Good morning, and welcome to the Palisade Bio conference call and webcast. As a brief reminder, all participants are currently in a listen-only mode. If anyone requires operator assistance during the event, please press star zero on your telephone keypad. Following the presentation, there'll be a question and answer session. Note that this webcast is being recorded at the company's request, and a replay will be made available on the company's website following the end of the event. At this time, I'd like to remind our listeners that remarks made during this webcast may state management's intentions, beliefs, expectations, or future projections. These are forward-looking statements and involve risks and uncertainties. Forward-looking statements on this call are made pursuant to the safe harbor provisions of the federal securities laws and are based on Palisade Bio's current expectations and actual results could differ materially. As a result, you should not place undue reliance on any forward-looking statements. Some of the factors that could cause actual results to differ materially from these contemplated by such forward-looking statements are discussed in the periodic reports Palisade Bio files with Securities and Exchange Commission. The documents are available in the investor section of the company's website and on the Securities and Exchange Commission's website. We encourage you to review these documents carefully. Additionally, certain information contained in this webcast relates to or is based on studies, publications, surveys, and other data obtained from third-party sources and the company's own estimates and research. While the company believes these third-party sources to be reliable as of the date of this presentation, it does not independently verify and makes no representation as to the adequacy, fairness, accuracy or completeness of, or that any independent source have verified any information obtained from third-party source. This presentation discusses product candidates that are at an early stage of clinical and pre-clinical development and which have not been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates. Further, any data discussed regarding clinical trials and progress are considered preliminary and subject to change. Joining us today on Palisade Bio's leadership team are JD Finley, Chief Executive Officer, and Dr. Mitch Jones, President and Chief Medical Officer. Also joining today is Dr. Florian Rieder, member of the Palisade Bio Clinical Advisory Board. I would now like to turn the call over to JD Finley, Chief Executive Officer. JD, please proceed. Thanks. Good morning, everyone, and thank you for joining us. We are very excited to be here today to walk you through what we believe is highly compelling data from our phase I, phase I-B fibrostenotic Crohn's disease trial. This readout is an important milestone for Palisade Bio and more importantly, a meaningful step toward providing patients relief for those living with Crohn's disease. We believe these results continue to support the potential of PALI-2108 as a differentiated next-generation therapy one that's designed to address both inflammation and fibrosis, which, as you know, is the core challenge in this disease. Taking a look at the study highlights. Patients with fibrotic Crohn's disease are among the most difficult to treat in all of gastroenterology. Once the disease progresses from inflammation to structural fibrosis, today's advanced therapies and biologics often lose effectiveness, and patients are frequently left facing surgery as their only option. With this phase I-B study, our primary goal was to establish safety and tolerability over two weeks of dosing. We're very pleased to report that PALI-2108 achieved that objective, giving us a strong foundation to move into longer duration studies. Beyond safety, these data also helped inform our dosing strategy. Our PK results show that we can achieve once daily dosing while maintaining IC90 coverage in both tissue and plasma. That's important because once daily dosing makes treatment simpler for patients without compromising the level of inhibition needed for the PDE4 pathway. Importantly, even though this is a small open label single-arm study, we saw encouraging signs of improvement, signs that are consistent with what we observed in our phase I-B UC study last year. We saw positive movement in key biomarkers like fecal calprotectin as well as SES-CD scores, which can be an important endpoint in Crohn's disease. Seeing changes in these objective markers after just two weeks is a strong early signal of PALI-2108's potential for having a real biological effect. Taken together, we believe these data further strengthen the positioning of our unique PDE4 inhibitor within the IBD landscape. Our goal with PALI-2108 is to address the full spectrum of disease, from inflammation through to fibrosis, and ultimately improve outcomes for patients. Looking at our accomplishments for last year. Before I hand things over to Drs. Rieder and Jones, I want to briefly highlight how far we've come as a company over the past year. Last August, we reported positive phase I-B data in ulcerative colitis, where we saw 100% clinical response and 40% clinical remission just after one week of treatment. Although this was also a small open label single-arm study, we believe these data are a strong validation of both the mechanism and the broader potential of our platform. It's important to note that we demonstrated safety and tolerability in this cohort using 30 mg BID dosing. Combined with our phase I-B in FFCD, we've now treated a total of 10 disease patients with results showing encouraging early clinical activity, safety and tolerability, and target engagement. The phase I-B UC data that we reported last August were instrumental in allowing us to complete $138 million transformational financing with some of the top fundamental health care funds. In addition, it served as the primary catalyst for strategic investment from the Crohn's and Colitis Foundation that was made earlier this year. We've continued to build on that momentum by presenting these data at major scientific conferences, helping increase both visibility and credibility within the GI community. At ECCO, for example, we shared RNA-seq data that further supports the anti-inflammatory and anti-fibrotic activity of PALI-2108. At the same time, we've strengthened the company operationally with key hires across clinical, regulatory, and financial operations, bringing in experienced leaders from organizations like J&J, Janssen, AbbVie, Vax, Teva, Bristol Myers, AbbVie, and JP Morgan, just to name a few. When you put all of that together, it really marks a major reset for the company and positions us to move forward with both momentum and confidence. Another important accomplishment is the caliber of clinical advisors and investigators we've been able to add to our Clinical Advisory Board. Not only is this a reflection of the work we've done internally, it's also a meaningful third-party validation of the potential of our program. We're fortunate to be working with some of the most respected leaders in IBD, many of whom are actively helping shape our clinical strategy. In addition to Dr. Bruce Sands and Dr. Florian Rieder, who've been with us for a couple of years now, we've recently added Dr. Vipul Jairath from Western University, Dr. Laurent Peyrin-Biroulet from the University of Lorraine, Dr. David Rubin from the University of Chicago, and Dr. Bram Verstockt from University Hospitals Leuven, all recognized leaders in the field. With that, I'd like to highlight Dr. Florian Rieder, who is joining us today. Dr. Rieder is a globally recognized expert in fibrostenotic Crohn's disease, and he leads the STAR Consortium, which is a collaboration of clinicians and regulatory experts working to establish approvable endpoints for FFCD studies. He works out of the Cleveland Clinic, serving in several leadership positions. He's the vice chair co-section head of or for inflammatory bowel disease. He's director for Global Inflammatory Bowel Diseases, and he's an associate professor in the Department of Gastroenterology, Hepatology and Nutrition. Dr. Rieder has authored more than 150 publications, and he's been deeply involved in shaping clinical guidelines through the European Crohn's and Colitis Organisation, including leading consensus work on intestinal fibrosis. We are very fortunate to have Dr. Rieder on our ClinAd board, and we thank him for sharing his perspective with us today. With that, I'll turn it over to Dr. Rieder to provide some broader context on the IBD landscape and intestinal fibrosis, before we move into the data presentation from our president and CMO, Dr. Mitch Jones. Dr. Rieder, it's all yours. Thank you very much, JD. As a representative of the Clinical Advisory Board, I gladly joined this call 'cause I'm very excited about the Palisade compound potentially addressing three large unmet needs that remain, which is moderate to severe luminal Crohn's disease, a safe and oral option in that space, and then drugs targeting not only inflammation, but also fibrosis, which is the new frontier in this area. Next slide, please. Crohn's disease is a progressive disease with a relapsing/remitting inflammatory disease course, which is depicted here in the blue line on the bottom. Underneath the threshold of obstructive symptoms, you have accumulating tissue damage that becomes apparent in more than half of patients with Crohn's disease in the form of scar tissue and stricture formation, which is then followed by internal penetrating disease, need for surgery or mechanical intervention such as endoscopic balloon dilatation. We really do not have any selective anti-fibrotic therapies available. There remains a big unmet need in luminal Crohn's disease, and the medications that we currently have are strong, but they hit an efficacy ceiling, with many patients failing to achieve long-term remission. There remains a critical need for potent, convenient, and oral therapy options. For fibrostenosis itself, we do not have any approved therapies, and we understand now well that patients with established tissue damage not only have the complications I just outlined, but also respond less to potent anti-inflammatory medications. Hence, medications with dual actions against fibrosis and inflammation may have a very high potential to work in this space. Next slide. Here delineated you see the approved Crohn's disease therapies that you're probably well familiar with. On the left, the anti-IL-12/23s and anti-IL-23s, the anti-TNFs and anti-trafficking agents. Then the only oral options for Crohn's disease, which is the Rinvoq from AbbVie. What becomes quite apparent is assessing the clinical remission and the endoscopic remission, that these drugs hit a ceiling in our patients with Crohn's disease, and that still there's a long way to go looking at the placebo-adjusted rates in achieving long-term remission in our patients, which is ultimately the goal to prevent disease progression and increase quality of life. Then looking further at the only oral option, Rinvoq, there are safety concerns. While this drug works very well, there have been reports on thromboembolism and MACE events, serious infections, pulmonary embolism, and so on. There remains an unmet need despite strong acting drugs that are approved for this indication. Next slide. What makes the PDE4 inhibitors unique is that these are pleiotropic drugs, and they increase cyclic AMP intracellularly. This has two big effects, anti-inflammatory and anti-fibrotic. It broadly decreases pro-inflammatory cytokines such as TNF and IL-23, which are known and efficacious targets in Crohn's disease. It decreases immune cell activation, trafficking, and broadly tissue inflammation, which as an end result, reduces inflammation. This has been shown across several inflammatory indications such as psoriasis, psoriatic arthritis, Behçet's disease, and COPD. In addition, and this holds promise to anti-fibrotic properties that are well established across organ fibrosis in different organs, PDE4 inhibition decreases fibroblast activation, collagen and scar formation. Collagen production and scar formation ultimately reduces tissue remodeling and scarring. A big breakthrough in the area of fibrosis was the approval of nerandomilast, a PDE4B inhibitor for idiopathic pulmonary fibrosis. Next slide. There are multiple commercial successes in the PDE4 space, and you can separate PDE4 inhibitors into pan PDE4 inhibitors and selective PDE4 inhibitors. A well-known example is Otezla from Amgen, as well as roflumilast from AstraZeneca, which is used for psoriasis and COPD respectively. There are novel formulations such as Verona, PDE3/4 inhibitor, or Arcutis with a topical PDE4 inhibitor which transformed the first generation roflumilast to improve tolerability and safety of the mechanism. I will talk in a couple slides about Mufemilast, who has now also data available in IBD. One can create selective PDE4 inhibitors for the same reason, and to increase tolerability, increase efficacy, and the best example recently is the PDE4B inhibitor, nerandomilast for idiopathic pulmonary fibrosis and then a PDE4B and D inhibitor Orismilast, which is currently in development with UNION Therapeutics. What makes the PALI-2108 unique is a once daily PDE4 inhibitor. It's a potent inhibitor as it comes as a prodrug that gets activated in the intestine and targets the terminal ileum and the colon, and has 10- to 20-fold higher potency levels compared to other PDE4 inhibitors. This leads to the conclusion that it likely effectively improves the therapeutic window and minimizes adverse events. The next couple slides, I will show you that we already have promising signals in inflammatory bowel disease using PDE4 inhibition. Next slide. The first example is apremilast, which showed a positive signal for clinical remission at 12 weeks in ulcerative colitis. This was an interesting dosing scheme in that the 30-mg BID dose, so the lower dose in this case, showed a very convincing signal for clinical remission in this population. At the higher dose, 40-mg BID, was less efficacious, which is suggestive of a bell-shaped dose response curve. Unfortunately, despite enthusiasm in the community about this drug that has been tested in 170 patients for this trial, that enthusiasm, this was not further developed, but not for safety or efficacy reasons, but for commercial reasons. Next slide. A very recently presented, a China-only phase II study in moderate to severe ulcerative colitis, 92 patients, which is mufemilast. It is developed by Hemay Pharma with quite impressive results. You see, on the left side, the full analysis set, on the right side, the per protocol set from the results. In the full analysis set, you have a clinical remission rate of 33.7% over placebo, and a mucosal healing rate at 50.5% over placebo already at week 12. There were a couple severe adverse events that may be on target that require further clarification, but overall, this data is in fact very impressive for a strong effect of PDE4 inhibition in ulcerative colitis. Next slide. What makes PALI-2108 different, and this is why I joined this Clinical Advisory Board and why I'm enthusiastic about supporting Palisade, is its once daily oral dosing compared to twice daily for instance, apremilast or Mufemilast. It is another target for inflammatory bowel diseases because no PDE4 inhibitors are currently approved for this indication. It is a gut-activated prodrug, the only PDE4 inhibitor that comes not as the active form, but needs to be activated in the intestine and acts in the terminal ileum and in the colon with high local tissue delivery and slow release into the systemic bloodstream. There's a belief that this improves a tolerability and minimizes common PDE4 inhibitor-related side effects, particularly its CNS and GI toxicity. Broadly, from a positioning perspective, I would differentiate PDE4 inhibition as a dual-action mechanism with a very well-established anti-fibrotic effect, and it has been shown across multiple fibrotic diseases in experimental systems, in addition to a potentially very potent and broad anti-inflammatory effect. With all of this, staying safe with a so far clean safety profile, which then supports the future oral or IV combination therapies. Because currently, combination IBD requires a safe backbone medication that is an add-on additional mechanisms of actions. This is, in summary, something as an IBD clinician and IBD expert, I would really like to see a novel drug. With this, I now hand it over to Mitchell Jones, the President and Chief Medical Officer of Palisade Bio. Thank you, Dr. Rieder. I'm Dr. Mitch Jones, President and Chief Medical Officer at Palisade Bio. It's really a pleasure to walk through these top-line data from our I-B study with you today of PALI-2108 in patients with fibrostenotic Crohn's disease. This study was an open-label, 2-week cohort study focused on a difficult-to-treat population with advanced Crohn's disease. These patients have confirmed terminal ileal stenosis and symptoms of stenosis. The primary objective was to evaluate the safety and tolerability of PALI-2108 under a once-daily dosing regimen, which was previously supported by our population PK modeling. We enrolled 5 patients and utilized a 10-day titration scheme across 3 dose levels: 20 mg, 25 mg, and 30 mg daily. Beyond safety, we conducted an intensive assessment of plasma and tissue PK and PD biomarkers via ileocolonoscopy, and we evaluated changes in the simple endoscopic score for Crohn's disease or SES-CD score. The executive summary of our findings is highly encouraging. PALI-2108 was well tolerated with no serious adverse events and no PDE4-related adverse events whatsoever. These events can be nausea, headache, vomiting and diarrhea. Critically, all patients achieved plasma pre-dose trough concentrations exceeding the IC90 by day 14, and we observed a robust increase in ileal cyclic AMP levels, approximately 41%. Importantly, even with just 2 weeks of treatment, 40% of patients achieved endoscopic response and 40% achieved endoscopic remission. To provide context on the patient population, these were individuals with significant disease burden. The mean disease duration was over 15 years, and 80% of patients were on concomitant biologics such as Humira or Remicade at the time of the study. The mean baseline SES-CD score was 8, which was higher than the Agomab study at 7.4, and the mean fecal calprotectin was nearly 300 micrograms per gram of tissue, underscoring the severity of their condition. When looking at the clinical activity, we saw a mean absolute reduction in SES-CD score of 3.8 points, representing a 47.5% improvement over baseline in just two weeks. Two of the five patients achieved endoscopic response and two achieved full endoscopic remission. While we acknowledge the small open label nature of the cohort, these 2-week results are numerically favorable when compared to 12-week benchmarks of established advanced therapies such as Skyrizi or Rinvoq. The PK data confirms that our gut-activated prodrug approach is working as intended. This is the first and only, as far as we're aware, demonstration of once-daily dosing with an oral PDE4 inhibitor, showing plasma trough concentrations above IC90 for all doses and all patients. As well, this is the first and only, as far as we're aware, demonstration of tissue PDE4 inhibitor drug concentrations at multiple doses above that seen in plasma, including greater than 3 x in the ileum and 5 x in the colon at steady state. In fact, we previously demonstrated that with systemic drug levels during the elimination phase, there's only a one-time drug concentration in the colon tissues of UC patients. This clearly demonstrates the benefit of local prodrug delivery. Importantly, this confirms that the 20 mg-30 mg daily dosing range provides the necessary coverage for steady-state efficacy and confirms our Pop PK modeling, supporting once daily dosing for both our phase II UC and Crohn's programs. Our PD data shows strong target engagement. The 43% increase in ileal cyclic AMP was greater than the 27% increase observed in colon tissue during our UC study. This study was done with a max tolerated dose. Furthermore, we saw a means of 59% reduction in fecal calprotectin during the study, which rebounded after treatment was withdrawn. In addition, there was a tight correlation between our PD biomarker cyclic AMP, which is a pleiotropic governor of inflammatory tone and fibrosis, and fecal calprotectin, which is an inflammatory biomarker collected from stool and coming from the cytoplasm of inflammatory cells in inflamed mucosal tissue. We believe this tight correlation provides a clear translational link between our mechanism of action and the reduction of inflammatory burden, which results in an improved clinical outcomes. We have now treated over 94 patients with PALI-2108, including 10 diseased patients with over 30 patient weeks in patients with disease and over 100 patient weeks of treatment overall. Safety remains a key differentiator for 2108, and previously we had evaluated only max tolerated doses in diseased patients. In this difficult and highly refractory population, the drug was generally safe and well tolerated, with no serious adverse events and no study or treatment discontinuations. All treatment emergent adverse events were mild, specifically one instance of abdominal discomfort and one of fatigue that were deemed possibly related to drug. Importantly, we saw no PDE4-related adverse effects at all. No nausea, no headaches, no vomiting, no diarrhea. Side effects often associated with traditional twice-daily, immediate release or systemically distributed PDE4 inhibitors. In conclusion, these data support a coherent translational signal. We've established robust PK in all segments of bowel. Strong target engagements correlated tightly with the most accepted inflammatory biomarkers and objective endoscopic clinical activity that supports moving into broader luminal Crohn's populations. Our next step is to assess the efficacy in moderate to severe Crohn's disease, where we will continue to evaluate antifibrotic effects earlier in the course of disease. With that, I'll turn it back over to the operator, for some Q&A. Operator. Thank you. We'll now be conducting a question and answer session. If you'd like to be placed into question queue, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. We ask you please ask one question and one follow-up. Once again, that's star one to be placed in the question queue, and please ask one question and one follow-up. Our first question is coming from Yasmeen Rahimi from Piper Sandler. Your line is now live. Good morning, team. Congrats on the outstanding data, and thank you so much for sharing it with us this morning. Two questions. First one is, given this data, maybe it'll be helpful to help us understand for the next steps in development in Crohn's and maybe the thought process for selecting Crohn's over stenotic Crohn's. That's question one. Question two is, I know you guys have been very, very busy trying to bring this data to the finish line, but also in the background, continuing to enroll into your UC study with data expected next year. If you could provide some color around the cadence of how enrollment is progressing, sort of the cadence of catalyst and, ensuring data, that would be really helpful. I'll jump back in the queue. Great. Thanks, Yas. I'll turn this over to you, Mitch, probably for both. I'll just kind of start off by saying that obviously we've been guiding that we wanted to wait to see these data from this study before we made any final study design decisions with regard to Crohn's disease. I think we've got a pretty clear indication that a broader population of luminal Crohn's patients is probably where we're headed. Mitch, why don't I turn it over to you to elaborate on that and then also address the question regarding kind of the timing moving forward in the various studies. Sure. Yeah. No, and maybe I'll start, you know, as well. I think I'd love to hear, you know, Flo's take on this. Obviously, Flo's probably the world expert in fibrostenotic Crohn's, and also has done grad work, including, I think, PhD on PDE4 inhibitors, anti-inflammatory, antifibrotic effects. I'll say something about Crohn's and then ask maybe Flo to make some comments, and then we'll, you know, I'll jump back on the enrollment and progress piece. We've chosen to focus on luminal Crohn's because it's the most straightforward, well-established regulatory path. It's a larger opportunity, and clearly, we have data that support our drug in luminal Crohn's. In contrast to fibrostenotic Crohn's, you know, we've worked with the team and our experts over the last six months to sort of really deeply understand, you know, the potential regulatory paths. I think, you know, it's clear that Crohn's, as opposed to fibrostenotic Crohn's, has a clear, much clearer regulatory path. It's also clear that Agomab will be blazing a trail and developing a regulatory path that we can potentially be fast followers with what we believe to be a really the best candidate in fibrostenotic Crohn's. As Flo pointed out, nerandomilast has an approval in IPF. We feel that our drug is good and will be good in that FSCD. Clearly there's a significant unmet need in Crohn's disease. There's only one approved oral, and that's the JAK inhibitor with a black box warning. And then clearly our data with our SES-CD score demonstrate quite a compelling anti-inflammatory response in a short period of time. But I think, in speaking with Flo, he had a few comments on this as well that he could potentially share with you, and then I'll get back on for the enrollment and timeline piece. Flo? Yeah. The approach that Palisade decided to take is a reasonable one. The anti-inflammatory effect seen in this population, and granted it's five patients, but all results point in the same direction, which in early development we look at when the numbers are small and they all point in the same direction. This is the hardest to treat population, so the disease duration is about double what you see in luminal Crohn's disease. They have established tissue damage. Their inflammatory burden was on the mild to moderate side in this patient population, and the effect was massive when you think about where this population, other drugs will not work at all or will have only a minimal effect. This, I think, produces confidence that in moderate to severe luminal Crohn's disease, where there is an unmet need for safe oral options, that this will be a very strong and fast-acting drug, that patient studies will need to show if this is truly the case, but it's very, very promising results in these five patients from the phase I-B study. I think treating remodeling, even in non-FSCD Crohn's disease, luminal Crohn's disease populations, holds promise for preventing progression of disease ultimately. I also think that starting in luminal disease, to Mitch's point, does not exclude a future study in fibrostenosis. Their regulatory path is currently being built through Agomab and others, and then Palisade could go in at a later time and bring in this oral option to fibrostenosing Crohn's disease patients. Mechanistically, I can hand it back to JD or the operator, but mechanistically, there is really no question in the community that increasing cyclic AMP through PDE4 inhibition has also anti-fibrotic properties. That is unique because none of the other approved drugs in Crohn's disease has this strong effect on fibrosis from other diseases and from mechanistic investigations. I think the data to me looks very, very promising in a population that's very hard to treat. Back to you, JD. Thank you, Flo, and I'll take this for the second question, sort of on timeline and enrollment. We've taken a pretty aggressive approach, as many of you know, on our enrollment plan. We have made a lot of development in the past months. We've selected PSI as our CRO with strong experience in running IBD trials. Iterative Health is gonna help us as an enrollment partner, and we've aligned ourselves very closely with them. We've built a focused plan around site selection, patient identification and recruitment. We're leveraging the various networks, including Iterative, to avoid the typical enrollment bottlenecks. We're on track for a second quarter IND filing, and our planned enrollment is already well advanced. Overall, we're confident in executing and achieving top-line data by the end of 2027. Thank you for those questions. Thank you. Next question is coming from Kaveri Pohlman from Clear Street. Your line is now live. Good morning, team. This is Wayne, for Kaveri. Congrats on the data, and thanks for taking our questions. We also got two. First one for Dr. Rieder. Could you share your view on these results, how meaningful you consider the data to be, how much having patients on background therapy may have impacted outcomes, and what read-through they provided on durability of response? Based on the results and overall biology of PDE4, what level of confidence you have in PALI-2108's potential to compete in both UC and CD IBD markets? One for the team, what factors are you considering in determining the final dose for subsequent trials? With data now from both UC and CD patients, do you expect to use the same or different dosing strategies for UC and CD going forward? Thank you. Yeah. Thank you. Great. Oh, sorry. Go ahead. Yeah, exactly. Yeah, go ahead, Flo. Yeah. Maybe I start. This is a really good question. To reiterate my prior comment, so in a population like this, very promising data for anti-inflammatory effects of the drug and potentially anti-fibrotic effects of the drug. In one patient, in fact, that had non-passable stenosis at inclusion, the stenosis I believe either completely or almost completely resolved after only two weeks of treatment, so quite impressive. Your point about the background therapy is an important one because four out of five patients were on background therapy and this was an add-on. That tells a couple things. The patients still had active disease on background therapy, so there was still active disease to be treated. This shows us that the effect of PDE4 inhibition is broad. If you are, let's say, on an anti-TNF when you go into the study and you add on the PDE4, that also suppresses anti-TNF, but also other cytokines, it clearly shows that it works in addition to the mechanism the patient was on. That was promising. The other interesting learning, and again, it's only five patients. I don't wanna get, like, over enthusiastic in a small study. The other positive finding is combination. There were no concerning signals of any sort that combining two drugs with each other was a problem. It was only two weeks, there was an observation period after. For the combination play, particularly in Crohn's disease, is a very current one in the field. A drug like this for oral combinations, which would be the optimal version if you have oral combo pill. Ultimately, this could be a very interesting partner in the future. I hope that answered your question. Thanks, Flo. Mitch, do you wanna talk a little bit about what we're doing in terms of the dose selection strategy? Yeah, sure. Previously, I think many of you know as well, we have developed a population PK model based on our phase I data, and that suggested that a 30 mg daily dose could achieve IC90 systemically, and we use that as a target dose. In our FSCD study, we wanted to start with slightly lower doses and evaluate 20 mg and then 25 mg and 30 mg because the population is advanced and potentially susceptible to issues with safety and dosing. We started at 20 mg, went to 25 mg and then 30 mg. Again, we saw excellent tolerability. I think what we didn't know that we found out here is, you know, this is the only once daily PDE4 out there. It's the only one we've seen discussed or published or described. The drug has a long half-life. We didn't know that we could, you know, we hadn't shown that we could go to oral once daily dosing over periods of time. What this shows is with doses as low as 20 mg, we were able to achieve greater than IC90 systemic drug concentrations. We saw that in all patients in the study. We also took samples of the ileum, ascending and descending colon in all patients by ileocolonoscopy. This was on, you know, this is difficult work to do. You do this baseline, you do at endpoint. There's a bowel prep, and patients take the drug. You know that previously in our UC study, we showed roughly a one-to-one tissue to plasma ratio on the 36-hour elimination profile of the drug. What we did in this study is we wanted to know at steady state what is that ratio. Between four and eight hours, we had patients taken in to have an ileocolonoscopy after dosing, and we saw patients with greater than a threefold tissue to plasma drug concentration ratio. We saw that was greater than 5x in colon, and that was in all patients. We saw, you know, incredible results here. We're gonna use those results together with a completed normal healthy study that's evaluating target phase II dosing. We are also working with a group on a population, a group that previously worked on Xeljanz on population PK modeling. We have an ongoing conversation with the agency. We'll use these data, the normal healthy data, and then the modeling data in our conversation with the agency to select final doses. We're very close. Thank you. Our next question today is coming from Alex Thompson from Stifel. Your line is now live. Great. Congrats on the data and thanks for taking our questions. I guess the first one, you know, on the therapeutic index that you're demonstrating here across both UC and Crohn's now, I guess can you talk about historically the PDE4 systemic adverse event time course and sort of your confidence in seeing this translation to longer studies? Then maybe as a follow-up, in the one patient that did not see any change in clinical activity score over the 14 days, were they on background therapy and what dose of drug were they on? Thanks. Yeah. Mitch, do you wanna take that? Sure. I think, you know, today we're not prepared to give individual patient data. We have, over the next few days, including tomorrow, we have a presentation, so we'll be able to speak to sort of individual patient data, you know, over time. Yeah, sorry, what was the first question? ...of this therapeutic index to longer studies and sort of historically how quickly... Oh, right. You see PDE4 adverse events. Thank you. 48-72 hours is when we have a peak in adverse events. In our phase I, SAD, MAD, and food effects, the peak adverse event number came 2-3 days after initiation of dosing, generally when we reach steady state. Thank you. Our next question is coming from Aydin Huseynov from Ladenburg Thalmann. Your line is now live. Hello, good morning team. Congrats with the great data in fibrosing Crohn's patients. I wanted to ask a question about the baseline SES-CD that you had on those 5 patients and how this compares to t he prior studies and prior CD trials that are currently in use. You know, it's you know how to interpret the remission and response rate compared to what we've seen in the past in general CD population. Mitch, do you want to answer that? Flo, did you want to take the baseline? Yeah, that's a good idea. Flo, did you want to take the baseline SES-CD score? I know that. Definitely. Question is very good. The SES-CD score of 8 in the study is on the milder side of moderate when you compare this to the conventional moderate to severe Crohn's disease studies. The conventional luminal Crohn's disease studies have a higher SES-CD, have a higher fecal calprotectin value, have less disease duration, so in this case, 15 years in these 5 patients. In moderate to severe Crohn's disease, the average disease duration 7 years. In comparison, this trial population has a higher exposure to prior biologics compared to moderate to severe luminal Crohn's disease, higher exposure to prior biologics, a lower endoscopic disease activity, a lower biomarker disease activity as measured by fecal calprotectin, higher degree of tissue damage, and longer disease duration. In totality, this makes this study population less likely to respond to an anti-inflammatory intervention, which is. I mean, the primary was safety tolerability in this study, which makes a ton of sense from a development perspective. I honestly didn't expect to see an anti-inflammatory signal because the population is so advanced. From that perspective, compared to available Crohn's disease data, it is very impressive to see anything from an anti-inflammatory perspective after 2 weeks because usually induction in moderate to severe luminal Crohn's disease 12 weeks. To put it into perspective, it's a mild, on the mild end of moderate population with severe tissue damage and long disease duration. Mitch? Yeah, no, I think one other data point is the Agomab baseline was 7.4 with a change over 12 weeks of 2. Thank you. Yeah. Does that answer your question, Aydin? How far do you think these patients were from potential surgery? I appreciate providing slide of Crohn's disease progression, you know, from luminal to fibrostenotic. How far do you think these patients were from potential surgery? I think maybe I can answer that. You know, there was one patient that sort of had pinhole stenosis, so in non-passable stricture. I believe that one patient by the end of two weeks had a passable stricture. Again, we're not, you know, we didn't wanna go through all of the sub-score data right now, but I do know that at least one patient had an impassable stricture and then passable by the end of the study. Thank you. Next question today is coming from Naz Rahman from Maxim Group. Your line is now live. Hi, everyone. Congrats on the data. I have a question for Dr. Rieder. I understand the small patient population, but based on all the data you've seen and generated, if this therapy were approved and the data was consistent in future studies, what do you think would be the ideal patient that you would prescribe the therapy to? What would that profile look like? Yeah, this is also a very good question. If you look at key features for a new drug, safe, that seems to fall into that category from what we've seen for this compound, but particularly from the class across diseases, the safe option. It's oral, so that's patient preferred in general. It's potentially highly efficacious. This together makes it a candidate for pretty much any clinical scenario. It could be a first-line moderate to severe luminal Crohn's disease drug because you have an effect on remodeling. Potentially, this is all theory obviously, but reading from all the existing data, Laurent Peyrin-Biroulet, treating inflammation and preventing accumulation of tissue damage as a first line. Given the broad anti-inflammatory effect inhibiting IL-6, TNF, IL-23 and others, other pathways, it could be a good drug for biologically exposed patients. This is what I had mentioned earlier. Four out of the five patients in this study were on concomitant biologic, and still you see this effect with an add-on of this drug, indicating that it has a very broad anti-inflammatory effect. I think biologically exposed patients has potential. In very advanced patients too. Pre-obstructive patients that have tissue damage and about to obstruct and close up the lumen or established a stricturing disease. In a population like the one that was included in this study, the event rate over 1 year, meaning need for intervention like balloon dilation or surgery, is about 30%. These patients are actually very sick and large portion of them is on their way to surgical resection. One additional thing that we haven't talked about, which may also be important, is extraintestinal manifestations. If you effectively treat luminal disease and you have some systemic exposure of the drug, the mechanism may also benefit extraintestinal manifestations like arthropathies, for instance, or other skin manifestations that you can find associated with IBD. Thank you. Our next question today is coming from William Wood from B. Riley Securities. Your line is now live. Hi. Thanks for taking our questions, and congratulations on the very nice data. I'm just trying to think in terms of you've shown the roughly a 40% endoscopic remission as well as a roughly 40% response rate at 14 days. How should we think about this in terms of 12-week or even longer term, you know, closer to a year data, you know, in terms of fibro? Then and additionally, on sort of the fibrosis score, you provided SES-CD, but I was curious as well as some biomarkers related to that. But I was curious if you could comment on specifically any improvements in fibrosis. I know you mentioned strictures at one point, but any additional color there could be very beneficial. Then I have a follow-up. Thank you. I mean, I can start maybe. So we do have a large number of biomarkers that have been included in the study for fibrosis. We've included a set of plasma biomarkers as well as superficial and deep histological biomarkers, including staining. Some of the earliest signs we believe of antifibrotic effects could be the engagement of certain pathways that have been well described by Dr. Rieder in the literature that are pathophysiologic driving pathways for FSCD. Looking to see, you know, which of those pathways by RNA-seq have been engaged. In this case, we've actually. We're working with the Cleveland Clinic and Dr. Rieder's lab on evaluating the anti-inflammatory and antifibrotic activity of specific cell populations within the lamina propria and comparing that to cells in PBMC. We're gonna be doing that single cell expression level work with Dr. Rieder. But I think the question is a good one. The other question was, you know, what we should expect at 12 weeks and even as long as a year? Dr. Rieder, do you wanna speak to that one? Definitely. Yeah, definitely. Across all approved drugs, the patient continues to get better from week 1 to week 12. The only examples where this was not the case is drugs that have been in development where half-life was short and only one dose was given, for instance, where you see a short-term effect and then patient gets worse again, or drugs whose mechanism doesn't work or only works for a very short time. In a mechanism like this that is quite broad, well-established, there is a very strong reason to believe that beyond 2 weeks the patients will get better. Even the 12-week time point that is used in luminal Crohn's disease trials is arbitrary. The only reason why it's 12 weeks is because when drug development started in Crohn's disease, the first study was done with 12 weeks induction, 48, 52-week maintenance. This is arbitrary because biologically, even after 12 weeks, the patient continues to get better with many of the drugs we have in luminal Crohn's disease. It was just purely a regulatory early precedent that was followed ever since. This likely, I assume, in the luminal Crohn's study for Palisade will be around 12-week primary endpoint, induction endpoint. There is good strong reason to believe the patient continues to get better from week two to week 12, and there is a rationale to be made. The patient may continue to get better from week 12 to the end of maintenance. Week 48 or 52 would be standard time points, as we have seen for anti-IL-23, for anti-TNF, for JAK inhibitors, many of the patients continue to get better. This is particularly the case when you consider the remodeling effect, because remodeling may take a bit longer, to take effect. Two weeks may be a short time for treating fibrosis. Still, we see a widening of the lumen and other indicators that this may work. Mitch commented on the biomarker work where we hope to see some effect. I'm comfortable saying I believe that even beyond 12 weeks that you will see further improvement after induction towards maintenance. Thank you. Next question is coming from Mitchell Kapoor from H.C. Wainwright. Your line is now live. Hi. Good morning. This is Katie on for Mitchell. Looking at your two patients with potentially related adverse events, were these the same two patients for both events, or are they different patients? Were either of these from the high-dose cohort? Neither were from the high-dose cohort. One was fatigue, one was discomfort, and they were different patients. Thank you. Perfect. Thank you. Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over for any further closing comments. Thank you everyone for joining us today, and special thanks to Dr. Rieder for sharing his expert perspective on the IBD landscape. Most importantly, we want to express our gratitude to the participants in the trial, the clinical site investigators and, you know, of course, the entire Palisade Bio team. Their dedication made this data possible, and today marks a significant milestone and step forward for our company and our mission to bring this important PDE4 inhibitor to the IBD community. We look forward to keeping you updated on our progress. Thank you. Thank you. That does conclude today's teleconference and webcast. You may disconnect your lines at this time and have a wonderful day. We thank you for your participation today.