Good day, thank you for standing by. Welcome to the Roivant Sciences investor call. At this time, all participants are in a listen- only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during this session, you'll need to press star one one on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Stephanie Lee. Please go ahead. Good morning. Thank you for joining today's call to discuss RVT-3101 phase II-B data. I'm Stephanie Lee with Roivant. Presenting today, we've got Matt Gline, Chief Executive Officer of Roivant, and Mayukh Sukhatme, President and Chief Investment Officer of Roivant. For those dialing in via conference call, you can find the slides being presented today, as well as the press release announcing these updates on our IR website at www.investor.roivant.com. We'll also be providing the current slide numbers as we present to help you follow along. I'd like to remind you that we'll be making certain forward-looking statements today during today's presentation. We strongly encourage you to review the information that we filed with the SEC for more information regarding these forward-looking statements and related risks and uncertainties. We'll begin with Matt Gline, who will give opening remarks. With that, I'll turn it over to Matt. Thank you, Steph, good morning, everybody. Thank you for joining. Appreciate the short notice here. It's obviously it's a great day to be getting on the phone, and we're obviously always happy to be talking about clinical data when we've got it to share. I'm excited to spend most of this morning's call on the data from RVT-3101, and I couldn't be more excited for what we've done in that study. Before I hand it over to Mayukh to walk through the results, I'm just gonna start on page 3, just with a quick reminder, which is we are really proud of the immunology pipeline that we have built at this point. obviously, sort of first on that list would be Daklinza, which is now obviously a commercial drug, that we're excited about, in psoriasis and with atopic dermatitis data coming soon, with RVT-3101 in both UC and Crohn's. You'll hear more about that today. With brepocitinib, our Tyk2/JAK1 inhibitor that we're studying in a number of important orphan indications with potentially pivotal data coming in necessarily later this year. With our full franchise in anti-FcRn antibodies, including the batoclimab and IMVT-1402 in Immunovant, and with others behind. Just overall, really proud of the immunology franchise we've built, and RVT-3101 is just one piece of it, although based on the data we're gonna present today, we think it's an important piece, and it'll undoubtedly be a big part of our future. Look, excited to talk more about many of these programs on other occasions, but for today, for right now, we're gonna focus on the exciting clinical data update that we've got here. I'm gonna hand it over to Mayukh Sukhatme, our President and Investment Officer. Mayukh, take it away. Thanks very much, Matt. Please turn to slide 4. I'm really excited to take the time to review our results for 3101. I'll start with just a few slides of background because up until about a month ago, Roivant investors weren't aware of this program in our portfolio, I think it's helpful to set the table briefly. RVT-3101 is a phase II-ready anti-TL1A antibody for ulcerative colitis, Crohn's and other indications. I'll be reviewing the data in later slides, but we saw extremely robust, statistically significant, and clinically meaningful efficacy in this large phase II-B study at each and every dose test. Response rates were enhanced in patients who were positive for a prospectively identified biomarker, covering roughly 60% of UC patients. We saw a favorable safety and tolerability profile. There's no question that UC and Crohn's are large, commercially validated markets, and we expect to expand to additional indications outside of IBD. RVT-3101 is first in class with a large data set in hand with over 300 patients across four dose arms and two studies to date, including the data we'll be presenting today, all of which was generated with sub-Q dosing. This allows us to avoid dose-ranging work in phase III. In fact, we expect to just take a single dose into phase III. Later in the first half of this year, we'll have the full data set, including the chronic period of the study, which patients are treated for 52 weeks of therapy in total. That will be the first chronic or maintenance data generated in the TL1A class. Finally, the program has a strong IP position with composition of matter until 2039+, including extension, as well as the fact that, of course, it's a biologic with 12 years of regulatory exclusivity following approvals. Please turn to slide 5. First, a brief primer on inflammatory bowel disease. It's a disease characterized by chronic inflammation in the digestive tract. There are two primary forms, ulcerative colitis, which is restricted generally to the colon, and Crohn's disease, which presents with skip lesions that can span the full length of the digestive tract. Together, these conditions affect more than 2 million people in the U.S.. These conditions have significant symptoms and morbidity. Patients experience GI symptoms like bleeding, frequent bathroom visits, or obstructions which can require surgical intervention. There are also constitutional symptoms of weight loss, fever, and fatigue. UC and Crohn's represent a rare and highly valuable opportunity for us. They comprise a large and well-established commercial market with approved agents that lack meaningful efficacy. Even the best advanced therapies typically produce clinical remission in just 10% to 15% of patients. That leads patients and physicians to use a trial-and-error approach to therapy, often toggling through many agents of varying mechanisms of action. Please turn to slide 6. As I just said, IBD is also notable for being just a huge commercial market. IBD is a $15 billion market in the U.S. alone and growing. It has consistently yielded blockbuster revenues for therapies across multiple classes. To date, the leading therapy for each novel mechanism has generated over $2 billion in annual sales in the U.S. alone. If you combine the leading therapies for each of the three major mechanisms, you get to $12 billion in annual sales in the U.S. alone. Please turn to slide 7. One of the reasons that we are incredibly excited about working on this new biology and why the investment community has taken notice is that TL1A blockade has broad applicability to a range of indications because it uniquely mediates both inflammatory and fibrotic pathways. As you can see on the left, TL1A is linked to a range of inflammatory diseases as well as to fibrotic diseases in a range of organ systems. We now have, across the field, clinical validation in UC and Crohn's already, with PSC, IBD and additional indications to be explored across the field. On the right, we also have really strong proof of biology data generated in the earlier clinical study from Pfizer. It's worth going through the TL1A biology briefly, as it is quite unique. To use a car analogy, where the car is immune system activity, TL1A is not the initial ignition, but it's the fuel behind disease processes. TL1A-mediated amplification acts on a variety of cell types to increase both pro-inflammatory and pro-fibrotic activity. When you use an antibody, like RVT-3101, to block this amplification, you see that the therapy breaks the TL1A-mediated amplification cycle by both lowering the abnormally high levels of inflammatory and pro-fibrotic cytokines in disease conditions and reducing the number of disease-associated cell types such as Th17 cells and fibroblasts. The earlier Pfizer study showed what happens at the tissue level before and after therapy, thus confirming in patient samples what was expected from the underlying biology. To bring this back to the car analogy, this is different and unique among most autoimmune blocking agents. Remember, we are just taking away the fuel. TL1A blockade shuts off the amplified responses of key cytokines and key pathologic cell types in diseased tissue without broad immune suppression and without increased infection risk. That allows for a very benign safety profile while delivering outstanding efficacy, potentially across a wide range of indications. Please turn to slide 8. Here's a brief recap of where we are on RVT-3101. The first clinical study for the drug was a so-called TUSCANY study, which was published in 2021. That was a 14-week induction study done IV with a single arm, dosed 500 milligrams IV every other week, testing both biologics-experienced and naive patients. An exploratory biomarker of interest was identified coming out of this study, which showed enhanced efficacy in the biomarker-positive patients. It was a global study with an NF 50 that showed positive data in that first validated the TL1A class. The second study on the right, for which we are reporting the induction period results today, is a so-called TUSCANY-2 study. This is a 52-week study, including an induction period and a chronic period. It was placebo-controlled for the induction period, and all arms were dosed sub-Q once per month. As is the norm these days, this enrolled both biologics-experienced and naive patients. This study built upon the learnings from the earlier TUSCANY study and employed a single prospectively defined biomarker, the same one that was employed in TUSCANY, to see if efficacy would be enhanced in the biomarker-positive population. This was a large global study with 245 patients. In fact, this is among the largest phase II-B studies ever conducted in ulcerative colitis. Please turn to slide 9. Here's the schematic for the TUSCANY-2 phase II-B study. After screening, patients were randomized to three different treatment arms or two placebo for the induction period. This was a simple sub-Q regimen dosed once monthly. There was no loading dose and no IV dosing used at any point. We think patients and physicians will like the simplicity, and the commercial marketplace has historically recognized the value proposition of biologics that can be dosed as a simple sub-Q injection at home. Endoscopy, which makes up one of the components of the clinical remission assessment, was performed at two weeks after the last dose in the induction period, so week 14. Thereafter, all patients were put on active drug arms for the remaining 40 weeks at either 50, 150, or 450 milligrams dosed sub-Q once per month. As we've been saying, this was a comprehensive study designed by Pfizer to get maximum information out of the phase II-B to permit a streamlined design in phase III. As we have previewed with the investment community, we think there is a lot of useful information about the TL1A class in this study. It is the first sub-Q study, the first 52-week study, and the first dose ranging study for the class. We think that this data set provides us with a competitive advantage, having studied multiple different doses already. As such, we will not be disclosing the identity of which of our arms is the go-forward phase III dose today because of the competitive advantage it provides us. We will be provide detailed data for both the pool data set, which illustrates the overall robustness of the drug, and detailed data for the expected phase III dose. Please turn to slide 10. Now, without further ado, let's take a look at the data from the induction period of TUSCANY-2. Please turn to slide 11. Here's a slide on subject disposition over the induction period. You see a high degree of compliance in this study. The placebo arm is smaller, but overall there is very high completion rate and disposition slightly favoring the drug arms. Please turn to slide 12. Here are the baseline characteristics. You can see that the pool data and the phase III expected dose baseline characteristics are well-balanced. We'll note here that the placebo arm was, by design, the smallest of the arms of the study. While it was overall well-balanced, there are some signs of a slightly less sick population in the placebo arm, including, for example, a slightly lower baseline Partial Mayo and a lower baseline concomitant steroid use on placebo. As many of you know, generally speaking, patients who are less sick at baseline tend to be more likely to improve than patients who are more sick at baseline. Before we get into the details of the study, I'd like to note that for approximately 20% of patients across the study, the biomarker was not analyzed due to lack of consent at specific sites. These patients are included in the all-comers analysis and are obviously excluded from the biomarker- positive analysis. Second, the P- value shown throughout the presentation reflects Pfizer's pre-specified statistical treatment in its SAP, which is one-sided P- value throughout, with significance set at P less than or equal to 0.025. For clarity, any instance in which the two-sided P- value would not be statistically significant is marked by NS or not significant. Please turn to slide 13. We saw robust efficacy results with statistical significance for both clinical remission and an endoscopic improvement on both the pooled drug cohort versus placebo, and for each and every one of the dose arms versus placebo. Here are the data for the overall pooled drug arm, just so that everyone can appreciate the robustness of this data set. We saw really strong efficacy in the all-comers population, with 32% achieving clinical remission with a placebo-adjusted delta of 21%. The numbers here and elsewhere occasionally don't exactly sum due to rounding. Data was even stronger in the biomarker- positive population, with a clinical remission rate of 37% and a delta of 25%. For endoscopic improvement, a similar pattern was seen. In the all-comers population, 40% of patients saw endoscopic improvement with a delta of 21%, and in the biomarker- positive population, 51% of patients saw endoscopic improvement with a delta of 41%. All values were statistically significant. Please turn to slide 14. On to the data for the expected phase III dose where we'll spend most of our attention. Here again, you see very strong data with statistical significance in both the all-comer population, with a remission rate of 31% and a delta of 20% on Modified Mayo. Even stronger data in the biomarker- positive population, with a remission rate of 40% and a delta of 30%. You see similarly robust data on other key, on the other key efficacy measure of endoscopic improvement. With 40% of patients at the phase III dose achieving this endpoint with a delta of 22%. In the biomarker- positive population, we saw that 56% of patients achieve this endpoint with a delta of 46%. Please turn to slide 15. As you can see, this builds upon the extremely strong data from Prometheus released in early December. I think what you can see here is strong validation for the TL1A class with meaningful efficacy now seen across multiple studies. Please turn to slide 16. Finally, and quite strikingly, we saw this really strong growth efficacy rate even when you go to the biologics-experienced patients in the biomarker selected population. As one might expect in this difficult population, the placebo rate goes down substantially, but the raw efficacy of RVT-3101 is maintained at 41%, resulting in a remarkable delta here of 41%, roughly two to four times larger than anything that's been reported in ulcerative colitis before. Very few programs have even reported this data. We've shown here a cross-trial comparison of every program that has reported efficacy in the biologics- experience population. As you can see, this is by far the best data seen across all mechanisms in this hardest to treat patient population. You see the same dynamic for endoscopic improvement. Here, we saw a 56% rate of endoscopic improvement with a delta of 56%. Again, this vastly outperforms all reported data in the indication to date. Again, what we think RVT-3101 offers is transformational potential in biologics-experienced patients who are biomarker- positive. Please turn to slide 17. Here's the Partial Mayo Score and how it changes over time. We saw rapid reduction in symptoms at the earliest time point measured, with a highly statistically significant difference versus placebo at all measured time points. Please turn to slide 18. How about safety? Consistent with the TUSCANY Study, RVT-3101 was extremely well-tolerated at all dose tested and at the expected phase III dose. There was nothing of note in any of the drug arms, and we've provided both the pooled data as well as the expected phase III dose breakdown. There were no dose-related trends for overall AEs. Severe and serious AEs were generally sporadic, not dose-dependent, and not drug-related. Taking a step back at the overall picture in this AE table, it's remarkable to see that the drug arms almost universally had AEs that were lower than the placebo arm. Importantly, we did not see immunogenicity seem to play a role here. There was no impact of immunogenicity in either clinical efficacy or safety. The ADA rate was 46%, and the neutralizing antibody rate was 8% at the expected phase III dose. These rates are in line with many other approved biologics, including in the TNF class as well as others. Notably, we also have a bit of this data from a portion of the chronic period, based on that data, neutralizing antibody rates are flat to down over 40 weeks. Again, that data appears to show no impact on safety or efficacy. Please turn to slide 19. As an overall summary, we saw statistically significant and clinically meaningful efficacy at each of the three different doses tested. We observed a statistically significant and clinically meaningful efficacy in both the overall population and the biomarker- positive population. Incredibly strong data in patients who are biomarker- positive in biologics- experience. The drug was well tolerated with no AEs of note and no dose-related trends in AEs and no impact of immunogenicity on clinical efficacy or safety results. Please turn to slide 20. I hope everyone can now see and appreciate why we've been excited and what the value proposition is for RVT-3101 in UC. We have shown in this study compelling efficacy data overall, even stronger efficacy data in biomarker-positive patients, and the strongest data yet seen in biologics-experienced patients. We think this data set provides a profile of an extremely safe and well-tolerated drug that can provide high-end efficacy upfront in the all-comers population regardless of biomarker status, with the ability to use a biomarker-guided strategy to get incredibly strong efficacy. Really, I'd say a leap forward in biologics-experienced patients versus currently available therapies, which opens up the possibility of also being the second line agent of choice. We think RVT-3101 has the potential to be the first therapy offering both high-end efficacy and safety in UC in a convenient once- monthly sub-Q dose. Please turn to slide 21. We focused on UC today, but we think that UC is just the beginning for our program. We plan to prosecute the drug in both Crohn's disease and in additional inflammatory and fibrotic diseases. We will be sharing more about these plans in the future. In addition, a reminder that we have the exclusive option to develop a second anti-TL1A antibody after phase I is complete. The efficacy data shown here today encourages blue sky thinking about the range of indications for TL1A. To explore this space in the fullest possible way, having a second agent really allows for maximum optionality and flexibility across indications. Please turn to slide 22. Finally, a recap. 3101 is the first-in-class anti-TL1A antibody. We have extremely robust 300 patient phase II data set across two studies in ulcerative colitis already in hand, with chronic phase data coming in the first half of this year. We have sub-Q efficacy data already demonstrated. We have efficacy across a broad dose range already demonstrated. We have shown strong data in all- comers regardless of biomarker status, even stronger data in the biomarker-positive population. Lastly, we've shown really high unprecedented efficacy in biomarker-positive biologics-experienced population already. RVT-3101 has also shown favorable safety and tolerability profile. There's a well-validated path to approval into a growing and well-validated commercial market. With the finishing elements coming together and with the chronic phase data, we have clarified our strategy around a streamlined phase III. We know the dose, the regimen, and no other clinical work is needed prior to the phase III. Next, the efficacy data in our biomarker-positive population builds upon the high-end efficacy in our all-comer population to create the possibility of a precision medicine approach in immunology to further enhance its response rates. Our simple diagnostic test identifies the roughly 60% of patients who could see significantly improved benefit as the second line agent of choice. We think that we're just getting started. There are multiple avenues for additional growth. This unique targeting of both inflammatory and fibrotic pathways leads to a unique indication set. We feel based on the underlying biology, the high degree of successful translation of good medicines in UC also work in Crohn's, and the initial validation from Prometheus that we have a high likelihood of successful expansion into Crohn's disease. There are many other indications beyond IBD that lend themselves to this mechanism, and we'll share our plans on that in the future. Finally, some important thank yous. First, we'd like to thank the investigators, the site personnel, the Pfizer study team, and importantly, the patients for their participation in this trial. Without all your efforts, these results would not have been possible. Second, I'd like to thank everyone at Pfizer more broadly for discovering and developing this molecule and for their trust and partnership with us on this program. It's the latest in our long-standing partnership, now covering multiple different programs over many years. Both Pfizer and we feel strongly that this is a great compound and exciting mechanism, and we are truly privileged to run with it and help bring it to patients in the years ahead. We think it will have a tremendous impact on patient care. With that, I'll turn things back over to Matt for some closing remarks. Thanks, Mayukh. We'll go to Q&A in just a second. I wanna reiterate all of the thank yous that Mayukh issued there. Yeah, it's again, it's an exciting day to be able to put out data of this quality, and it's an exciting month to be able to add a program like this to our portfolio. All in all, a great start to the year. On slide 23, I just wanna remind everybody, this is really just the very beginning of an extraordinary year for Roivant ahead. You know, in addition to 3101, we'll hit on another upcoming event there. We expect ongoing commercial data from our Vyepti launch, including expanded coverage and reach of the drug. We're excited to talk more about that in our upcoming quarter and beyond. We have, as you'll remember, our phase III trial in atopic dermatitis reading out in the first half of this year, with an opportunity to access a market four times as large as the psoriasis market pending success in that set of studies. In RVT-3101, the subject of today's call, we have the ongoing chronic phase data, which we'll put out again in the first half of this year. That would be the first ever chronic data associated with an anti-TL1A antibody, so we're excited to share that. In the middle of this year, data from IMVT-1402, which is our next- generation anti-FcRn antibody at Immunovant, which we hope validates the performance of that compound as having best in class IgG suppression with no or minimal impact on albumin LDL. Finally, we have a potentially pivotal readout from brepocitinib, our TYK2/JAK1 inhibitor in SLE in the second half of this year. A lot of really important major pivotal clinical data coming over the next 12 months, and excited to get back on the phone multiple times in forums like this one to share those updates. With that, I'll wrap up for today and I'll turn the line back over to the operator for Q&A, and looking forward to taking all of your questions. Thank you. Thank you. As a reminder, to ask a question, you'll need to press star one one on your telephone. Please stand by while we compile the Q&A roster. Our first question comes from David Risinger with SVB Securities. Your line is open. Thank you very much, and congratulations on the phenomenal results. I have lots of questions. I'll limit it to three. First, could you discuss the selection of the one-sided P-value statistical analysis? Second, could you provide more color on the subcutaneous formulation that you studied in phase II and your plans for phase III? When do you expect to provide more details on your UC phase III trial plans and your Crohn's development plans? Thanks very much. Yes. Thank you, Dave. Thanks for listening. Thanks for the great questions. You know, on the one-sided P-value, I guess the thing that I'll say overall there is, look, we inherited this program just one month ago, and this is the kind of study, not necessarily that a biotech company would have designed, but that a big pharma company would have designed to answer every possible question about a drug planning to go into phase III. There were a lot of design decisions made in the study that geared towards answering questions in sort of a, the Pfizer context. I don't have specific context on why going into that they chose the one-sided P-value. I don't know. I'll hand it over to Mayukh in a second to see if he does. I think it was a design decision that was one of many by Pfizer that came down to the way the study was run and the robustness of the study, the number of dosing arms and so on. Mayukh, any further comments on that? No, nothing really. I mean, as we noted, you know, we just decided to hew in this presentation, as I think everyone would want us to hew to how Pfizer themselves had done their statistical plan, and they called for this one-sided P-value calculation throughout. Thanks. Just a reminder, we use the threshold of 0.025 there, which is effective equivalent to two-sided P-value 0.05. On the sub-Q formulation, I wanna be a little bit careful here because as we've said before, we're not disclosing our specific choice of phase III dose for competitive reasons. What I'll say overall is, you know, the sub-Q formulation is clearly a good formulation. You can see it in the tolerability data. You can see it in the overall data that demonstrated strong efficacy in sub-Q, which is something that only we have. My expectation is, we will go to phase III with a somewhat improved sub-Q formulation, even relative to the one in phase II, and that our phase III administration will be a convenient patient friendly format. Feeling good about where we are on the sub-Q, and I think that'll be, frankly, an advantage for us in the world. Then in terms of more detail on phase III plans for UC and Crohn's, I think at this point now that this data is out there, it's easier to talk about sort of what we're planning to do and why. I think you can expect to hear more or less continuous updates from us over the course of the next six-10 months as we make those plans, put them into place, and as we share the maintenance data, which obviously also will inform our, our development strategy. Over the course of this year is the answer to that question. Thank you, Dave. Great. Thank you very much. Thank you. One moment. Our next question comes from Dennis Ding with Jefferies. Your line is open. Hi. Good morning. Thanks for taking my questions. two for me, please. Number one, can you talk about what goes into the biomarker testing and, you know, how this is defined and how this could compare versus TL1A competitors out there? Number two, maybe talk about the rate of ADAs and how did these rates compare with other biologics for UC. I know in your slides you said they were comparable, but can you give a little bit more details there? Thank you. Yeah, perfect. Thanks. On the first question, you know, obviously we are really happy both with the structure of our biomarker, with the fact that it covers, again, 60% of the addressable patient population, which is obviously different than our competitors. With the quality of the clinical data coming out of the biomarker with a strong efficacy delta improvement for biomarker- positive patients. You know, we're being a little bit careful not to tip our hand on the specific nature of the biomarker given that we see it as a potential competitive advantage in the market. I'm not gonna comment on sort of exactly what goes into it, but I like frankly where we are on the curve, thinking both about the addressable breadth of patient population and the efficacy delta that we've observed in the study, which I think are taken together really exciting. You know, on the rate of ADAs, I guess a couple comments. First of all, just to hit it super directly and head on. I'll say again, and Mayukh said it, and it's in the presentation, we saw no impact from ADAs or neutralizing antibodies on safety or efficacy. That was true in the main phase of the study. That was true in the early look of the maintenance data that we've got. Overall, not particularly concerned candidly about immunogenicity. You know, as far as other, there's lots of other data about other compounds. I'll take, just take one example. I'm looking in front of me at a, at a bunch of different Humira studies and Humira biosimilar studies. You know, I'd say the ADA rates in the studies that I'm looking at here range from, you know, mid 30s up to 60s and 70s%. The neutralizing antibody rates, again, this is for Humira and biosimilars, range from, it looks like on this side, like 9-20% or 9-25%. That's, that's for one obviously very well established anti-TNF antibody. I think you find similar data across a range of anti-TNF antibodies and there's plenty of other biologics in similar category as well. Mayukh, anything you can add there? I mean, I think obviously, yeah, you see that kind of pretty consistently for the TNF class. I think, if you look at actually like, you know, Skyrizi as another example of like a, you know, a drug in the sort of, in that space, if you get like an ADA, you know, rate of 20% and a, and a neutralizing antibody rate of, you know, 8% or 10%. Again, kind of same ZIP code. Two other things I'd just say. One is that the details of the biology of TL1A is a little bit unique. It's a, it's a, you know, it's something that trimerizes, which I think kind of lends itself to, you know, sort of higher order immunogenicity. We've seen that that doesn't seem to have an effect as Matt's already noted. I think it'd be, I would also say, you know, it's difficult to compare, you know, ADA results across different antibodies. These are, you know, different, you know, different assays with different specs. I think I'd caution against kind of a cross program comparison, you know, within the same mechanism. Got it. Thanks. That's very helpful. Thanks, Dennis. One moment. Our next question comes from Louise Chen with Cantor. Your line is open. Hi. Thanks for taking my questions and congratulations on the great data. First question I had for you is, you know, how do you define an average placebo rate for a UC trial? I noticed that your placebo rate was meaningfully higher than your competitors, so, you know, any thoughts on that? Secondly, what are the complexities and challenges of moving from an IV formulation to a subcutaneous formulations? What did you guys experience in doing that, or is it a relatively simple process? Last question I had for you is how do you think about induction efficacy versus the chronic treatment efficacy? Is there any precedence as the data matures over time? Thank you. Thanks, Louise. Appreciate it. All great questions. Starting with the placebo question. Look, the truth of the matter is that UC trials are pretty variable from a placebo response rate perspective. I'd say ours was on the higher end. I'd say our competitor's was definitely on the lower end. Yeah, I think that's in part, as Mayukh mentioned, it can be a function of sort of incoming patient disease severity. I think one of the things you can see, I think in our loose opinion, looking at the baseline characteristics, is that our placebo patient population was probably the least sick. Our drug population, especially in our phase III dose arm, was pretty comparable to our competitor's phase III dose population, and their placebo patient population was sicker than their drug population. I think those things combined, you know, sort of support the profile that I think we've seen here, which is, you know, that our placebo response was meaningfully higher in this case. Yeah, I don't. I think the to be honest, I think you're looking at a pretty clear set of bookends, with theirs at the very lowest end and ours at the higher end in terms of what we've seen historically. I think we've seen kind of the full range in between. In my opinion, you know, you should expect trials in this space to continue to yield placebo response rates in that range. Mayukh, anything to add there? Yeah. I'm just gonna add that, you know, our placebo arm was actually like the smallest arm of this study and in that sense, like the smallest arm of all the arms that we're talking about here today, including our competitors, you know, both drugs and placebo arm. In that context, you know, you add to both the, you know, the pattern that Matt alluded to with this specific drug, this specific study's placebo arm being a little bit less sick than the other arms and being sort of a smaller arm, you've just got greater uncertainty around that point estimate. Look, in terms of the challenges of going from IV to subcutaneous, this is something we have a lot of experience with across the Vant family. It was something that presented enormous challenges in the translation of IMVT-1402 into a sub-Q drug as well as batoclimab originally. It can be hard. It's not easy. In some cases it's not possible. This work was successful, and we're very happy with the formulation that we're taking forward into phase III. Look, it's always great to be able to go into a phase III study having sub-Q data in hand and knowing that you have efficacy that you're happy with, in a sub-Q format. That's obviously an important thing versus having to run any kind of bridging study or whatever. Yeah. I was just gonna add there that, yeah, you mentioned, Matt, that, you know, our experience is internally at with IMVT-1401 and IMVT-1402, but we've also seen a lot of other players in this field say that it would be really easy to, you know, go to sub-Q and generate efficacy data there. You know, so far, that hasn't panned out in the FcRn class. Yeah. Thanks. That's a good point. In terms of induction efficacy versus chronic efficacy, you know, there's precedent for improvement in some mechanisms from induction dosing to chronic dosing. It's hard to say with a new class of drugs. Obviously, the biology here is unique and interesting. We've only seen a little bit of the leading data so far, so it's hard to comment on it. I'll say we're looking forward to sharing that chronic data portion of the study and excited to be sort of the only ones currently testing in a 52-week setting. Thank you. Thank you. Thank you. We have a question from Corinne Jenkins with Goldman Sachs. Your line is open. Hi, good morning, and congrats on the data. First question from me, how should we think about enrollment criteria in the phase III study, just given the emphasis you've made throughout the data here on the best-in-class potential, particularly in a second-line biomarker-selected population? Yeah. Thanks, Corinne. We'll share a lot more color about our phase III trial designs over time. That said, I think just to highlight a feature of our data that we're incredibly excited about, you know, Mayukh mentioned, I think the data that this class has put out and the data that our drug has put out here is clearly exciting enough to be considered in an all-comer setting. It's extraordinary data, and we think it has the potential to be a first-line drug of choice in an all-comer setting. I think what's exciting about the dataset we put out today is in the biomarker-positive group, we also showed some really extraordinary, basically unprecedented data in second-line biologics-experienced patients as well. The way that I see this is we have the opportunity to be a great all-comers drug for first line and an opportunity to be a treatment option of choice, particularly in the biomarker-positive population, maybe overall in later line patients, which is a large prevalent market today of patients currently on therapy. You know, we see a number of different opportunities to win there. Mayukh, anything you'd add to that? No. No. I think you said it well. Thanks, Corinne. Just one more from me. In terms of you mentioned kind of evidence from other biologics and ADAs, I'm curious what evidence we see from there and how it might kind of extrapolate from induction to maintenance in terms of how the evolution of efficacy kind of happens as patients stay on therapy for longer? Yeah, thanks. You know, I think it's hard to quibble with the long-term efficacy of Humira and Skyrizi is the first thing I'll say is obviously those are compelling drugs with similar ADA and NAB rates to ours and have been enormous commercial successes and have generated some really exciting, frankly, long-term clinical data. I think that's sort of the general point. There's plenty of other examples as well. I guess I'll also just reiterate, we have seen in our own chronic data in a small sample, mostly, that our NAB rates are sort of flat to down over time, and they don't appear to impact efficacy or safety in our own chronic data as well. We'll know that for sure when that study concludes. In the meantime, it's just an early cut, but I'll just reiterate that as well. Great. Thank you. Thank you. Our next question comes from Brian Cheng with JP Morgan. Your line is open. Hey, good morning, guys. Thanks for taking my question, and congrats on the data. Maybe a couple on your data. Would you be able to provide a bit more color on the sicker patients with an endoscopy score of 3, in terms of, like, how they look in terms of a clinical remission, and any insights on the dose response? A follow-up on the biomarker- positive prevalence. Do you expect the biomarker- positive population to be about the same percentage in the real world as 60%? I'm just curious if that's in line with what you saw based on literature. Thanks. Yes. Thanks, Brian. I'll start with that last one. The answer to that is yes. We expect the 60% to be approximately the same in the real world based on literature, based on the large study that we've done at CDL. You know, and then on dose response, what I'll say on dose response is, I would love to share this data. The challenge here is that we are the only anti-TL1A antibody that has run a proper dose ranging phase II-B. And obviously, FDA cares significantly about dose ranging, both for proceeding to critical studies. We view that as a competitive advantage, and we wanna preserve that advantage for phase III study design. We're not sharing dose ranging information for that reason. You know, I think it's important to note we saw statistically significant clinical meaningful efficacy at every dose we tested. I think it was a, it was a strong sort of signal overall. In terms of more color on sicker patients with the endoscopy score of 3, I'll hand it to Mayukh in a second. I guess I'll say I think the cleanest cut of the data we've provided here on performance in sicker patients is probably just to look at that second-line performance for the biomarker-positive group, and I think that's one cut of what this data looks like for sicker patients who are obviously in need of further therapy. We haven't shared specifically sort of subsets of performance by other measures. Mayukh, anything you kind of add there? No, really nothing more to add. I mean, I think, Matt, you said it well. We're not gonna provide sort of more detail on sort of other specific slices here, but I would say nothing overall that would appear surprising to any. Okay. Maybe one more, if I may. How does the next-gen TL1A fit into this, you know, new Vant that you have established? Specifically, how does that differ from 3101, and is this next-gen program more of a lifecycle management strategy? Thank you. Yeah. Thanks. Thanks, Brian. It's a great question. It's a good question in particular because we get it a lot from the buy side, it's nice to be able to address it here as well. You know, I'll say one thing head on, I'm confident that they would say the same thing if you ask them because we get the question all the time. There was nothing about 3101 that led Pfizer to develop or focus on the next- gen program. The next- gen program is a different construct on the target. We can't say much more than that. It's not our program right now. We have an option on the after the phase I study reached out. The way that I think about it, is look, this data that we've put out today and the data that Regulus has put out, this suggests real blue sky thinking for the class in terms of the potential reach of anti-TL1A as a mechanism. We see opportunities in other indications, in orphan disease across the board to do things with a follow-on compound in the portfolio. There's nothing about our data set and nothing about 3101 that wouldn't make us excited to develop 3101 as our main drug in these indications. Great. Thanks, Matt. Thanks. Appreciate the questions. Thank you. We have a question from Yaron Werber from Citi. Your line is open. Hey, guys. Thanks for taking the question, and congrats on the data. Just to follow up on the previous question on the next- gen, I guess, what would you wanna see from the phase I study for the next- gen, you know, in order to feel comfortable opting in on that program? Another follow-up on just the, some of the subgroups in the TUSCANY-2 study. It does look like, and I know obviously small numbers, does look like maybe the biologics- experienced patients who are biomarker- positive performed a little bit better than the biologics naive patients who may have been biomarker- positive. I guess just any thoughts on that, and is that trend extrapolatable to the broader patient population as well? Thanks. I'll start with the question on the next- gen. Look, the next- gen compound was really designed to answer different scientific and clinical questions, their phase I study is being designed to answer some different scientific and clinical questions. It's hard to talk about specifics there until we can talk about exactly that trial design. Look, we'd like to see the data speak to the ability to do things that are sort of different from 3101. The opting into that program is a $0 upfront option to us to a co-development, co-promote with Pfizer. Given the quality of the data coming out of the TL1A class, if that drug is active, I would imagine we would opt into it and think about creative things to do with it as a part of the franchise. You know, we'll know more once we see that phase I data. on the subgroups question, maybe I'll hand it to Mayukh to take a look at that. Yeah. Sorry, I missed exactly what the subgroup question is, Nina. The question was, it looks like the biologics- experienced biomarker- positive performed better than the biologics naive group a little bit. Yes. Yeah. I guess I would say that that's not. That's probably mostly a function of just, like, where you're getting placebo responses from. I think actually, like, the data just on gross rates across sort of any different cut for the drug arm was remarkably similar. I'd direct you just to look at, I think in the go forward phase III dose, our sort of gross efficacy rate in biomarker- positive patients was about 40%, and the delta was about 30% 'cause there was about a 10% placebo response. Basically, going into the bio-experienced patient population, we just drop all the placebo responders 'cause it's very hard for patients that are that sick to respond to placebo. And so we kept the approximately 40% gross efficacy, but lost the placebo responders. Got it. That's helpful. Thank you. Thanks, Nina. Appreciate the questions. Our next question comes from Robyn Karnauskas with Truist. Your line is open. Hi, guys. Congratulations on the data. Good way to start off the year, I think. I guess I have two quick questions. Number 1, Matt, you said that you might want to do a little bit more work on the sub-Q formulation before phase III. Is that volume? Would you have to do, you know, any small bridging study? Could you extrapolate a little bit more on that? Second, just going back to the biology and the differences in, in Prometheus' products, maybe the next- generation products. Can you talk a little bit about how well you inhibit the TL1A pathway with the sub-Q formulation, and how that there might be differences between the products just biologically so we can maybe think about differences that might show up in phase III? Thanks. Yeah. Perfect. Thanks, Robyn. First of all, we've already done that work on sub-Q, we're happy with where the sub-Q formulation is now, and there's no more clinical work at all required to go into phase III. And the benefit is, we think we've got a somewhat higher concentration basically than that. On the biology, look, in my opinion, in part the clinical data speaks for itself in terms of how well we're hitting the pathway, and I think you can look at our gross efficacy, you can look at the super adjusted and gross efficacy in the biomarker- positive biologics- experienced patient population as pretty good evidence that our sub-Q is performing comparably to the IV data we've seen from the class, both from our own phase II-A and more importantly from our competitor data. I think that's to be honest, that's probably the cleanest evidence. You know, we're probably not gonna share that much sort of specific PD data because it might give some information away on dosing and things like that. Hopefully that gives you a signal. Mike, anything you'd add to that? No. No. Thanks. Thank you, Robyn. Thanks. I agree, it's a great way to start the year. Thank you. Our next question comes from Aaron Weber with Cowen. Your line is open. Great. Good morning and congrats on really terrific results. I have a couple of interrelated questions, Matt, to you or Mayukh Sukhatme. It looks like for Crohn's at least, it looks like you're planning or Pfizer was planning on taking the 150 mg sub-Q months forward. Should we then surmise that potentially is the phase III dose for you, that's the middle dose? For the phase III, is there a thought to do two different studies potentially in sort of frontline and experienced population? Or is it a thought that you ultimately look at biomarker enrich versus all- comers as sort of stratification factors for whatever number of phase III studies you might run? Thank you. Thanks, Jerome. On the first question, I'd say two things. One is, look, I think Pfizer had some clinical trial plans up for a phase II study in Crohn's. They never started that study because they anticipated this deal and wanted us to have control over the design of the Crohn's studies. I think we're glad they did that, and we have our own thoughts and opinions on how the study should be designed. I would not read anything into previous indicators of study design for Crohn's. I'm not gonna tip my hand on what our go forward dose is in UC or Crohn's just based on our data set and what we think we have from a competitive perspective. And then in your comment on phase III study design, and others on the call can comment as well here. First of all, we're not gonna say a bunch about phase III design right now. In general, I think you'd get that. You'd expect that people would include a wide variety of patients in their phase IIIs and not run like separate studies for different subpopulations, but we'll share more about our plans when we're ready. Mayukh, anything? Yeah. Okay. Thanks. Appreciate the question. Thank you. We have a question from Douglas Tsao with H.C. Wainwright & Co. Your line is open. Hi. Good morning. Thanks for taking the question, and congrats, Matt, and to the rest of the team. Just one quick one on the subcutaneous formulation. You said it's a higher concentration. Would that be amenable to an auto-injector? I think the short answer to that question is, yes, the concentrations would be amenable to an auto-injector. Great. Just in terms of the follow-up 52-week data, is there anything in particular that you're looking for? I mean, obviously, we're looking for maintenance of effect and perhaps improved efficacy, but anything that could have influenced the design of the phase III study and the dosing, or do you feel pretty convicted in terms of where that's headed? I'm not a superstitious person, but I feel weird saying that nothing about the chronic study could affect the way that we think about proceeding. I think we feel good about the data and the information we have from the infection study, and so I think we're looking to the chronic study to confirm the insights we've already got. Mayukh, anything you'd add to that? No. Just one final one. I think you made a comment in one of your responses, Matt, about you're happy with what you've seen before. I know Pfizer had some sort of interim looks at the data in this study, in TUSCANY-2, before the full readout. Have they had or have you had any looks at the 52-week data or the ongoing data so far, even on a limited basis? Yes. We have had a look at a limited cut of chronic maintenance data, basically a snapshot in time of where patients were at the time. It's a limited look, so we're not gonna talk about in specific much of the content of that data now. We're gonna wait for the study to read out, as I think is scientifically appropriate. Nothing that we saw in that data, nor anything we think Pfizer saw in that data, gave us any cause for concern. I don't think there was anything in that data that made Pfizer think differently about the program. The only comment we have made about that data today is we think the neutralizing antibody levels supported in that data are supportive of the idea that immunogenicity is not looking like it's playing a role in either short or long-term safety or efficacy. Matt, was any of that data cuts for any patients out to 52 weeks, or was it just to cohorts at certain points up to that cut, you know, sort of within that? You know, it was a snapshot in time, and so some of the patients were at 52 weeks in the set of data that we saw. Okay. Notably, we've seen everything that they've seen. There's nothing that Pfizer has seen that we have not seen. Great. Thank you very much. That's very helpful. Thanks, Doug. Doug. Appreciate it. Thank you. There are no other questions in the queue. I'd like to turn the call back to Mr. Matthew Gline for closing remarks. Thank you very much. Thanks to the operator. Thanks to everybody for listening this morning. look, it's an exciting day to be able to put out some really sort of promising clinical data and to be able to move as a class afoot in what has been a game of inches. Proud to be a part of it. Looking forward to continuing to provide updates on this program and everything else going on at Roivant. Hope to speak to you all soon. Thank you, have a good day. This concludes today's conference call. Thank you for participating. You may now disconnect.