually showing that evidence in the clinic, which we're starting to do. You know, that has taken a lot of time and a lotof learning and reps to build that connected AI engine end to end. it's it's a huge amount of work where you actually have your data sets build the models the models then actually you see the predictions uh work out in the experiments and those experiments and that data teaches the models this sort of recursive learning that technical aspect of it and actually having team members that are bilingual that can actually understand both science and ai that is not an easy thing to build so i think reps in terms of that closed loop learning system is an incredible area of differentiation for us. It's something we continue to build on every single day. And then the third is, how does any company compete that has differentiated assets? At the end of the day, it's about competing based on really valuable data that's scientifically, medically, and commercially critical to get better medicines for patients. And you see us having that as well. In that diversification and having that end game in mind is very critical. last thing i'll say we live in a space where 90 of biology is unknown 80 of diseases don't really have disease modifying drugs there's a huge amount of white space so uh looking forward to the entire sector whether it's the frontier labs whether it was pharma whether it is you know biotech companies like and then ai biotec companies like us all make progress here you've heard about fap you've hurt about oncology programs for patients that are so late line treatment on the path to palliative care and trying to get data there and see activity and have them be asymptomatic from disease, there's so much room for us to all play here. So we're excited about that. But our position is we want to be known as the company, the real deal in terms of making differentiated medicines using AI. All right, next question. This is a question from Dennis at Jefferies on REC 1245. RBM39 chemotherapy has shown about 17% ORR, 7 months TOR, 3.9 month PFS, 12 month OS, etc. With the endometrial expansion core starting, what target profile are you expecting? And perhaps can you comment on whether this MOA, if there's a benefit that can be seen via ORR or PFS, OS, et cetera? And lastly, how do you think RBM39 could fit in the late line endometrial given Mark's TRIP2 ADC data at ESMO and Gilead's TROP2 as well in upcoming Q4? I'll have Vicky start with that question. Thanks, Najat. I mean, first, just to note, again, as you've heard in the webinar, RBM 39 is novel biology. We're potentially first in class. This is again, based on recursions engine, and we're seeing really promising data coming out of this. So just to contextualize the data that we shared today is from a dose escalation cohort. These are patients heterogeneous and heavily pretreated, right, so a very difficult patient population to treat the early phase one population. And in spite of this being a late line population, we're seeing substantial evidence of activity. So we have two confirmed responses in patients with endometrial cancer. That means they had two scans, one that showed an initial response based on resist, and then a second that showed confirmation of that response. And then one unconfirmed response in hepatocellular carcinoma. and again, at a dose where we've been able to select a dose that's tolerable for patients to move forward into expansion cohorts, which we've now initiated recruiting. So those expansion cohorts will give us a better sense of the activity and the safety in well-defined patient populations. We will take those data and compare them both to historical response rates for agents such as chemotherapy in this setting. We will be looking, of course, at response rate and at duration of response, as well as the safety profile to say, where do we go next with this particular drug in these particular tumor types? And of course we're watching the competitive landscape very carefully, including the TROP2 ADCs. I will note that both of the endometrial cancer responders that we had in the dose escalation cohorts had received prior ADCs, including one of them who had received a trope 2 ADC, and we see that activity in patients specifically who've had a prior exposure to ADCs. So we see potential for a monotherapy approach. We see potential für combination approaches, including in patients who've received prior ADCs, I'm sorry, including combination with ADCs and these expansion cohorts. We're looking forward to sharing more data that will help guide what those next steps are for the molecule. Thank you, Vicky. And yes, I mean, just the other thing to build on that is, you know, in terms of RBM39, the MOA is distinct from ADCs. I think that gives us the potential for synergistic value. And then also the fact that these patients are such late-line patients, as Vicky mentioned, and have actually progressed on these ADCs and we're still seeing single agent activity is something that's encouraging for us, but a lot more work to come on the expansion boards. All right, so the last question we're gonna take from Sean from Morgan Stanley. Following the recent finance, and you now have runway into 2029, while guiding to lower operating expenses in 2027, how do you balance capital discipline with the opportunity to accelerate higher conviction or high conviction programs? And under what circumstances would you choose to meaningfully increase investment behind REC 4881, REC 1245 or additional platform generated assets? It's a great question. I mean, you know, one of the things, and Ben mentioned this, that's really important for us. I mean it's not common to be lowering guidance and we are doing that in a couple of different ways. One is really concentrating capital on areas that we have high conviction and it is purely data driven. So we see that with REC 4881, REC 1245, and we're fully funding those programs and accelerating them. Some of the other additional programs in the pipeline, again, as we see data roll out next year, we'll do the same. I think the fact that we're incredibly disciplined based on data and our capital allocation has really helped us a lot as we have increased focus, ambition, and discipline. The other thing I'll also say in terms of the platform perspective and partnerships, you know, we just crossed $535 million in cash inflows. I mean, nine milestones in the last two years, over $100 million in milestones. And I think that repeatability is very encouraging to see with our partners such as Roche Genentech and also Sanofi. And that's something we'll keep progressing and we invest really effectively in them. And then the last thing is the AI platform. I mean, part of it is we're seeing productivity in our engine that is really, really helping us stretch every dollar and be much more productive, whether it is in the design of molecules or even the generation of maps, which we're faster at, more efficient and more effective. So all in all, it's all about being data driven, making sure we stretch our every single dollar, making Sure, we, you know, return value, of course, for our patients and our shareholders. So with that, I just want to say a big thank you to everyone for joining today. This was a combination of both our earnings and also a mini FAP day, a huge thank you to Dr. Decker, Dr. Katona, and also patients at the end of the day, this is why we do what we do like Lindsay and Jessie and Laura that are experiencing FAP and the dramatic and challenging impact of those diseases every single day. We do this for you. So thank you for joining us. Thank you for sharing your stories and thank you all again. And we will talk very soon.