Hi everyone and welcome. I'm Najat Khan, Recursion's Chief R&D and Chief Commercial Officer, and incoming CEO and President. Let's jump right in. Today is an important moment for Recursion, for our teams, and most importantly, for the FAP patient community. We are here to share updated safety and efficacy results from our ongoing Phase 1/2 TUPELO study evaluating REC-4881 in FAP. Before we begin, please note that today's presentation includes forward-looking statements about an investigational asset. Actual results may differ materially, and I encourage you to review our SEC filings for a full discussion of risks and uncertainties. What you will see today is proof points of the arc we've been building towards at Recursion, from an unbiased platform insight to emerging clinical evidence, and we are very pleased to showcase that through the positive Phase 1b/2 results from this ongoing study. First, the unmet need in FAP is undeniable. FAP affects more than 50,000 patients across the U.S. and EU5, and as often is the case in rare diseases, the true prevalence may be higher once medical therapies become available and the diagnostic rate goes up. Most patients face a lifetime of escalating interventions, from frequent surveillance, endoscopies, and repeated excision of precancerous polyps and adenomas, which ultimately leads to a series of ever more debilitating, life-altering surgeries, such as the Whipple procedure. Today, there are no approved pharmacotherapies for FAP, and the natural history work our team completed with the Amsterdam University Medical Center reinforces what clinicians already see: that this disease is relentlessly progressive. What makes this program so uniquely meaningful for Recursion is how it started. MEK1/2 inhibition was not a target anyone was pursuing for FAP clinically. It emerged from an early version of our unbiased AI-enabled phenotypic platform, the Recursion OS, which highlighted selective MEK1/2 inhibition as a mechanism capable of rescuing the abnormal phenotype of APC-deficient cells, and because APC loss of function is the central driver of adenoma initiation and precancerous polyp growth in FAP, the hallmark of the disease, this finding pointed us to a mechanism that could directly address the underlying biology of the disease, not just the symptoms or the downstream consequences, and it is that mechanistic insight which ultimately led us to in-license REC-4881 from Takeda, a high-quality allosteric MEK1/2 inhibitor that was deprioritized after being studied in a solid tumor setting. We then redirected the molecule towards FAP, a disease, as I mentioned before, with no approved pharmacotherapies. It's a reflection of what at-scale AI-enabled biology first platform can surface when you don't start with a preconceived hypothesis. Now we're starting to see that insight translate into the clinic. At week 13, the majority of patients experienced rapid reductions in polyp burden. Importantly, at week 25, this is 12 weeks after stopping therapy, most patients demonstrated durable reductions. That off-treatment durability is particularly encouraging and exciting when we anchor it against the natural history, which shows the rapidly progressive nature of the disease when left untreated. Safety remains consistent with MEK1/2 class expectations, with primarily Grade 1-2 events, low Grade 3 rates, and no Grade 4-5 events observed to date. The top treatment-related adverse events include acneiform dermatitis, CPK increase, and rash, all in line with MEK1/2 class effects. Finally, our ClinTech and real-world data capabilities have been instrumental for the study, informing eligibility, contextualizing the single-arm data set, and helping ensure we really understand the disease in the real world, not just through trial snapshots. Overall, this represents the first clinical validation of the Recursion OS platform, demonstrating our ability to translate unbiased AI-enabled insights into differentiated medicines for areas of extremely high unmet need. Moreover, REC-4881 is the first precision medicine approach truly directed at the causal biology of FAP. As a next step, we look forward to engaging with the FDA in the first half of 2026 to discuss a potential registrational pathway. In parallel, we're also expanding the eligible patient population from greater than 55 years to greater than 18 years and continuing to optimize the dosing schedule, with the ultimate goal of bringing a much-needed therapeutic option to this community. But before we transition fully into the REC-994 data, I want to take a moment to acknowledge the momentum, the broader momentum across Recursion. Momentum that comes from the work of many teams and from the trust of our partners that have been placed in us. Across both our internal and partnered programs, we're starting to see real green shoots, places where AI-enabled biological insights, design work, and innovative clinical work are beginning to translate into differentiated programs. These efforts don't just advance individual assets. They also help us learn, iterate, and strengthen the Recursion OS platform itself with every single cycle. Our partnership momentum is accelerating. Across all of our collaborations, we have now generated over $500 million in total cash inflows. For example, with Roche and Genentech, our teams have now created and advanced six Phenomaps, four in GI oncology and two in neuroscience. The teams are hard at work to translate those maps into novel programs. With Sanofi, we've achieved four milestones in the past 18 months, and we anticipate additional possible milestones ahead. This momentum gives us a strong foundation and reflects a company-wide commitment to rigorous science and tech-first strategy and execution. Now, let's dive into the Recursion OS platform. The Recursion OS 2.0 platform we utilize today has grown significantly since the early days of the company. It is a true end-to-end engine focused on applying AI where it can have the biggest impact in R&D. This includes multiple modules from integrating AI-powered deep biological understanding with advanced chemistry design and AI-powered clinical development strategy and execution. Now, let's dive into how the platform was leveraged from one of our earliest programs. Let me briefly and transparently describe the contribution. This program began with an AI-enabled biological insight. We used an early version of the Recursion OS platform, our unbiased phenotypic screen in APC-deficient cells, which consistently revealed a signal. Selective MEK1/2 inhibition restored key aspects of APC-dependent biology, and as I mentioned earlier, this insight led us to in-license REC-4881, a high-quality allosteric MEK1/2 inhibitor previously deprioritized in an unrelated oncology setting, and why did we do that? Because this profile aligned with the biology our platform consistently surfaced. It was this biology-first insight that allowed us to direct it into a disease with no approved therapies, and since then, we have advanced the program using the full power of the Recursion OS 2.0 platform, including our ClinTech platform real-world capabilities and AI approaches, all of which have strengthened the translational path and informed the current clinical development strategy, so let's dive into that a little bit more. You know, I often get asked about our ClinTech platform, which has been a ground-up build over the past year. Let me briefly highlight how our capabilities have shaped this program, which has been essential to really understanding the real-world patient experience. Now, look, natural history data is fundamental in rare diseases, and regulators are increasingly expecting it. Yet for FAP, historically, there's been very little quantified evidence on how patients progress outside of the clinical trials. To fill that gap, our ClinTech team deployed large-scale real-world evidence capabilities, examining more than 1,000 U.S. FAP patients and over 250,000 physician notes using a custom LLM-based algorithm. This gave us a clear picture of the FAP patient burden in everyday practice, the frequency of interventions, and the relentless progressive nature of the precancerous polyp growth. We then extended this work through an academic partnership with Amsterdam University Medical Center, where we collaborated on the analysis of one of the largest and longest-running FAP registries in the world, nearly 20 years of follow-up in about 200 patients. This allowed us to quantify, for the first time at this scale, the true natural progression of polyp burden in this trial-relevant population. Across both data sets, the story is striking and consistent. Untreated FAP shows predictable year-over-year polyp growth, a benchmark that is important to contextualize the magnitude of potential benefit we're about to show you with REC-4881. This is ClinTech at its best, augmenting clinical development with unbiased real-world insight, informing our single-arm design in ways aligned with FDA guidance, and anchoring our future regulatory conversations in the lived reality of patients and providers. Today, I'm excited that you'll hear from our very own FAP clinical lead, Dr. Beth Bruckheimer. Dr. Bruckheimer brings more than two decades of experience across all phases of drug development and previously led the largest Phase 2 trial ever conducted in FAP. She'll walk you through the disease, our program, and the latest efficacy and safety data. Following that, I will join our Chief Medical Officer, Dr. David Mauro, and we'll host a fireside discussion with two outstanding experts in the space. First, Dr. Jessica Stout, a principal investigator for TUPELO and a double-certified GI specialist who has extensive experience managing complex GI diseases, including the long-term multi-organ care required for FAP. She will be joined by Dr. Alfred Cohen, former Chief of Colorectal Surgery at Memorial Sloan Kettering and former CMO of Cancer Prevention Pharmaceuticals. Dr. Cohen brings over 50 years of experience in colorectal cancer treatment and research, with a career-long focus on improving quality of life for patients with inherited and GI diseases. With that, I'll hand it over to Dr. Bruckheimer to walk you through the data. Thank you, Najat. It is my pleasure to present the results from the ongoing REC-4881-201 trial and our FAP natural history analysis. So let's start by reviewing some background on FAP so we can better understand the significance of our results. Familial adenomatous polyposis is a rare orphan disease caused by autosomal dominant mutations in the APC gene. As a result of this loss of APC, patients will develop hundreds of thousands of adenomas or polyps in their colon and rectum by their late teens and early 20s. In the absence of surgery, these patients have a 100% risk of developing colorectal cancer by the age of 40. These precancerous adenomas progressively accumulate, and there is little evidence of spontaneous regression. As Najat mentioned, currently, there are no approved pharmacotherapies for FAP. Patients face a lifetime of endoscopic surveillance, frequent excisional interventions, and life-altering surgeries that impact quality of life, morbidity, and long-term outcomes. There are greater than 50,000 patients across the U.S. and EU5 with FAP, where the only option is the standard of care surgery and excisional interventions. However, this does not slow disease progression. Given this unmet need, our goal is that REC-4881 may fill this gap and provide another treatment option for patients with FAP to slow disease progression and therefore improve quality of life. FAP is a lifelong continuum of disease progression and intervention driven by chronic polyposis. As mentioned, in adolescence and early adulthood, patients typically develop hundreds of thousands of precancerous adenomas in their colon and rectum. As disease burden increases, most will require a colectomy to remove the colon and manage disease progression and cancer risk. While this addresses immediate cancer risk in the colon, it does not stop adenoma formation in the remaining rectum, pouch, or duodenum. Post-colectomy, patients still require decades of repeat endoscopies, excisional procedures, and approximately 50% of these patients will eventually undergo and require removal of the remaining rectum, pouch in order to manage that uncontrolled polyposis. This, too, is a life-altering surgery that impacts quality of life. Progression continues in the upper GI tract, where approximately 90% of FAP patients will develop duodenal adenomas, and these can often be difficult to manage endoscopically. Around 6% of these patients will undergo duodenectomy or Whipple surgeries. Of these, these are some of the most significant life-altering surgeries associated with high morbidity and mortality. So to better understand the extensive patient journey and unmet need, we used our ClinTech platform that consists of large databases of electronic health records. We applied custom large language foundation models on approximately 1,000 FAP patients with more than a quarter of a million physician notes. This analysis showed the continual polyposis progression, frequent surveillance, and extensive excisional and surgical interventions that patients face to manage their disease burden. These notes revealed insights such as "polyp burden is too extensive to be feasibly removed endoscopically," "multiple revision surgeries were needed post-colectomy," or "even a Whipple surgery was needed to manage duodenal and ampullary polyp burden. Together, from the literature and our ClinTech initiative, you can see a high unmet need for patients with FAP and the need for therapies that can meaningfully slow disease progression and improve a patient's quality of life. This is where REC-4881 comes in. As mentioned, FAP is driven by a loss of function mutation in the APC gene. This drives cell proliferation and adenoma development over the course of a patient's lifetime. Our goal was to identify molecules that could rescue the loss of APC, guided entirely by a cell's phenotype rather than any prior knowledge or assumptions on the mechanistic hypothesis underlying the disease. Using version 0.1 of our unbiased, AI-driven phenotypic platform and screening thousands of compounds, we identified REC-4881 specifically to rescue from the loss of the APC gene. As you can see in the heat maps, REC-4881 demonstrates a strong pheno-opposite effect, suggesting it can rescue from this loss of the APC gene. Indeed, in cellular phenotypic assays, REC-4881 treatment reverted cells from a disease phenotype to a healthy phenotype following the loss of APC, and now, on the right-hand side, screening through a large panel of kinases, we also demonstrated that REC-4881 is a potent and selective allosteric MEK1/2 inhibitor, so overall, what is unique is that our platform led us to identify MEK1/2 inhibition as a mechanistic strategy to exploit a therapeutic vulnerability due to the loss of APC in FAP. We identified a molecule that had been discontinued after development in a solid tumor setting. It was then in-licensed and redirected to FAP, making REC-4881 the first MEK1/2 inhibitor ever to advance for this disease clinically. This insight emerged solely because the Recursion OS platform looks at biology differently by reading phenotypes at scale. We feel that REC-4881 is uniquely positioned for FAP with regards to the mechanism of disease and then the mechanism of action of the compound. The loss of APC results in aberrant signaling, including the Wnt and MAP kinase pathway that drives proliferation and disease progression. REC-4881, by inhibiting MEK1/2, selectively blocks the activation of ERK, thereby suppressing cell proliferation and the downstream consequences of APC inactivation. We believe that REC-4881 has the potential to be a first-in-disease and best-in-class therapy for FAP. It is pharmacologically active at a four-milligram dose, and it has a beneficial PK/PD profile that is really well-suited for the treatment of FAP. This includes a long half-life of 48- 60 hours and an ADME profile that allows for enriched unmetabolized exposure in the GI tract, the primary site of the disease. So this is really important. So with that data in hand, we evaluated REC-4881 in the APC-Min mouse model for FAP. In our preclinical studies, REC-4881 demonstrated a significant dose-dependent reduction in polyp count. This even outperformed celecoxib, which can be used off-label for the management of FAP clinically. On the right-hand side, and more importantly, REC-4881 also reduced the percentage of these high-grade precancerous adenomas in this model. So now let's move on to the results from our ongoing Phase 2 TUPELO study and our natural history analysis. The TUPELO study was designed to evaluate the safety, tolerability, PK/PD, and efficacy of REC-4881 in patients with FAP. As shown on this slide outlining the phase II portion of the trial, patients needed to have a confirmed APC mutation, they were post-colectomy, and had to have adenomas or polyps in the upper and lower GI tract. At baseline, patients undergo an upper and lower endoscopy to measure that baseline polyp burden. Polyp burden is defined in the study as the sum of all polyp diameters. Following baseline assessments, patients were treated with a 12-week course of four-milligrams REC-4881. Today, we're focusing the data on that four-milligram QD cohort, where 14 patients were in the safety evaluable population, meaning that they received any amount of REC-4881. Of these 14 patients, 12 were efficacy evaluable, meaning they had measurable disease at the end of baseline endoscopy. They received at least 75% of study drug during the first 12 weeks of treatment and had at least one post-baseline endoscopic assessment. For this study, efficacy is defined as a percent change in polyp burden from baseline to a time point post-REC-4881 treatment. Back to the patient journey on this trial. After receiving 12 weeks of treatment, patients undergo another upper and lower endoscopy at week 13, and this is where we measure that primary efficacy endpoint. Following that point, patients go off treatment for another 12 weeks. That is followed by an upper and lower endoscopy at week 25. This is to determine the durability of response, so the effects on polyp burden 12 weeks after REC-4881 treatment has stopped. Let's recap. Overall, we assess the safety and tolerability of REC-4881. Efficacy is measured as a change in baseline polyp burden for this portion of the study. Also just a little hint for what's to come in a few slides. In parallel to the REC-4881-201 study, we also analyze real-world data from Amsterdam University Medical Center's FAP registry in order to contextualize the data from this open-label trial to the natural history of FAP. Let's start with some of the baseline characteristics from part two of the trial. The average age of this population was approximately 62, and the primary disease site for the majority of these patients, around 80%, was the duodenum. This is really typical for this age group as they have more duodenal disease. Duodenal disease tends to be a little more indolent and occur later in life. We also used the Spigelman staging system to classify upper GI disease severity in these patients. We saw that the majority of patients were Spigelman 3. Lastly, we had sufficient polyp burden at treatment initiation, where the median total polyp burden at baseline was 132 millimeters. Now moving on to safety. The four-milligram dose of REC-4881 is consistent with the MEK inhibitor class of compounds. The vast majority of treatment-related adverse events, or TRAEs, were grade one or two, the most common of which were dermatitis acneiform, CPK increases, and rash. Again, these are primarily grade one, two in severity. We observed two patients who had grade two asymptomatic left ventricular ejection fraction decreases. There were three grade three events, one dermatitis acneiform and two blood CPK increases. Of note, and what is really important, is that there were no grade four or five TRAEs and no unexpected safety signals. Turning to efficacy, the week 13 waterfall plot shows a clear and rapid treatment effect with REC-4881. 75% of evaluable patients demonstrated a reduction in total polyp burden by week 13, where the median reduction was 43%. More importantly, of these, 60% of patients achieved reductions of 30% or greater. We also saw consistent activity throughout the GI tract, where polyp burden reductions occurred in both the upper and lower GI regions separately. So together, these results suggest that REC-4881 is capable of impacting disease burden across the entire GI tract in patients with FAP. As you may recall from our previous presentation in May, we had one unusual result with a non-responder. Following that data cut, and as described in the footnote one on this slide, we did a quality review and identified that this patient had a suboptimal bowel prep at baseline. So to ensure for an accurate and like-for-like assessment, polyp burden was reevaluated using video review restricted to the clean regions of the GI tract at all time points, so baseline, week 13, and week 25. What we are really excited about is on the next slide. This shows that the effects by REC-4881 are durable. Even after stopping therapy for 12 weeks, 82% of patients remained responders at week 25 with a median reduction of 53%. Furthermore, 73% of patients maintained a durable response of greater than 30%. These results suggest that REC-4881's biological effect persists well beyond the dosing period. We feel the next slide really exemplifies that. Here we show the trajectory of the responses to REC-4881. On the left, during the treatment phase, you can see a clear and immediate downward shift in polyp burden in nearly all patients. However, what is really striking is what happens on the right-hand side after treatment stops. During that 12-week off-treatment phase, most patients maintained a reduction in polyp burden, and more importantly, in some cases, these reductions further deepened. This pattern supports the potential for REC-4881 to deliver a durable biological effect that is meaningful and persisting and even deepening beyond that dosing period, so we're very excited about this. As mentioned, since the 201 trial is an open-label trial, we really wanted to contextualize this in terms of the natural history, so in collaboration with Amsterdam University Medical Center, we analyzed real-world data from their FAP registry, and this was done in a cohort of 55 patients with a similar profile to our inclusion and exclusion criteria. In contrast to the reductions observed with REC-4881 treatment, the natural history analysis shows that 87% of untreated patients experience annualized increases in polyp burden. This was a mean annualized increase of around 60%, and what this data and analysis really underscores is the impact of REC-4881 treatment, so natural history shows disease progression, whereas REC-4881 treatment shows potential disease regression. So rounding out these analyses, in addition to polyp burden, we also assess Spigelman stage, which, as described earlier, is used to really determine the impact on upper GI disease severity. At week 13, 40% or 4 out of 10 of these patients demonstrated a one-point or greater reduction in Spigelman stage compared to baseline. Encouragingly, at week 25, following that 12-week off-treatment period, all four patients maintained at least a one-point stage decrease from baseline. Additionally, leveraging again our natural history analysis with AUMC, we can show that in the natural history of disease under routine care, Spigelman scores typically increase and do not decrease. So this suggests that REC-4881 can impact not just polyp burden reduction, but also reduce upper GI disease severity. So now that we've gone through all the details of our analyses, let's summarize our key takeaways and next steps. REC-4881 represents a major milestone for Recursion. It is the first clinical validation for the Recursion OS platform, with the potential to be both a first-in-disease and best-in-class molecule for FAP. Recursion's unbiased AI-driven phenotypic platform uncovered that selective MEK1/2 inhibition rescues cells from loss of APC and revealed that REC-4881 could be a potential targeted therapeutic candidate for FAP. We are the first to test MEK1/2 inhibition clinically for FAP, where we have demonstrated activity of REC-4881 at the four-milligram dose. From a safety perspective, the profile is consistent with MEK inhibitor class, with a low rate of Grade 3 events and no grade 4 or 5 events reported. Efficacy was rapid and substantial. By week 13, we saw a 43% median reduction in polyp burden, with 75% of patients responding. Current investigational agents have reported only 17%-29% reductions over a 12-month time period. In addition to polyp burdens, we also observed 40% downstaging of Spigelman at week 13, which is again really critical for looking at upper GI disease severity. What is more important as an outcome from this study is that the REC-4881 response is durable at 12 weeks post-therapy. So by week 25, again, after patients have been off treatment for roughly 12 weeks, we saw a deepening of the effect with around 53% median reduction, and the response rate was even higher at 82%. Other investigational agents have yet to report any durability of response. And then lastly, since this is an open-label trial, the clinical activity was further contextualized by the results from our natural history study, which showed an 87% annual growth in untreated FAP patients. Together, these results show the power of our platform to generate novel mechanistic insights leading to the identification of REC-4881 as a targeted pharmacotherapy that may address the underlying biology of FAP. So what is next for REC-4881? There is a high unmet need for a pharmacotherapeutic option for patients with FAP that can really slow disease progression, reduce the impact of frequent surveillance, those invasive procedures they experience over the course of their lifetime. So looking ahead to fulfill that unmet need, we are expanding our trial to the broader FAP population 18 years and older and exploring alternative dosing regimens to see if we can broaden that benefit-risk profile for REC-4881. Secondly, we plan to engage the FDA in the first half of 2026 to initiate discussions on a registration path. This strategy involves leveraging our data generated thus far, looking at the magnitude, speed, and durability of effects of REC-4881 treatment, and then combining that with our real-world evidence to support that potential registration path. And then to close out, and last but not least, we would like to extend a heartfelt thank you to all the trial participants, their families, and clinical sites who made the research we presented today possible. So thank you. Now, I am pleased to pass the baton over to Dr. David Mauro for a fireside chat to discuss these results and their impact on patient care. Over to you, David. Thank you, Beth, and good morning. I'd like to introduce myself. My name is David Mauro, the CMO at Recursion. I want to switch gears and welcome our expert panel of physicians who specialize in treating FAP. I'm pleased to reintroduce Dr. Jessica Stout and Dr. Alfred Cohen. Dr. Stout is an assistant clinical professor at the University of Utah and serves as one of the principal investigators on the TUPELO study. Dr. Alfred Cohen brings decades of experience, having served as the former director and CEO of the Markey Cancer Center at the University of Kentucky and was also the former head of the Colorectal Service at Memorial Sloan Kettering. Thank you both for taking the time to join us today. Let's begin by discussing patient management from different perspectives. Dr. Stout, from a medical standpoint, could you walk us through some of the patient's typical journey from FAP diagnosis to their initial treatment? And also, what are the main non-surgical clinical concerns you have when managing these patients over the long term? Absolutely, Dr. Mauro. Thank you guys very much for having me here. I think it's important to keep in mind the very intimate relationship that patients with FAP have with their gastroenterologists. I mean, I see these patients at minimum yearly to do procedures. Oftentimes, I meet them in the middle of their journey somewhere. Maybe most of them have already had surgery, and I'm just continuing on very frequent endoscopic surveillance for them and removing small polyps, hopefully small polyps, every year or whatever the right interval is for them. I think one of the most significant unmet clinical needs for these patients, there's an obvious answer here, but I want to save it for last. To me, one of the most significant unmet clinical needs is rigorous upper GI surveillance. Because colon cancer is essentially 100% in these patients with FAP, I think we do a really good job pulling the trigger and saying, "Hey, it's time for surgery." And then after surgery, as I mentioned, I'm still performing pouchoscopy or some form of endoscopy yearly. And we do such a good job in FAP at preventing colon cancer that now duodenal cancer has actually taken over as the leading cause of morbidity in patients with FAP. Another significant unmet clinical need, I think, is that patients really should be referred for genetic counseling. This should be standard of care, but studies and then my anecdotal experiences is that the minority of patients with FAP get referred. I just think knowledge is power. I also think having genetic counseling and genetic testing early on with these families who know that there's an FAP gene mutation could help to expedite and make their screening process better and maybe avoid surgeries. Finally, I wish I had effective chemoprevention to offer my patients with FAP to reduce their polyp burden and their overall morbidity and mortality. I mean, I think that's why we're all here, right? Dr. Cohen, you made a great point when we were chatting earlier. We say reduce the polyp burden, but not all polyps in the GI tract are necessarily precancerous. However, in FAP, essentially all the polyps that we see are adenomas. Or sometimes we'll say neoplastic, or we'll say dysplastic. All of these are words to mean precancerous. These polyps are actually little ticking time bombs that will eventually become cancer if we don't remove them endoscopically or surgically. There's a huge need for something better to offer these patients, and chemoprevention would be such a great adjunct. Dr. Stout, it sounds that these patients are living with a lifetime of disease that need constant management. Sort of the relationship that you are building with these patients is over decades. Is that true? Yes. I mean, I am early in my career. When I took over here at University of Utah as one of the main gastroenterologists who was managing FAP, you can look back through, as you said, decades of records, and I review decades of records. These patients have been coming to see us for so long, they and their family members, and again, every year, they'll be seeing us having some sort of endoscopic procedure. And they have very complex medical and surgical histories sometimes. Great. Thank you. Dr. Cohen, similar question to you. I wanted you to focus, though, a little bit more on sort of the surgical management of these patients over the course of their disease. And also, in particular, could you speak to some of sort of the key decision points in when you would trigger surgery along the way? Thank you, David. The issues when patients are referred to surgery are complicated by personal preferences by patients and family members, as well as medical drivers that determine the need for surgery. As an example, if a patient is totally asymptomatic, but their mother died of colon cancer at age 28, not a common situation from a generation or two ago, excuse me, those patients, independent of their polyp burden in their large bowel, they're going to drive for surgery earlier. But once you sit down and talk with patients about the reality of having what's called prophylactic or preventative surgery to avoid cancer, and they hear about the reality of what their bowel function is going to be like, there is much less interest in going ahead when you're an adolescent or a young adult, or you've just gone to college, just taken a job, just gotten married. And the thought of having multiple bowel movements a day, six, eight, 10 bowel movements a day, or having soiling in your underwear, nighttime soiling, other complexities that impact adversely on your quality of life, patients are much more interested in trying to delay the need for this life-altering surgery. So that has been involved with multiple polypectomies. But we are in a good position to identify patients now at higher risk for cancer. Those are patients with FAP, but who have what are called advanced adenomas. That has been discovered over the past 25 years that patients with adenomas over 10 millimeters or, on biopsy, high-grade dysplasia, which is just a microscopic finding, or some others such as the villous feature, again, a pathologist's microscopic finding. It's possible, not just based on having hundreds of polyps, but severe numbers of precancerous polyps that drives patients to surgery. Knowing that, what we're going for, what we're thinking about, David, as we move ahead is not only controlling the overall polyp number, but the numbers of these precancerous polyps. If we can prevent such precancerous polyps, we can delay the need for these life-altering procedures to something that's much more convenient for the patient, etc. It's an exciting opportunity, and it's really the unmet medical need is, yes, we want to prevent cancer, but preventing cancer by taking out your large bowel, rectum, and duodenum is not an attractive option for patients. So if you can have something that's an adjunct to the endoscopic management that Jessie does all the time, that will make a tremendous difference in terms of the lifetime of management of these patients. Dr. Cohen, one quick follow-up. You talked a little bit about prophylactic surgeries. How often in your career have you dealt with patients that have had multiple prophylactic surgeries? And maybe the only other prophylactic surgery that I'm aware of with regard to cancer management is mastectomies for breast cancer. Can you talk a little bit about the comparison in terms of how a surgeon might approach or think about a prophylactic surgery for breast cancer versus those for FAP patients? It's a good distinction, David. So in breast cancer, once a family with an identifiable BRCA gene mutation has been identified, there is no good way of knowing at what point the patient's going to develop breast cancer. We know that the large majority will develop breast cancer, some at age 25, some at age 50. The difference for us in the FAP world is we can identify patients who are progressing rapidly towards invasive cancer, which, of course, we want to avoid by identifying these high-risk precancerous adenomas and trying to remove those endoscopically if possible. From my perspective, the goal in the lower GI is protecting the rectum. So it is quite possible in doing prophylactic surgery, whether it's patient preference or based on more advanced adenomas. If one can control the disease in the rectum using a pharmacotherapy agent, then one can take out the large majority of the colon but leave the rectum. And that prevents most cancers but provides a much improved quality of life. In the upper GI, the goal, of course, is to try to avoid a Whipple or duodenectomy. These are normally done for cancer, but most Whipples in FAP are done just by virtue of many precancerous adenomas. And that's a disease that's associated with morbidity and mortality. So again, a drug that can obviate, delay the need for any type of surgery would be greatly beneficial. Thank you. Dr. Stout, just a follow-up question maybe. From your perspective as a PI on this study, and when you look at the data that Beth just shared, what is the most compelling takeaway from REC-4881 from an efficacy and safety perspective, just in conjunction with sort of the unmet need that you just mentioned? And what's its potential as a therapeutic option? I mean, we have some ways to go, but when you think about FAP patients and the need for more pharmacotherapy beyond the relentless interventional and life-altering surgeries that occur today? Great question. I think the most compelling piece of data that Beth and that you highlighted is the durability of REC-4881 from week 13- 25, the fact that the biological effect persists after the dosing ends, and right now, there's no end in sight as to how long this effect may last based on the current data that we have. I mean, that's so exciting. I think this initial trial data could position the drug as something that's taken daily or perhaps we'll find it's effective in a cyclic fashion, which might be a really alluring option for a patient who's experiencing a side effect, etc. And also just to follow up on the conversation that we were having, I mean, my job is to hopefully prevent patients from going to Dr. Cohen. I mean, again, we've kind of acknowledged that colon cancer is such high risk in most of these patients that they need a colectomy. But in some of these very aggressive phenotypes, I'm bringing these patients back as often as every three to six months. I mean, can you imagine having endoscopy that often? And so hopefully, some sort of chemoprevention could at least, at the very least, lessen the burden of endoscopy for these patients and then allow us as endoscopists to hopefully refer for surgery more often. But to run back to your question, the durability of the REC-4881 is very exciting. Yes. And thank you. That's really clarifying. And that's one of the reasons why we're looking to further optimize the dosing schedule, have multiple options potentially for patients given the chronic and progressive nature of the disease. Maybe just a quick follow-up on that. From a patient perspective, I had a chance to shadow some GI specialists as well just to understand the disease burden a little bit for FAP from the patient perspective. Can you speak a little bit to that, especially starting younger and progressively over time? What would be most meaningful for patients here? So as much as I like to think that my patients love to come and see me, I am sure that they would be happy to have less frequent visits with me. I also just think it's important to consider it's not just that they're coming for endoscopy, but the patients in this particular region of the country, too, there's so few centers that consider themselves centers of excellence for FAP. And I have patients who drive or even fly over 500 miles to come and see me. So I think that's really important, too. We think about the endoscopic risks and the amount of procedures they need, but can you just imagine the amount of time they spend? Yeah. And especially having a solution that's an oral, daily, or cyclical, as you mentioned, really changes the burden on the patient significantly. Dr. Cohen, maybe just a similar question. Let me just follow up on that. Yeah, please. Just try to imagine what it's like being 20 years old and sitting in a chair and the doctor is saying, "Well, you don't really need surgery, but you're going to have to have an endoscopy every six months for the next 50 years." You'd have to lift them off the floor after you've told them that. So it is a lifetime disease. Anything that can not only prevent cancer, prevent the life-altering surgeries and the morbidity and mortalities associated, but anything that can impact on the interval of surveillance endoscopy, if you can document that the patient is a responder to your pharmacotherapy, and then go instead of every six months, every year, or every two years, just like we've done with colon cancer endoscopy. We used to do it on a yearly basis for prevention, now every five and ten years. Yeah. Now, I think that bleeds very nicely into the next question, Dr. Cohen. Just wanted to understand a little bit, contextualizing what the patient is going through: 20-year-old, 30-year-old. I can't even imagine a Whipple procedure that you mentioned that's usually preserved in an oncology setting. To some of the results from REC-4881 from the study you heard about today, what stands out to you the most from a therapeutic perspective for patients? Well, I always go back to 25 years ago when celecoxib was approved as the only pharmacotherapy, and the benefit was 30%. And everybody said, "Wow." But the physicians quickly realized there was very little, if any, benefit from that type of regression. So as you think back to the slides that were shown about the benefit and the durability, if we can show that the majority of patients taking the drug are going to have these types of major and durable regression, that will clearly translate into a major benefit from the patients and from a commercial point of view. Let me just add one other thing about the importance of durability. A lengthy study from the Amsterdam group showed 5% of patients become non-compliant, so no matter how personable the gastroenterologist may be, the patients after a couple of years say, "I'm okay," and they stop coming, so something that can be an adjunct so that, again, coming back to frequency of surveillance, patients getting surveillance endoscopy every two or three years rather than every six months, much higher compliance. Absolutely, and that comes back to the patient burden, too, that Dr. Stout, you mentioned in terms of sometimes having to drive 500 miles to be able to see their physician, having an oral therapy changes the game. I think about so many other therapies. I remember when there was nothing approved for psoriasis, and today, with the management of care for psoriasis, it's incredibly different. And that's not only the impact on these families if they know that their children at age 10 test positive for the mutation, but they don't have to go through the same management algorithm that they went through, that there's going to be some drug, it can be put off until they're married and have a life there and not having to undergo endoscopy or life-altering surgery at age 18 or 20. Thank you. One of the things that, as I was looking at the data that was impressive, was in my mind, I was looking for an efficacy profile that can demonstrate activity in both lower and upper GI and also nice durability. So as I look at our data in comparison, it seems as though the potential to even increase the level of polyp reduction. I think it has a relatively high potential, but don't want to put words in your mouth, but would like you to provide your thoughts. Dr. Stout? Yeah. I think what we're seeing so far with this drug, just in the few clinical patients that we've performed procedures on already, is very exciting. Just visually seeing that there are fewer polyps or that the polyps that were there before, you remember, "Oh, yeah, I remember that little guy at the 5 o'clock position, so many centimeters into the duodenum. Wow, it looks a little bit smaller." I mean, I think this is all quite exciting. And important that the natural history is such that, as was mentioned, 90% of patients end up with duodenal disease, but the bulk of those also have, whether they have a residual rectum or the so-called ileal pouch, will develop adenomatous disease in the remaining bowel. So having a drug that impacts both the retained rectum or the pouch and the duodenum avoids the potential need as patients age of having a permanent bag or having to have a Whipple procedure. So the combination of effectiveness at both locations, I think, is absolutely a critical observation. Yeah. I mean, if we're actually interfering with the natural history of this disease, which is progressive, that's also a very exciting thought. Thank you. Najat? Yeah. No, great conversation. Maybe just to round it out, as you think about the future landscape of FAP treatment, we've touched on a little bit of this, right? Elements of, Dr. Stout, as you said, can you actually bend the curve in terms of the natural progression of the disease, which is relentlessly progressive? Can we have impact upper and lower GI? Can we maybe reduce the polyp burden reduction where some of these, in some cases, they're carpeted with polyps? So it's even hard to discern the ones that are larger versus not, or even to have surgical excisions that are as accurate as possible. And the list goes on. And durability and the patient need and the patient burden, and how do we actually improve that? Any other components that come to mind as you think about the future of FAP treatment? The unmet need is undeniable, but any other things that we should keep in mind also as we progress this program through the next stages as well? Dr. Cohen, maybe starting with you. So we are looking at development of a program, and I think that's where we are headed, that's something that has acceptable minimal side effects that does not need to be taken every day for the next 50 years, but can be potentially done on various intervals, the exact to be worked out probably once it's on the market. Thank you, Dr. Cohen. Dr. Stout? Yeah. I think we use the word precision medicine so often, right? But if I just think about the future landscape of FAP in this perfect world eventually, future management, I think, will increasingly incorporate this genotype-phenotype correlation in order for us to individualize surveillance intervals and also the surgical timing and then chemoprevention strategies. APC genetic testing helps predict polyposis severity, the rectal involvement, which Dr. Cohen talked about multiple times, other non-GI cancers like desmoid tumors, etc. And I think that if we can incorporate genotype-phenotype correlations, we'll be able to give personalized treatment decisions for these patients. And again, what does that actually mean? Currently, when I perform endoscopy for a patient with FAP, it's not incredibly clinically relevant for me to know the details about their genetics other than they have an APC gene mutation. Maybe I can make guesses about whether the mutation is on the end or in the middle of the APC gene based on the number of polyps I see. What I hope and foresee in the future is that someday I, or maybe future gastroenterologists, may use a patient's genetics to make precise endoscopic decisions about polyp excision, follow-up, when to refer to surgery. Then, most importantly, again, the reason that we're all here is hopefully use that information to figure out who we need to start on chemoprevention. Maybe even someday, we'll have enough options for chemoprevention that we can even choose which drug to use based on the patient's genetics and their phenotype. That's where I see this going in the future. Thank you. Couldn't agree more. Thank you, Dr. Stout and Dr. Cohen, for joining us today. On behalf of David Mauro and I and the entire Recursion team, thank you for joining. Much more to come, and we look forward to continuing the dialogue.