Good morning, everybody. Let's kick this off. Welcome to the Goldman Sachs Healthcare Conference. We are thrilled to have Ventyx join us this year, Chief Executive Officer, Raju Mohan, and Chief Financial Officer, Martin Auster, together with my colleague, Steven. We're very pleased to have you here, get a chance to hear about the latest with Ventyx, sort of go through the line of all sorts of data events that are gonna come. Immunology is, yeah, it is my favorite space. I think that obviously there's like tremendous unmet need, large markets, enough in the way of blurriness with questions in terms of how we should really be treating patients, that this generates opportunity. There's innovation happening with novel mechanisms of action, which is very much the story here. I think from the standpoint of investors, looking for opportunities that are not just levered entirely to one asset, but multiple assets and a really thoughtful approach to kind of strategizing your clinical development path. Raju, thank you for joining us. Maybe just a quick note in terms of where we are and your strategic priorities at this point, because I think there's a lot to look forward to as we head into the back half of the year. Thanks, Chris. Thanks, Steven. I'm happy to have Marty here with me this morning. I think just reflecting back on where we are today, and I'll come to the priorities. You know, it's, it seems only yesterday, it was 2001, when we brought the assets together and formed Ventyx, bringing in the S1P1 molecule, bringing in an RP into what was old Ventyx, which only had a TYK2 inhibitor. A company of about 11 people. This was in 2001. We are now up to about, what, Marty? 85 or so. That's right. We're building a commercial team now. We have a clinical team that's running four bona fide phase 2 trials right now. We have a proof of mechanism CAPS study. Again, planning for future studies that we'll talk about here today. In terms of priorities of this year, and, you know, this year has gone by very fast, and we're now, you know, looking to the second half of the year. As we announced a week or so ago, we've completed enrollment in our two phase 2 trials, one for S1P1 for ulcerative colitis. Mm-hmm. The phase 2 for plaque psoriasis for VTX958, our TYK2 inhibitor. As you look towards the top line data, which we've projected in early fourth quarter for the S1P1 drug, and 4Q for the TYK2 inhibitor, there's a lot of work still to be done in making sure we're executing on now completing the trials, the last patient in. We then have to then look towards getting the data ready, understanding the top-line results that internally, and then obviously releasing those results out to you all, to the investors. That's one of the main focus of the teams now, to make sure that we don't lose any time in processing and executing on the data release. The second set of priorities really is focused on getting ready for the phase 3 trials. Mm-hmm. As you know, there's a lot of planning that goes from phase two to phase three. Typically, planning starts 9 months to 1 year before, and begins with making sure you have all of the supplies, the package, the studies that enable you to then seamlessly move from phase two to phase three, and that includes drug supplies, drug substance, drug product, making sure our DDI studies are all in line, to ensure maximum recruitment in the phase three trials, regulatory meetings, regulatory processes. Those are the key priorities that we have to focus on in addition to also managing the other trials that are ongoing. We have a CAPS trial in RP. We just initiated dosing in our CNS penetrant in RP. Mm-hmm. All that goes on, you know, of course, we have key priorities that we just talked about, which is completing the 2 phase 2 that we talked about, making sure that we are now moving on track for the phase 3 trials next year. Right. You make reference to your team, and certainly, many investors are familiar with Marty, and so, his formidable experience, both in industry and on the street as well, I think is very useful for investors when they think about, whether this team is being thoughtful and preparing and understanding how to weigh the pros and cons. When you think about the outlining of strategy, Marty, can you just share with us a little bit about, you know, how you feel where things are at? Again, because, yes, your title is CFO, but you've, you've worn many hats in the past. Well, as Raju said, we're not busy at all this year. No, I mean, it's a tremendously complex effort to run, you know, four, five phase 2 trials in parallel, phase 1, bringing up preclinical compounds. We continue to have research and discovery efforts that are not slowing down. We continue to have ambition to try to bring, you know, a product into clinic each year, give or take. That's, that continues to be one of the kind of core tenets of Ventyx. You know, not here with us today, as you know, is our, you know, our President, CMO, Dr. Bill Sandborn, has been instrumental. Yes. He joined us a little over a year ago. Mm-hmm. Obviously a, you know, world-renowned KOL in the GI space, but he's also rapidly adapted to the derm space. Mm-hmm. As we're kind of focused on both right now. We've built an excellent clinical team. You know, a lot of the hiring that we've done obviously has been on the clinical side and on the drug product side. You know, the nice thing is, a company that's focused on immunology, we do get a lot of synergy out of the different programs. You look at, like, for example, the VTX002 S1P1 UC study. Right. We're able to kind of learn a lot about which sites are the most active, who's recruiting well- Mm-hmm. -who's, you know, sort of who's responsive, who makes sense, and we can kind of fold that into our planning for the Crohn's trial for VTX958, and we can kind of leverage some of those learnings and kind of synergize off that, both, you know, from our own internal clinical team working with CROs as well. That's, that's all kind of part of it. Yep, totally makes sense. You mentioned William Sandborn. He was one of the most well-respected KOLs. Wall Street loved him, and it was very compelling to see him vote with his feet, go into the company. Very much a story where I think people have to be aware of that, GI, IBD, Crohn's, UC opportunity here as well. Front and center is more immediately, and a lot of the focus on comparing is around the TYK2 assets, the TYK2 market opportunity. Stephen, maybe I'll turn it to you to talk about, that context, their asset and the competitive market dynamic. Sure, yes. Let's talk about VTX958. maybe starting more broadly, obviously, there is an approved TYK2 inhibitor on the market right now for plaque psoriasis. Can you just comment on kind of learnings you've seen from that launch to date and how that translates over to your program? Yeah, I think, in our development focus doesn't really change. You know, a lot of discussion about the success, the launch of the TYK2, and I would remind people it's still early days. The main focus of this right now is essentially giving the drug away for free. I think we'll have to look at scripts towards the end of the year to really get a good sense from it. People we speak to, our prescribers, our friends, dermatologists, are super excited about TYK2. I think that's where we have to pay attention to and really wait for some of the other metrics that will read out towards the end of the year. I think that's sort of the best way we look at it. I think coming back to the target, TYK2 is a really exciting target. It has now 2 oral drugs that have shown efficacy and promise in plaque psoriasis. BMS is for TYK2, of course, the Nimbus Takeda compound. That's, you know, again, outside of the IL-23s, which was the initial excitement for TYK2. Having 2 oral drugs now proven mechanism in psoriasis is really exciting for us because we believe at the end of the day, that we will have a drug that is differentiated from these 2 drugs, that we've shown that in our phase 1 study with extensive dose coverage, the safety profile, and the ability to cover the target of interest, which is IL-23. Sort of unmatched coverage with our dose range. Having two compounds precede us with metrics in psoriasis, now, we're poised to get our data out end of the year. Pretty excited about getting that trial done and really seeing the hypothesis of what a trough IC90 coverage means in terms of efficacy and the endpoints of psoriasis that we've talked about extensively for the other two drugs. Got it. That's all helpful. Maybe let's dig into the phase two a little bit deeper. You recently announced that enrollment has completed. Can you just comment on how the pace enrollment was during that open period and, on any physician feedback they've garnered to date? Yeah, so you know, going into any of these trials, whether it's psoriasis or it's, UC, we don't take anything for granted, even though historically, psoriasis trials, recruit a lot faster than UC trials. We have a lot of experience in UC from folks that have done it, and William Sandborn was part of, both drugs, Ozanimod and [uncertain]. You know, what we do is starting out with making sure we have the best CROs, indication appropriate, so we don't have a generic, CRO for all trials. The psoriasis trial, we had a CRO that's well experienced in these trials. They have, bonafide sites, high value sites, making sure the right patient recruitment, the right criteria are met. That's absolutely critical for derm indications. We base our projections on what's historically known for these trials, given that there's a number of competing drugs out there, competing for patients for plaque psoriasis. What I will say is, was very pleasantly surprised that we were able to bring the enrollment in faster than we had projected, and that's, A, due to the high quality CRO. It really is a testament to the teams that worked tirelessly, making sure that they had investigative meetings. They went to each site, patient education. All of us actually traveled to these sites and just get people aware of these new therapies out there. Also, I think it shows the power of an oral drug and the attractiveness of an oral drug for these patients that have choices. That, I think, is one of the main reasons why these trials or this trial recruited so efficiently, because patients are still hungry and willing to enroll in oral therapies, be it experimental therapies. Got it. No, I think that's helpful commentary, and I think goes back to Christopher's point, people vote with their feet and patients do the same. I think that just reflects some of the enthusiasm around the agent. Thinking about the readout later this year in the fourth quarter, help us frame expectations. I know there's been a debate now that we've seen competitive agents in the space, a couple phase 2 datasets. How should we be thinking about some of these points, but PASI 75, PASI 100. I think there's a key debate, how can I really push the PASI 75 higher, or are we really just looking at the 100 outcome? Can you walk us through how you're thinking about that? Yeah, actually, you know, since Marty Auster, he has maybe, he can start with this. You know, this is some of the endpoints we've discussed before. Go ahead. Yeah, I think it's gonna be the totality of the data, right? It's gonna be across PASI 75, 90, 100. They're all important endpoints. If you look at the development in the space, obviously, Sotyktu kind of laid the groundwork. Their phase 3 trial had PASI 75s in the mid-50s. You know, PASI 100s that were, you know, sort of below biologic levels in the kind of 20-ish ballpark. You know, the Takeda phase 2 presentations at AAD sort of looked like they may have moved that bar up a little bit. The PASI 75s are in the mid-upper 60s, and the PASI 100 approached around 30%, a little above 30%, which is kind of the low end of what you see with biologics, which can range from, you know, 30%-50% on PASI 100. I guess where we see... You know, our drug is, you know, we went through the phase 1 and obviously had that update last summer. As you know, we've, you know, we've been able to achieve, you know, we think is a safe target range that can get us to trough coverage pretty much for the whole day on IC90 levels against IL-23. We think we can really maximize target inhibition, and we expect that should put us in the ballpark of kind of, you know, where Takeda, kind of delivered data is sort of a base. We think we're getting IL-12, 23 coverage that's superior to that drug in our upper part of our dose range. We're optimistic that we can kind of continue to evolve the efficacy bar for the TYK2 class, and that's what we're hoping to see. Got it. Maybe moving on to the safety profile. We know some of the class has shown adverse events such as folliculitis, CPK elevations, neutropenia, lymphopenia, increased risk of COVID, we saw in one of the recent trials. Can you speak to if you think these are a class effect of TYK2 inhibition, or if those are maybe more molecule specific, and we shouldn't really be expecting any of those signals? Yeah, you know, I think Bill has paid a lot of attention to both, you know, our trial, our phase one trial, and also looking across the drug that you've talked about in terms of the safety concerns. I think that the primary focus that of this discussion really comes down to the derm effects. I think in terms of infections and COVID, you know, these trials are recruiting in some of these trials, especially the one you talked about, was recruiting in a time of very active COVID infections. I think we just have to take that as one of the confounding factors. I think a lot has been sort of discussed as to whether the derm effects, the folliculitis that you talked about, whether it's whether it's on target or off target. You know, our premises, our thesis is that it's really not on target. Why do we believe that? One, if TYK2 is the target, which is now the IL-23 is the focus, then this type of phenomena, this type of adverse effect events that we've seen for both the TYK2 and for the Nimbus Takeda drug, has not been seen to this extent. And Bill will tell you, he's a practitioner, and he's treated patients with a number of IL-23 drugs, and none such prevalence of these events have been seen across IL-23s. To bring back to our TYK2 mechanism, as we showed and talked about in our phase 1 data release, when we compared 14 days of dosing of our molecule with what's been seen with both Nimbus and the Bristol compound across a similar dosing timeline, the magnitude of derm effects that we saw, and was minimal, and it was the high doses that we talked about, the 2 cases, the 2 papules that we saw at the high doses. Again, IC90 coverage for 24 hours at the top dose, relative to what has been shown with the other 2 compounds. We don't believe it's, it's on target. What the target is or how, what the mechanism is, I think it's, it's unknown. One can speculate that there's a common target that both drugs are hitting, or there's a separate target they're hitting, either primarily or through a metabolite. It just remains to be seen. The preponderance of data that is out there, both from IL-23s, also from our own trial and our own dose range, and the extensive coverage of TYK2 pathways, suggest that these are not on-target effects. Okay. No, that's helpful framing as we're thinking ahead to later this year. Maybe we'll ask one more on psoriasis, and then, Chris, you could probe into some of the Crohn's opportunity. Yeah, a question we get a lot from investors is, if you're suppressing the IL-23 pathway, so that seems like a promising aspect, why don't we just use an oral IL-23 inhibitor? Can you talk about the competitive dynamics there, and why you think TYK2 inhibition is really the right way to go? I think TYK2 inhibition is the only in that class of drug you're talking about, so a TYK2 inhibitor versus an oral IL-23, the only data that's out there, obviously, is the TYK2 data for psoriasis right now, right? That's the data from, again, from Sotyktu and from the Nimbus Takeda drug, and we'll have our data at end of the year. There'll be three drugs with psoriasis data now by the end of 2023. In terms of, I mean, again, I'm not trying to be glib. There is no efficacy data for an oral IL-23, and we'll have that in a couple of weeks, I believe, in early July. It remains to be seen what an oral IL-23 molecule looks like in terms of its parent IL-23 injectable or another oral drug, a TYK2 inhibitor, which is now going after the IL-23 pathway as well. We have to, you know, we have to see what the data looks like, whether it looks more like a TYK2 inhibitor in terms of the base case that Marty talked about, which is the Nimbus molecule. Or whether the efficacy starts to now approach more like its parent or parental partner, which is an IL-23 or Skyrizi, one of those drugs in that class. We just have to wait and see what that looks like. I think another key aspect of the story, and very importantly, is just thinking beyond plaque psoriasis, which obviously gets a lot of investor attention. Logical, given the kind of competitive dynamic as well as proximity to data. Let's talk about the GI opportunity here, in particular for Crohn's. Here's sort of again, the table setting involves deucravacitinib, which did not succeed in some of the phase 2 work you see and in Crohn's. To a certain extent, I think the temperament in thinking about this opportunity involves a little bit more skepticism and to an extent, a view that perhaps doses need to be higher. Talk about the context about why you believe, and I believe the case is that you guys are using the same high dose in terms of the dose-ranging work that you've done and what you're moving in your phase 2 clinicals for Crohn's as well. Help us feel confident in your decisions. I'll start, Alan, and maybe Marty can add to this as well. You know, we've addressed this in a thoughtful way, starting when the Bristol data came out or the, or the lack of efficacy in their first UC trial. That's when the first sort of skepticism came in about, is this pathway only limited to, for example, psoriasis or psoriatic arthritis? Or is Crohn's or UC surmountable via this pathway? Are you really a bona fide IL-23 mimic as an oral drug? Unfortunately, if you look at the Bristol data, it's very clear that they are their target coverage for IL-23, for example, has no amplitude in the sense of IC90 coverage for any part of the day. The doses that they took in were not even covering IC50 for 24 hours, right? In contrast, as you've seen for drugs for IBD, whether it's the biologics or even if they're oral drugs, you need more drug, more target coverage when you go into IBD versus non non-GI indications. We can first start with an oral drug, as you know, for RINVOQ, for example, the dose for RA is 15 milligrams, and the dose for UC is 45 milligrams. Right. always higher doses. The same is true for the biologic. The same is true for risankizumab SKYRIZI. Mm-hmm. Look at psoriasis versus Crohn's. Our thesis, and obviously we understand the skepticism, you know, we have to prove this with our, with our trial in Crohn's, which will read out sometime in 2024. We'll have more guidance on that trial towards the end of the year. We're going into our Crohn's indication with doses, and Chris, you're right, we have the same dose for all three phase twos, the top dose. Having the same dose also is a dose that we are covering IC90 for the entire day, for better part of the day. We're really going in with maximum coverage, not just for IC50, but for IC90, and coverage that we believe is more biologic-like coverage for the target of blockage. We'll see. In our case, we've, you know, the die is cast and we're going in with backed by the thesis that you need to have higher coverage, longer coverage for IL-23 to see efficacy in GI versus what you need for psoriasis. Okay, great. I think in about the 7 left, minutes left that we have for our allotted time here, Stephen, why don't you touch on the UC opportunity with S1P? I want to save you 2 minutes at the end. I want to close in terms of thinking about the longer strategic arc and ultimate prospects for commercialization. Sure. Let's focus on VTX002, S1P1 modulator. The upcoming phase two readout will be the most near-term readout. I think definitely a critical piece of the story, although the TYK2 aspect definitely seems to take the stage for the majority. Let's get into that readout. I think you've previously mentioned that you have a high bar for advancing this asset into phase three. Can you talk about what that means quantitatively in terms of some of the efficacy you'd like to see? Yeah. you know, super excited to talk about S1P1. We've always been excited about this program. We understand the interest in TYK2, you know, and we understand the investor interest in TYK2. For us, S1P1 has always, you know, been an equal child in terms of the way we've executed on this trial. Again, we've talked about the psoriasis recruitment. We're just really pleased that we're able to bring this trial back again, given the complexities of UC. I'll start off with what we showed at the R&D day, where we're able to achieve 70-plus% reduction in ALC, the lymphocyte count. It's unmatched. The drugs were able to reach only about 50 or so%, particularly for etrasimod. We believe, based on the discussion that we had and that Bill shared with folks, there are precedents from Gilenya, where a higher remission rates and efficacy is shown when you can achieve such magnitude of ALC reduction. What are we looking for at the end of the year? Obviously, the bar, you know, the bar is high, and I think the bar is high, not just for UC, the bar is high for all our drugs, right? Very competitive space. We're talking about oral drugs. We're talking about other mechanisms. We talked about, you know, I know we haven't talked about other pathways. The bar is always high for us. We don't go into this, sort of, you know, wanna play in the same game everybody else does. Our compounds are designed to be differentiated. Specifically in terms of where the bar is, I think similar to what Marty talked about in terms of VTX958, where the base case was, is a Nimbus, then of course, from there you have the continuum to what we can see with the biologic. I think here we have a drug like etrasimod, let's just give it about a 20% delta. I think what we've seen now with the new data coming out, especially from the TL1As, is the bar or the ceiling has been raised much higher, as sort of the 25% delta that they showed. We're just excited that, A, we're able to show a higher PD readout with our ALC reduction, similar to, again, there's a lot of parallels in the way we approach this, the IC90 coverage for TYK2. Mm-hmm. In this case, a higher ALC reduction, and we believe that should translate into a meaningful difference in terms of the efficacy readout. Think again here, the base case being sort of a 20% delta, and the ceiling there that we have to now reach or break is the efficacy seen with the TL1As and perhaps with RINVOQ, which has the black box label. Stay tuned, because that's sort of aspirationally where we are going for, with the way that we've approached the design of this trial and the maximal effects on the PD marker. Okay, great. Obviously, looking at the delta that this will show and some of the key outcomes, really depends on the placebo rate as well. I think we have seen kind of variable rates, depending on the number or% of biologic-refractory patients. I know at your recent R&D date earlier this year, you kind of positioned this as a potentially pre-biologic therapy, in terms of positioning it across the patient's journey. Can you speak to kind of what types of patients you're recruiting in the trial, and then maybe comment on what% you expect to be biologic experience? We've, you know, been very consistent. We really don't sort of divulge the exact naive versus exposed patients in here. I think it's fair to say that, you know, we're not going to be cowboying. There's plenty of history here. Again, Bill have been part of these trials, the other two drugs as well, and history in this space. Certainly learnings from that. They say, just don't expect anything dramatically different from some of the more successful trials in this area in terms of the patient selection. That, I think, bears into the whole idea of how do you manage placebo rates? I think you just have to have a good, well-executed trial. You manage the sites, you manage the percentage of patients from each site that you have. You diversify your sites. Obviously, we have a combination of European and North American sites, as most people do. Well-recruited trials, a good balance, as you said, of naive and exposed patients and then just, you know, see where we end up. Got it. I'm very much looking forward to that readout in the fourth quarter. Maybe one last quick question, which kind of threads across both your S1P1 program and your TYK2 program. What are, what are you thinking for the higher dose of deucravacitinib in this UC trial? You know, we don't know exactly what the dose is. You know, it's gonna be somewhere in between the early trial and Phase 2b. I really don't know what the doses are. I don't think even at the higher doses, they're gonna get the type of coverage that we just talked about. Perhaps a little longer, IC50 coverage. I don't think they'll cover IC90, and I'm not sure they'd even cover IC50 for 24 hours. I don't think the trial has been designed to be any kind of a meaningful endpoint, mostly biomarker-driven. We'll see when that comes out, data comes out, but I don't think it has any sort of meaningful readout towards any judgment on whether TYK2 is appropriate for IBD. Just to close out, Marty, just a couple quick ones. I know the Marty Auster playbook in terms of thinking about anticipating commercialization. Certainly from your R&D day, you had some folks who clearly have that being their focus and thinking about as you're designing these clinical trials, ultimately getting to regulators and commercialization. Just remind us the current perspective on commercializing these drugs, if we assume success and development. Psoriasis is a vast opportunity, right? Also the GI indications. Just give us a little bit of perspective there, remind us what the balance sheet health is, so that we understand in terms of how you feel the runway there. Yeah, it's a point that I, you know, was hoping we'd get to earlier when we were talking about psoriasis. This isn't going to be a winner-takes-all market, right? There's a $24 billion global market right now in psoriasis. There's 7 blockbuster players between the TNF-alpha, the IL-23, the IL-17, the TL1A. Yep. We expect there to be several winners in this field. you know, again, our focus is on developing the best drug with the best target coverage that's safe and effective, and we think that's going to end up being very competitive. We'll do quite well if we can, you know, sort of expand that beyond psoriasis, psoriatic arthritis into IBD with the TYK2. That's another, you know, between Crohn's and UC, you're looking at another $20-plus billion market. Basically, the size of psoriasis, it's a little bit less well saturated. Certainly fewer oral options, particularly in the Crohn's disease size. Given that the efficacy amongst orals is really limited to JAKs right now, really nothing on the oral side that doesn't have black box warnings and restrictions of use. I think, you know, really, really nice green space, on the IBD side with TYK2, and that's why it's, you know, obviously been a part of this, focus of this conversation and a lot of our investor meetings kind of heavily focused there. Turning to the balance sheet, we had $370 million in cash at the end of Q1. you know, that burn, the burn rate we've had will kind of sort of continue to trickle up as we get deeper into our you know, 4, 5 phase 2 trials and start planning for our phase 3s. We do have capital on hand to get into 2025, so we have room there to deliver all the Phase 2 data for the TYK2, the Phase 2 data for the S1P, all the prep work we need in the initial launch phases for the Phase 3 psoriasis trial as well, is all included within that assumption. Certainly based on the data that we read out in the fourth quarter of this year, we'll have to start making sort of prioritization and strategic decisions about, you know, what we do ourselves, what we partner. Mm-hmm. You can imagine that we're being very thoughtful in considering a range of scenarios as we prepare for this big readout later this year. Okay. Very data-rich back end of the year that we're going to have here. Very much. Some strategic decisions that'll come. Raju, Marty, on behalf of Steven and myself and the Goldman team, thank you very much for this update. It's always a pleasure. Thank you, guys. Appreciate it. Yeah. Thank you.