Good afternoon, ladies and gentlemen, and welcome to the Ventyx Biosciences First Quarter 2023 earnings conference call. At this time, all participants have been placed on a listen-only mode, and the floor will be open for your questions following the presentation. If you would like to ask a question at that time, please press star one on your telephone keypad. If at any point your question has been answered, you may remove yourself from the queue by pressing star two. Others can hear your questions clearly, we ask that you pick up your handset for best sound quality. Lastly, if you should require operator assistance, please press star zero. As a reminder, this conference call is being recorded. I would now like to turn the call over to Dr. Martin Auster, Ventyx's Chief Financial Officer. Please go ahead. Thanks, Angela. Thank you everyone for joining us today and good afternoon. Welcome to Ventyx Biosciences conference call and webcast, where we'll be discussing our first quarter 2023 financial results and providing a business update. As a reminder, the company's most recent investor presentation can be found on our website at www.ventyxbio.com in the Investors tab in the News and Events section. Before we begin the call today, I'd like to remind everyone this conference call and webcast will contain forward-looking statements about the company, including without limitation statements about the anticipated timing of commencement, enrollment, and completion of clinical trials for our product candidates, the anticipated timing of release of clinical trial data and other information about our product candidates, the market opportunity for our product candidates, and the expected timeframe for funding operations with current cash equivalents, and marketable securities. These statements are subject to risks and uncertainties that could cause actual results to differ. Factors that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward-looking statements are discussed in greater detail in our most periodic reports filed with the SEC, including our Form 10-Q for the first quarter, which ended March 31st, 2023, which we anticipate filing later today. Please note that these forward-looking statements reflect our opinion only as of the date of this call, and we undertake no obligation to revise or publicly release the results of any revisions to these forward-looking statements in light of new information or future events, except as required by law. With that said, I'll hand the call over now to Dr. Raju Mohan, Ventyx's Founder and CEO. Raju, please go ahead. Yeah. Thanks, Marty. Good afternoon to all again, and thank you for joining Ventyx's first quarter 2023 financial results conference call. Let me briefly run through this afternoon's agenda. Given that we just had our call in late March, I'll be brief and keep my comments focused on high-level business update. Will Sandborn, our President and Chief Medical Officer, will then provide updates across our pipeline programs in a bit more detail. Finally, Marty will present an overview of our first quarter 2023 financial results before we open the call for Q&A. As I always like to remind our audience, the foundation of Ventyx is our mission to bring differentiated, safe, and effective oral medicines to large immunology markets and markets with high unmet medical need and that are currently dominated by injectable biologics. With 2023 shaping up to be a transformational year for Ventyx, we're off to a great start. Our team is executing across the board with five, and I repeat, five phase II clinical trials now ongoing across our wholly owned pipeline of internally discovered small molecule drug candidates. With VTX958, we remain confident that we are developing a potential best-in-class allosteric TYK2 inhibitor. Based on class-leading target coverage and safety that we observed in phase I, we see great potential to not only establish a differentiated profile in psoriasis and psoriatic arthritis, but also to be a first mover among TYK2 inhibitors in Crohn's disease, where we believe our ability to achieve trough IL-23 IC90 coverage will be particularly important. We have three phase II trials now underway in plaque psoriasis, psoriatic arthritis, and Crohn's disease. Will will discuss these in more detail during his section in his comments. On the development of an extended release tablet for QD dosing for VTX958, we continue to make progress towards the target profile, the TPP, and we remain confident that we will have optimized once-daily tablet to advance into phase III trials in 2024. As we have previously disclosed and discussed, our development strategy for this path incorporates an iterative process that allows us to sequentially evaluate multiple prototype formulations in humans. We look forward to providing a more detailed update in the early second half of 2023. With our S1P1 modulator, VTX002, we believe we will be the first to truly explore the full potential of this mechanism in ulcerative colitis, and our aspirations for this asset have always been very clear, which are to demonstrate efficacy in moderate to severe UC patients, ulcerative colitis patients, that is unambiguously differentiated from both etrasimod and ZEPOSIA and is competitive with or superior to levels achieved by biologics. This efficacy profile, if achieved, should position VTX002 as a potential class-leading safe oral agent in ulcerative colitis. Again, Will will provide more color on the progress of this trial. Beyond these lead programs, we continue to advance our novel NLRP3 inhibitor portfolio, including our peripheral NLRP3 inhibitor VTX2735, which is now in phase II trials in CAPS patients, and a CNS penetrant NLRP3 inhibitor VTX3232, which is expected to advance into phase I studies this quarter. With that, I'll hand the call over to Will Sandborn for a more detailed pipeline update. Will? Thank you, Raju. Good afternoon, everyone. I'm excited to provide a brief pipeline update today and to highlight recent achievements across our portfolio. I'll begin with VTX958. As you are all aware, we are now well underway with three phase II trials of VTX958, including the SERENITY trial in moderate to severe plaque psoriasis, the HARMONY trial in moderately to severely active Crohn's disease, and the TRANQUILITY trial in active psoriatic arthritis. Across this program, we believe we will be the first to explore near full suppression of the TYK2 pathways with the top dose in each of the 3 trials expected to achieve approximate trough IC90 coverage of IL-12 and IL-23. We are really pushing towards biologic-like suppression of the IL-23 pathway, and we expect this to translate into differentiated efficacy closer to that observed with the anti-IL-23 antibodies. This is our expectation not only in plaque psoriasis and psoriatic arthritis, but also in Crohn's disease, where we continue to see a tremendous unmet need for a safe and effective oral therapy and where we believe our class-leading therapeutic window may afford us a strong position relative to competitors. Looking more closely at the psoriasis market, we remain very excited about the commercial opportunity for orally delivered small molecules to gain both market share versus legacy biologic therapies, as well as to continue to drive expansion of the treated population within the $28 billion projected 2023 global psoriasis market. We are particularly optimistic for the potential of the TYK2 inhibitor class and point to strong signs of early uptake for SOTYKTU, the first approved TYK2 inhibitor with indications of strong early share gains relative to both biologics and less effective oral options. We expect that the market opportunity for oral therapeutics and TYK2 inhibitors, specifically, to continue to expand in the coming years with the potential for greater TYK2 target inhibition to drive an enhanced efficacy profile, which we think will be a strong determinant of the projected total market share potential for and within the TYK2 class. As Raju mentioned, the team has done an excellent job getting the VTX958 phase II program up and running over the past 6 months, and we have made tremendous progress in enrolling the SERENITY plaque psoriasis trial. As we've stated previously, we are on track to report top-line data in the fourth quarter. We are looking forward to carrying this operational momentum into the other VTX958 phase II trials, including the TRANQUILITY trial in psoriatic arthritis and the HARMONY trial in Crohn's disease. We continue to expect top-line results from both of these trials in 2024. Shifting to VTX002, our S1P1 receptor modulator in phase II development for ulcerative colitis. I think Raju put it well when he said that the goal here is to be the first to truly explore the full potential of this mechanism in ulcerative colitis. This is similar to the story with VTX958, where we talk about achieving differentiated coverage of the target pathway. You will recall that we previously shared data from our phase II open label extension trial demonstrating that our high dose of 60 milligrams is achieving steady-state absolute lymphocyte concentration or count reductions in the range of 70+% compared to approximately 50% per etrasimod and ZEPOSIA. We believe that this differentiated pharmacodynamic effect will translate into improved efficacy in ulcerative colitis. If we take a step back and look at the landscape in ulcerative colitis, this is a large market currently dominated by biologics, which achieve placebo-adjusted clinical remission rates of around just 10% or slightly higher. The anti-TNF-alpha, the alpha-4 beta-7 integrin inhibitors, and so on all share this characteristic. There is a significant opportunity for a safe and oral therapy that can exceed this efficacy benchmark. Based on our conversations with physicians, we fully expect the S1P class will grow robustly as ZEPOSIA continues to build volume. Meanwhile, the potential approval of etrasimod is expected later this year. If we can achieve our target product profile with VTX002, which is placebo-adjusted clinical remission of around 20% or better, then we believe there is an opportunity for VTX002 to become a class-leading drug in ulcerative colitis. As we mentioned in the press release, enrollment in the phase II trial of VTX002 has continued to progress very well. We're excited about this program, and based on a 13-week primary endpoint, we are on track to report top-line data in the second half of 2023. Finally, I'll briefly touch on our portfolio of novel oral NLRP3 inhibitors. On our last earnings call, we announced that we have initiated a phase II proof of concept study of our peripheral NLRP3 inhibitor, VTX2735. Familial cold autoinflammatory syndrome or FCAS, which is the most common subpopulation of cryopyrin-associated periodic syndromes or CAPS. With our CNS penetrant compound, VTX3232, we expect to initiate a phase I trial in healthy volunteers this quarter. Our goal is to position both of these NLRP3 inhibitors as phase II-ready clinical candidates by establishing a differentiated profile in terms of safety, pharmacokinetic, and pharmacodynamic activity. We believe that there is a wide range of high-value indications for future development of both our peripheral NLRP3 inhibitor VTX2735 and our CNS penetrant molecule VTX3232. On the peripheral side mechanism, such indications include cardiovascular, dermatologic, and rheumatologic diseases. With regard to NLRP3 inhibition in the CNS, there's a strong biologic rationale to potentially address devastating neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, among others. In summary, this is a very exciting period for Ventyx and our portfolio of novel small molecules. Execution has been strong across the pipeline, and we are very much looking forward to announcing top-line data for VTX958 and VTX002 in the second half of this year. Before we move on to Q&A, I'd like to hand the call back to Marty for a brief discussion of our financial results. Marty? Yeah. Thank you, Will. You'll find details from our financial results for the first quarter ending March 31st in our press release, I believe the Form 10-Q filing is also hit on the website. I'll summarize those results here. R&D expenses were $35.4 million for the first quarter of 2023, compared to $17.4 million in the first quarter of 2022. This increase reflects the advancement of our pipeline in the later stages of clinical testing, including execution of the ongoing phase II trial of VTX002 in ulcerative colitis and the phase II programs for VTX958 in psoriasis, Crohn's disease, and psoriatic arthritis. As we previously mentioned, we continue to expect R&D expenses to increase directionally throughout 2023, with some quarter-over-quarter variability expected as our phase II trials progress and as we conduct our CMC activities in preparation for the potential launch of phase III trials on VTX002 and VTX958 in 2024. G&A expenses in the quarter were $7.1 million versus $5.3 million in the first quarter of 2022. The net loss in the first quarter of 2023 was $38.9 million, compared to $22.7 million for the first quarter of 2022. Cash, cash equivalents, and marketable securities totaled $376.9 million as of March 31st. This reflects an increase from our end-of-year cash and equivalents balance of $356.6 million and reflects proceeds from the sale of stock on our ATM facility, which occurred during Q1, offset by our first quarter cash spend. We continue to believe that our current cash equivalents, and marketable securities are sufficient to support planned operations into 2025. With that, we conclude our prepared remarks for this afternoon's call. I'll turn the mic back over to Angela to begin the Q&A session, where I'll be joined by Raju and Will. Operator? The floor is now open for questions. At this time, if you have a question or comment, please press star one on your telephone keypad. If at any point your question is answered, you may remove yourself from the queue by pressing star two. Again, we ask that you pick up your handset when posing your questions to provide optimal sound quality. Thank you. Our first question is coming from Michael Yee with Jefferies. Please go ahead. Hey, guys. Thanks for the question. Thanks for the updates. We had two areas we wanted to ask on. The first was actually on the S1P1. I know you have data coming up later this year. There have been some studies that I've read out recently, you know, had no placebo. Of course, some studies like the TL1A had a very low placebo. Can you just help us understand what things you have in place and what strategies and what you expect to have for a placebo in your upcoming study and how to think about that versus some of the other recent UC studies that I've read out in the past couple of months? The second question is you also have an update on the ER tablet VTX958. Can you just remind us, are you testing multiple different technologies in that, or is that one technology at different doses? Thank you. Yeah. Excellent. Thanks, Mike. Good to hear from you. Let me have Will talk about the S1P1 and trials and placebo, and then I'll come back with the ER tablet. Will? Yeah. So it's a good question, Mike. You know, I think that trials without placebo arms that are not controlled are not easy to interpret. You know, you just have to take those data with a grain of salt. Placebo rates can vary. The average placebo rate in moderate to severe ulcerative colitis trials is about 7.5 or 8%. It can sometimes be as low as, you know, 2% or 3%, and it can be as high as the low teens. More or less, the way you try to manage for this is to keep good control of the trial to monitor the disease characteristics of the patients that are coming into the trial, and we do that robustly. You can also, sort of monitor the outcomes and pool blinded data. To see, you know, if the magnitude of response that you're seeing is, you know, just barely crossing the threshold to be a response or, you know, whether it's a deep and a robust response. I'm not gonna get into the details around any of those things, except to say we're well aware of all the characteristics, and we've monitored the trial very carefully as it has progressed. Good. Anything else on that, Michael Yee? Very helpful. Very helpful. Then on the ER tablet, shed some light on that, what's going on with different technology, development technology? Yeah. On the ER tablet. Yeah. Yeah. It's a good question, and thanks for asking. Can clarify that. We have a couple of different technologies, but I think it's important to understand that these are sort of complementary technologies. What we do is we use one technology to make sure we're sort of using biorelevant dissolution methods, which is what's, you know, what's happening in the, in the absorption dissolution absorption phase in humans. Then we complement this with the technology that actually simulates what's actually gonna happen, the, the dynamics, the motility of what actually happens on absorption. You really are sort of, you know, using multiple technologies to make sure, for lack of a better word, checking a box in or checking the appropriate boxes for both technologies. If you maximize your chance of then when you go into human data, you've now made sure that you've simulated what you see, both in terms of dissolution fluids and dissolution rate and also absorption distribution in terms of what actually happens in a system where you've got, you know, bile salts and motility, all of those factors. That's sort of the path we take with each iteration that we're doing towards our target product profile for the ER tablet for QD dosing in phase III. Thank you. You're welcome. Thank you. Our next question comes from Yasmeen Rahimi with Piper Sandler. Good afternoon, team, and thank you so much for all the great updates. Two questions for you. Maybe the first one is to start off on S1P1. I know most of the analysts and investors are very familiar on what the bar is in regards to efficacy into that data readout in the second half. But maybe what would be helpful is, Dr. Sandborn, if you could educate us on what do we wanna see from a safety perspective out of this phase IIB that could highlight differentiation. So that's question number 1. Question number 2 is, you know, tomorrow morning we're gonna see, you know, some phase I data from the IL-23 oral product and would love to, you know, as we're looking at that data, think about how you guys are like... I guess could we look at that and being able to predict sort of, what the I guess the comparisons or the TAK-2 class versus the IL-23 class could offer, obviously just on based on phase I data. I'll jump back into the queue. Let me address the Protagonist question. Yes, again, good to hear from you. Yes, the phase I data is supposed to come out tomorrow at the ISID meeting, followed by the more detailed efficacy data that's gonna come out sometime in, I believe, the July timeframe. Again, I think we had a similar question at the last call, I think we have to wait for the data. You know, I think the PK/PD itself might be illustrative to some extent, but the real meat is gonna be in the phase II data and how it compares to what we've seen with, you know, drugs in this class, the biologics and the orals that have come out recently. You know, it's really, you know, difficult to speculate on something we have no idea about. You, you and I have talked about the press release. Mm-hmm. that came out early on. I think let's wait for this data. Mm-hmm. PK/PD. It'll give us a little more color on this class of compounds, and we have none. We'll wait for the efficacy data and have a meaningful discussion on this class of drugs in particular. Let me just hand it over to Will for the S1P1 question. Yeah. Just to frame the perspective, remember that the S1P class of medications has had regulatory approval in the U.S. since 2010 when Gilenya was approved for multiple sclerosis. There's about a million patient years of exposure with Gilenya, and their marketed dose has lymphocyte reductions in the low 70s, which is exactly where we are targeting for the higher of our 2 doses. The context of the data that we release in the second half of the year for, from a safety perspective will be in the context of a very well understood class of drugs with respect to, you know, all the potential safety issues. The second thing is to say is that, you know, we'll be releasing 13 weeks of safety data, you know, that's a limited period of time. It, you know, it's not typical that you see a lot of important, what I would say are big ticket adverse events anyway in an early trial. You know, the data will be what they are. If you look specifically what you like to see for drugs that are effective, typically the and well-tolerated, you typically will see completion rates for 12 or 13 weeks in the single digits. Having patients complete the induction course of therapy is one measure of safety and tolerability. Of course you're looking at the proportions of patients that have severe adverse events and have discontinuation sort of related and flip side of that. The relatedness of adverse events and severe adverse events to the compound as judged by the investigators. We'll look at all those things. Then narrowly in the S1P1 class, you can see heart rate reductions and AV blocks, and those can be, you know, substantially mitigated with dosing titration regimens. We think we have a good dosing titration regimen. Seeing what the rates of bradycardia is in the first 13 weeks by treatment group and seeing, you know, if there are any cases of AV block and those sort of things, those will be of interest and would allow comparing and contrasting with other products which may or may not be titrated. The other things that you see with S1P drugs are generally, you know, rare and you're not likely to see in a phase II induction study. Thank you so much, Dr. Sandborn, for your comments. The next question comes from Derek Archila with Wells Fargo. Please go ahead. Hey guys. Thanks for taking the questions, just a couple from us. Maybe just first, we wanted to get your take on why we won't see a plateau for the TYK2 class, even at IC90 coverage. I guess, you know, some folks point to this Pfizer molecule, which allegedly had IC90 coverage for 24 hours, and their 12-week data looking fairly similar to deucravacitinib and Takeda's drug at PASI 75 and PASI 90. Just love to get your thoughts there. Also, can you just remind us how many sites you have in the S1P1 trial and the geographic distribution of those sites? Any color on the split you would expect for advanced therapies versus naive would also be helpful. Thanks. Yeah, Derek, good question. You know, we've seen some of that analysis out there, so, you know, we'll address it again. I'll have Will Sandborn again talk a little bit about this because we have taken it there. Let me just start out on some of the analysis being done out there in terms of coverage or modeled coverage in IC70s, IC80s, and IC90s that people have put out there in particular. Let's get outside the Pfizer compound. Let's focus on some of the analysis been done for SOTYKTU and for the two Takeda doses that have been done. Look, cross-trial comparison with small number of folks is really challenging. You know, the data are what they are, right? I think our belief is that within those three examples, again, we'll leave Pfizer out of there. The SOTYKTU, 12-milligram dose that people are using to model out the IC50 coverage for about 18 hours, I think. The TAK-279, which is the IC70 for 24 hours. This is data that's been put out there. I think it's pretty consistent with what you can read from the various Nimbus disclosures. 30 milligrams is IC80, right? Now what we've said is we are going into our phase II trial, in particular for psoriasis, with trough coverage of IC90 at our top doses and then significant coverage for across other doses we have in the trial. We are going in with dose and doses that cover IC90 for 24 hours, right? Our data are gonna read out in the fourth quarter. You know, we'll see, you know, and our aspiration, as we've said this before, to see differentiated efficacy across multiple readouts. IC50, 75, and IC90, and differentiated efficacy from other compounds that we are now talking about, right? That really is the crux of the argument. We're going in with maximal coverage, and we hope to show differentiated efficacy from what you've seen here, right? Again, it's... Yes, I've seen the analysis. We've seen the analysis, and this sort of always leads to this plateauing effect, in particular when people are sort of myopically focused on PASI 75. Let me have Will and see if he wants to add a little more to this discussion that, you know, we've had before as well. W ill? Yeah, I would just say that if when the dosing is sufficient to approximate a biologic-like effect with interleukin antibody therapy at the optimal dose, what you see is a consistency across the outcome measures of trends for PASI 75, 90, and 100. In phase II trials, you can have outliers sometimes. For instance, if you look at the highest dose of the Takeda product in phase II, the PASI or sorry, the PASI 100 is in the zone, but you would see with full biologic coverage, but the PASI 75 and 90 were not. There's an inconsistency there that is different from what you see with the well-dosed drug at the plateauing of its pharmacodynamic effect. It, it just doesn't make sense that eventually, with adequate target coverage, you wouldn't be able to reach an antibody-like efficacy because with antibodies, as you dose down, you will see, you know, left shifts of all the, of the efficacy across the PASI 75, 90, and 100. As you go up on the dose, and have enough patients, you'll see, you know, consistency across those measures all shifting up in unison. I, you know, we'll have our data when we have the data, but we think that a well-dosed drug will just show that consistency as you move through the dose range of relation, the expected relationships for PASI 75, 90, and 100. Coming to the UC trial. I think we probably won't comment in detail on exactly the characteristics of the patients that we have recruited. We have a substantial number of sites in multiple countries, pretty standard for the industry and, you know, this looks like a typical, internationally conducted, phase II trial. We've conducted it relatively quickly and, you know, that's what it looks like. The, you know, from a monitoring perspective, what we do will be as we have pooled blinded data, you can stratify patients for high-enrolling sites versus non-high-enrolling sites, specific high-enrolling countries versus rest of world, advanced therapy naive versus advanced therapy failure. What you're looking for is that you see consistency across those stratified analyses in the rates of the different outcome measures. I feel good about the consistency of our data in biologic naive and biologic failure in high-enrolling countries versus rest of world. I think, you know, we're conducting a robust trial. I'm not gonna lay out all the exact patient population characteristics today. You'll see those when the data come out in the second half. From a trial monitoring perspective, I'm very pleased with the consistency of the data. Good. Got it. Understood. Super helpful. Thank you, guys. Yeah. Thanks, Derek. The next question comes from Alex Thompson with Stifel. Please go ahead. Hey. Yeah, great. Thanks for taking my questions. I think for timelines for the rest of this year, I think previously you had mentioned that you expected VTX002 data sort of late 3Q, early 4Q, then the VTX958 data after that. Just wanted to sort of confirm that those timelines are still what you're expecting. Then maybe for Marty, if you could talk a little bit about what's embedded in your cash runway guidance in terms of spend. Thanks. Yeah. For S1P1, we've always guided people to second half of the year, it's gonna be sometime late third quarter, early fourth quarter. Then, for the psoriasis trial, for 958, fourth quarter. Late fourth quarter I would probably guide people. Hey, Alex, it's Marty. Our cash runway is expected to carry us into 2025, and what's included in that, in those assumptions then is completion across all the phase II studies that Will spoke about today on the call. It's the CAPS trial for VTX2735, the psoriasis, psoriatic arthritis, and Crohn's trials for VTX958, as well as the UC trial for VTX002. We anticipate being able to complete the phase 1 trial for VTX3232, our CNS-penetrant NLRP3 inhibitor under that capital. We expect to be able to produce materials and conduct necessary kind of like pre-phase III trial costs around CMC and things like that. Getting into 2025 obviously does not necessarily get us through completion of any of the phase III trials we might be running, based on data we get out of our phase II readouts, later this year. Great. Thanks. Yeah. Thanks, Alex. The next question comes from Chris Shibutani with Goldman Sachs. Please go ahead. Thank you very much. Two questions, if I may. The first, I believe on ClinicalTrials.gov with the phase II psoriasis study, it appears that in a posting that there's a slight change with a 16-week long-term extension arm that was added. Is this new? If so, what drove this decision? Or is it just an updated aspect of the posting and the study has always been designed this way? Secondly, reflecting on the TYK2 development strategy and commercialization that Bristol has had. You previously commented for deucravacitinib that you expected a negative outcome from the Crohn's disease phase II. This has played out. Can you talk about your impressions and if this has any influence on your thinking going forward on Crohn's? Secondly, with SOTYKTU's commercial performance, they'd recently talked about how that's done relative to Otezla. I think they talked about a 40 versus 60% share. How has this performance compared with your expectations? Maybe share with us your views updated on the commercial opportunity as a result of how SOTYKTU is delivering thus far. Thank you. Christophe, that's three questions, not two. 2A, 2B. Let me have Will comment on the clinical trials then. So for the study design, when we initially did the regulatory filings, we had, you know, toxicity coverage, tox study coverage for up to 16 weeks of therapy. The trial was designed with that in mind, and the primary endpoint was and remains week 16. Subsequent to that, we have had sufficient long-term or chronic tox data to extend the duration of treatment beyond the 16 weeks, and we went through the regulatory filing process for that, and the ClinicalTrials.gov update indicates that we'll do another year of therapy. It was just availability of supporting data. With respect to Crohn's disease in TYK2, I don't think that we always expected that the outcome of the study would be negative. We'd know that with IL-23 antibodies, that you need doses that will plateau at a high level past C75 in the 85%-90% range. You need at least those doses, if not higher, to see efficacy in Crohn's disease. Of course, the SOTYKTU dose that was studied was well below that and had estimated IC50 coverage of about 16 hours and IC90 coverage of 0 hours. No reason to believe that would work in Crohn's disease, and sure enough, it didn't. We always knew that was what was happening and that we expected the trial to fail. It's a completely different proposition from the hypothesis of our trial, where we are studying doses up to 24 hours of IC90 coverage that we think will show class-leading efficacy in psoriasis and will likely show strong efficacy in Crohn's disease as well. It doesn't change our thinking at all. We completely factored that in. On the commercial? Yeah, on the commercial side, you know, we'll keep it brief. First, we've, you know, just recently hired a head of commercial here, you know, with our forward thinking across our trials and, you know, looking beyond the psoriasis trial and other indications as well. I think this, you know, Otezla analysis for what it is, first, the analysis always lag. As now we've begun our own discussions as part of our commercial planning with prescribers and KOLs. You know, there's a huge amount of excitement in this class of drugs, right? Big markets, you know, in oral, which is clearly differentiated from Otezla. I think the market will grow. It's gonna benefit us as we come into the market, as we move along our trials. I think with a drug, with a TYK2 class, with safe drugs, with efficacy that's comparable but certainly better than what's been shown with SOTYKTU, I think the market would appreciate that. We continue to feel very bullish about this class. The prescribers that we're talking to now are bullish about the TYK2 inhibitor. I think we just have to. You know, it's still relatively early days from the launch, and I think we have to just appreciate what's happening in terms of not just Otezla, but what's the whole prescribing ratio in terms of biologic patients, naive patients, and folks that are switching over from Otezla. Anything else to add, Will? No. Great. Thank you for sharing your thoughts. Of course. The next question comes from Emily Bodnar with H.C. Wainwright. Please go ahead. Hi. Thanks for taking the questions. I guess for the first one, kind of following up on the previous question, Bristol noted that they're gonna have high-dose data in the UC study later this year. Curious on any expectations you have for that study and how that might impact your views for VTX958. Maybe also if you can comment on VTX2735, how you kind of plan on determining which indications you might want to take that asset into following the phase II CAP study. Thank you. Again, I think Will has addressed, he's discussed it before in terms of the SOTYKTU and UC, the second trial they're running. Why don't you take that first, and I'll just come back please. You know, it's not public, to my knowledge, exactly what the dose is. I, you know, in phase I, they had a dose of 12 milligrams BID. Our calculations are that that would give approximately 24 hours of IC50 coverage and still 0 hours of IC90 coverage. I'll remind all of us that 78% of patients had skin organ class toxicity on that dose. It was really not tolerable. You know, there have been rumors that they're studying, you know, 8 BID or 10 BID or even 12 BID. It's difficult to imagine it's 12 BID from a tolerability perspective. Even if it is, it's exactly the answer that I gave previously for Crohn's disease. Even at 12 BID, it would not give coverage that you would expect to work in inflammatory bowel disease. Just to remind us, what you also see is that the effect size with anti-IL-23 antibodies is larger in Crohn's disease than it is in ulcerative colitis. You typically see differences between drug and placebo at optimal doses of 20%-30% in Crohn's disease, and it's more in the 10%-15% range in ulcerative colitis. The Lilly phase III program showed a 10% gain over placebo with mirikizumab, and both AbbVie with risankizumab and Janssen with guselkumab have recently reported 14% better than placebo in their phase III studies in ulcerative colitis for induction studies. As I recall, the quotes high dose deucravacitinib study is 40 patients per arm, drug and placebo. If they are seeking to show a difference of 14%, which I think is the best case scenario, if you had a fully dosed antibody or a TYK2 inhibitor that has IC90 for 24 hours, you'd be trying to show a 14% difference with 40 patients per arm. That's not gonna work. I predict it will fail. All right. There you have it. For NLRP3, as we said in our R&D day, you know, our goal for this year, for 2023 is to position both molecules, VTX2735, VTX3232, as phase II-ready compounds. With respect to VTX2735, this is a peripheral compound. We believe this is the best in class, NLRP3 peripheral molecule out there. We've done the phase I. We announced the phase I data last year. We've done the tox work. We've done the CMC work to support the phase II trial. What we also are very clear about this last discussion was with our focus on driving the phase II trials for TYK2 with VTX958, with our focus on the UC trial for VTX002, we would sort of shift the focus from VTX2735 towards the end of the year. Again, this will be a phase II-ready molecule. We have previously shared the excitement across a number of disease indications where IL-1β and IL-18 have been implicated, and a lot of sort of validation from different trials out there, in particular from the biologics. We'll make a decision towards the end of the year with this phase II-ready compound, how we proceed with the development, whether it's with a partner, whether we go it alone. For now, what we've done is position these as phase II-ready compounds, focus on delivering on our promise with both trials for UC and for VTX002. Just stay tuned for VTX2735. Great. Thanks so much. Yeah, you're welcome. The next question comes from Sam Slutsky with LifeSci Capital. Please go ahead. Hey, good afternoon, everyone. Thanks for taking my questions. Just two quick ones for me. One, on the oral IL-4 receptor α program, remind me on the profile that you're looking for in your lead candidate, and then what target coverage do you think is needed for an oral IL-4 receptor α to be effective? Again, now we are not gonna go into too much detail on that program, Sam. As you know, it's we're one of the few folks that has sort of, you know, embarked upon this challenge. We've disclosed our lead, just a sort of, you know, little data on our lead compound in terms of the excitement we have. Obviously, we're going against a extremely successful drug out there, dupilumab, Dupixent. What I would say, just stay tuned. We're, you know, moving along the lead op program here. We've got all of the assays in place. You know, we've said that we'll come back towards the end of the year and talk a little bit more about this as the program matures. Stay tuned. Okay. Just lastly, for the phase I study with VTX3232, since you plan to take that into neuroinflammatory indications, just curious on how you're thinking about measuring the PD effect and then what you would wanna see with that for a CNS drug. You know, there's really no precedent for or there's no data for any NLRP3 that's been taken into a phase I or a phase IB trial. There was an indication that the Inflazome compound had been taken, and there's no data released from that particular trial. For us, it's really, we think this is a best in class compound. It has a really good CNS penetrant profile in terms of, you know, Kp,uu, the distribution across the CSF, what we expect to be the free fraction in the interstitial fluid in the brain. Our goal for the phase I study, it's a two-part goal. First is to do a phase I study where we look at, of course, exposure. We'll look at safety and exposure both in blood, plasma, as well as in CSF, which is a surrogate for free fraction in the brain, and also a surrogate for what you expect in the interstitial fluid in the CNS as well. That's part one. What we're actually looking at now, and we will disclose our final intent, is looking at potentially looking at biomarkers in a phase IB trial as well. As you know, that's. It's very complicated, and we have to make sure we understand what we're looking for and calibrate that before we do something like that. Again, we feel very confident that a phase I standalone SAD with efficacy PK in particular, looking at exposure in the CSF is a very relevant path forward for the eventual development of this compound in longer phase II studies. Again, the precedent for looking at CSF levels and calibrating those to brain levels as well. I think in terms of biomarkers, you know, of course, the ultimate biomarker for NLRP3 activity is IL-1β. Again, we'll also be conscious of if and when we go into a disease population, what biomarkers do we expect to modulate in those patients? Are they really sort of, you know, consistent with the duration of these trials? Are they really meaningful in terms of what would guide us through a phase II trial? Stay tuned for VTX3232 news coming out. You know, as we said, we're gonna dose the phase I healthy volunteers in this quarter. Then we'll talk more about that future of the phase I trials and 1B trials in later discussions. Got it. Thanks. Yep, you're welcome. Thank you. I would now like to turn the call back to Dr. Raju Mohan for some closing remarks. Yeah. Well, again, thank you all. You know, we just spoke a few weeks back. It's always great to get together with you all and, you know, address the questions, very thoughtful and appreciate the interest in our programs. You know, let's, we'll see you guys again in a few months. Thanks again all, and thank you team. This concludes today's Ventyx Biosciences first quarter 2023 earnings conference call. Please disconnect your line at this time and have a wonderful day.