Ventyx Biosciences - Q3 2022

Transcript

Operator (participant)

Welcome to the Ventyx Biosciences third quarter 2022 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. So 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. You may begin.

Martin Auster (CFO)

Thank you and good afternoon, everyone. Welcome to Ventyx's conference call and webcast, where we'll be discussing our third quarter 2022 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 today, I would 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, 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 recent periodic reports filed with the SEC. Please note that these forward-looking statements reflect our opinions 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. With that, I'll hand the call over to Dr. Raju Mohan, Ventyx's Founder and CEO. Raju, please go ahead.

Raju Mohan (CEO)

Yeah. Thanks, Marty, and thanks everyone for joining our call this afternoon. To start, let me briefly run through the agenda for this afternoon. I'll provide a high-level business update and review recent highlights, and then I'll hand the call over to our President and Chief Medical Officer, Bill Sanborn, and Bill will provide updates across our pipeline programs, a more detailed update across various programs. I'll turn the call back to Martin for a brief overview of our third quarter financial results before we open the call up for Q&A. It's been just over a year since our IPO last October of 2021, and I couldn't be prouder of what the Ventyx team has accomplished over the last year, and there is a lot more to come.

Let me first start with this quarter. We presented positive top-line results from our allosteric TYK2 inhibitor, VTX958 phase I results. As we've disclosed, we believe these data demonstrate a potential best-in-class safety profile, and this may drive clinical differentiation in relevant disease populations by allowing us to target levels of TYK2 inhibition comparable to currently prescribed biologics. We also believe greater TYK2 suppression and greater suppression of TYK2-mediated pathways has the potential to yield improved efficacy in indications such as psoriasis and psoriatic arthritis than previously shown by deucravacitinib or Sotyktu. For indications where greater levels of cytokine inhibitions are required, such as for Crohn's disease, we believe VTX958 may demonstrate greater efficacy than less selective TYK2 inhibitors, and Bill will provide additional details and commentary during his remarks.

During the third quarter, we were also pleased to see the FDA grant approval of Bristol Myers Squibb's TYK2 inhibitor, Sotyktu, as the first approved TYK2 inhibitor. Notably, the drug label is quite different from other oral anti-inflammatory classes such as JAK inhibitors and contained no black box warning. This lack of black box warning we believe will support long-term physician and patient uptake of this important new therapeutic class. We believe the $20 billion-plus global psoriasis market is ripe for disruption as new competitive agents emerge, and we believe that the TYK2 inhibitor class is well positioned to be a key driver of this change. Again, with VTX958 positioned as a potentially best-in-class drug.

Finally, in mid-September, we completed a successful private placement of common stock that yielded gross proceeds to Ventyx of $176.6 million, extending our capital runway to well over two years into 2025. This strong cash position is expected to provide us with resources to generate meaningful phase II proof-of-concept data across our portfolio of oral immunology drug candidates and allow us to seamlessly prepare for future phase III trials. Before I turn over to Bill to highlight and more detail progress across our portfolio, I do wanna remind the audience today that Ventyx at its core is much more than VTX958 or any other single drug candidate in our portfolio. At our core, we are driven by our passion to discover and develop innovative medicines that have a meaningful impact on the lives of patients.

To that end, I am very happy to announce we are planning a science-focused R&D day on January 26th of next year in New York City. At this event, we will provide additional details on our internally discovered wholly owned pipeline of drug candidates, along with updates on our development plans for what is shaping up to be a very busy 2023. With that, I'm gonna hand you over to Bill.

Bill Sanborn (President and CMO)

Thank you, Raju, and good afternoon, everyone. While VTX958 remains a central part of the Ventyx story, there is so much opportunity within our pipeline to improve therapeutic options for patients, and I'm excited to be providing an update on our clinical progress with you this afternoon. Let's start with VTX958. We are very enthusiastic about the potential of this compound. Following our successful phase I results, we have been working to rapidly advance this program and product into phase II, and we remain on track to initiate phase II clinical trials in psoriasis, Crohn's disease, and psoriatic arthritis during this quarter. We expect the first phase II trial to be in moderate to severe plaque psoriasis patients. We intend to explore the dose response of VTX958 as TYK pathway inhibition is increased.

We will dose VTX958 to achieve exposures in our phase II trial across a range that includes IL-12 and IL-23 target coverage that approximates so TYK2 exposure levels that we at the approved dose of 6 mg QD, which would provide IC50 coverage for approximately 9 hours, as well as doses that would achieve exposure levels that we anticipate would provide trough coverage of TYK2 around the IC90 level. In psoriatic arthritis and Crohn's disease trials, we will emphasize robust target coverage. As Raju mentioned, we will be hosting an R&D day in January, and we look forward to sharing more specific details and trial design for all three of these phase II trials at that time. I should also add that launching three phase II trials with VTX958 this quarter is a substantial undertaking.

In the last several quarters, we have assembled a truly talented and dedicated group of individuals who have come together to form an amazing team. While we're gearing up for the three planned phase two trials, we have been conducting pre-clinical evaluations of an extended release formulations of VTX958 that can approximate the duration of TYK2 coverage that we demonstrated in our phase one trial with convenient once daily oral dosing. We expect to evaluate our extended release formulations in human relative bioavailability studies in early 2023, and to be in a position to provide an update in the H1 of 2023. Our goal is to have an extended release formulation of VTX958 ready for use in phase three trials, which we expect could begin in 2024.

Now let's turn our attention to VTX002, our selective S1P modulator, which is in an ongoing phase II induction trial for the treatment of moderate to severe ulcerative colitis. This trial is designed to enroll approximately 180 patients across three cohorts, low dose and high dose arms of VTX002 and a placebo group. The trial's primary efficacy endpoint is clinical remission at 13 weeks using the three-component modified Mayo score. We believe that VTX002 has the potential to improve upon other S1P1 receptor modulators, Zeposia and Etrasimod, in patients with ulcerative colitis through rapid and greater lymphocyte reduction, which, if achieved, may correlate with higher rates of clinical remission and improvement in other clinical response measures. We have been guiding for top-line data in 2023, and we remain comfortable with that guidance.

Recent enrollment trends have been strong, and based on the current trajectory, we estimate phase II enrollment to be complete by mid-2023. Next, let's look at VTX2735, our peripheral NLRP3 inhibitor compound. NLRP3 remains a very exciting target with potential to impact a broad range of dermatologic, rheumatologic, and cardiovascular diseases. We released phase I data for VTX2735 in the second quarter, which demonstrated a safe and well-tolerated profile in addition to strong evidence of target engagement and pharmacodynamic effect, including substantial impact on key markers of inflammation, such as high sensitivity C-reactive protein. We plan to initiate a trial in an ultra-rare disease resulting from gain-of-function mutations in the NLRP3 gene known as CAPS in the fourth quarter.

We believe that this small study will confirm clinical proof of mechanism while providing incremental safety data and evidence of target engagement in a patient disease setting. Meanwhile, we have been actively narrowing down the large list of potential indications in the disease areas that I mentioned earlier, and we intend to provide an update on the selection of an additional phase II indication during our R&D event in January. This indication will be focused on a larger commercial opportunity. Our fourth pipeline candidate is our CNS penetrant NLRP3 inhibitor compound VTX3232. We remain on track to initiate a phase I trial in the first quarter of 2023.

We are very excited about this novel drug candidate, which we believe has the potential to be a first mover among truly CNS penetrant NLRP3 inhibitors and may have the therapeutic utility in a number of neuroinflammatory diseases with high unmet need, including Parkinson's disease, and Alzheimer's disease, among others. We believe that it also has potent peripheral NLRP3 inhibition. This concludes our pipeline update for now. In summary, we continue to make great progress across our wholly owned, internally discovered portfolio of drug candidates. I'm so proud of the team's efforts, and we look forward to sharing more with you during our R&D day in January. Before we move to Q&A, I'd like to hand the call back to Marty for a brief discussion of our financial results.

Martin Auster (CFO)

Thanks, Bill. I'll briefly summarize our financial results from the third quarter now. R&D expenses were $25.5 million in the third quarter of 2022, compared to $10.5 million in the third quarter of 2021, reflecting advancement of our pipeline into later stages of clinical testing. We continue to expect that our R&D expenses will trend upwards over the balance of the year into 2023 as we launch the three phase II trials for VTX958 and continue to build out our clinical pipeline, as Bill alluded to earlier. G&A expenses in the quarter were $6 million, compared to $2.2 million for the third quarter of 2021, and net loss in the third quarter was $30.5 million, compared to $12.8 million in the third quarter of 2021.

Approximately $4.2 million of this net loss in the third quarter of 2022 represents non-cash stock compensation expense. Cash, cash equivalents, and marketable securities were $412.4 million as of September 30, 2022, and we believe our current cash equivalents and marketable securities are sufficient to fund planned operations into 2025. This concludes the prepared remarks from this afternoon's call, and I'll now turn the call back to the operator to commence the Q&A session, where I'll be rejoined by our CEO, Dr. Raju Mohan, and President and CMO, Dr. Bill Sanborn. Operator?

Operator (participant)

Thank you. 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 question to provide optimal sound quality. Thank you. Our first question comes from Michael Yee of Jefferies.

Jiajun Wen (Managing Director)

Hi, good afternoon. This is Jiajun Wen for Michael Yee on the line. Maybe two questions for me. We're aware that a competitor will be reporting phase II top line data for their TYK2 programs pretty soon. Could you comment on, first of all, your differentiation for your molecule? Ben, maybe comment on how you would integrate the read-through of the results and how should market view it for Ventyx. Second, for the S1P program, I understand you're guiding data in 2023. Could you comment on what do you want to see in the study and your expectations? Thank you.

Raju Mohan (CEO)

Great. Yeah, and thank you. Let me take the first question, and I'll have Bill address the S1P1 question. In terms of how we differentiate from competitive compounds, we've shown the differentiation on a molecular basis with deucravacitinib. We've shown extremely high selectivity, 4,000-fold more selective for the TYK2 allosteric domain. We've shown how this translates into selectivity for TYK2 pathways. We hit all pathways robustly, IL-12, IL-23, and interferon alpha. We have no interaction with JAK1 pathways. We have no interaction with no inhibition of IL-10, IL-22, IL-4, IL-6, interferon gamma. We've shown the molecular differentiation with deucravacitinib. More importantly, we've shown clinical differentiation in terms of target coverage as well as the safety, which is the key to achieve meaningful coverage of IC50 and IC90.

Bill Sanborn (President and CMO)

Bill, during the phase I data dissemination, actually compared it with deucravacitinib and the competitor compound in terms of what has been seen across head-to-head trials in phase I in terms of significant effects on dermatological effects as well as other hematological effects as well. We believe with our profile that we've demonstrated, again, on a molecular basis against Sotyktu, and more importantly, on a clinical basis for what data is publicly available, remember, for deucravacitinib and the competitor compound that you just mentioned, we have shown meaningful differentiation, target coverage, but more importantly, ability to cover the targets IC50 and IC90.

Raju Mohan (CEO)

22-24 hours without any significant impacts on being able to dose escalate given the profile of VTX958. Now, in terms of how we position ourselves with respect to this competitor data, I think it all depends what the data are and how the data are in terms of efficacy versus safety of this compound. What we can position ourselves is what we've seen thus far, which is again the safety manifestations or safety events that have shown up for these compounds, Sotyktu and the competitor, versus what we have seen, which is a very well-tolerated program or a molecule all the way up to the highest dose in MAD.

Ability to cover the target IC90 for 22-24 hours, and fewer mild events that Bill had shown, compared to what competitors have shown in head-to-head trials. I think any more follow-up questions on that? Otherwise, I'll hand it over to Bill. All right.

Bill Sanborn (President and CMO)

All right. With regard to our S1P modulator, VTX002, this is a relatively short half-life drug with a 20-hour half-life that compares to about 30 hours for Etrasimod and many days for the dominant long-acting metabolite with ozanimod or Zeposia. The short half-life allows the drug to act quickly. The design of our trial is a one-week dose titration period to address the first dose heart rate reduction effects that you see with this class, and we very carefully worked that out in phase one. Then a full 12 weeks of target dosing with the two active doses. The primary endpoint is remission, and some of the key secondary endpoints include things like endoscopic improvement, so pretty typical.

If you look at other S1P modulators, there are four approved in the multiple sclerosis arena. There's fingolimod or Gilenya and ponesimod, Ponvory, and siponimod or Mayzent, in addition to ozanimod or Zeposia. The other three drugs besides Zeposia in the multiple sclerosis setting are dosed to have lymphocyte reductions in the sort of 65% up to high 70, 78, 79 percent range from baseline. By contrast, you see about 45%-50% reduction with Zeposia, and you saw reduction in the 40s with etrasimod in phase II and phase III trials. It's really considerably lower lymphocyte reduction. There are hints that as you get up to that greater lymphocyte reduction in multiple sclerosis that you see greater degrees of efficacy.

Our trial is really designed to have the top dose be up in that higher range of lymphocyte reduction, which has not yet been tested in ulcerative colitis. We believe based on the multiple sclerosis experience, that that could lead to incremental efficacy over the efficacy that's been observed with both Zeposia and Etrasimod.

Raju Mohan (CEO)

Operator?

Operator (participant)

Thank you. Yes, sir. We'll take our next question from Yasmeen Rahimi of Piper Sandler.

Swapnil Jaswa (Managing Director)

Hey, this is Swapnil on for Yasmin. Thank you for taking our questions. Just two for us. One is, can you provide a little bit more color on how are you thinking about the difference in doses for Crohn's versus the psoriasis study? And then the second part is like, what are some of the steps that are remaining in order to initiate the phase II studies in this quarter?

Raju Mohan (CEO)

Yeah. Let me have Bill address both of those. Bill, why don't you take them?

Bill Sanborn (President and CMO)

Yeah. I think from the dosing, what we had in our earlier prepared remarks is that we will look across the range of doses that really for all of the drugs that at the top end allow for exposures that would cover IC90 for much of a majority of the day. We think that is very different from the doses that have been achieved with other competitor product or the co-target coverage that has been achieved with other competitor products, and particularly in the context of dermatologic adverse event off-target tolerability. For Crohn's disease, we sort of think of. It's equally true actually for psoriasis.

You have PASI 75 and 90 and 100 rates with psoriasis that are considerably higher with anti-IL-23 antibodies, where we believe that IC90 coverage for IL-23 would be 24 hours. There's already that. There's a delta between what you see with the approved TYK2 inhibitor for those outcome measures and what you can see with monoclonal antibodies. It's that difference in target coverage that we think will give differentiated efficacy in psoriasis, but that's also what makes it possible to see efficacy in Crohn's disease. We think that it's essential to have IL-23 IC90 coverage for most or all of the day to see robust efficacy in Crohn's disease, and our dose range in the Crohn's trial will encompass you know exposures up to that level.

Raju Mohan (CEO)

Yeah. In terms of what remains to be done, you know, we've publicly stated we'll start all three phase IIs this year. It's November. You know, a lot of work is, you know, for three trials, just, you know, all the work that goes into prep. Everything's on track and we're, you know, planning to initiate all 3 trials in, you know, less than two months, right? Stay tuned.

Swapnil Jaswa (Managing Director)

Thank you.

Operator (participant)

Thank you. Again, if you would like to ask a question, please press star one at this time. Our next question comes from Sam Slutsky of LifeSci Capital.

Sam Slutsky (Managing Director and Senior Research Analyst)

Hey, thanks for the update and, thanks for taking the questions. Got a few questions from my end. The first is, given that there's proof of concept with deucravacitinib in lupus at this point, curious on how you're thinking about that indication for VTX958, and then when might be the right time to expand development there, if you wanna go that route.

Raju Mohan (CEO)

Yeah. Again, thanks, Sam. You know, obviously, we've thought a lot about this since the deucravacitinib data came out at EULAR. Let me have Bill give you some color on our thoughts, and obviously we'll, you know, talk a lot more about this at our R&D day. For now, let me have him address this.

Bill Sanborn (President and CMO)

Yeah. I think we saw the deucravacitinib data presented at EULAR as robust evidence of efficacy in lupus. There's every reason to believe that phase II data with deucravacitinib reads through to other TYK2 inhibitors who would have similar or greater interferon alpha target coverage in the IC50 and IC90 levels. We certainly will have coverage that meets and exceeds the coverage that demonstrated efficacy with deucravacitinib in lupus. We're still considering the options about you know whether we would trigger a program in lupus or not. We haven't made a decision about that. We believe that all the translational medicine data indicates strongly that the efficacy that was seen with deucravacitinib reads through to our compound.

Sam Slutsky (Managing Director and Senior Research Analyst)

Got it. Okay. Next one I have is just there's some interesting data recently from Janssen, where they combined an IL-23 inhibitor with a TNF inhibitor for UC, and they saw higher remission rates, compared to either therapy alone. I guess, given your pipeline, curious on how you're thinking about the potential for combination approaches overall, and then would it make sense to do a TYK2/S1P1 combo at some point in the future or some other kinda combination approach?

Bill Sanborn (President and CMO)

Let me just say that at a high level, I think our company thinks that combination therapy is very interesting and will play a role in the future therapy of inflammatory bowel disease and potentially other autoimmune diseases. That Janssen data in ulcerative colitis with the combination of an anti-TNF and an anti-IL-23 is very interesting. It essentially doubled the remission rates. Really with the way that we plan to dose VTX-958 at the higher end, we think we have very close to anti-IL-23 antibody target coverage for the target. You could even imagine something more simple and straightforward than what you were proposing, which is to mix VTX-958 with a TNF blocker.

We need to sort out the safety and efficacy and dose response, you know, first with the clinical trials, as monotherapy, and that's our focus right now. The potential is there for the future. I think mixing, you know, a TYK2 inhibitor with a S1P modulator is interesting. It would require a lot of thought and diligence around what you anticipate the benefit to be on one hand and any risk on the other. It's a great question, something we will think through in the months to come and years to come, but it's not the focus of our current development plan.

Sam Slutsky (Managing Director and Senior Research Analyst)

Got it. Okay. Just last one from me. Just on the new formulation of VTX-958, the QD one, I realize it'll be in the clinic soon. But just anything more you're able to say on kind of the animal data you have to date and translatability historically of that?

Raju Mohan (CEO)

Yeah. The beauty of the approach we have is that we build and test, you know, our ER formulations prototypes in a human setting right from get go. Really optimizing the prototype in a sort of build and test model from human data, right? We lay out a plan with a clear target product profile, which is to achieve the QD dose, the unmatched coverage we see, which is IC90 for 20-24 hours. We have a number of methods where we validate this ER tablet and its exposure profile for QD dosing to have this target coverage, which is part of the TPP.

Then we'll take it into a human PK study, and then rapid iterations once we get the first read to the target profile. We're really optimizing from a base camp all the way to our target peak. As Bill said, we hope to wrap that up in the H1 of the year and we'll you know happy to show and share that data on the QD tablet. All on track, all good. Stay tuned.

Sam Slutsky (Managing Director and Senior Research Analyst)

Got it. Okay, thanks.

Operator (participant)

Thank you. We'll take our next question from Emily Bodnar of H.C. Wainwright.

Emily Bodnar (VP of Equity Research)

Hi. Thanks for taking the questions. Two for me. First, do you anticipate that you'd have any data from either of the phase II studies that you're planning to initiate for VTX958 in 2023, or when is kind of the earliest that we should be looking for results? For VTX-002, do you expect to initiate any studies for other indications besides ulcerative colitis like Crohn's disease or atopic dermatitis? Thanks.

Raju Mohan (CEO)

Yeah. On data from phase II, so our first trial to kick off is our trial in moderate to severe plaque psoriasis. All three will start this year, but we expect the psoriasis data to read out in 2023. You will see phase II data for the phase II trial, moderate to severe patients with VTX958 in 2023. On the second question, Bill, why don't you just address that about other indications for VTX002 that we might consider?

Bill Sanborn (President and CMO)

Yeah. You know, other products in that field that are being evaluated have indications that include Crohn's disease. There's a trial on eosinophilic esophagitis and a trial on atopic dermatitis. Those are all possibilities. I think we're watching the landscape play out. We're a little busy at the moment for all the reasons we've been discussing this half hour, but we do see, you know, the interesting potential in some of these other indications and, you know, other possibilities are certainly in our mind.

Emily Bodnar (VP of Equity Research)

Got it. Thank you.

Operator (participant)

Thank you. As a reminder, management asks that you please limit yourself to one question. We'll take our next question from Alex Schwartz of Stifel.

Alex Schwartz (Managing Director)

Hey, thanks for taking my question. I guess I wanted to follow up again on upcoming data from Nimbus. I guess in the phase III for deucravacitinib, at 12 weeks, they showed about a placebo-adjusted PASI 75 around 40%. I do wonder if assuming there's no safety issues in the NIMBUS trial, if they don't succeed in getting a better PASI 75 rate than that, how much confidence can we have in this better exposure efficacy hypothesis for TYK2 inhibition? Thanks.

Raju Mohan (CEO)

You know, we are positioned to have the best-in-class coverage. We have the best-in-class coverage for IC90. You know, there is limited data on coverage, but there is data from the phase II trial in particular for deucravacitinib, where they had higher coverage for IC50 for 16-18 hours at the 12 mg dose and about nine hours for the 6 mg dose. There is data out there that suggests you can get meaningful incremental differences in PASI 75 and even PASI 90 as you get higher coverage. While IC90 data doesn't exist right now for efficacy for oral TYK2s, we have, you know, enough precedent from biologics. To get biologic-like efficacy, you need biologic-like coverage.

You know, obviously we'll wait and see what Nimbus's data look like, right? There's clearly a data set out there from biologics on coverage and also from deucravacitinib across not just the psoriasis trial, but that dose efficacy response is available for psoriatic arthritis as well. Bill, you wanna add anything to that?

Bill Sanborn (President and CMO)

Yeah. Just to reframe what you said slightly. If you think about dose finding, as Raju said, you know, with deucravacitinib in various trials, we've seen 3 mgs BID and 6 mgs once a day, and then 6 mgs BID and 12 mgs once a day. The difference between three BID or six once a day, and then stepping up to six BID or 12 once a day, you improve by as much as, you know, 70, 80% the IC50 coverage going from eight to nine hours to maybe 15 hours. But the IC90 coverage is not hit at all in any of those doses. Recall in phase I with deucravacitinib, as you went up to 12 BID, you had 78% of patients having skin adverse events.

That product is really locked in by the off-target adverse event in the skin manifestations. Yes, there's dose finding with deucravacitinib, but the whole range of doses are not really leading to the exposure range that is an interesting experiment because it's limited by the therapeutic window. You know, as other competitor data reads out and you see different doses and whether there's dose response and what the maximum PASI 75 and 90 and 100 responses are, you'll want to ask yourself whether the real exposure response for IC90 coverage of IL-12/23 was done, and if the doses and the resulting exposures are not getting to, you know, most of the day coverage of IC90, then you haven't really. The question hasn't really been addressed.

Alex Schwartz (Managing Director)

Great. Thank you. Thanks for the color. Appreciate it.

Bill Sanborn (President and CMO)

Thanks, Alex.

Operator (participant)

Thank you. We'll take our next question from Jeff Jones of Oppenheimer.

Jeff Jones (Managing Director and Senior Analyst)

Thanks, guys, and appreciate you taking my question. On the S1P front, Pfizer talked a little bit more about Etrasimod on their earnings call, and I guess, in that context, they talked about the non-complex dose titration. Interested in your thoughts on the dose titration versus not in adoption and use, as well as the population they studied in, being the bio-naive, JAK-naive population, and the population you're using for your ongoing phase II. Thank you.

Bill Sanborn (President and CMO)

Yeah. Let me have the S1P one expert address this. Well, I think defining a dose titration regimen as complex is an overstatement of the facts. It's a blister pack and, you know, you have pills that you push out of the blister every day. It's not a big deal. I don't think that is an important limitation. In terms of patient populations, Etrasimod recruited patients with moderate to severe ulcerative colitis, and there was a mixture of biologic or advanced therapy naive and advanced therapy failure patients. As I recall, it was something like a 60-40 split of naive to failure.

You know, it's our trial's still running. You have different countries coming on at different times, so you don't know what the final mix will be till the trial is fully recruited. We are recruiting a mixture of advanced therapy naive and failure patients similar to other drugs in the class.

Jeff Jones (Managing Director and Senior Analyst)

Okay. Thank you.

Bill Sanborn (President and CMO)

Yeah. Thanks, Jeff.

Operator (participant)

Thank you. We'll take our next question from Tiago Fauth of Credit Suisse.

John Nuss (Managing Director)

Hey, guys. John for Tiago. Thanks for taking our question. On VTX-zero zero two, can you just talk about the significance of its selectivity for S1P receptor one specifically, and the implications of avoiding receptors two through five? What are the potential trade-offs, if any, in terms of efficacy or safety, for having a more selective approach? Thanks.

Bill Sanborn (President and CMO)

Yeah, great question. So look, there's a plethora of data for efficacy for S1P1, and let's not just limit ourselves to UC. There's data across multiple MS trials and the biology of S1P1 class, the biology of how S1P1 class of drugs mediates its efficacy primarily through lymphocyte sequestration. It's really S1P1 receptor or S1P1 modulation that drives that efficacy. So as a class, you see compounds that are selective for S1P1. Most of these drugs cross over to some extent into S1P5, even though they're highly selective S1P1. Really not a consequence to us. S1P5 is primarily expressed in the CNS and was eventually thought to be of consequence for MS.

Our drug, let me remind you, is a non-CNS penetrant compound, so that S1P5 activity is really inconsequential in driving efficacy. It's driven through S1P1. Now, we've seen reference to S1P4 with one particular compound, I think it was with Etrasimod in particular. From our point of view, first of all, there's not enough data on S1P4 class of drugs, but just as a biology, S1P4 is primarily involved in dendritic cell trafficking. So again, no real relevance to S1P1 and its role in IBD or UC or the mechanism. So not having S1P4 is again highly selective drug. No side no non-selective non-relevant crossover. So again, a highly selective compound.

Unlike Etrasimod, it doesn't even hit S1P4, and there's only positive consequences to being selective for a drug.

John Nuss (Managing Director)

Got it. Thank you so much.

Bill Sanborn (President and CMO)

Sure. Welcome.

Operator (participant)

Thank you. I would now like to turn the call back to Dr. Raju Mohan for some closing remarks.

Raju Mohan (CEO)

Yeah. Well, thank you all. Thanks to the team here. You know, we're really pleased to present our accomplishments for this quarter to highlight attributes of VTX958, VTX002 in our NLRP3 portfolio. Really like to welcome you all to our R&D day in New York, January twenty-sixth. Mark the date. We'll be sending out more details on that event in the near term. I'll look forward to seeing you all there and answering questions in person. Thank you all again.

Operator (participant)

This concludes today's Ventyx Biosciences third quarter 2022 earnings conference call. Please