Roivant Sciences Ltd. (ROIV) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen. Thank you for standing by. Welcome to the Roivant Sciences' Investors Call. [Operator Instructions] Please be advised that today's conference may be recorded. I'll now hand the conference over to your speaker host, Stephanie Lee. Please go ahead.

Good morning, and thank you for joining today's call to review the chronic period data for RVT-3101 from the TUSCANY-2 Phase IIb study in ulcerative colitis. I'm Stephanie Lee from Roivant Sciences. Presenting today, we have Matt Gline, CEO of Roivant; and Mayukh Sukhatme, President and Chief Investment Officer. 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 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'll give opening remarks. And with that, I'll turn it over to Matt.

Thank you, Steph, and good morning, everybody, and thank you for joining. We are very pleased to host this call. And obviously, as you'll hear in a moment, very excited about the data we're going to share today. We are privileged that this is, I think, third call this year, which we've shared a new positive data and in some ways, our fourth major study results, all of which have been great. So it's a real privilege. So I'm not going to spend a lot of time on preamble. But on Slide 3, just as a reminder, we're talking today about the chronic period data for RVT-3101, our anti-TL1A antibody in ulcerative colitis. But that situates within what we think is just a tremendously exciting late-stage portfolio in inflammation immunology, including our commercial product currently on the market in psoriasis, VTAMA for which we put out great data in atopic dermatitis earlier this spring, RVT-3101 the drug we're talking about today, Brepocitinib, our dual inhibitor of TYK2 and JAK1. And then our franchise in anti-FcRn antibodies where we expect some important data coming at the end of this summer. So look, we think this is a really exciting overall pipeline, and we think it has the potential to be, frankly, one of the largest commercial portfolios in I&I as we go from here. So we're very proud of what we've built. Today is an important new brick in that wall. And to talk us through that, I'm going to hand it over to Mayukh, who's going to remind everybody about the mechanism and then go into data.

Thanks so much, Matt. Good morning, everyone. I'm very excited to take the time to review our results for the chronic portion of the RVT-3101 TUSCANY-2 Phase IIb study. Please turn to Slide 4. So I want to start by taking a moment to review the novel biology of TL1A. There are really 2 key aspects of this mechanism that underpin our excitement for RVT-3101. The first key aspect is that RVT-3101 mechanistically hits 2 distinct axis, anti-inflammatory axis and an anti-fibrotic axis. We believe this is unique as a mechanism and allows for applicability across a spectacularly broad range of indications. As you can see on the left, TL1A is linked to a range of inflammatory and fibrotic disease affecting multiple organ systems. We now have enhanced across the field clinical validation in both ulcerative colitis and Crohn's with SSc-ILD currently being explored and additional indications on the way. The second key aspect is the way in which RVT-3101 actually interacts with the immune system. TL1A is a cytokine that is crucial for amplifying multiple arms of the immune system and the fibrotic cascade. By inhibiting TL1A activity, RVT-3101 corrects pathogenic over amplification in multiple arms of the immune system that we know are individually involved in inflammatory bowel disease. Finally, we had already generated strong proof of biology data from their earlier Phase II clinical studies, where they looked at changes in patient samples before and after treatment with RVT-3101 that elegantly shown that RVT-3101 treatment functions as an effective inhibitor of the Th17, Th1 and Th2 arms of the immune system in disease tissue, functionally combining the mechanisms of multiple therapeutics into just a single molecule. I also want to state again an important point. TL1A blockade via RVT-3101 does not reduce or knock down arms of the immune system. It simply inhibits local over amplification at the site of disease tissue and therefore, would not be expected to carry the safety risks associated with immune suppression. What does all of that mean for our program? Going into this week 56 data readout, the hope was that we would maintain our very strong efficacy from the induction period, that even a few percentage points of improvement in efficacy would be the grand slam case to borrow [indiscernible]. Please turn to Slide 5. Here are the highlights of the chronic period of the TUSCANY-2 Phase IIb study. Candidly, we were completely blown away by the efficacy data we have here. Patients who were signed the expected Phase III dose throughout the entire study saw meaningful improvements in efficacy from week 14 to week 56 in both clinical remission and endoscopic improvement endpoints. This is off of what was already very strong data just -- after just 14 weeks on drug. To call it what it is, this is better than even the grand slam case. We saw a really exciting top line efficacy rate as the expected Phase III dose growing from 29% at week 14 to 36% at week on clinical risk and growing from 36% at week 14 to 50% at week 56 of endoscopic improvement. These data gets even more impressive when we look at the biomarker positive population. Clinical remission rates of the expected Phase III dose grew from 33% at week 14 to 43% in week 56 and endoscopic improvement rates grew from 47% at week 14 to 64% at week 56. This was all achieved with a remarkably clean safety profile across all doses tested. And importantly, there was no impact of immunogenicity on clinical efficacy or safety. This combination of unprecedented clinical efficacy results and clean safety profile sets RVT-3101 apart from anything in the space. This data in sub showed that RVT-3101 has truly transformative potential for patients with ulcerative colitis. Please turn to Slide 6. Here, again, is a brief recap of the clinical studies completed to date for the program. The first clinical study for RVT-3101 was the so-called TUSCANY study, which was published in 2021. That was a 14-week single-arm induction study dosed at 500 milligrams IV every other week. Exploratory biomarker of interest was identified coming out of this study, which showed enhanced efficacy in biomarker-positive patients. The second study for which we reported the week 14 induction data back in January and are reporting the chronic period results today is the so-called TUSCANY-2 study. This is a 56-week study, which included an induction period and a chronic period. It was placebo-controlled for the induction period, and all arms were dosed subcutaneously once per month. As has been known these days, this enrolls both biologic experience 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 IIb studies ever conducted in ulcerative colitis. Please turn to Slide 7. As I think many people in the investment community appreciate, this is a large study meant to answer many questions at once, and we thank Pfizer for running it this way because it provides us with the richest data set in the field by far and allows us to run a streamlined design in Phase III. So here's the schematic for the TUSCANY-2 Phase IIb study. After screening, patients were randomized to 1 of 9 arms labeled A through I on schematic shown here. Patients were assigned to their dose level for both the induction period and the chronic period at day 1, and both patients and physicians remain blinded to assignments throughout the study. There was no ability for physicians to electively go up or down on the dose. Whatever arm was assigned, was fixed. In January, we presented data as specified in the Pfizer statistical analysis plan. That is to say the data reflected a pooling of arms that had the same dose during induction. In fact, that's how we ourselves received the data at the time. Today, in accordance with the Pfizer statistical analysis plan, we will be presenting data both overall and for the most relevant individual dose arms. This was a simple subcu regimen dosed once a month. There was no loading dose and no IV dose used at any point. As we all know from many historical commercial precedents, the simplicity of a fully subcutaneous regimen without the need for an IV infusion or reduction or loading will be preferred by physicians and patients. Endoscopy, which makes up one of the components of the clinical remission assessment, was performed at baseline and at week 14 as noted in the arrows at the bottom of the schematic, which was 2 weeks after the last dose in the induction period and at week 56, which was 4 weeks after the last dose in the chronic period. Importantly, this was a Treat-Through design, meaning there was no selection criteria such as clinical response, excluding patients from continuing into and being counted in the chronic period. Most of the studies use a so-called rerandomization design, which introduces a selection bias that artificially [ inflates ] efficacy rates in the maintenance period in those studies. These data are without precedent in their strength and take a clear and consistent picture, and we look forward to presenting these data in full at a future medical meeting. As we have discussed with the investment community, we believe the detailed results of this study and the insights it provides us are extremely valuable and a major competitive advantage of Prometheus and Merck and the rest of the field. So for now, for those competitive reasons alone, we will not be disclosing our Phase III dose of further subsets. We've communicated this strategy to the investment community ahead of time, acknowledged that this might be a bit frustrating for some but hope that everyone understands. Again, we look forward to presenting this data from the study in full at a future medical meeting. For today's presentation, we will first be presenting data for the constant expected Phase III dose, which is 1 of either arms, D, E or G. Now if you turn to Slide 8. And then we'll present data for the overall study, arms A though I. For clarity and for reference, on all sides reporting data, we will highlight which arms or groups of arms we are talking about in a banner at the top of the slide. Please turn to Slide 9. So now let's look at the data from the chronic period of TUSCANY-2. Please turn to Slide 10. First, here's the subject disposition for the chronic period. The major study goal of the chronic period was to understand the degree to which week 40 response rates are maintained and potentially improved with additional duration of dosing RVT-3101. Therefore, as was prespecified in the Pfizer's statistical analysis plan, we will be reporting data on the so-called modified intention to treat or mITT population, which is defined as the full population who received at least 1 dose of RVT-3101 in the chronic period. We did also look at the data for the ITT population, which were generally in line or varied only slightly from that of the mITT population. As a final note, we were particularly pleased by the roughly 80% completion rate, which compares very favorably to other trials and is consistent with the high degree of patient enthusiasm we have heard from study investigators. Please turn to Slide 11. Here are the baseline characteristics for both the overall population in the chronic period and then the arm that was assigned the expected Phase III dose throughout the study. As you can see, this is an extremely sick population overall on the left and that the arm [ aside ] the expected Phase III dose is perhaps a bit sicker still than the overall population. I'll draw your attention to the difference in, for example, the Phase III dose having a higher Modified Mayo Score study entry, 6.9 for that arm versus 6.7 overall. A higher proportion of patients with the baseline endoscopy score of 3, which is the highest possible endoscopy score, scale is 0 to 3, that 66% for the constant expected Phase III dose versus 54% overall, and a higher proportion of patients exposed to 2 or more prior advanced therapies, 31% for the constant expected Phase III dose versus 25% overall. As many of you are aware, the sicker the population, the harder it is to get a response. Please turn to Slide 12. Again, to help make through which population we are talking about in any given data slide, you can see the banner at the top right of the slide. So here, it's a constant expected Phase III dose arm, all comers regardless of biomarker status and all comers regardless of prior experience biologics, meaning both biologic-naive and biologic experienced patients. Note that the change in values listed throughout may not exactly match the difference between week 14 and week 56 values because [indiscernible]. So now to the figures. For patients assigned the expected Phase III dose throughout the study, an additional 40 weeks of data led to meaningful improvement in efficacy of what were already quite impressive data at 14 weeks. In the left panel, the proportion of patients achieving clinical remission grew from 29% at week 14 to 36% at week 56, an increase of 7%. In the middle panel, the proportion of patients achieving endoscopic improvement grew from 36% at week 14 to 50% at week 56, an increase of 14%. And in the right panel, we were very excited to see that the proportion of patients achieving endoscopic remission grew from 11% at week 14 to 21% at week 56, an increase of 11%. For those who may not be aware, endoscopic remission is an extraordinarily stringent measure of efficacy, requiring an endoscopy score of 0, which means normal mucosa. Most programs in ulcerative colitis don't even disclose and discuss the remission rates because they are so low. Please turn to Slide 13. Again, just to orient people using the banner at the top right, this is the same arm as the last one, the constant expected Phase III dose arm, but now just the biomarker positive subset. So you can see that the degree of improvement was even greater for biomarker positive patients who have signed the expected Phase III dose throughout the study. On the left, the clinical remission rate grew from 33% at week 14 to 43% at week 56, an increase of 10%. In the middle, the endoscopic improvement rate grew from 47% at week 14 to 64% at week 56, an increase of 18%. And finally, on the right, the endoscopic remission rates grew from 13% at week 14 to an unprecedented 36% at week 56, an increase of 22% and just an outstanding absolute number. We are unaware of any other therapy that has been able to show an endoscopic remission rate any higher than the mid-20s regardless of trial design. So the produced 36% is really extraordinary. Please turn to Slide 14. It's also important for physicians and patients to know that once a patient gets a response, it is likely to be maintained. This is the concept of sustained efficacy. If you achieve success in a given parameter at week 14, what percentage of those patients remain a responder on that parameter at week 56. So for patients to find the expected Phase III dose throughout the study, 75% of the patients who experienced clinical remission at week 14 maintain their response at week 56 and 80% of patients who experienced endoscopic improvement at week 14 maintained their response at week 56. What is that really telling us? It's telling us that for patients who saw a response with RVT-3101 at 14 weeks, the vast majority saw that response maintained through the end of the study. And as we saw on the data we just reviewed, additional responders get added with long duration of dosing. Anybody familiar with the IBD space is well aware of the unfortunate reality that low remission rates and poor persistence of effect leads to a trial and error paradigm, where patients continue to cycle through drugs that either don't work or may provide relief at first, but ultimately fail to address the patient's disease. This efficacy package in total suggests that RVT-3101 can really change that treatment paradigm for patients suffering with ulcerative colitis. Please turn to Slide 15. Although we focused on the constant expected Phase III dose, as it is the most important arm, we want to briefly zoom out to share data from all patients in the chronic period regardless of dose and regardless of line of therapy. The data overall paint a remarkably consistent picture as to the efficacy of this molecule. The robustness of this data set will be abundantly clear when full data get presented at a future medical read. We felt it was important to give you a sense of that here today. On the left, you'll see that the rate of clinical remission was not only maintained, but slightly improved from 31% to 34%. And on the right, you see that the rate of endoscopic improvement was not only maintained, but slightly improved to 38% to 41%. Please turn to Slide 16. For our last key efficacy slide, we wanted to talk about the performance of RVT-3101 in the biomarker-positive biologic-experienced population. This is an area of extremely high unmet need that we have heard so much about from both KOLs and investors a lot. Efficacy of other agents really drops dramatically in this biologic-experienced population, and it is so exciting that in our biomarker positive cohort, which covers around 60% of the overall population, we continue to see transformative outcomes and improving efficacy in this extremely difficult-to-treat population. Looking across data from all patients, we saw that on the left, clinical remission rate at week 56 was 34%, an improvement of 5% from week 14. And on the right, the endoscopic improvement rate at week 56 was 45%, an improvement of 3% from week 14. These are really striking data that again thoroughly outperform anything reported in the... Please turn to Slide 17. Let's turn to safety. The key takeaway here is that the favorable safety profile previously reported for the induction period is maintained through the chronic period. Shown on the left are rates of adverse events and the common treatment-emergent adverse events seen in the induction period. And on the right are the AEs that recurred during the chronic period. Note that these are nonoverlapping periods of time, so with the chronic period, of course, is a much longer interval than the induction period. During the induction period, the rates of AEs are effectively the same to the expected Phase III dose as compared to all patients on the drug and both are in line with placebo. In fact, AEs were generally lower in the drug arm than they were on the placebo arm. When we look at the table on the right, which is the data for the chronic period, we see rates for the expected Phase III dose that are in line with the overall population. Recall, there was no placebo arm during the chronic period. Also in the prior period, we saw that RVT-3101 was well tolerated to week 56, and all this -- and in fact, no dose response was observed for drug-related treatment emergent adverse events, severe AEs or serious AEs. Serious AEs were sporadic and determined not to be related to drug. Rates of infection were very low with no severe infections observed. There were no dose response observed for injection site reactions with all cases considered mild except for one, which was not at our expected Phase III treatment. Overall, we're extremely pleased with the clean and safety profile we're seeing with RVT-3101. Please turn to Slide 18. Finally, there's been a question in the minds of some investors around immunogenicity for the drug and whether there would be an effect on clinical efficacy. We said back in January that we saw no impact on the efficacy data during the induction period and that on a week 40 update, the neutralizing antibody track was flat to down. I'm excited to report a very attractive picture now out to 56 weeks. Turning first to ADA. The last most bar shows the clinical remission rate for those patients who are negative for ADA. And on the right are the clinical remission rates for those who tested positive for ADA, bucketed into quartile based on increasing magnitude of maximum titer from left to right. If after 56 weeks of dosing, ADAs were having a negative impact on clinical efficacy, we would expect to see the slope of this curve putting down as you go from left to right. That is to say, with increasing levels of ADA titers, there would be a decrease in the clinical remission rate. This graph clearly shows that this is not what we are seeing with RVT-3101. Neither the presence nor the amount of ADAs had a negative impact on the long-term clinical efficacy of RVT-3101. Given the lack of a trend line, this seems to be just uncorrelated though. There is no observable relationship between ADAs and efficacy. On neutralizing antibodies, the rate that we said was flat to down at week 40, went all the way down to 0, in fact, and patients assigned the constant expected Phase III dose. Put simply, this data clearly puts the immunogenicity questions to bet once and for all. Between this picture and the safety picture, this is a drug that can be used chronically for the long term. The drug just keeps working better and better over time. This isn't just the best-in-class efficacy and safety profile. It's the best in IVD profile with the mechanism that is extensible into other indications. Please turn to Slide 19. I wanted to conclude our data slides with a few cross-study comparisons to help contextualize this data set. First, an obvious question we want to answer for ourselves was, how does RVT-3101 stand up in terms of the broader landscape of therapies for ulcerative colitis? One challenge when comparing our data to that of other programs is that most studies have utilized a rerandomization study design where only responders were taken into the maintenance period. This results in a selection bias that overstates the benefit of additional duration of dosing for patients overall. As we've discussed, TUSCANY-2 utilized a Treat-Through design for patients continued into the chronic period regardless of their responder status at week [ 40 ], comparison to other studies with a similar design allows the most apples-to-apples assessment of how different molecules behave. Shown here our data from every relevant treatment study, the recent Phase III VARSITY study comparing HUMIRA and ENTYVIO as well as a recent 52-week S1P study. Note that the VARSITY study used an alternate definition for clinical remission that unfortunately cannot be directly compared on that metric. And certainly, our data looks stronger than every comparable study. That's all the more impressive when you further account for the fact that these other studies had a less sick and less pretreated population with a higher proportion of biologics-naive patients. And, for example, in the VARSITY study, if they were exposed, had only been treated with the TNF inhibitor. TUSCANY-2 studied a more refractory population. In sum, we believe that the efficacy shown for RVT-3101 at the expected Phase III dose compares quite favorably regardless of biomarker status with a further enhancement in biomarker-positive patients. Please turn to Slide 20. We also wanted to focus on a concept that has been generating a great deal of interest in the KOL subject of combination therapy in ulcerative colitis. Recent strong data from the VEGA Phase II study, which was conducted only in biologics-naive patients is shown here in pink. VEGA combined an intensive regimen of an IL-23 dosed intravenously in combination with an anti-TNF during induction and continued patients on the anti-IL23 subcutaneously in maintenance. It was suggested that combination therapy could be the only way to break through low efficacy rates seen within the current landscape of approved therapy. We were excited to see that RVT-3101 not only surpasses the bar set by VEGA, but does so as a monotherapy. In blue is the data for the expected Phase III dose in biologics-naive patients as that was the population studied in VEGA. Note, like TUSCANY-2, VEGA utilizes Treat-Through design. The results here fit with what the biology of TL1A blockade predicted. We saw 50% clinical remission rate and a 69% endoscopic improvement rate in frontline patients regardless of biomarker status. RVT-3101 is functionally combining the mechanisms of multiple therapeutics in a single [indiscernible] and by preventing [ aberrant ] over-amplification rather than reducing or knocking down different arms of the immune system. RVT-3101 is able to have this effect without inducing immunosuppression and its associated risks. I want to make sure that this data doesn't get lost in the nuance of discussion around combination. These are really strong data. With such profound efficacy, we believe RVT-3101 has the potential to become the frontline therapy of choice for every newly diagnosed ulcerative colitis patient. Please turn to Slide 21. I hope I've been able to convey at least a small part of our enthusiasm for this mechanism and for this molecule, one we believe has the potential to be best-in-class across IBD as well as a broad range of additional indications. It is also clear that we are well positioned to be first in class and well positioned to go to market with the most attractive commercial presentation. Over 400 patients have been dosed with RVT-3101 across all studies completed to date. In addition, we have about 250 patients worth of induction data, over 200 patients of maintenance data out to 1 year, all with the subcutaneous formulation. Over 250 patients of dose-ranging data across both an IV and 3 subcutaneous doses, over 200 patients worth of data showing enhanced efficacy for a prospectively defined biomarker covering around 60% of the overall population, the same biomarker that is locked and will be used in Phase III. And we will be ready to go to market with a simple auto-injector dosed once per month with no IV loading dose, no off-body subcutaneous infusion for any of that complication. What does all of this mean? It means that we are uniquely ready for a streamlined simple Phase III program. We don't have to guess that a dose will bring more than one dose into Phase III. We don't have to guess at how a subcu may behave in Phase III based on limited IV and bridging. And we don't have to go into Phase III with a different biomarker that then would characterize into Phase II. Please turn to Slide 22. Finally, it's worth bringing this data package back to the implications for this mechanism. We commented back in January that the really strong induction data encouraged some blue sky thinking for our program. A remarkable of that has changed in just the last 6 months. Prometheus reported really strong induction data in both UC and Crohn's disease. We then reported our really strong induction data. Prometheus was acquired [ opposed ] to $11 billion, and it's clear that Merck and others have recognized the TL1A blockade could be the next potential super class of therapeutics. First, we start with inflammatory bowel disease, which is already a $15 billion category in the U.S. alone, growing. This is, as everyone appreciates, a large commercial market in spite of efficacy, that's modest and durability that's modest for existing options. The Phase IIb data set indicates that we can achieve high-end efficacy combined with a very favorable safety profile. We have a drug that can be used to treat all patients, and I mean everyone regardless of line of therapy, regardless of biomarker status, regardless of disease severity. This data set makes us want to go after every segment of this market. This data set shows that patients will be able to stay on drug chronically with efficacy that increases over time and a continued benign safety profile. And finally, at long last, we have the promise of bringing precision immunology to the field to further enhance efficacy. That is something that physicians and patients want and it's something that we think will be useful with payers as well. And all of this is really just the beginning of what's possible. Again, it all comes down to the unique mechanism of action of TL1A blockade, its ability to simultaneously act across multiple arms of the immune system correcting dysregulation at the site of disease tissue. This sets up a very different way to think about treating inflammatory disease generally where you can have a single molecule potentially recapitulate or even improve upon standard of care therapeutics that can -- each can target only a single or a small number of related paths. And TL1A blockade can do this with a remarkably clean safety profile. We show the potential in IVD that the real power of this approach extends more broadly to any indication where TL1A has been shown to play a role in amplifying cascades and driving disease. To get a sense of the blue sky potential on the top right, here are just some examples of extraordinarily large inflammation-driven indications where TL1A has already been shown to play a role and where, in many cases, there remains a great unmet need for drugs with better efficacy and a benign safety profile, just like in IBD. These 5 indications alone currently constitute more than $50 billion of annual sales in the U.S. alone. And then on the bottom right, we have the other access to which TL1A blockade can exert therapeutic benefit, its ability to modulate fibrotic cascades. This not only contributes to efficacy inflammatory disease like IBD, which have a fibrotic component, but also opens up indications for which there is a real lack of effective therapies and a tragically profound unmet need. Diseases that have features of intestinal fibrosis, pulmonary fibrosis or liver fibrosis. Please turn to Slide 23. So with that, I'd like to summarize a few key takeaways. First, RVT-3101 has generated the largest and most comprehensive data set by far in ulcerative colitis. Unlike others in the space, RVT-3101 is derisked and ready for Phase III study. A single dose has been selected, there is no IV to subcu translation risk, and we are locked with our biomarker. Second, RVT-3101 has demonstrated outstanding efficacy regardless of line of therapy with efficacy that improves over time. The vast majority of responders maintained their week 14 induction response through week 56 at the end of the study. Third, our biomarker has the ability to select for the roughly 60% of patients that could see significantly enhanced efficacy from RVT-3101. This is exciting for patients and for physicians who are desperate to break out of the trial of error paradigm that currently defines treatment in IBD, which we talked about earlier. Finally, there are multiple avenues for additional growth. In Crohn's disease, we recently started a Phase II dose ranging study designed to rapidly give us dose and biomarker information for a streamlined Phase III. We ultimately expect time to market to be in line with competition, and we plan to fully prosecute the biology of TL1A inhibition in additional indications to be announced in the future. That can show the true breadth and versatility of this new super class therapeutic expense. Finally, some important thank you. First, we'd like to thank the investigators, the site personnel, the Pfizer study team and importantly, the patients who participated in this trial. Without all your efforts, these results would not have been possible. And once again, I'd like to thank everyone at Pfizer more broadly for discovering and developing this molecule and their trust in collaboration with us on this program. It's the latest in our long-standing partnership covering multiple different programs over many years. Both Pfizer and we feel strongly that this is a great compound and an exciting mechanism. And we are truly privileged to run with it and help bring it to patients in the years ahead. We are excited to have the opportunity to fundamentally transform millions of patient journeys with this program. We are confident RVT-3101 will have tremendous impact on patient care. And with that, I'll turn it back over to Matt.

Thanks, Mayukh. Appreciate it, and thank you, everybody, for listening to that. We're obviously very, very excited about this data and looking forward in just a moment, taking some Q&A. I'll wrap up very quickly on Slide 24, just by reminding everyone that 2023 is just a crazy year for us at Roivant. This is the -- as I said at the beginning of the call, really, the fourth major data set we've put out this year with the TL1A induction data, 2 AD studies, both come -- and the 2 atopic dermatitis studies both coming before it. And we have a number of other major data catalysts, including multiple studies in IMVT-1402 with batoclimab, our FcRn franchise as well as our lupus study in Brepocitinib. So a big second half to the year ahead, really exciting and we think successful first half of the year and most importantly for today, a drug at RVT-3101 we feel very, very good about taking forward and that we are excited to deliver to patients. So look, thank you, everybody. I'll echo [indiscernible] thanks. I appreciate you joining this morning. And with that, I'm going to hand it back over to the operator to begin Q&A.

[Operator Instructions] Our first question coming from the line of Brian Cheng with JPMorgan.

Congrats on the data. Can you give us a directional sense of the next step toward a Phase III study in UC for the remainder of the year? How would the registrational program here look like compared to what we typically see? And are you still shooting for all comers? And you mentioned that there's the optionality about market positive patients? So how should we think about this optionality piece? And then I have a follow-up.

Yes. Perfect. Thanks, Brian. Those are great questions. Thank you for joining this morning. I think I'll answer the latter of your questions first. We are absolutely still expecting this to be in all comers, all lines of therapy Phase III study that is designed to get the broadest possible applicability of the drug to patients irrespective of biomarker status, irrespective of biologics experience. What we will do is we will study the biomarker in our Phase III as a sort of secondary endpoint with an idea that we can generate and produce that data and use it as an additional option for physicians and patients as they're sort of deciding on their treatment paradigm, but also with the ability to prescribe the drug regardless of biomarker status. And we think, in particular, that may be helpful commercially and with payers in providing some optionality, which I think was the meaning behind that comment. As far as the path forward, so first of all, we will meet with FDA shortly here. And that's obviously going to be the most important step here in locking in the trial design. And we expect to communicate about our exact trial plans after that meeting is done, and we're sure of what we're doing. That said, our expectation is in line with what we shared before that we're going to go straight to a Phase III program here that the trial design will look like a modern UC program, probably relatively similar to what was done for efgartigimod. And that will begin as soon as possible. And I think our competitors have given guidance around early next year, I think we'll be in line with our competitors.

Great. And maybe just one more follow-up. So you have indicated the number of possibilities beyond UC and CD this morning. I think that's back to the next question of what's your latest stand on potential collaboration for 3101 in other indications? And also, what could be the cadence for the next set of indications here?

Yes, thanks, Brian. And look, I think the first thing to say is this data, as I said, with the induction data, encourages blue sky thinking, encourages thinking about all of the places in which an anti-TL1A antibody could work. Obviously, Mayukh mentioned, we've already begun the study in Crohn's, but even beyond IBD and other inflammatory and fibrotic conditions. I will have -- I'll share it up with you as soon as we have it. But suffice it to say, we are sprinting at this program for every direction, including figuring out the ways to generate data beyond IBD. Mayukh, anything to add there?

No. I think that covered.

And then, on the partnership question, look, I don't have much to say right now about it. I think we are really excited about the mechanism. We're really excited about the drug. We know there's a lot of enthusiasm in the world forward. And we're committed to doing whatever is best for the drug and best for patients.

And our next question coming from the line of Corinne Jenkins with Goldman Sachs.

Yes. Maybe I'll tee-off on his most recent question. You talked about addressing a broad spectrum of disease with a single Phase III program. Are there any implications to the size of the program that you'll run in order to kind of demonstrate efficacy across, for example, naive and experienced patients, the biomarker-positive group, I'm just curious how you're thinking about that?

Yes. I guess, the short answer to that question is, look, it's going to be a robust program as all UC programs generally are. We are confident it ought to be smaller than our competitors' program simply because they will still have to do dose ranging and other work. And I don't believe that powering for any of these subsets is going to wind up being the rate limiter on size. I think it's just going to be the overall needs of the program for approval. But Mayukh, anything you would add to that on size?

No, not really. I mean, look, I think given the really robust efficacy results we've got here, I think, as Matt alluded to, I don't think that this is going to be an extraordinarily large study. It's going to be a typical UC study, very streamlined and we'll be able to cover kind of every corner of the market within that study.

All right, maybe 1 more for me. You alluded to it, but can you more specifically contextualize the sustained clinical remission rate data as it compares to other available therapies and railroad treatment in UC?

Yes. I don't have a lot of specific data to call in. I'll give it to Mayukh in a second, he maybe able to give a little more context. I guess the one thing I'd say is -- as I'm sure you're aware, many of the other clinical trials earlier in these diseases were rerandomization designs, where basically the way those designs work is during the induction period clinical responders are identified, and then those responders are carried through on therapy and the rest aren't. I guess, in my way of thinking the sort of standard remission rates here, sort of a more stringent version of that where you're cutting the data the first approximation and the induction period on remission instead of response and we're looking at sustained response or sustained remission rates. In some ways, I think that makes it sort of at least useful to contextualize rerandomization data. But Mayukh, anything you'd add on sort of contextualizing the standard remission rates?

Yes. I mean I think broadly speaking, look, this is kind of another one of those things that we don't have a lot of comps for, but sustained efficacy metrics across the field are typically in the 50% to 60% range, so it'd be printing 75% and 80% numbers here is, again, pretty remarkable.

And our next question coming from the line of Louise Chen with Cantor Fitzgerald.

Congratulations on the impressive data and all your successes this year. So I wanted to ask you if you think the efficacy could actually extend beyond the 56-week period? Or how do you think about that? And then secondly, with the data you saw today, how do you think this could change the treatment paradigm for UC? And then last question is, is there any read through from the UC data you've seen into your Crohn's study?

Thanks, Louise. Appreciate the questions as always, and appreciate your joining. On the first question, efficacy beyond 56 weeks. I'll ask Mayukh, I'm not aware of too many studies that have studied UC treatment beyond a year. So I don't think there's a lot of comp data for that. That said, I think if we look at the trajectory -- if we look at the trajectory of the data, it continues to improve, and I think there's a possibility that patients will continue to benefit especially, frankly, on some of the -- we talked a little bit like endoscopic remission, especially on some of the really different endpoints where we continue to see an effect on the disease. So that was your first question. Sorry, I'm blanking out on the second question.

How could it change the treatment paradigm -- but more frontline usage?

Thank you. Thank you. Thank you. Yes, look, I think -- look, I think there's a couple of answers to that. First of all, obviously, it's a privilege in UC to begin with that we are now using clinical remission and endoscopic remission as like the endpoints that are effectively the point of the realm, that's what people are thinking about is what amount to clinical cures for these patients at some level. And I think now that we have a monotherapy agent, which in the biomarker population, is comfortably in the 40s or above. In terms of these endpoints, I think you're looking at a different world for these patients and for our ability to treat them. So I think the first thing is just it really raises the efficacy bar, and I think that will have a real impact on how patients think about these diseases as diseases. So I think that's the first answer. I think the second answer is, this is really one of the first late-stage potential applications of a biomarker in immunology broadly. And I think it's going to be interesting to watch how it plays out and to better understand how treating physicians think about that and how it can fit into the treatment paradigm. Obviously, the way we're running the program is flexible to that point, but I think it's going to be an interesting thing to watch commercially and it's an interesting thing to watch scientifically. Mayukh, anything you would add?

Yes. I was just going to say, I mean, just in terms of like the treatment paradigm, look, I think based on this data set, and if this data set as we [indiscernible] Phase III, I think this really will transform that paradigm. I mean keep in mind, Louise, that patients at present typically go on a drug for between 6 and 12 months only and then drop off, right? And that's because either it didn't work very well in the first place or you had efficacy and you lost it or there's something to do with the safety profile of that drug. And I think this program, RVT-3101 has none of those issues, right? We have strong efficacy data out of the gate. That efficacy gets better over time. We have extraordinary high efficacy in the frontline setting. We have high efficacy in the second-line setting where we know that existing options simply don't work very well at all. And everything suggests this efficacy should improve over time. I think you had a question on Crohn's, right?

Yes, I think the last question was on translation to Crohn's.

Yes. Look. Go ahead.

We think it's predictive is the answer. Look, we think Crohn's and UC are pretty similar diseases. There's a lot of biology and mechanism sort of reasons for overlap, particularly the fibrotic prong here. Obviously, Crohn's is also a fibrotic disease.

And arguably, even more of one than ulcerative colitis. So yes.

And then we can -- obviously, we were pleased to see Prometheus' data in Crohn's earlier this year. It was an open-label study, but it showed good efficacy in the context of other trials and so on. So look, I think there's a lot of reason to believe that this will translate. Obviously, we're excited to see the actual data from that study next year.

And our next question coming from the line of Robyn Karnauskas with Truist Securities.

It's very rare that the data is so good. We don't have a lot of questions. So congrats on that. I guess, one of the key things, I think, that people are trying to get to is the additional indications, and I know you had a question on partnership. But how do we think about spend and how you allocate -- like how bold do you go to start looking quickly and aggressively? And how has that influence been? And then I have a follow-up.

Yes. Thanks, Robyn. Look, thanks for listening and thanks for taking the questions. I appreciate the commentary on the data. Obviously, we're excited about it, too. I think the first thing is one of the great things about TL1A and one of the great things about this data set is IBD is a very large opportunity. There's no question that even IBD alone, this is a really large sort of transformational potential. So we're focused on that now and focused on not giving up any ground. It's a competitive race. We're focusing on getting those studies up and running. We're focused on being first in IBD. That said, this data is really compelling and works -- clearly, TL1A works across a variety of anti-inflammatory and anti-fibrotic axis. And as we've said a few times, we think there's a lot of other opportunity. I think right now, what we are thinking through and working on aggressively is proof of principle to lay out the sort of shape of the playing field, right? How broad can we go, looking at fibrotic disease, looking at inflammatory disease, thinking about the different paths forward so we can get a sense for what the tree looks like. In the broadest possible version, it will impact spend, but that will be for a great reason, namely, if TL1A lines are working across a variety of inflammatory and fibrotic conditions, we will want to develop it broadly. And I am highly confident that we will have many, many, many different ways to make sure that development takes place. Otherwise, I think from a spend perspective, until some of that principle is developed, you could think of the significant majority of spend...

The only thing I'd add to that and stay tuned on sort of our plans here, but I think that there is a way to prosecute some of these questions with, in essence, a relatively limited amount of capital spend in the proof of concept stage.

Got it. And then the other question was just I was curious, you outlined 3 possible doses. Was there a dose response like and why not disclose the dose? Is this for competitive reasons? Or have you decided on which one it is yet? That's it.

Yes. We are locking in on dose. We have a lot of very helpful information about dose response. We think it is helpful for FDA. We think it is helpful commercially. We think it's helpful for making sure we run a low-risk Phase III program. And the only reason we have not shared it is competitive, is that Prometheus did not run a dose-ranging study. And so Merck is presumably still trying to figure out exactly what they want to do from a dosing perspective.

And they're going to have to kind of carry those questions and answering those questions in Phase III, which ultimately makes for less simple, less clean study design than I think we're expecting to have. And just to clarify, I guess, 1 last, I think embedded question there. Yes, we have our -- we have the dose we're going to use in Phase III. That's the expected Phase III dose. That's at a constant dose that we identified in the induction phase. So it was the same thing that we reported in January and then now in new chronic phase.

And our next question coming from the line of Douglas Tsao with H.C. Wainwright.

Congrats on the data. First, Matt, I think you spoke or Mayukh, you spoke about how you're thinking about Phase III and powering and that would be -- obviously, it's an all-comer study, but just curious, in terms of the biomarker population, are you thinking about getting that powered and powered sufficiently so that you could get it included in the label?

Yes, there is a short answer to that question. The biomarker covers 60% of the patients. And so it's not going to be that hard to get a power for inclusion in the label, but absolutely, yes, our expectation is...

Okay. And would you anticipate enriching the population just to make sure -- I mean, it doesn't sound like it will be hard, but just to make sure that you do have a proper number of patients, both biomarker positive as well as maybe sort of non-biomarker-positive patients?

Yes, Doug, we won't get enrich. We don't think we need generic. We have a very good sense. There was no enrichment done in either of the prior studies, and we think that we have a very good bead on the 50% in an unenriched population.

Okay. And then just 1 follow-up for me. Just curious how the data at week 56 compared to the week -- data at week 40. So obviously, we did continue to see some improvement from week 14 or 16 -- not enough coffee this morning. The induction phase. I'm curious, did we continue to see the trend lines up or did it reach sort of maximum efficacy by week 40?

Yes. Thanks, Doug. I haven't had coffee either so I'm sympathetic, but I'll hand it over to Mayukh to answer your question.

Yes. Yes. The punchline is we did continue to see improvement. Keep in mind, of course, that at least 40, we don't have endoscopies, right? That was only done at week 14 and at week 56. So we're sort of missing part of that equation. But in other parameters, we absolutely continue to see improvement.

And 1 quick follow-up. I mean, would there be a reason to think that further out, we would continue to see further gains as mentioned for patients?

I guess, a little bit around, I'd say our data gives us no indication that we have plateaued. And so I think it's reasonable to expect continued improvement.

Our next question coming from the line of Neena Bitritto-Garg with Citi.

Congrats on the data. So just a follow-up on the biomarker-positive patients. I didn't hear this on the call, but could you tell us what the sustained clinical remission rate and sustained endoscopy improvement rate was for patients that were at the expected Phase III dose who were biomarker positive? And then can you also remind us in terms of the actual biomarker assessment, how easy that actually is to do clinically. I think you've said before, you don't need an actual separate companion diagnostics. But just from a practical kind of commercial perspective, how easy is to actually identify the biomarker patient population?

Yes. Thank you, Neena. Thanks for listening, and thanks for the questions. As far as the assessment, we haven't commented on specifically how it's collected, but we've said it's not going to be any kind of commercial liability. So we think it will be straightforward is the answer. And then look, I think the short answer on the sort of sustained remission rates is broadly consistent. But Mayukh anything you'd add to that?

Yes, broadly consistent, better than the sort of bar that I alluded to earlier in the call across all of those metrics.

And our next question coming from the line of Dennis Ding with Jefferies.

Congratulations on the great data. Two quick ones for me. When you look back at the induction data on a modified ITT basis, remission was 29% in out-comers and 33% for the biomarker positive, and these are all at the Phase III dose. I recall back when the data was reported in January, the induction data, the delta was closer to around 10%. So how should we interpret this and the utility of the biomarker -- of a biomarker approach given this data or is this just a dynamic of small numbers and variability? And then my second question is around Phase III, what strategies can you take to minimize the placebo effect?

Yes. Thanks, Dennis. I appreciate the questions. They're good questions. On the first one, I'll say, first of all, this is not a function of mITT versus ITT. The differences between those 2 were truly minimal and just related to really a couple of patients different in exclusion. The delta here relative to the data we reported in January was that this is just -- it's a different cohort of patients, right? These are only the patients who were on the Phase III dose for a full 52 weeks, while the data we reported in January, which is as sort of Pfizer had given it to us, was all of the data for all of the patients on the Phase III dose during the induction period. So this is a smaller subset of patients. As you can see, if you compare the baseline characteristics between the 2, this is a slightly sicker population. And so the numbers are probably a little bit lower for that reason. Overall, I think when we take a step back and look at the totality of the data, and I think this will be clear with the general medical meeting, our view on the biomarker is fundamentally unchanged from where it has been here. We think the biomarker delivers a real meaningful benefit on the order of what we shared in January. And we think it will be helpful commercially. Again, still no intention to limit the study to just biomarker patients, but we think that will appreciate having the option. So that's on the biomarker question. Anything you'd add to that?

No, not really. I mean, I think you sort of pointed out 1 kind of -- 1 data point, but if you look again in totality, even across like all the different metrics, all the time, of course, as you just see, I think, a really clear and consistent sort of pattern of enhanced efficacy in the biomarker-positive population.

Even in the data we shared today, like the endoscopic improvement data looks really, really good. And the endoscopic remission data is frankly remarkable. It's an unprecedented level. On placebo, I think, obviously, the proper extension Phase III study is high on the list. Frank, if you want to just share any thoughts on execution there?

Sure, happy to. I think one of the things that we benefit from is, this is the largest study in this mechanism to date. And we have site-level performance from the entire Pfizer study from both induction and maintenance. And we can say which sites were really good sites, how do they perform? How do those patients perform? And I think that level of site level intelligence gathered from so many sites from so many patients here really gives us a leg up into thinking about how we minimize placebo effect going into Phase III.

And the only other point I'll add on placebo just as a baseline thing to keep in mind. Look, I think our placebo rate in the induction phase here was normal, probably like the higher end of the band of normal, but pretty normal. And so look, and I think our data was exciting in that context. So I guess I'm feeling pretty good about kind of where we...

It's also just worth reminding if we talked about in January that the placebo rate that we printed, like while Matt said, it was sort of normal or maybe upper end of normal, it was also the smallest of the arms in the induction portion of the study. And so in a certain sense, the uncertainty around the point of aspect and the ability of a placebo responder to kind of move that percentage up was higher. And then beyond that, I think as we talked about back in January, the placebo patient cohort was actually the least sick of the cohort study. And I think back then kind of looking across all the induction portion -- induction arms, we really saw our placebo arm being the least sick, our expected Phase III dose arm being a bit sicker in sort of overlapping with the Prometheus dose arm and then Prometheus' placebo arm being kind of the most sick.

And our next question coming from the line of David Risinger with SVB Securities.

This is Brian on for Dave. I guess, first off, congrats on the data. I just had a quick question. I kind of wanted to understand what proportion of the patients here were on background therapy? And how many of them, if any, did you have discontinued background therapy in the maintenance period?

Thanks, I appreciate the question. Thanks for listening. I'm going to ask Mayukh to take that on the specifics, but they're good questions.

Yes. Across the study -- sorry, I'm just kind of looking here quickly. But something on the order of, I think, really around 40% of patients were on steroids at baseline and then over the course of the maintenance period, there was sort of tapering was encouraged but not mandated. And so roughly -- again, broadly speaking, roughly half of the patients were able to reduce their steroid dose.

And nothing other than corticosteroid was coming as background therapy.

And our next question coming from the line of Yaron Werber with Cowen.

This is [ Julius ] on for Yaron. And I'll just add my congrats on the data. Maybe just looking at another slice of the data, are you able to comment on what you saw specifically in the biomarker negative patients and maybe what was the magnitude of the delta there between the biomarker negative versus the biomarker-positive cohorts? And then maybe just more broadly, how are you thinking about competitive positioning on the biomarkers between you and your competitor?

Yes. Thanks. I appreciate the question. Thanks for listening. I think -- so the short answer is we had compelling efficacy in biomarker-negative patients. That was broadly consistent across arms and so on. The reason we haven't reported it on the Phase III dose, just because you start to get to relatively smaller end once you compound these various effects and the fact that the biomarker population is significantly negative, population is significantly smaller than the biomarker-positive population. But I'll say we saw a compelling efficacy for biomarker negative patients across cohorts, and feel broadly good about this drug, both as an all-comers drug and for biomarker-positive patients. So we have sort of a good understanding of our performance in those groups. In terms of positioning versus the competition here, I think everything we've said before still attains. This data shows that we have an effective biomarker that clearly separates from the all-comers population and offers an incremental benefit to patients in identifying responders. And -- so we think it's going to be an important tool. We think on the curve, it will deliver based on what we've seen so far and obviously, there's more data to come from our competition. We'll see so far, we think a sort of broadly comparably efficacious biomarker in a larger patient population, which we think will be more attractive to physicians and patients. So that's sort of at a high level, I think, how we've positioned the biomarker.

Yes. I'd just add to that. If you look, I think we're -- again, we're locked and loaded. I think we've got this huge data set that builds upon the earlier clinical study as well, and we've got our biomarker set and we see this again pattern kind of no matter how you slice it of enhanced efficacy on top of an already great based all-comers data set in the biomarker positive population covering 50% of patients. So really, I'd say that the question really is probably 1 more for Prometheus and Merck or Merck, I guess, at this point. They're playing catch up. And right now, they're not locked and loaded and they're starting with a much, much smaller biomarker-positive cohort.

And I'm showing no further questions in the queue at this time. I will now turn the call back over to Mr. Matt Gline for any closing remarks.

Great. Look, thank you, to the operator. Thank you to everybody who dialed in this morning and listened. Again, I'll echo my huge thanks to the Roivant team, the [indiscernible] team, the folks at Pfizer, who are our partners and all the investigators and patients who worked on the program. We could not be more excited to be counting this forward. It's a privilege to work on a program like this one. And the privilege to have produced all of the data that we produced so far this year, and I'm looking forward to more data coming in the balance of the year. So thank you, everybody, and look forward to talking to you all soon.

Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.