Good day, and thank you for standing by. Welcome to the EMERALD-1 Top Line Results Conference Call. At this time, all participants on a listen only mode. After the speaker's presentation, there will be a question- and- answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference call is being recorded. I would now like to turn the conference over to you for your speaker today, Chris Erdman. Please go ahead. Thank you, Lisa. It's a great day at Morphic. I would like to thank everyone for taking part in this call. Before we share our thoughts on the EMERALD-1 data that many of you have already seen, I'll take care of a little bit of housekeeping. First, the EMERALD-1 press release and the slides that accompany this call, along with our first quarter 2023 financial results are available now on our website at morphictx.com if you'd like to access them. Next, on slide two, I'd like to caution everyone that during this call we will be making forward-looking statements under the Safe Harbor Act. 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 actual results to differ materially from those contained in the forward-looking statements. These and other risk factors can be found in our most recent Form 10-K and Form 10-Q filed with the SEC. As such, we advise you to refer to the risks and uncertainties of our business outlined in these filings to learn more about an investment in Morphic. Now let's turn to the matters at hand. You can see here the agenda on slide three. Joining me this morning on the call are Praveen Tipirneni, the CEO of Morphic, Brihad Abhyankar, our head of clinical development, Bruce Rogers, our President, and Marc Schegerin, our Chief Operating Officer and Chief Financial Officer. We also have an incredibly special guest here today, Dr. Bruce Sands. Dr. Sands is the Dr. Burrill B. Crohn Professor of Medicine at Mount Sinai, and as many of you know, a preeminent gastroenterologist with a tremendous body of work in this space. Dr. Sands is also a key member of our clinical advisory board for the MORF-057 program. Looking at the agenda, Praveen will provide some perspective on the EMERALD-1 study. Dr. Sands will give his thoughts on the ulcerative colitis treatment landscape today. We will walk through the top line data. After that, we'll of course, open the floor for a discussion. The results we reported this morning from EMERALD-1 represent the outcome that we at Morphic have planned for and worked towards for several years. We're really excited today to share these data with you. I'll pass the call over now to Praveen. Thanks, Chris. Welcome everyone to Morphic HQ. Before we discuss the data, let me just take a moment to tell you how we got here. We believe in major value innovation on behalf of patients. This is why we do not benchmark ourselves against the competition of choosing between injecting 1 drug or another with a percentage point or 2 of difference in efficacy. We don't want to add yet another candidate to a crowded field. What we want is transformative value innovation for patients. How can we dramatically change people's lives? We think that the profile we have always targeted for MORF-057 would provide a radical change in patients' lives, tolerability, efficacy, in an on-the-go Skittles format. Our data today brings us 1 giant step closer to our goals. Let's move on to today's topic, EMERALD-1, our phase II-A data. Nobody wanted us to do this study, and there were some very good reasons. We were told that it'd be better to just run a large randomized control study. We were told that every small IBD study has shown widely variable and inconsistent results. We were told that the study would be indeterminate because of the small study size. We saw things a little bit differently. We don't roll the dice with huge uncertain capital investments. At Morphic, we are drug developers and advance our medicines in a rigorous, methodical manner with step-by-step evidence. We really wanted to know what we were dealing with. This program is in a uniquely favorable situation. Each progressive data set that we have generated to date, from rodents to primates to healthy human volunteers in phase I, has been sequentially and consistently in line with the expected results, and importantly, corresponded to the respective parameters in the development data set from vedolizumab. However, there was one missing puzzle piece, that same data set in IBD patients. Moreover, all this was in the context of a broader reference class data set where 100% of systemic α4β7 inhibitors that have reached mid-stage trials have successfully demonstrated clinical activity. Now in our EMERALD-1 study, we continue that uninterrupted trajectory of success for systemic α4β7 inhibitors. Now with an oral pill called MORF-057. With that, let me now pass the mic to Dr. Bruce Sands. He will provide some context on today's IBD treatment landscape. Dr. Sands? Thank you, Praveen. It's a pleasure to be here this morning. My job this morning is just to provide a little bit of context for the current landscape of treatment for primarily ulcerative colitis. I'll just give you a little quick survey. I mean, we're thinking of conventional therapies at the beginning of treatment, but this is really appropriate for mild to moderate UC patients. In particular, if we think about the 5-aminosalicylates, those are a platform of therapy for mild to moderate UC patients. If you look at really rigorous outcomes that we look at in modern clinical trials, it's probably at best only about a third of patients who achieve those outcomes. Many of those patients end up failing over time and eventually requiring corticosteroids, upon which we really think that they fall into the category of moderately to severely active ulcerative colitis. thiopurines have not a very good safety profile. They do have the convenience of oral dosing. They're also not terribly effective in ulcerative colitis. That brings us to more modern-day therapies, such as we have with biologics. Of course, that all began about 25 years ago with the advent of TNF inhibitors, infliximab given intravenously, more recently in biosimilars, tried out subcutaneously, but also the subcutaneously dosed adalimumab, golimumab. These are certainly effective in ulcerative colitis, some more than others. Adalimumab, certainly not the most effective agent that we have. But clearly, we all know the limitations in terms of safety. All of these agents, of course, as biologics are being delivered intravenously or subcutaneously, which is not what the majority of our patients desire. Vedolizumab was a real innovation in the treatment of ulcerative colitis and IBD in general because it provided a much safer biologic therapy. It clearly has a superior safety record, particularly in ulcerative colitis, but at least in the United States, still has the necessity of being given intravenously. In other parts of the world, of course, it can be given subcutaneously as maintenance dosing, but still, parenteral dosing is what is needed. Vedolizumab is effective in ulcerative colitis. We all know that. We have ustekinumab, again, a parenterally dosed biologic, also shown to be effective in patients with moderate to severely active ulcerative colitis. Then to bring us to more recent innovations, we have a number of advanced oral therapies. We have the JAK2 inhibitors, first tofacitinib and more recently upadacitinib, unquestionably very effective agents, but also with the baggage of black box warnings, a number of serious concerns, including skin cancers, other cancers, deep venous thrombosis, major adverse cardiovascular events, and even risk of mortality, according to the black box warnings. That box warning really puts these oral agents, convenient but not especially safe, into second-line position after failure of TNF inhibitors. Finally, we have the class of oral therapies, the S1P1 receptor modulators such as ozanimod and probably soon etrasimod. These are effective agents. They have convenient oral dosing. They're effective as first-line therapies. Again, they do have a number of safety limitations, including cardiac effects, a number of ocular effects, certainly lymphopenia, herpes zoster, and so on. There are a number of limitations that would prevent us from using this class of agents in a broad swath of patients with moderate to severely active ulcerative colitis. You can see that we have different agents that meet different characteristics of therapy. We have agents that are effective but have safety concerns. We have agents that have safety concerns but lacking in convenience of oral dosing. We do not have one agent, really, that hits all the marks that our patients desire, which are a highly effective agent that is safe as well as convenient. The hope is that we will find such an agent and that this will become a platform of therapy for ulcerative colitis and potentially for all of IBD. With that, I think I'll turn things over to Brihad Abhyankar to give you the results. Yes. Thank you. Thank you, Dr. Sands. This is Praveen again. Let me now pass it to Brihad Abhyankar, the leader of the EMERALD-1 trial. For those of you who do not know, Brihad is a GI doc who has been developing UC drugs for over 20 years, and we're super privileged to have him on the Morphic team throughout the conduct of EMERALD-1. Brihad, go ahead. Thank you, Praveen. On slide 5, let me give you an overview of the study so we can fully appreciate the results. EMERALD-1 is an open-label, single-arm study in patients with moderately to severely active ulcerative colitis, designed and powered to show a change from baseline in the Robarts Histopathology Index, or RHI, at 12 weeks. We enrolled 35 patients in the main cohort of the study who were both advanced treatment naive and experienced. Let's now look at some of the key enrollment criteria. To qualify for the study, the patients had to have a history of prior failure with either conventional or advanced therapies. They were also required to have a modified Mayo score of five to nine with a centrally read endoscopy score of two or more. Additionally, our patients had to have a centrally read RHI score of 10 or greater at the start of the study, which is on the scale of zero- 33. This is consistent with the underlying moderate to severe disease. A key exclusion criteria for this main cohort was any prior exposure to vedolizumab or other integrin inhibitors. The primary endpoint of the study was change in the baseline RHI at week 12, and the secondary endpoint was a change in the modified Mayo score from baseline at week 12. We also evaluated several pre-specified exploratory endpoints. These included RHI remission, modified Mayo response and remission, safety, biomarkers, and multiple PK/PD parameters. Next on slide six, let us look at some of the key demographic features. For this study population, nearly half were female and 20% came from the U.S., and the rest 80% came from Poland. These 35 patients had a mean RHI score of 22.7 at baseline and a mean modified Mayo score of 6.7. About half of the patients had a Mayo endoscopy subscore of 3. 37% of patients had previous exposure to 1 or more advanced therapies, and around 26% were on corticosteroids at baseline. These data tell us that the UC population in our study is difficult to treat with a high disease burden. Turning to slide 7. Let us cover the 12-week safety data first. Overall, MORF-057 was generally well-tolerated, with no safety signals observed. In EMERALD-1, there were no serious adverse events or deaths. In the study, 2 patients had an adverse event of grade 3. Both these events were due to exacerbation of their underlying ulcerative colitis, and 1 of these led to an early discontinuation. Only two patients had an adverse event that was deemed related to treatment, both low-grade. The most frequent AEs were exacerbation of UC, as previously described, and anemia, where all three patients were anemic at baseline. Additionally, there were no significant hematological or biochemical findings in the study. Finally, many patients have now been on the study for much longer than the 12-week induction period. As of today, no other safety signals or AEs have been reported. Overall, I'm very pleased to say that adverse event profile observed in the study is consistent with the difficult to treat UC population. I will now hand over to my colleague, Bruce Rogers, to discuss the efficacy data. Thanks, Brihad. As Praveen mentioned, we, since the start of our α4β7 program, produced data that every step along the way has sought to replicate that of an infused antibody in an oral convenient pill. We first did that with the design of MORF-057 using our MInT Platform. In vitro and in vivo data early in the program confirmed it, and we carried that through the tolerability PK/PD studies in our phase I program. Turning to slide nine. One of the most common questions we've heard after releasing our healthy volunteer study was what do you expect to happen in patients? As you can see from the data on slide nine, we observed PK, shown here in red for day one, blue for week two, and green for week 12, that conforms with our previously reported phase I studies shown here in white and gray. In fact, while consistent, the mean trough concentrations are slightly higher than in phase I. Further, modeling of this data confirms that high trough concentrations are sustained throughout the 12 weeks of dosing and are quite consistent with our phase I results. Now onto slide 10. From the concentration versus receptor occupancy plot on the left of this slide, you can see that the majority of patients shown here in red are achieving trough drug exposures sufficient to sustain saturation of α4β7. The mean trough α4β7 receptor occupancy was greater than 98% at week 12, and the α4β1 projected receptor occupancy was below the limit of quantitation, with mean trough RO estimated to be less than 15%. It is also important to note that no lymphocytosis or changes to circulating naive T cells were observed, consistent with low RO at α4β1. Although we're not going to present the data here specifically today, this level of exposure also produced impressive α4β7 expressing lymphocyte subset changes, again, consistent with our phase I results. With our PK, PD, and tolerability data recapitulating what we've previously seen, the key data that remain are all clinical activity. On slide 11, we summarize what we think are fantastic results. The primary endpoint for this study, as Brihad mentioned, was mean change from the baseline in RHI. Here we observe a statistically significant decrease with a mean reduction of 6.4 points and a P value of 0.0019. It's very reassuring to see such a statistically significant result on an objective histological measure. The primary endpoint of RHI reduction is accompanied by a key secondary measure, a mean reduction from baseline in modified Mayo score of 2.3 points. Clinical remission, as defined by the 3-component Modified Mayo Clinical Score, is also a key measure and is the FDA's current registration endpoint for UC studies. Remission is also the primary endpoint of our ongoing randomized phase II-B study, EMERALD-2. This measure of remission uses a combination of clinical and endoscopic measures representing 1 of the best tools for an objective measurement of UC activity. MORF-057 achieved a 25.7% remission rate in the EMERALD-1 study population. For context, the endoscopic component of MMCF is centrally read, which confers an additional element of objectivity. These results far exceeded our expectations. In addition to remission, the clinical response rate for EMERALD-1 study was 45.7%. Finally, we observed an RHI remission rate of 22.9% in this study. For context, to illustrate the difficulty of achieving RHI remission, our patients started at a mean of 22.7 points, and the pre-specified criteria for RHI remission is a decrease to three or fewer points. In our study, all patients in RHI remission scored at two or lower. It should be noted that we've seen the expected relative differences in clinical activity that one would predict based on a historic observation in patients who have previously received advanced therapies for their IBD and those who are advanced therapy naive, with naive patients responding more favorably across all of these clinical measures. Given the well-characterized α4β7 pathway and our previous results, we hoped and even expected that we would see activity comparable with vedolizumab with our oral selective α4β7 inhibitor. The consistency of these data across all parameters, especially in this small trial of patients with this severity of disease, is highly reassuring to us. Today, we presented a top-line look at what is an incredibly rich data set, and we look forward to sharing the full results later this year at an IBD Congress. Let's move on to slide 12. I wanna note that this and the following slide are obviously depictions of some results from several distinct ulcerative colitis studies. Therefore come with limitations associated with making cross-trial comparisons, and comparing results of different trials may be unreliable due to a number of factors. We believe it should, however, serve as an excellent view of historic results in UC trials, both for approved and investigational agents. On slide 12, we look at some historical data to better contextualize the activity of MORF-057 as measured on the RHI in EMERALD-1. You can see that results from MORF-057 are clearly in range with ENTYVIO and HUMIRA from the VARSITY trial in both magnitude and variability. In addition to the significantly larger study size of VARSITY, there are a number of key differences between these studies, including study design, as noted on the slide. Also, our endpoint was measured 2 weeks earlier, providing reduced duration and exposure for MORF-057. Our study population was more severe as measured by baseline RHI, and our study had approximately two times the percentage of advanced therapy-experienced patients. While we cannot draw direct conclusions based on the results from different trials, we believe that the EMERALD-1 results are very strong and obviously support the continued development of MORF-057. Let's advance to slide 13 as we look at some historical remission rates. In our opinion, this slide sort of speaks for itself. Our phase II-A study of MORF-057 delivered in pill form shows clinical effects in line with leading approved agents and agents currently being studied in the clinic. In the past, we theorized, based on the mechanism of action, that if we could saturate α4β7, then we really should expect clinical activity with MORF-057. We humbly joked that this trial was simply designed to prove that the Earth is round. Now, we have further evidence that it indeed is. Looking forward, the data that we have shared today encourage us to believe that if later trials of MORF-057 continue to recapitulate this profile, tolerability, clinical activity, doctors and patients may one day, for the first time, be able to choose an oral, well-tolerated and efficacious therapy instead of sacrificing one or more of these three critical attributes. Let me turn it back to Praveen. Thanks, Bruce. Before opening the call for questions, let me just thank a few people. We are extremely grateful to all of the patients for their participation in the EMERALD-1 study. Thank you. We also thank all of our investigators and their teams. You have contributed immensely to the EMERALD-1 trial to date and continue to in the ongoing maintenance phase. I'd like to thank our founder, our outstanding board, our outstanding investors, without whom we could have never formed and capitalized the company and advanced our pipeline to this point. Finally, a shout-out to everyone at Morphic. The Morphic team worked creatively to design an oral selective α4β7 inhibitor development candidate, a task where others had failed repeatedly, then tenaciously developed it through preclinical phase I and now phase II trials. I thank you all for delivering today's results. Okay, everybody ready for questions? Let's roll. Operator? Thank you. Just as a reminder, if you would like to ask a question, please press star one one on your telephone. One moment while we compile the Q&A roster. The first question will be coming from Gregory Renza of RBC. Your line is open. Great. Thanks. Good morning, Praveen and team. Let me provide my congratulations on the data this morning. Thanks, Greg. Praveen, maybe just Thank you. maybe Praveen, just a couple questions from me. Certainly, as Bruce spoke about that slide 13, looking sort of at the absolute c omparisons across trial, and we certainly understand the limitations. Just curious, maybe for Dr. Sands and also for you, Praveen, and your team, to just help put a finer point on looking at some of that in context, certainly with the remission that you've put up on this trial. Also as we compare to RINVOQ, certainly looking, you know, slightly better, but there will always be these limitations. Perhaps you can just provide some context of how you think that this stacks up against the other orals, but also the IVs. Then I'll have a follow-up as well. Sure. Thanks. That's a great question. For that, it's a great landscape question. For that, let me pass it to Marc. Dr. Sands, if you have any comment, if you'd like, after Marc, please do so. Go ahead, Marc. Great. Thanks, Greg. good morning. I mean, I think the shortest way to answer that question is to say that in UC, safety is king. You're right, you can look at these different trials and look at a couple, or a few percentage points difference, here or there from drug to drug and trial to trial. At the end of the day, safety is really king. Is really key. Remember, these folks are typically young and otherwise healthy at diagnosis, and they're just being saddled with this, with this diagnosis and all the symptoms that come with that, daily. To think about accepting the side effect profile that Dr. Sands talked about before, things like sudden cardiac death and infections and infestations and DVT and the list goes on and on, different types of cancers, including lymphomas. It's really just too much for most patients to bear. At the end of the day, yes, there's a variety of attributes that are very important related to safety and efficacy and how the convenience the delivery is. But really, as we always say, in this particular disease, safety is king. You brought up one particular drug, but, you know, that class and other systemically immunosuppressive agents really suffer from a lot of the safety issues that Dr. Sands brought up earlier in the call. Dr. Sands, any comment, if you'd like? Yes. Yeah, happy to comment. I completely agree that our patients really do emphasize safety as they make their decisions. Many analyses in the past have looked at how people evaluate, patients evaluate different attributes of medications, and very often they put safety over efficacy. That wouldn't be every patient, but most patients do feel that way. We would never put upadacitinib in the same context as vedolizumab, for example. We would not use them for the same kinds of patients. We're really confined to using that class of agents, the JAK1 inhibitors, really for refractory patients, people who are refractory to TNF inhibitors in particular, at least in this country, and I think that's largely true in other parts of the world as well. I, you know, they're not really comparable. We would use these drugs in different ways. While safety is king, I would not sneeze at the objective efficacy data that you just saw. When you see blinded endoscopic data, when you see histologic data, which also is blinded, showing results that are comparable to what we see with other agents, again, with the limitations of small sample size and so on, you really have to be... I think it's kind of impressive in a study of this sort. While the study itself was not blinded, those outcomes were, I think that's very important to point out. Thank you, Dr. Sands. That's great. Praveen, if I could just add one more question. Certainly a great deal of strategic activity across the space and the sector. Also a great deal of competitiveness in the development stage of these assets as well as the market. How does this data today maybe shape your handling of MORF-057 as you think about the asset more strategically? Thanks so much, and congrats again. Thanks, Greg. Yeah, let me, I'll again pass that to Marc. Marc is our CFO and COO and also leads the corporate development. Let me pass that question as well to Marc. Thanks, Greg. Yeah, another great question. We've seen there's been a lot of deal activity in the space of late and of course, IBD is a huge global market. What we've always said, really for years is that on the one hand, we have the capital and we have the ability to continue to take this program forward for the foreseeable future. We also understand that there's a huge global unmet need. If you really care about what's doing what's right for patients, you do have to, at some point or another, really try to maximize both the breadth of the development activities that you're doing in terms of the number of indications and types of people that you can show safety and efficacy in, as well as expand your geographic footprint. There are a lot of folks in the world who are IBD experts in the space and already have a global footprint. At some point, you know, we'll keep our head up, and we'll make that sort of determination at the right time. For now, we're excited to continue to take this program forward as we're very well equipped to do. Next question. Thank you. One moment while we prepare for the next question. Our next question is coming from Ritu Baral of Cowen. Your line is open. Good morning, guys. Congratulations on this data. Thanks for taking the question. I'm gonna relinquish my own questions for the client questions that are coming in, so, bear with me. I'll just blob a couple. One is, on safety. Just very specifically, have you seen any LFT elevations, or any changes in fecal calprotectin and CRP, and what most common treatment-associated AE, did you see? I think there were two cases. Yeah. Yeah. Let me just say today we are presenting the top line results, but let me pass to Brihad to answer those questions. Thank you for the question. As we said, we have not seen any hematological and biochemical abnormalities of any clinical concern in the study, and that includes LFTs. The two biomarkers you mentioned, fecal calprotectin and CRP, we are not reporting any data on those today, but as we have said, most of the endpoints we evaluated are in line and in consistency with the data you have seen. These may be disclosed in future IBD Congress. Does that answer the question? Yeah. Most common associated AE, treatment-associated. Right. Most common associated adverse events, there were four patients who had UC exacerbation. One of them discontinued, and other three were advanced treatment experienced patients, so they had failed both biologics as well as some of these oral advanced therapy agents. Other three are still in the study. The other three cases that we report, which are of anemia, these three patients started the study with anemia. If we look at the Crohn's & Colitis Foundation website, they report that one in three patients of IBD have anemia. Both of these, you know, ulcerative colitis exacerbation and anemia are part of the symptoms and, you know, issues that these patients face. They're part of the underlying disease paradigm. These patients did well on oral iron supplements, and they're continuing the study. Great. The follow-up I'm getting, what do you guys think the 200 mg would've done here? Should we be expecting this response when the phase II-B data does come out? Yeah. Why don't we, I'll have Bruce speak to that. Yeah, sure. Thanks for the question, Ritu. I think that the... You know, we thought very carefully about our dosing strategy for our phase II-B study, and we did include a 200 BID dose. One of the things you'll notice from the phase I to the phase II PK is there's inherently a little bit more variability when you go from a controlled phase I setting into a real world setting. I think there's an incremental potential benefit to making sure every patient has saturation. In this case, I think the lowest measurement you can see from the concentration receptor occupancy curve is around 85% receptor occupancy in one of the patients. We think that that would be able to drive us up to even higher levels of drug concentrations. I think it might be incrementally better, but we'll test that, and we'll see that data in our II-B study. Great. Thanks for taking the questions. Thanks, Ritu. Thank you. One moment while we prepare for the next question. Our next question is coming from Michael Yee. Your line's open from Jefferies. Hey. Great. Thanks. Good morning, guys, congrats on really great data. We had two questions. Hi, Michael. One was. Yeah. One was for Dr. Sands. Appreciating its cross trial comparisons, you talked a lot about reflecting on the Mayo Remission data as well as the RHI. Do you have reason to believe that this is upper end efficacy that you see on slide 13, such as with anti-TL1A and with RINVOQ? Do you see this as at least as good as vedolizumab on the left-hand side of that chart? I'm just trying to think about maybe for Dr. Sands and even for the company, how do you put into context the 26% and, you know, put it in what bucket of efficacy versus what you see there? Appreciate it's an oral integrin inhibitor. The second question was also for the company. There's also a 200 mg QD as well as 200 mg BID for the phase II-B. Remind me the 200 mg QD dosing, which could probably be important. That shows essentially the same receptor occupancy in PK/PD. Thank you. Thanks, Michael. Why don't we start with the first question, a landscape question. Marc, do you wanna start and then we can go to Dr. Sands? Sure. Absolutely. Happy to start. I mean, I think as we mentioned in the prepared remarks, we're over the moon with the outcome on re-remission for MORF-057 in this study. As Bruce mentioned, this is, you know, significantly in excess of our expectations and certainly requirements for this kind of outcome. As he also mentioned, it's very difficult to make cross trial comparisons in a relatively small study. If you ask me, yes, I'd say this is the upper end of the efficacy range for the treatments that kind of exist, whether approved or not approved. Ultimately the final profile of the product will be defined in subsequent studies, and we'll really be able to tell apples to apples or as close as we can get, how all the different profiles stack up. I mean, again, as we've said for a long time, it's not all about one efficacy measure or even one aspect. We're really trying to exist in the center of a sort of three circle Venn diagram of good tolerability, good efficacy in an oral and convenient pill form. You know, currently there's no one who exists in the center of those of that Venn diagram. That's kind of high level where we feel like we came out. Thanks, Marc. Dr. Sands, is there any comment you'd like to make on this? Sure. I mean, of course, I'm an academician. I'm more conservative by nature. You know, the comparison that was made has many, many limitations. I think it's fair to say you can see that MORF-057 is clearly within the ballpark of all the upper end and effective agents. Even if the efficacy is vedolizumab like, you would still have a drug that would have, you know, probably the safety, the efficacy of vedolizumab, yet with the convenience of an oral dosing medication. Even if the efficacy is exactly like vedolizumab or even slightly better, you would still have an extremely valuable agent that could be a platform therapy for UC and potentially also for Crohn's disease, I would say. Perfect. Thanks, Dr. Sands. Michael, on your second question, I think we need a little bit of a clarification, actually. Bruce, you wanna speak to that? Yeah. Let me talk to the actual doses that we've disclosed and what we actually haven't disclosed in the context of this. What we've said is that we're looking for a full range across a dose response curve to be able to understand what the optimal dose is for this study. The top dose in the study, we've disclosed that at 200 mg twice daily. The mid dose is 100 mg twice daily, the same dose we had within the context of the results we just presented. The other dose is a once a day dose, we actually haven't disclosed the actual strength and drug concentration of that yet. That's simple. It's for intellectual property considerations. We will disclose it as we disclose the results from the study then. Got it. Thank you. Thank you. One moment while we prepare for the next question. Our next question is coming from Derek Archila of Wells Fargo. Your line is open. Hey, everyone. I wanted to add my congrats on the great data. Well done. Just a couple of questions for us. Yeah. First question, I guess maybe what stands out most in terms of the activity measures or the patient population from the phase II-A study that you really feel de-risks the phase II-B trial that's ongoing right now? Okay. Let me just take that first and then maybe let me pass it to Bruce to speak to that as well. You know what I think we find really compelling about the data set besides, you know, some of the things that we've talked about, like the absolute modified Mayo results, as well as others, is really the consistency across all measures. You know, I've been in many investor presentations, I've said that, you know, we've been in this very fortunate situation where you've seen consistency from, you know, the rodents to the primates to the subjects and to now the IBD patients. You can compare that to a commercial drug on the market oral, I mean, injectable vedolizumab. I think the remarkable thing is that in a very small study, seeing that consistency across all the parameters is really what we find striking about the study. Let me pass it to Bruce if there's any other additional comment. Yeah. I think the thing I would add to what Praveen said is something that Bruce Sands actually mentioned a little bit earlier, and that is a number of the endpoints in the context of the study are actually blinded from a measurement perspective. If you look at how RHI is done, it's a blinded reader that looks at a sample. There are blinded components to the study. If you couple that with what Praveen just said in the consistency of the data and across all of the different endpoints, we know that we're saturating the receptor. We have great PK of this compound. We're not seeing safety signals yet and with this small molecule in our dosing paradigm, as Brihad articulated, all of the efficacy endpoints are either hitting statistical significance, which our primary did, and then aligning with that. It's really the consistency along with how these measurements are actually done. Got it. Helpful. Maybe second question, I'll ask it to Dr. Sands, but you guys can also offer some thoughts here. You know, given the patient population enrolled in EMERALD-1, I guess, what would be your estimate on how a placebo arm might have acted, you know, given the baseline criteria of these patients? Go ahead, Dr. Sands. Yeah. Probably you would see something like 5% or 6% for clinical remission. I, you know, I think you would see. Again, you would see a vedolizumab-like efficacy in terms of treatment effect. Yeah. You. Sorry. Thanks, Dr. Sands. Brihad will also comment on it here. Thank you, Dr. Sands. I think our estimation also was mid-single digits. Thank you. Got it. Maybe last question. In terms of the geography of the patients, I mean, you know, were there any differences in terms of efficacy or safety based on the patient geographies? I think it was both Poland and the U.S., just quick question on that? Yeah. Sorry. I can take that, Praveen. Yeah. You know, I think the key thing is that, it's an important question and we'll talk about the full layers of details relative to the discussion when we have the disclosure, at an IBD Congress. You know, looking broadly at this, you know, we had advanced therapy naive patients as well as advanced therapy patients in both the U.S. and in Poland. There was a balance across the two different jurisdictions. We don't think it really affects necessarily any of the outcomes or results. Got it. Well done, gentlemen, and thanks for taking the questions. Thanks, Derek. Thank you. One moment while we prepare for the next question. The next question will come from Evan Seigerman of I'm sorry, of BMO. Your line is open. Hi. Hi, guys. Thank you so much for taking my questions and really congrats on the data. One for Dr. Sands. Thanks, Evan. Thank you. Thank you. One for Dr. Sands. Taking a step back, you know, how would you use this, you know, in the real world, kind of given what we have with oral options, antibodies, how does this fit in, you know, given it's a limited data set, to what could potentially be a treatment for, IBD? Then a follow-up, you know, thinking ahead to, the, you know, EMERALD-2 trial, you know, any other major differences that we should be thinking about other than patient numbers, clearly larger, and any other nuances that we should be focused on, as we think about kind of handicapping that trial? Great. Go ahead, Dr. Sands, and then here, Bruce will speak to question number 2. I think in the real world, we could expect to see this used, really as a first-line therapy, definitely in moderate to severely active ulcerative colitis. I wouldn't preclude its use in mild to moderate ulcerative colitis, although that isn't what was studied here, and that isn't, I think, what will be studied in the phase III. There is potential for that as well. I told you the limitations of 5-aminosalicylate's efficacy. I think you would see broad use as first-line therapy. We also know that vedolizumab can work as a second-line therapy as well in ulcerative colitis, I'm sure that you would see it used there. I think a lot of what would drive this would be the safety profile and the convenience, in addition to good enough efficacy, really good efficacy that we see with vedolizumab. You know, I think it's no secret that vedolizumab has become a platform therapy among biologics, and you see there's no reason that an sort of equivalent, but orally dosed medication could supplant that entirely. Thanks, Dr. Sands. The second question on EMERALD-2, why don't we have Bruce here comment on that? Yeah, thanks for the question. It's actually a really important one. How I look at this broadly is that I think this study really gives us confidence that we've actually designed the right study. The study has three doses, and I think that's an important element, of what we're trying to explore. We're now using the modified Mayo as our primary endpoint, as one would expect within the context of that study, expanding it to additional jurisdictions, in terms of countries, and really trying to get a, a good read on the overall efficacy. It's really about execution at this phase. We've got everything in play. The study is running. Now we need to just execute it. One final follow-up. I know in, you know, there were more treatment-experienced patients than, say with the INTUVAX trials. Can you talk about kind of how that nuance may have impacted the data? I mean, the data's fantastic, but just some of that nuance there. Also, what do you think about those additional two weeks of treatment for the INTUVAX trials? Does that matter? Why don't we have Bruce speak to that? Praveen, if you have a comment after that, feel free to jump in as well. Yeah. You know, I think it's hard to put in the context of 35 patients how much it matters. Clearly, when you look even at the INTUVAX study at the differences between the advanced therapy patients, and those that had never received any kind of advanced therapy, there's a difference in their responses, and we saw that consistency within the context of our study as well. I think that the real endpoint that's important here is to consider that with 37% of our patients having been on, you know, TNF inhibitors and/or some of the new orals that are out there, on the variety of advanced therapeutics that are out there, that's a tough to treat patient population. Sick patients don't get better spontaneously. They really require a therapeutic. I think having that difficult to treat moderate to severe patient population, it actually adds to our confidence level that the results that we're seeing today are real results, and they matter and will matter to patients. Praveen, anything to add to that? No. Great. Thanks. Excellent. Thank you guys. Really appreciate the follow-up. This has been great. Thank you. Thank you. Thank you. One moment while we prepare for the next question. Our next question is coming from Alex Thompson of Stifel. Your line is open. Hey, good morning. Congrats on the data. Couple questions from me. I guess could you maybe comment on, you know, as a follow-up to the last question, maybe the proportion of clinical remission patients that were bio-naïve or bio-experienced? Maybe another efficacy subgroup question around any commentary around endoscopic remission rates or improvement rates as well. Thanks. Sure. Well, today we are just presenting the top-line results. We will have, you know, all the results later this year. Anything to add to that? I think the broad comment to just reinforce there is that we saw the typical, is what I call the differences between these two patient populations, and that was a statement. All the data will be included, though, within the context of our disclosure at IBD Congress. Okay. I guess then one follow-up question. Just maybe if you could put sort of the clinical response rate in context versus other more recent studies and how you think that may impact decision-making. Thanks. You want to speak to that, Brihad? Sure. I'll make a few comments and maybe ask Dr. Sands to follow on. You know, we saw a clinical response rate of 45%, 46%. It is in line with the range that has been seen in some of the recent studies. Some have been as high as 55%, 60%, but we are clearly still in that ballpark range. Some patients do have reduction in their disease activity, but they don't reach the pre-specified endpoint of remission, but they're still improving. I'll ask Dr. Sands to maybe add from his experience. Yeah. I agree. This is in the right ballpark for this patient population, about 37% of whom had failed advanced therapy. I think that that's a perfectly reasonable endpoint estimate, understanding that this is only 35 patients. Yeah. Thanks, mate. Thanks a lot. Thank you. Thank you. One moment while we prepare for the next question. Our next question is coming from Julian Harrison of BTIG. Your line is open. Hi. Good morning. Congratulations on the data. Thanks if you take my questions. Hi, Julian. First, just kind of an overarching question. I'm curious how dependent you think the addressable market for MORF-057 is on ENTYVIO's exclusivity being extended? Specifically interested in how we should be thinking about possible payer dynamics there down the road. I'm also wondering if you have an updated outlook for Crohn's disease in the wake of the UC results today? Great. You know what? I'll have Marc comment, and then, and I may have a follow-up comment. Let me start with Marc on those two. So the one is related to, you know, kind of the market essentially in relation to where Vita will be at that time. The second one related to Crohn's. Sure. Happy to. Thanks. We've actually done pretty extensive, third-party and primary research on these type of topics related to landscape pricing, formulary payers, different geographies and regulatory authorities, et cetera. The short answer to your question without getting into the specifics is no, it doesn't make much difference at all. I mean, I think, you know, especially if you're willing to be reasonable on price and the other issues, it's really makes a de minimis impact the timing of either a sub-Q entry or a biosimilar entry of vedolizumab. Second one, related to Crohn's, actually I can just comment on it, is that, you know, we're prepared to do Crohn's. You know, we just got these results, and we're looking through them. These are the top-line results, and we're moving as fast as we can into, you know, all the clinical development needed to really optimize this drug. Fantastic. Thanks again. Thank you. Thank you. One moment while we prepare for the next question. The next question comes from Mike Kratky of SVB Securities. Your line is open. Hi, everyone. Thanks for taking our questions. Congrats on the data. Without necessarily going into too much detail, can you comment on whether you saw any difference in clinical remission rates looking at the baseline steroid use? Again, these are the top-line results, but let me have, Brihad comment on it. Thank you. As Praveen said, these are top-line results. Again, we will be disclosing the details about patients with or without the baseline steroids in a forthcoming congress. Like, we said earlier, though, all results were very consistent with what we expected. Yeah. I think the only other thing to add to that, Praveen, is that, you know, we only had 25% of our patients on baseline steroids. If you look at some of the other studies t hat are reported. You know, VARSITY is a very close study. They've actually detailed that they have closer to 50% of their patients on baseline steroids. There's really a fairly low percentage of patients on baseline steroids within the context of our study as well. Understood. Thanks. Thanks, Michael. Thank you. That concludes the Q&A session. I would like to go ahead and turn the conference back over to Dr. Praveen Tipirneni. Please go ahead. Yeah. Thanks, operator. We will, of course, keep everyone updated on our progress. Before we conclude, I'd just like to make one comment as we look forward. IBD treatment, we believe, is still in the early days. There are multiple horizons in the evolution of IBD therapy in the years and decades to come. This is how we look at it. Horizon one was the era of injectable biologics. This, of course, set the stage. Horizon two, the dawn of oral therapy, where we are today. In horizon three, we'll blast through that efficacy ceiling of current IBD treatment with all oral combinations, with hopefully MORF-057 as the foundation. Someday, when we reach horizon four, we'll have genetic and other approaches to ultimately cure IBD. There is still a long way to go, but we expect to lead the charge toward these new horizons. As we reach horizons three and four in the future, we will automatically look at today when we unlock the dawn of horizon two. For today, this is the end, but there's a lot more coming from Morphic, I promise. Thank you all for participating in today's conference call. This concludes today's conference. You all may disconnect, and everyone, enjoy your day.