Good day, and welcome to the Morphic Therapeutic conference call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session, and instructions will be given at that time. As a reminder, this call is being recorded. I'd now like to turn the call over to Chris Erdman, Head of Investor Relations. You may begin. Thank you, Michelle, and thanks everyone for joining this morning. We will get going in just a moment, but first I'd like to caution everyone that during this call we will be making forward-looking statements. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainties that may cause the actual results to differ materially from those contained in the forward-looking statements. These and other risk factors can be found on our most recent Form 10-Q filed with the SEC. As such, we advise you to refer to the risks and uncertainties of our businesses outlined in the SEC filings. Now, on slide 3, we'll get going in just a moment, and we're glad to take this opportunity to review the detailed findings of the EMERALD-1 study of MORF-057 in ulcerative colitis, in conjunction with a presentation at UEG Week 2023, where posters are being released this morning. The EMERALD-1 study was designed to test the hypothesis that MORF-057 is a clinically active alpha four beta seven inhibitor for the treatment of IBD. The top line data of MORF-057 in EMERALD-1 were released in April, and those results answered that question with a clear yes. The EMERALD-1 study met its primary endpoint with statistical significance, and each of the clinical indices measured in this study were also positive, exceeding our expectations in many ways. In parallel with the EMERALD-1 study, we are conducting the randomized, double-blind, placebo-controlled, dose-ranging EMERALD-2 study to further underpin the safety and efficacy profile of MORF-057. We want to take this moment, though, to acknowledge recent questions in the market and use this time specifically to conduct a comprehensive review of the EMERALD-1 data, including maintenance data well beyond this 12- week induction period, and of course, answer questions from the audience. Before we get started, though, it's important to give an update on Praveen. Anyone who knows our CEO, Praveen Tipirneni, would immediately understand that for him not to be on this call while he is out on medical leave must be extremely difficult for him. However, I'm incredibly happy to report today that Praveen continues to recover at home, and I think I can speak for everyone on the Morphic team, as well as a legion of friends and colleagues who've relayed their well wishes, that we're sending our absolute best. Now, taking a look at the agenda. Today on the call, our first speaker will be Brihad Abhyankar, our SVP of Clinical Development, and he'll give an overview of the Emerald One study, the safety findings, and the PK/PD results. Then Bruce Rogers, President of Morphic, will review the clinical efficacy data, and Marc Schegerin, our COO and CFO, provide some closing thoughts and corporate updates. We're also very fortunate and grateful to have a special guest today joining the question and answer portion of this call, Dr. Brian Feagan. As many of you know, Dr. Feagan is Professor of Medicine at the Schulich School of Medicine and Dentistry, a gastroenterologist at London Health Sciences Centre, and Senior Scientific Director of Alimentiv, Inc. Dr. Feagan has been at the forefront of IBD clinical research for the last two decades and is one of the top global, global opinion leaders in the field, and we look forward to his participation today. Now I'll hand the call over to Brihad. Thanks, Chris, and thanks to everyone joining today. I'm glad to have this opportunity to review the EMERALD-1 study and its outcomes to date. EMERALD-1 is an open-label induction trial of MORF-057, orally dosed at 100 milligrams twice daily in patients with moderate to severe ulcerative colitis or UC. The primary endpoint of the study was change in the Robarts Histopathology Index, or RHI, at 12 weeks. The secondary endpoint was change from baseline in the modified Mayo Score at 12 weeks. There is a 40-week maintenance phase of EMERALD-1 that is ongoing, as well as a 26-week open-label extension study. Before we move on to the baseline disposition of the patient population, it is informative to understand the inclusion and exclusion criteria for EMERALD-1. Patients enrolling in the study were required to have Modified Mayo Score between 5 and 9 points, with centrally read endoscopy score of at least 2. They were also required to have a baseline RHI of at least 10. In addition, patients could have had prior failure to up to 3 advanced therapies from 2 mechanisms. Patients who previously received vedolizumab or other integrin inhibitors were not eligible for inclusion in the primary cohort. Next slide. The EMERALD-1 study met its enrollment target with 35 patients ahead of schedule. This patient population, as you can see on slide 7, was a representative UC population with high disease burden. The study enrolled 80% of its patients in Poland and 20% in the United States. I want to call your attention to the mean RHI score of 22.7, which puts this group at the higher end of the disease activity spectrum. Their mean baseline modified Mayo Score was 6.7 points. The split between Mayo endoscopic scores was virtually even between 3s and the 2s. Approximately a quarter of patients were on baseline corticosteroids. As is usual with IBD studies, patients on steroids were required to maintain that regimen through 12 weeks of induction. Notably, 40% of the patients had previously failed at least one advanced therapy, also referred to as AT. For example, anti-TNFs, JAK inhibitors, anti-IL-23s and S1P.... Overall, as I mentioned at the outset, this is a moderately to severely active UC cohort, but taking into account their baseline clinical characteristics, endoscopic scores, and prior AT experiences, they are skewed more towards severely active end of the spectrum, and as such, a difficult to treat population with high disease burden. Now, on slide 8, we see a highly detailed breakdown of patients' baseline disposition by prior treatment status and by Mayo Endoscopic Scores. We present this for your review, and I will call out some areas, but I do want to take a careful look at the baseline disease burden and prior therapeutic experience for patients in various subgroups. What you see in the baseline clinical measures is, as one would expect, overall higher severity of disease in those patients with prior advanced treatment experience and also higher endoscopic scores. In the AT experienced patients, who comprise 40% of overall population, 10 out of these 14 patients had endoscopy score of 3, and 5 of these 14 were on baseline corticosteroids. Moving briefly now to the safety results on slide 10, which continue to be favorable since reporting top-line results. As you see on the slide, we have observed no new serious adverse events or grade 3 treatment-related adverse events. Just a reminder that an oral, safe and tolerable, and efficacious treatment for IBD patients has been an elusive goal in this field, and we aspire to satisfy that acute need for these patients. Although we won't spend much time this morning on safety, it is clearly one of the most important attributes of any IBD treatment, and we are extremely encouraged by the emerging profile of MORF-057 to date. Moving on to the pharmacokinetic effects, we disclosed these α4β7 receptor occupancy data in April with top-line results of EMERALD-1, and I show them again as a reminder. In short, the data observed in EMERALD-1 were very consistent with the experience in healthy volunteer studies, where we saw sustained saturation of α4β7 receptor rapidly in the vast majority of patients at 100 mg twice daily dose. The mean trough α4β7 RO was more than 98% at week 12, and α4β1 projected RO was below the limit of quantification, with mean trough RO estimated to be less than 15%. Again, no lymphocytosis or changes to circulating naive cells were observed, consistent with low levels of RO for α4β1. That leads us to some important new pharmacodynamic data on slide 13, where we see substantial lymphocyte subset changes, consistent with the engagement of alpha-four beta-seven receptor that further confirm our mechanistic hypothesis. A significant increase was observed in circulating levels of effector memory T cells, central memory T cells, and switched memory B cells. These changes are consistent with the phase 1 trial observations, as well as with published real-world vedolizumab data. On slide 14, we show new data looking at fecal calprotectin decreases from baseline, an important and specific marker of disease severity and improvement in UC. Please note that we did not require any specific elevation of calpro for inclusion in the EMERALD-1 study, thus, the data are shown here for 29 patients with baseline calpro above 250 milligrams per kilogram. In the chart on the left, you will see the percentage of patients who had elevated baseline levels of calprotectin that decreased to less than 250 after 12 weeks of MORF-057 treatment. As expected, 35% of overall population normalized their calpro, and this normalization was also highly correlated to the extent of clinical improvement. Similarly, in the chart on the right, we look at the% reduction in calpro from baseline by response status and observe the same expected pattern. While also anticipated, it is reassuring to observe that these results correlate with those seen with other effective treatments. On slide 15, we see changes in the C-reactive protein or CRP. CRP is a non-specific biomarker, commonly used to measure inflammation. We observed the anticipated changes in CRP, with 24% of patients who had a baseline CRP greater than 3, achieving levels below 3. 33% of responders and remitters also achieved the levels below 3. Before I turn over to Bruce, let me summarize these data. In a population of UC patients with high disease burden, many of whom were refractory to current advanced therapies, we see favorable safety data coupled with a PK profile in line with our targets and biomarker results consistent with previous MORF-057 studies. Further, these data are very much in line with our expectations, considering our knowledge of alpha-4 beta-7 inhibition activity in patients with ulcerative colitis. Bruce? ... Thanks, Brihad. Before we take a deep dive into the details of the clinical efficacy data from the EMERALD-1 trial, I want to take just a minute to review the scoring measures that we used in this study to ensure a clear understanding of the magnitude of changes required to achieve the results that we observed with MORF-057 in EMERALD-1. As you all know, change from baseline in the Robarts Histopathology Index, or RHI, was the primary endpoint in EMERALD-1, and this was achieved with statistical significance. A key point I want to convey here is that RHI was developed to provide physicians with a reproducible, granular measure of changes in UC disease activity. This validated tool is predicated on centrally read histopathology samples and has a wide dynamic range of 33 points based on four individually weighted scores. A second takeaway that I want to leave you with is that achieving remission on RHI is a very stringent measure, with an RHI of less than or equal to 3 required on a scale of 33. For context, the graphic at the bottom of this slide shows there, where each of our 35 patients entered the EMERALD-1 study and scored at the outset of the trial. Note that patients were required to have an RHI of greater than or equal to 10 to enroll, and that our patient population, right shifted on this graph, is clearly weighted toward the more severe category. As a side note, our guest today, Dr. Brian Feagan, was instrumental in the development of RHI, and we're glad to have him here today to lend his expertise in answering questions. Let me also quickly review the Modified Mayo Score, which is the metric used by the FDA in UC registrational studies. I'm assuming some level of familiarity with this score as well, but we want to point out a few important nuances. The modified Mayo Score is comprised of measures of stool frequency, rectal bleeding, and Mayo Endoscopic Score, or MES. Each is measured on a three-point scale, with stool frequency and rectal bleeding comprising clinically observable measures, while the MES is determined with an endoscope. In EMERALD-1, patients underwent endoscopy at baseline, at week 12 upon completion of induction, and will have an endoscopy at week 52 with the completion of the maintenance phase of the study. The data you see today will include the 12-week Modified Mayo Score and its subscores, as well as symptomatic improvement and remission data out to 44 weeks, as measured by the clinical reportable components of stool frequency and rectal bleeding. Here, a rectal bleeding score of 0, with a stool frequency score of 0 or 1, with greater than a 1-point reduction is required for symptomatic remission. There's been a great deal of interest in the endoscopic improvement score reported for EMERALD-1 in the UEG poster abstract, so I thought I'd pick out a few specific comments here, as well. Endoscopic improvement requires a Mayo Endoscopic Score of 1 or less, so we should keep top of mind the composition of the patient population in any study. In ours, half had a baseline MES of 3. In addition, EMERALD-1 used a centrally read endoscopic scoring process. For those who are clinical trial aficionados, the centrally read endoscopic scoring process has raised the bar for MES determination and led to higher reproducibility across clinical trials for the same drugs. Its introduction into contemporary trials, as published, has achieved higher sensitivity and lower placebo rates in endoscopic scoring. Now, on slide 19, I want to remind you of the primary goal of EMERALD-1 was to show a rapid initial signal of MORF-057 clinical efficacy on target with our expectations. The data shown here, coupled with the current safety profile, tell us, unequivocally, that we have achieved this goal. So far, we have an oral, well-tolerated alpha four beta seven inhibitor that is clearly active in UC patients. I recognize that there are more, there's a more detailed discussion to be had today, but this is our interpretation of the top-line data that you've all already seen. Looking closely, we see several important clinical measures of activity. In each of these, we see a clear and consistent activity in UC patients. EMERALD-1 achieved its primary endpoint with a statistically significant reduction in RHI from baseline of 6.4 points, with a P value of 0.0019. The RHI remission rate of 23% is also consistent with the Modified Mayo remission rate of 26%. I want to note here that the endoscopic improvement rate is in fact identical to the Modified Mayo remission rate. This is due to the fact that the 9 patients who achieved a centrally read endoscopic improvement threshold also improved dramatically on the 2 clinical measures, qualifying them as remitters as well. It's also instructive to note that this has occurred in other recent studies. We expect endoscopic improvement rates to continue to increase with additional MORF-057 exposure and eventually differ in a larger study. Finally, the 2.3-point mean reduction in modified Mayo at week 12 is also a strong overall result. Slide 20 starts to dive into increasingly smaller subsets of analysis of MORF-057 activity at 12 weeks, going even further than our UEG poster, which is just released. Here, we divide our patients into important factors, driving a deeper understanding of the severity of disease in this UC patient population, namely advanced therapy status and Mayo endoscopic score. The first obvious thing here is that on every measure, at 12 weeks versus baseline, from the primary endpoint of mean change in RHI to the mean change in modified Mayo, to each subset shown in this table, a higher percentage of patients improved that were either AT naive or had an MES of 2, than patients that were AT experienced or had an MES of 3. A clear and consistent trend that most studies in UC have shown. I mentioned on, I mentioned on the last slide that this study was powered for change in RHI, and we're extremely encouraged by these strong results, with approximately half of patients experiencing a 7 or greater point drop in RHI and 34% of patients showing a 50% or greater drop in RHI. I want to spend just a little more time here discussing the RHI results, noting a few key points. First, the statistically significant outcome of the full 35 patients, now split out by AT status or MES status, shows a clear and consistent trend. Patients in both groups responded and achieved RHI remission with an RHI score of less than 3. In fact, here, the most severe patients, represented by both AT experienced and MES of 3, responded to MORF-057 on RHI, with 36% and 41% respectively, changing by 7 or more points. In addition, we saw RHI reductions of 50% or more across all of these subpopulations. Now, moving further down this table to the Mayo scores, the same trend persists. Patients generally improved after 12 weeks, independent of their baseline status. For example, clinical responses were observed in 52% of naive patients and 36% of AT experienced patients, with a similar trend observed among patients who had an MES of 2 versus an MES of 3. As a reminder, 10 of the 14 AT experienced patients were also very severe, starting this study with an MES of 3. Moving down to clinical remission, the highest bar for improvement. You'll notice that we did not observe remissions in the group of 14 AT experienced patients, but did observe a 43% remission rate in the naive group of 21 patients. Likewise, a third of the MES 2 patients went into remission, and 18% of the MES 3 patients achieved this threshold. As we've mentioned, this trial was not powered for the modified Mayo on its entirety, let alone for these subsets, but we believe that the variability observed, especially for this binary outcome, is likely due to random chance. We fully expect these numbers to converge in larger trials, such as EMERALD-2, given the significant increased power of large randomized trials. In addition, a trend that will become obvious as we follow these patients out past 12-week induction period, that I'll walk you through in a few moments, show that even the most refractory and severely diseased patients tend to improve over time. Slide 21 shows us two forest plots illustrating the changes in RHI and modified Mayo from baseline to week to 12 weeks, broken out by the main subgroups we've already discussed this morning, AT experienced versus naive, steroid use upon induction, and baseline MES. What I take from this is a clear and consistent set of results that are in line with the literature describing activity in UC with alpha-4 beta-7 inhibitor treatment. These results are comparable to the literature, directionally positive, and demonstrate the expected variability by severity and prior failure of the advanced therapies that you'd expect with an effective UC therapy. I won't spend much time here on slide 22 since we've already covered this data in other slides, but briefly, this is a simple graphic that clearly depicts what we've already described. The majority of patients derive benefit from MORF-057. Consistent with other trials, we see less refractory patients had a greater and earlier response, but the profound thing here is that we see benefit across this entire population. On slide 23, we move to the subgroup analysis to a broad look at MORF-057 efficacy in EMERALD-1 through individual patient Mayo data score changes at the end of this 12-week induction period. This waterfall plot shows the change from baseline on modified Mayo for each of the 35 patients in this EMERALD-1 study. This is simply the underlying patient-by-patient data from the last slide. While EMERALD-1 is a small study, you can see the consistent breadth and depth of responses through this data visualization. I believe these data speak for themselves, and this is just our jumping-off point for a much deeper dive into this data. So let's drill down. If you look down at slide 24, we've layered on top of this waterfall plot a very rich set of individual patient data, including notations on whether each patient experienced clinical remission or response, experienced a reduction in RHI of greater than or equal to 7 points, had baseline and therefore concomitant steroid use throughout the 12 weeks, was a 2 or a 3 at baseline on the Mayo endoscopic score, and finally, prior advanced therapy use. For simplified viewing and interpretation, we've coded each of the bars in the waterfall markings to denote patients' prior treatment status combined with their baseline MES. As one might extrapolate from the clinical improvement observed in 77% of patients overall, you see response- Across the board, whether the patient is naive or experienced to advanced therapy, or whether the patient had an MES of 2 or 3 upon enrollment. But let's really get into the numbers for just a moment here. So I'll start with an observation. Over 70% of the advanced therapy experienced patients started in this study with a Mayo Endoscopic Score of 3. While we did not see a remitter in these 10 severely refractory patients, we did see that 4 of the 10 patients who started with an MES of 3 and had had prior advanced treatment, did indeed experience a clinical response with MORF-057. This is a high bar to achieve in just 12 weeks. While so far I've focused here on the most difficult to treat patients, let's touch for a second on the response in patients with moderate to severe disease who have yet to be treated with advanced therapies. You can clearly see on the left half of this graphic, that 43% of patients who are AT naive, regardless of their MES status, achieved remission in EMERALD-1. This is an excellent and impressive result, exceeding our expectation, and along with the favorable tolerability profile in pill form, starts to establish MORF-057 as a potential foundational treatment option for patients. Now, let's move on to some data beyond the 12-week induction time period for EMERALD-1. Please note that these data are ad hoc analyses and as such, are subject to change during our clinical trial completion process. However, we're sharing the most up-to-date data possible from this ongoing trial. Looking at this latest cut of data in hand on slide 26, we're providing you with the symptomatic remission data via two separate methods at the 44-week period. All patients have either completed their 44-week visit by now or have discontinued in this study. First, a word on symptomatic remission for those unfamiliar with this term. Symptomatic remission is a clinical two-component Mayo score comprised of stool frequency and rectal bleeding, requiring a rectal bleeding score of 0 and stool frequency of 0 or 1, accompanied by a decrease of greater than 1 overall. On the left, the intent-to-treat analysis includes all 35 patients, while the right count calculates only those that have completed an assessment at that relevant time point in the study. Obviously, the study is not yet completed, and we could have additional patients withdraw or additional hard-to-treat patients continue to improve. Now, what you can see clearly is that naive patients respond more quickly. In fact, they respond already by week 6, and then they sustain that response throughout the measured time points to date. Predictably, patients who were refractory to previous therapies take longer to achieve symptomatic remission. By the first visit post week 12, you can see the proportion of AT experienced patients in symptomatic remission increases, and as with the naive patients, sustains that level of symptomatic remission. I must reinforce that we're looking at even smaller patient numbers here than those we cautioned you about at the outset. The dips can, and in some cases are, driven by a single patient. Nonetheless, these data demonstrate that responses and also symptomatic remission rates are like all of our other data, where they are more likely in naive patients, but with time, AT experienced patients show growing and sustained improvement. On slide 27, we divide the modified, the Mayo endoscopy scores into 2 or 3, and plot symptomatic remission rate changes from baseline through week 44 visit for both the ITT population and by patients who have completed their week 44 visit. As we've seen previously, time to response differs predictably by severity of disease, but is once again durable, durable upon onset. Also, the patients with an MES of 3, depicted in red, take longer to experience remission, but experience durable benefit once they do. Finally, on slide 28, we look at the changes over time in mean PRO2 for the sum of the stool frequency and rectal bleeding scores. On the left, we see PRO2 scores comparing the AT experienced patients in red, the naive patients in blue, and the overall scores through a dashed green line. What is clear from these data is a continued improvement over time in PRO2, all the way out to the 44 weeks, which we have data for today. I know we've spent a considerable amount of time today diving deeper into the 12-week trial data and moving beyond that out to the 44-week clinical trial and safety data. Developing a safe, effective oral therapy for IBD patients has always been our goal with MORF-057. This small open-label trial has not only clearly achieved its primary endpoint with statistical significance on RHI, the data shown also, as I said at the outset today, tell us clearly, yes, so far we have an oral, well-tolerated alpha-4 beta-7 inhibitor that is active in UC patients. Now I'll turn the call over to Marc for some concluding thoughts and a corporate update. Thanks, Bruce. So just to recap, given that this was a relatively small open-label trial, we could not have been more pleased with the outcome. For starters, safety can always be a question mark as you move from antibodies to small molecules, and especially critical in this young, active, otherwise healthy patient population... I really, I realize we didn't spend a lot of time on this today since there isn't too much to discuss, but to me, this is one of the most critical attributes of this or any approved or potential IBD treatment. Aside from safety, the other results seen in EMERALD-1 should not have been a big surprise to anyone. We already knew what saturating alpha-4 beta-7 receptors in the circulation does for patients from more than 1 million patient years of data with vedolizumab. We showed in multiple phase 1 studies that MORF-057 does just that. I'm very much looking forward to the results from our ongoing EMERALD-2 study and focusing on preparations to enable a rapid start to phase 3. As a reminder, EMERALD-2 is statistically powered to show a clinically meaningful difference over typical placebo rates and will explore both higher and lower doses than EMERALD-1, as well as BID and QD dosing regimens. Unfortunately, there remains a clear and urgent need for a safe and effective agent in pill form that isn't systemically immunosuppressive, and we're committed to developing the first such treatment for the millions of folks suffering from these conditions around the globe. Now, at slide 31, I'd like to zoom out for just a minute and kind of review our clinical plans for 057 and just give a very quick corporate update. As you can see from the illustrative graphic on page 30, the randomized placebo-controlled EMERALD-2 trial is well underway, and you see patients enrolling nicely. We also expect to initiate a similar study, but in Crohn's patients early next year. The phase 3 trials in each indication will follow the phase 2b trials and incorporate regulatory feedback, of course, as always. And lastly, just given the outstanding team here at Morphic and significant capital reserves, we're very well equipped to conduct these efforts, as well as progress our proprietary preclinical pipeline into the second half of 2027. So with that, I'll turn the call over to the operator for Q&A. Thank you. To ask a question, please press star one one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Michael Yee with Jefferies. Your line is open. Thank you, guys. Good morning. We had a question for the doctor and a question for Morphic. Perhaps I know there's... For the doctor, there's a lot of questions around the endoscopy improvement scores, and wanted to ask what your explanation was or the team's explanation for why the numbers were kind of the same as Mayo and not significantly higher. I heard you say that there was central reads, and is that critically important? I think you were sort of implying that. And all nine of the improvements were in treatment-naive patients, not refractory. So I'd like for you to comment on some of that. And then, my second question is related to the timelines of the program and whether or not, I guess, the view here is that it's an active drug, and we're just gonna read this all the way out to the Phase 2b, albeit it's 2025. So maybe just comment on those two things. Thank you. Dr. Feagan? Yes, I'll, I'll take the first one. Well, in this study, I think it's important to remember what the goal of the program was, and that was to really get a proof of concept signal with the most sensitive measure possible. And we thought long and hard about how to do that, because really, the primary intent was to ensure that there was saturation with the drug of alpha-4 beta-7 in the peripheral blood. And I think many of you will be aware of programs that have failed with oral alpha-4 beta-7 antagonists because they did not achieve saturation in peripheral blood. So that was the primary intent. That was clearly achieved. And then the secondary goal was to go, no-go with regard to an efficacy signal. So as I mentioned earlier, we thought long and hard about what signal to use, and their histopathology is actually a very sensitive measure in induction, and that's contrary to popular belief in the clinical community. It's come out of data that really has evolved in the last three or four years. The RHI was a purpose-built, continuous measure to detect change in early drug development. You know, when you're developing a new measure, clinicians always want remission, but this, this measure was designed to show change, and it clearly did in this study based on a number of criteria. Most importantly, there was a reference benchmark of what a meaningful change was, and that was the comparative study named VARSITY, with vedolizumab and direct comparison to adalimumab. In that trial, vedolizumab was showed superior on all measures, virtually all measures, against adalimumab, and the histopathology change on the RHI was approximately 6 points with both drugs. So we have an external benchmark with two effective therapies, and Morphic's drug met that criteria, which is pre-specified. So that's a long-winded explanation getting back to your question of endoscopy. So endoscopy response is really a binary endpoint, and it's not terribly efficient. So in a small study, the data are imprecise, and you can get, you know, signals that aren't consistent with what we know about the relationship between clinical remission and endoscopic response. Remember, the Mayo Clinic score is a composite measure. It accords clinical criteria and endoscopic response. If in fact, if you see a divergence between the clinical response rate and the endoscopic response rate, it's likely due to imprecise- ... estimates of those due to small numbers, because there's a very high correlation between the two. So that, that would be my explanation for that one. And then the issue around, the data in the patients who had failed advanced therapy, these are the hardest patients to treat, and we have data. Every trial shows the same thing. These patients are really refractory. I think if you look into the demographics of the Polish patients, which constituted, a majority of the patients in the trial, these are patients who have failed advanced therapy. They're treatment refractory, and the sample size is small. So, I think if you look at the numbers, not without seeing remitters in that group, it's likely to play a chance, especially 'cause if you look at the more sensitive outcome measures, in small numbers, they're going to be more likely giving a signal. The continuous variables show response in those patients. So I think, again, this is a phenomenon related to the small sample size. Mike, maybe just if you could remind us of the second question from the team here? The second question was from a mucosal catalyst perspective, is the message here that you're confident that this is going to work, it's well powered, and we will see you in 2025 for the data? That's exactly right, Mike. I think, you know, the data from EMERALD-1 definitely give us confidence and sort of positive read-through to EMERALD-2. And as we mentioned on this call, enrollments is going well, and so we're on track to deliver those results shortly as well. That's what we're all focused on here. Very good. Thank you. Thanks. Thank you. Our next question comes from Gregory Renza with RBC Capital Markets. Your line is open. Great. Thanks, guys. Good morning, and thanks for holding this call, and thanks for taking my questions. Also, let me just send our best to Praveen as well. Maybe just to start for Bruce, I know as we just saw from the previous question as well, with respect to endoscopic improvement as certainly identical to remission and those 9 patients improving dramatically, as you said. I know you commented about this occurring in recent studies and also maybe some expectations about it differing in subsequent studies. Just wanted to give you an opportunity to perhaps elaborate on that and just give us a point of reference there. And then, secondly, very helpful to see the 44-week ad hoc. Now, as we start with those 35 patients, I'm just curious as the ones that, that, as observed, I think it's down to 17 patients or so, just I wanted to hear your thoughts on talking about just the expectations on, on those dropoffs, if you have a sense of, of, how that sort of met your trajectory and expectations with the discontinuations and what the drivers of those were. Thanks so much, and appreciate all the detail here. Yeah, so I'll start on this and, and, maybe others can add to this as well. You know, the, the difference in the, the lack of a difference, if you will, between the endoscopic improvement score and clinical remission, you know, we attribute that to the small nature of this study. Would we like to have seen, a, a point or higher with the patient responding? Absolutely, we would have. There's a number of other studies, though, that are out there, and in fact, just before we released our data, six months or so ago, the VEGA study was published. And if you look carefully at that study, one of the arms has an identical endoscopic remission to the clinical response. Again, it's a smaller study size, as well. Another arm has only a 2-point difference between those two factors. We think that central reading factors somewhat into this. Historically, when trials like the early vedolizumab studies were run, they used local reading of endoscopic scores. And Dr. Feagan, for example, has published a paper in this space that shows that as you go to a centrally read endoscopic scoring system, the scores there become more stable across trials, for one, and they're more reproducible and more accurate in terms of their overall assessment. And I think it's an important thing to think about. Now, as we go into larger and larger clinical trials, we fully anticipate those numbers to start to separate from one another. How much they separate, you know, we're not gonna guide to that today, but we do believe that they're gonna start to separate out. There was another question in there about what our thoughts are on patients that are dropping out of the studies. I'll let Brihad actually take that question. Um, sorry? The numbers of patients are decreasing as we go out past 44 weeks. Oh, okay. Thank you. As you can see, we started with 35 patients, and now we have 19 patients in the study at the moment. That's around 55%. Now, we have to take into account what type of design we have. So a lot of studies in IBD or ulcerative colitis re-randomize the responders, and those are different kinds of studies. Ours was a study where patients continued on the same drug throughout. Those are called treat through studies. If you look at a recent study like that, for example, Entyvio or ELEVATE 52, it also had approximately similar dropout rate at week 52 of around 55%. If you look at some of the previous ones, like ACT 2, ULTRA 2, etc., you will see very similar range of 50%-60% dropout. These dropouts are usually because patients' circumstances change. They have some of, some have adverse events, some have loss of response. So a variety of reasons that you can always see in the- ... you know, when the data are published, and we will do ours as well in future. But to us, this is very much in the expected range for a typical moderate to severe UC population. Is that- That's very, very helpful. Thank you so much. Thank you. Our next question comes from Derek Archila with Wells Fargo. Your line is open. Hey, good morning, and thanks for taking the questions and thanks for sharing all this detailed data this morning. Just two questions from us. Maybe just piggybacking on the last question there, just in terms of, you know, what's the median time on therapy for these patients in the trial, including the dropouts, just from a safety perspective? Like, how much, again, kind of exposure data are you getting, and for how long? Second question, I just, you know, wanna understand the difference between the advanced treatment naive and experienced patients on remission using both RHI and the modified Mayo. 'Cause it looks like, you know, the naive patients had a higher, you know, response on the modified Mayo, lower on the RHI remission, and that was actually the opposite for the advanced therapy experienced patients. So I guess the question is, like, I guess, which is more of a stringent endpoint? And I guess the explanation around the discordance or, you know, of, of that data. Thanks. I think with respect... Derek, thanks for the question. With respect to median time of exposure, we haven't given a precise calculation, but I think- I mean, we- Brihad can answer that, and we can flip to the second one. So, that's a good question, and as you know, this study is still running. As you can see, we have 19 patients at the moment, and from 35 at week 12, we have seen some patients drop out. Well, at the end of the study, we will be calculating and reporting on the pharmacokinetic exposure and, you know, its relationship with efficacy and safety and so on. But at this moment, while study is ongoing, you know, our systems are not designed to calculate that now. If you just wanna remind us of the second question, please, Derek? Sure. Just again, the discordance between, you know, kind of the different remission definitions, so on the Modified Mayo and the RHI. Just in the advanced treatment naive, you know, you saw, you know, I think a lower rate on RHI, higher on Modified Mayo, but the opposite in the experienced patients. So again, what's kinda driving that, and I guess, which is the more stringent endpoint? Yeah, I think there's two pieces that can come into play here, and maybe I'll ask Brian, since he's the expert on RHI, to kind of frame what RHI is really telling us, and then I'll come back and give some thoughts to the company, too. Yeah, I think, again, we're back to the problem of small sample size and cutting the data in various ways with multiple endpoints. With regard to the operating properties of RHI versus endoscopy, it's early days. As I mentioned, RHI has just started to become a preferred method for looking for single and proof of concept studies in ulcerative colitis. For years, we've used the binary endpoint of clinical remission, and it's statistically not very efficient. So we're just feeling our way right now with it. But as I mentioned earlier, we've got a very strong signal from that VARSITY study of the value of change in RHI with treatments of known efficacy and the magnitude of change that you'd expect. Really, the information we have from EMERALD-1 is consistent with a therapeutic benefit that's clinically meaningful and commercially viable. That was the important takeaway. I think my guess is that RHI is actually a better endpoint for early drug development than endoscopy, even when endoscopy is used as a continuous, well, semi-continuous, because it's a four-point categorical scale, the Mayo Endoscopic Sub Scale score. The reason for that is with endoscopy, you're forced, because of the central reading paradigm you have, if you're operating a global study, you have to have multiple readers and multiple time zones. There's more noise than with pathology, where you can use, you know, a single pathology reader. I think that is important when you've got small sample sizes. So when I saw the data, these data for the first time, I was impressed that we met the benchmark. The benchmark was valid because from the VARSITY study data, and I wasn't so fussed about perhaps the discordance that came up earlier about clinical remission versus endoscopic response. Got it. Thanks so much. Thanks, thanks for that, Brian. And, and the only thing I would add to that is that, you know, if we come back to the overall scoring here, you know, you're talking about eight patients that are in RHI remission. Remember, the definition of RHI remission means that a patient has to go from their starting point, of which we were an average of 26 in our study, to less than or equal to three. So they have to have a very dramatic improvement in order to be able to actually reach that RHI remission. And so I think that the scores of a 7-point change is something that's been used to really give you that leading indicator of what's starting to happen in patients. And then when they're seeing greater than a 50% reduction as well, you're really starting to get these patients a, a deeper understanding. You know, that subtle difference is really a patient or two in terms of our overall scores. You know, we also don't think if you look at the remission rates in AT naive patients of 43% we don't necessarily think that number is gonna hold through every large study as well, and we really think these numbers will coalesce around a mean, if you will, or median, as we move into larger and larger clinical trials. Got it. Understood. As a reminder, to ask a question, please press star one one. Our next question comes from Evan Seigerman with BMO Capital Markets. Your line is open. Hi, team. This is Keith on for Evan this morning. Firstly, thanks for the thorough presentation. We appreciate it, and thanks for the shout-out to the clinical trial aficionados on the street. We appreciate that. Our—I guess our question is, you know, looking at the data, one key difference between you and, you know, what some consider, you know, a comparator in a prominent failure from April 2022, was really the lack of concordance across the totality of the data in that other asset versus what you're seeing in yours. This seems like a key point you've emphasized, you know, over the presentation, but I'm just wondering, could you walk us through why these data are important? What are maybe the key pieces? Does this lend itself to efficacy, safety, sort of tolerability over time, and then perhaps why receptor occupancy is key here, and what you know, maybe compare it to the, what I'll refer to as the April 2022 asset? Marc, do you wanna take that? Sure. Happy to. Thanks, Evan. So I may just draw your attention right now to slide 21, for example. Although I could use several of the slides from our deck today. I think on one picture, this one kind of tells the story, I think, in its totality from a high level. You can look at whether it's modified Mayo or RHI, whether it's all the different subsets based on the starting characteristics of all these patients, and you can see that across the board, folks got better, which is great. And they got better on average in a magnitude that you would expect from not just vedolizumab, any of the effective approved therapies today. That's very concerning to us to see, aside from the safety aspect, which we all touched on as well. The second thing you see is the expected differences in the overall average among the groups based on severity and refractoriness of disease. This is also kind of concerning to see, because it's seen in all the other drugs. What you see is that across the board, kind of consistent, directionally positive effect on all these endpoints. Again, we've talked about the small numbers many, many times. It wasn't powered for any of these exploratory endpoints, except for the change in RHI, which of course, is a very small P value. Other than that, it wasn't powered for these. But still, the purpose of this trial was to kind of look at the totality of the results, see a consistent effect, aside from the PK and PD markers, of course, which was confirmatory, and to kind of ask ourselves, could an ineffective drug or could a placebo or could a poor drug have possibly created these results? And so clearly, you know, to us anyway, the answer to that is no. This looks like one of the more effective or approved therapies across the board, and that's what gives us so much confidence going into Phase III. The only thing I would add to what Mark said as well, is that if we also showed you data out into 44 weeks, and while we can't get the endoscopic scoring at these visits, you could really see these nice changes that seem to be sustainable once they're achieved and continue on as we progress down the study. So that also gives us a lot of confidence around what we've set up for our EMERALD-2 study. Perfect. And we were doing some digging and saw the data on lymphocyte migration, which was impressive. So thank you for that. That does it for me. Thanks again. Thank you. There are no further questions. I'd like to turn the call back over to Chris Erdman for closing remarks. Thanks, Michelle, and we want to thank everyone for joining today. I know that we've covered a lot, and we appreciate everybody's interest. A couple things. We will, of course, post the slides from this presentation after the call. And for any of you who will be making the trip to UEG Week this weekend, we look forward to seeing you in Copenhagen. And certainly, please join us on Sunday after the poster. As many of you know, we'll be hosting a reception, and we'd be glad to answer any further questions, both then and, as always, at any time. Have a great day. Thank you for your participation. You may now disconnect. Everyone, have a great day.