Ventyx Biosciences Q1 2023 Earnings Call Transcript

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Provided by Quartr
May 11, 2023

Key Takeaways

  • Ventix launched five Phase 2 clinical trials in Q1 2023 across its internal pipeline, including BTX-958 in plaque psoriasis, Crohn’s disease and psoriatic arthritis, VTX-2 (an S1P1 modulator) in ulcerative colitis, and two NLRP3 inhibitors in FCAS and CNS indications.
  • BTX-958’s top dose is designed for 24-hour IC90 coverage of IL-12/23 to mimic biologic efficacy, with topline data from the Serenity psoriasis study expected in Q4 2023 and results from psoriatic arthritis and Crohn’s trials in 2024.
  • VTX-2’s 60 mg dose has demonstrated >70% lymphocyte reduction, targeting a ~20% placebo-adjusted clinical remission in moderate-to-severe ulcerative colitis, with Phase 2 topline results anticipated in H2 2023.
  • R&D expenses rose to $35.4 M in Q1 2023 (vs. $17.4 M in Q1 2022) reflecting pipeline advancement, G&A was $7.1 M, net loss was $38.9 M, and the company ended March with $376.9 M in cash and securities.
  • Beyond lead programs, Ventix advanced its NLRP3 portfolio with VTX-2735 now in a Phase 2 FCAS trial and the CNS-penetrant VTX-3232 slated to enter Phase 1 in Q2 2023.
AI Generated. May Contain Errors.
Earnings Conference Call
Ventyx Biosciences Q1 2023
00:00 / 00:00

There are 11 speakers on the call.

Operator

Afternoon, ladies and gentlemen, and welcome to the Vintex 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. As a reminder, this conference call is being recorded. I would now like to turn the call over to Doctor. Marty Oster, FinTech's Chief Financial Officer.

Operator

Please go ahead.

Speaker 1

Thanks, Angela. Thank you, everyone, for joining us today, and good afternoon. Welcome to Ventex 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.ventix on 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, on 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 with current cash, cash equivalents and marketable securities.

Speaker 1

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 Q1, which ended March 31, 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 and 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 Doctor. Rajeev Mohan, Fintech's Founder and CEO.

Speaker 1

Rajeev, please go ahead.

Speaker 2

Yes. Thanks, Marty. So good afternoon to all again and thank you for joining Quentix's Q1 2023 Financial Results Conference Call. Let me briefly run through this afternoon's agenda. And given that we just had our call in late March, I'll be brief and keep my comments focused on high in a level of business update.

Speaker 2

Bill Sanborn, our President and Chief Medical Officer, will then provide updates across our pipeline programs in a in a bit more detail. Finally, Marty will present an overview of our Q1 2023 financial results before we open the call for Q and A. As I always like to remind our audience, the foundation of Ventex 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 Ventix, we are off to a great start. Our team is executing across the board with 5, and I repeat, 5 Phase 2 clinical trials now ongoing across our wholly owned pipeline of internally discovered small molecule drug candidates.

Speaker 2

So with BTX-nine fifty eight, we remain confident that we are developing a potential best in class AllosterectyK2 inhibitor. Based on class leading target coverage and safety that we observed in Phase 1, We see great potential to not only establish a differentiated profile in psoriasis and psoriatic arthritis, but also to be a first mover among TIG2 to inhibitors in Crohn's disease, where we believe our ability to achieve trough IL-twenty three IC90 coverage will be particularly important. We have 3 Phase 2 trials now underway in black psoriasis, with psoriatic arthritis and Crohn's disease, and Bill will discuss these in more detail during his section in his comments. On the development of an extended release tablet for QD dosing for 958, we continue to make progress towards the target profile of 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.

Speaker 2

We look forward to providing a more detailed update in the early part of early second half of twenty twenty three. With our S1P1 modulator, VTX-two, we believe we will be the 1st to truly explore the full potential of this mechanism in ulcerative colitis and our aspiration 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 zircosia and is competitive with or superior to levels achieved by Biologics. This efficacy profile, if achieved, Should position BTX-two as a potential class leading safe oral agent in ulcerative colitis. And again, Bill will provide more color on the progress of this trial. Beyond these lead programs, we continue to advance our novel NRP-three inhibitor portfolio, including our peripheral NRP-three 3 inhibitor VTX-two thousand seven hundred and thirty five, which is now in Phase 2 trials in CAHPS patients and a CNS penetrant NLRP-three inhibitor VTX-three 3,232, which is expected to advance into Phase 1 studies this quarter.

Speaker 2

So with that, I'll hand the call over to Bill Sanborn for for a more

Speaker 3

detailed pipeline update. Bill? Thank you, Raju, and good afternoon, everyone. I'm in the Q1. I'm excited to provide a brief pipeline update today and to highlight recent achievements across our portfolio.

Speaker 3

I'll begin with PTX-nine fifty eight. As you are all aware, we are now well underway with 3 Phase 2 trials of BTX-nine fifty eight, including the Serenity trial in moderate to severe plaque psoriasis, the HARMONY trial in moderately to severely active Crohn's disease and then 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 three trials expected to achieve approximate trough IC90 coverage of interleukin 12 and interleukin 23. So we are really pushing towards biologic like suppression of the interleukin-twenty three pathway, and we expect this to translate into differentiated efficacy closer to that observed with the anti IL-twenty three antibodies. This is our expectation not only in plaque psoriasis and psoriatic arthritis, and where we believe our class leading therapeutic window may afford us a strong position relative to competitors.

Speaker 3

Looking more closely at the psoriasis to 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 28,000,000,000 on the 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 Sotyc2, 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 BTX-nine fifty eight Phase 2 program up and running over the past 6 months, and we have made tremendous progress in enrolling the serenity plaque psoriasis trial.

Speaker 3

As we've stated previously, we are on track to report top line data in the 4th quarter. We are looking forward to carrying this operational momentum into the other VTX-nine fifty eight Phase 2 trials, including the TRANQUILITY trial in psoriatic arthritis in the HARMONY trial in Crohn's disease, and we continue to expect top line results from both of these trials in 2024. Shifting to BTX-two, our S1P1 receptor modulator in Phase 2 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 VTX-nine fifty eight, where we talk about achieving differentiated coverage of the target pathway.

Speaker 3

You will recall that we previously shared data from our Phase 2 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 plus percent compared to approximately 50% for etrasimod and symposia, and we believe that this differentiated pharmacodynamic effect will translate into improved efficacy in ulcerative colitis. And if we take a step back and look at the landscape in ulcerative colitis, This is a large market currently dominated by biologics, which achieved placebo adjusted clinical remission rates of around just 10% or slightly higher and the anti TNF alphas, the alpha-four beta-seven endocrine inhibitors and so on, all share this characteristic. There is a significant opportunity for 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 Sapozia continues to build volume. Meanwhile, the potential approval of etrasimod is expected later this year.

Speaker 3

If we can achieve our target product profile with BTX-two, which is placebo adjusted clinical a remission of around 20% or better, then we believe there is an opportunity for BTX-two to become a class leading drug in ulcerative colitis. And as we mentioned in the press release, enrollment in the Phase 2 trial of VTX-two has continued to progress very well. So 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 twenty twenty On our last earnings call, we announced that we have initiated a Phase 2 proof of concept study of our peripheral NLRP3 inhibitor, BTX 2,735 in familial cold auto inflammatory syndrome or FCAS, which is the most common subpopulation of cryopyrin with associated periodic syndromes or caps. With our CNS penetrant compound, BTX-three thousand two hundred and thirty two, We expect to initiate a Phase 1 trial in healthy volunteers this quarter. Our goal is to position both of these NLRP-three inhibitors as Phase 2 ready clinical candidates by establishing a differentiated profile in terms of safety, pharmacokinetic in pharmacodynamic activity.

Speaker 3

We believe that there is a wide range of high value indications for future development of both our in peripheral NLRP-three inhibitor, VTX-two thousand seven hundred and thirty five and our CNS penetrant molecule, VTX-three thousand two hundred and thirty two. With regard to NLRP-three inhibition in the CNS, there is a strong biologic rationale to potentially address devastating neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease among others. Has been strong across the pipeline, and we are very much looking forward to announcing top line data for BTX-nine fifty eight and BTX-two in the second half of this year. Before we move on to Q and A, I'd like to hand the call back to Marty for a brief discussion of our financial results. Marty?

Speaker 1

Yes. Thank you, Bill. You'll find details from our financial results for the Q1 ended March 31 in our press and I believe the 10 Q filing is also hit on the website. And I'll summarize those results here. R and D expenses were $35,400,000 for the in the Q1 of 2023 compared to $17,400,000 in the Q1 of 2022.

Speaker 1

This increase reflects the advancement of our pipeline in the later stages of clinical testing, including execution of the ongoing Phase 2 trial of VTX-two in ulcerative colitis and the Phase 2 programs for VTX-nine fifty eight in psoriasis, Crohn's disease and psoriatic arthritis. As we previously mentioned, we continue to expect R and D expenses to increase directionally throughout 2023 with some quarter over quarter variability expected as our Phase 2 trials progress and as we conduct our CMC activities in preparation for the potential launch of Phase 3 trials on 2 and 958 in 2024. G and A expenses in the quarter were $7,100,000 versus $5,300,000 in the Q1 of 'twenty two and the net loss in the Q1 of 2023 was $38,900,000 compared to $22,700,000 for the Q1 of 2022. Cash, cash equivalents and marketable securities totaled $376,900,000 as of March 30 this reflects an increase from our end of year cash and equivalents balance of $356,600,000 and reflects proceeds from the sale of stock on our ATM facility, which occurred during Q1, offset by our Q1 cash spend. And we continue to believe that our current cash, cash equivalents and marketable on the line of sight.

Speaker 1

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 and A session, where I'll be joined by Raju and Bill. Operator?

Operator

If at any point your question is answered, you may remove yourself from the queue by pressing star 2. 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.

Speaker 4

Hey, guys. Thanks for the question. Thanks for the updates. We had 2 areas we wanted to ask on. The first was actually on the S1P one.

Speaker 4

I know you have data coming up later this year. There have been some studies that I've read out recently, had no placebo. Then 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. And then the second question is you also have an update on the ER tablet 958.

Speaker 4

Can you just remind us, are you testing multiple different technologies in that or is that one technology at different doses? Thank you.

Speaker 2

Yes, excellent. Thanks, Mike. Good to hear from you. Let me have Bill talk about the S1P1 and Trials in placebo and then I'll come back with the ER tablet, Bill.

Speaker 3

Yes. So it's a good question, Mike. I think that trials without placebo arms that are not controlled are not easy to interpret. And so you just have to take those data with a grain of salt. Placebo rates can vary.

Speaker 3

The average placebo rate in moderate to severe ulcerative colitis trials is about 7.5% or 8 It can sometimes be as low as 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 to monitor the outcomes and pool blinded data to see if the magnitude of Response that you're seeing is just barely crossing the threshold to be a response or whether it's a deep and a robust response. I'm not going to get into the details around any of those things except to say we're well aware of all the characteristics and we've monitored to the trial very carefully as they just progressed.

Speaker 2

Good. Anything else on that, Mike?

Speaker 4

Very helpful. Very helpful. And then on the ER tablet, I shed some light on that, what's going on with

Speaker 2

different technology. Yes. So it's a good question. And thanks for asking to clarify that. So we have a couple of different technologies, but I think it's important to understand that these are Sort of complementary technologies.

Speaker 2

So what we do is we use one technology to make sure we're sort of using bio relevant dissolution methods, which is what's happening in the absorption dissolution phase in humans. And then we complement this with the technology that actually simulates what's actually going to happen, The dynamics, the motility of what actually happens in absorption. So you really are sort of using multiple technologies to make sure, for lack of better word, checking a box in or checking the appropriate boxes for both technologies. So if you maximize your chance of then when you go into human data, you've now made sure that you simulated what you see both in terms of dissolution fluids and dissolution rate and also absorption in terms of what actually happens in a system where you've got bile salts and motility, all of those factors. And that's sort of a path we take with each iteration that we're doing towards our target product profile for the ER tablet for QD dosing in Phase 3.

Speaker 5

Thank you.

Speaker 2

You're welcome.

Operator

Thank you. Our next question comes from Yasmeen Raheemie with Vibra Sandler.

Speaker 6

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, Doctor.

Speaker 6

Sanborn, if you could educate us on what do we want to see from a safety perspective out of this Phase 2b that could highlight differentiation? So that's question number 1. And then question number 2 is, tomorrow morning, we're going to see some Phase 1 data from the IL-twenty three oral product and would love to as we're looking at that data, think about how you guys are I guess, could we look at that and being able to predict sort of what I guess the comparisons or the TIG2 class versus the IL-twenty three class could offer, obviously, just on based on Phase 1 data. And I'll jump back into the queue.

Speaker 2

Yes. So let me to address the protagonist question. Yes, and again, good to hear from you. So yes, the Phase 1 data is supposed to come out tomorrow at the ISID meeting, followed by the more detailed efficacy data that's going to come out sometime in, I believe the July timeframe. Again, I think we had a similar question at the last call, and I think we have to wait for the data.

Speaker 2

I think the PKPD itself might be illustrative to some extent, but the real meat is going to be in the Phase 2 data and how it compares to what we've seen with drugs in this class, the biologics and the orals that have come out recently. It's really difficult to speculate on something we have no idea about. And you and I have talked about the press release It came out early on. So I think let's wait for this data. Let's look at the PKPD.

Speaker 2

It will give us a little more color on this class of compounds and we have none. And then we'll wait for the efficacy data and have a meaningful discussion on this class of drugs in particular. But let me just hand it over to Bill for the S1P1 Question.

Speaker 3

Yes. So just to frame the perspective, remember that the S1P class of has had regulatory approval in the United States since 2010 when Gilenya was approved for multiple sclerosis. And there's about a 1000000 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. So The context of the data that we release in the second half of the year from a safety perspective will be in the context of a very well under with respect to all the potential safety issues. The second thing is to say is We'll be releasing 13 weeks of safety data.

Speaker 3

And so That's a limited period of time. So 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, but 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 pick typically, we'll see completion rates for 12 or 13 weeks in the single digits. So having patients complete the induction course of therapy is one measure of safety and tolerability.

Speaker 3

Then 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. So we'll look at all those things. And then narrowly in the S1P1 class, you can see heart rate reductions and in the comments and we think we have a good dosing titration regimen. So seeing what the rates of bradycardia is in the 1st 13 weeks by treatment group and seeing if there are any cases of AV block and those sort of things.

Speaker 3

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 rare and you're not likely to see in a Phase 2 induction study.

Speaker 6

Thank you so much, Sandra, for your comments.

Operator

The next question comes from Derek Archila with Wells Fargo. Please go ahead.

Speaker 7

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 some folks point to this Pfizer molecule, which allegedly had IC90 coverage for 24 hours and their 12 week data fairly similar to Duprava and Takeda's drug at PASI75 and PASI90.

Speaker 7

So just love to get your thoughts there. And then also, can you just remind us how many sites you have in the S1P 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.

Speaker 2

Yes, Derek, good question. And we've seen some of that analysis out there. So we'll address it again, and And I'll have Bill again talk a little bit about this because we have taken it there. But let me just start out on some of the analysis being done out there with in terms of coverage Or model coverage in IC 70s, 80s 90s that people have put out there in particular. And let's get outside the Pfizer compound.

Speaker 2

Let's focus on some of the analysis that's been done for SYDIC II and for the 2 Takeda doses that have been done. And Look, cross trial comparison with small number of folks is really challenging, but 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. So the So take to 12 milligram dose that people are using to model out the IC50 coverage for about 18 hours, I think. And the TAC-two seventy nine, which is the IC-seventy for 24 hours.

Speaker 2

And this is data that we put out there. I think it's pretty consistent with what you can read from the various Nimbus disclosures. 30 milligrams is IC-eighty, right? Now our what we've said is, we are going into our Phase 2 trial, in particular for psoriasis with trough coverage of IC90 at our top doses and then significant coverage for Across other doses behind the trial, but we are going in with dose and doses that cover IC90 for 24 hours, right? And our data are going to read out in the Q4.

Speaker 2

And we'll see in our aspiration as we've said this before to see differentiated efficacy across multiple readouts. So IC50, 75 and IC90 And differentiated efficacy from other compounds that we are now talking about, right? So that really is the crux of the argument. But going in with maximal coverage and we hope to show differentiated efficacy from what you've seen here, right? So 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.

Speaker 2

But let me have Bill and see if he wants to add a little more to this discussion that we've had before as well. Bill?

Speaker 3

Yes. I would just say that 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-seven thousand five hundred and ninety and one hundred. And in Phase II trials, you can have outliers sometimes. So For instance, the if you look at the highest dose of the Takeda product In Phase 2, the PASI 75 sorry, the PASI 100 is in the zone of what you would see with full biologic coverage, but the PASI 7590 were not.

Speaker 3

So there's an inconsistency there that is different from what you see with the well dust drug at the plateauing of its pharmacodynamic effect. So it just doesn't make sense that Eventually, with adequate target coverage, you wouldn't be able to reach in antibody like efficacy because with antibodies as you dose down, you will see left shifts of all the across the PASI 7,591 100 and as you go up on the dose and have enough patients, you'll see consistency across those measures all shifting up in unison. So we'll have our data when we have the data, but we think that a well dosed drug We'll just show that consistency as you move through the dose range of relation the expected relationships for PASI 7,590,100. Coming to the UC trial, so 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 This looks like a typical internationally conducted Phase 2 a trial.

Speaker 3

We've conducted it relatively quickly, and that's what it looks like. The 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, at the high enrolling countries versus rest of world, advanced therapy naive versus advanced therapy failure. And what you're looking for is that you see consistency across those stratified analyses in the rates of the different outcome measures. And I feel good about the consistency of our data in biologic naive and biologic failure in high enrolling countries versus rest of world. So I think we're conducting a robust trial.

Speaker 3

I'm not going to lay out all the exact patient population characteristics today. You'll see those when the data come out in the second half. But from a trial monitoring Effective. I'm very pleased with the consistency of the data.

Speaker 7

Got it. Understood. Super helpful. Thank you, guys.

Speaker 2

Yes. Thanks, Derek.

Operator

The next question comes from Alex Thompson with Stifel. Please go ahead.

Speaker 8

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 2 data sort of late 3Q, early 4Q and then the 958 data after that. Just wanted to sort of confirm that those timelines Are still what you're expecting? And then maybe for Marty, if you could talk a little bit about what's embedded in your cash runway guidance in terms of

Speaker 2

Yes. So for S1P1, we've guided people to second half of the year. So it's going to be sometime late third quarter, early fourth quarter. And then for the psoriasis trial for 958, 4th quarter, so late Q4, I would probably

Speaker 1

in the 2020 5 and what's included in those assumptions then is completion across all the Phase 2 studies that Bill spoke about today on the call. So it's the CAPS trial for 2,735, psoriasis psoriatic arthritis and Crohn's trials for 958 as well as the UC trial for 2. We anticipate being able to complete the Phase 1 trial for for BTX-three thousand two hundred and thirty two, our CNS directed NRP3 inhibitor, that capital and we expect to be able to produce materials and conduct necessary kind of like pre Phase 3 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.

Speaker 8

Great. Thanks.

Speaker 2

Yes. Thanks, Alex.

Operator

The next question comes from Chris Shibutani with Goldman Sachs. Please go ahead.

Speaker 5

Thank you very much. Two questions, if I may. The first, I believe in clinicaltrials dot gov with the Phase 2 psoriasis study. It appears that in the posting that there's a slight change with a 16 week long term extension arm that was added. Is this new?

Speaker 5

And if so, what drove this decision? Or is it just an updated Aspect of the posting and it's the study has always been designed this way. And then secondly, reflecting on the TYP-two Development strategy and commercialization that Bristol has had. You previously commented for DUCRAVA that you expected a negative outcome from the Crohn's disease Phase 2. This has played out.

Speaker 5

Can you talk about your impressions and if this has any influence on your on Crohn's. And then secondly, with Certikdu's commercial performance, we had recently talked about how that's done I think they talked about a 40% versus 60% share. How has this performance compared with your with your expectations and maybe share with us your views updated on the commercial opportunity as a result of how Sotiktu is delivering thus far? Thank you.

Speaker 2

Chris, those are 3 questions, not 2. So Yes.

Speaker 5

2a, 2b.

Speaker 2

Yes. Let me have Bill comment on the clinical trial

Speaker 3

Yes. So for the study design, when we initially did the regulatory filings, we had in the Q3 filings. We had toxicity coverage tox study coverage for up to 16 weeks of therapy. And so 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 talks data to extend the duration of treatment beyond the 16 weeks, and we went through the regulatory filing process to that and the clinicaltrials dot gov update indicates that we'll do another year of therapy.

Speaker 3

So it was just Availability of supporting data. With respect to Crohn's disease and tick 2, I don't think that We always expected that the outcome of the study would be negative. We know that with IL-twenty three antibodies that you need doses that will plateau at a high level, PASI 75% and the 85% to 90% range. You need at least those doses, if not higher, to see efficacy in Crohn's disease. And of course, the SOTIC-two dose that was studied Was well below that and had estimated I see 50 coverage of about 16 hours and I see 90 coverage of 0 hours.

Speaker 3

So 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 and 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 be show strong efficacy in Crohn's disease as well. So it doesn't change our thinking at all. We We completely factored that in.

Speaker 4

And on the commercial?

Speaker 2

Yes. On the commercial side, we'll keep it brief. So Taurus, we've just recently hired a Head of Commercial here with our forward thinking across our trials and looking beyond the psoriasis trial and other indications as well. I think this Tesla analysis for what it is, first, the analysis is always lagging as now we've begun our own discussions as part of our commercial planning with prescribers and KOLs. There's a huge amount of excitement in this class of drugs, Right.

Speaker 2

Big, big markets, in oral, which is clearly differentiated from Otezla. I think the market will grow. It's going to benefit as we come into the market, as we move along our trials. And I think with the drug with TIC II class with safe drugs, with efficacy that's comparable, but certainly better than what's been shown with Sotixu. I think the market would appreciate that.

Speaker 2

So we continue to feel very bullish about this class. And the prescribers that we're talking to now are bullish About the TYK2 inhibitor. So I think we just have to 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 Otasli. Anything else to add, Bill?

Speaker 5

Great. Thank you for sharing your thoughts.

Speaker 2

Of course.

Operator

The next question comes from Emily Bodnar with H. C. Wainwright. Please go ahead.

Speaker 9

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 going to have high dose data in the UC study later this year. So curious on any expectations you have for that study and how that might impact your views for BTX-nine fifty eight.

Speaker 9

And then maybe also if you can comment on VTX-two thousand seven hundred and thirty five, how you kind of plan on determining which indications You might want to take that asset into following the Phase 2 CAF study. Thank you.

Speaker 2

Yes. So again, I think Bill has addressed He's discussed it before in terms of the Sotyqtu and UC, the second trial they're running. Why don't you take that first and I'll come back to it.

Speaker 3

Yes. It's not public to my knowledge exactly what the dose is. In Phase 1, 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, and I'll remind all of us that 78% of patients had skin organ class on that dose, so it's really not tolerable. So there have been rumors that they're studying no 8 BID or 10 BID or even 12 BID.

Speaker 3

It's difficult to imagine it's 12 BID from a tolerability perspective. But 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. And then just to remind us, what you also see is that The effect size with anti IL-twenty three antibodies is larger in Crohn's disease than it is in ulcerative colitis. So you typically see differences between drug and placebo at optimal doses of 20% to 30% in Crohn's disease, and it's more in the 10% to 15% Range in ulcerative colitis.

Speaker 3

So the Lilly Phase 3 program showed a 10% gain over placebo with mirikizumab And both AbbVie with risankishumab and Janssen with gasecumab have recently reported 14% better than placebo in their Phase 3 studies in ulcerative colitis for induction studies. As I recall, The high dose to ducravasitinib 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 I see 90 for 24 hours. We'd be trying to show a 14% difference with 40 patients per arm.

Speaker 3

That's not going to work. So I predict it will fail.

Speaker 2

All right. There you have it. So in the RP3, as we said in our R and D Day, our goal for this year, for 2023, is to position both molecules, 2,000 735,000 3,000 232 as Phase 2 ready compounds. With respect to 2,735, this is a peripheral compound. We believe this is the best in class NLRP3 peripheral molecule out there.

Speaker 2

So we've done the Phase 1. We announced the Phase 1 data last year. We've done the TOX work. We've done the CMC work to support the Phase 2 trial. What we also are very clear about this last discussion was with our focus on driving the Phase 2 trials for TYK2 with 958, with our focus on the UC trial for 2.

Speaker 2

We would sort of shift the focus from 2,735 towards the end of the year. Again, this will be a Phase 2 ready molecule. We have previously shared the excitement across a number of disease indications where IL-one beta and IL-eighteen have been implicated and a lot of sort of validation from different trials out there, in particular, in the biologics. So we'll make a decision towards the end of the year with this Phase III compound, how we proceed with the development, whether it's with a partner, whether we go it alone. But for now, What we've done is position these Phase IIa compounds focus on delivering on our promise with both trials for UC and for 2.

Speaker 2

So just stay tuned for 2,000,000,000 35.

Speaker 9

Great. Thanks so much.

Speaker 2

Yes, you're welcome.

Operator

The next question comes from Sam Slutsky with LifeSci Capital. Please go ahead.

Speaker 10

Hey, good afternoon, everyone. Thanks for taking my questions. Two quick ones for me. 1, on the oral IL-four receptor alpha 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 alpha receptor alpha to be effective?

Speaker 2

So again, we're no, we are not going to go into too much detail on that program. Sam, as you know, it's a it's we're one of the few folks that has sort of embarked upon this a challenge. We've disclosed our lead just a sort of a little, little data on our Lead compound in terms of the excitement we have. Obviously, we're going against an extremely successful drug out there, defilumab, Dupixent. And so what I would say, just stay tuned.

Speaker 2

We're moving along the lead op program here. Put all of the assays in place. 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. So stay tuned. Okay.

Speaker 10

And then just lastly, for the Phase 1 study with VTX-three thousand two hundred and thirty two, since you plan to take that into neuro inflammatory indications. Just curious on how you're thinking about measuring the PD effect and then what you would want to see with that for a

Speaker 2

Yes. Great question. So there's little There's really no precedent for or there's no data for any LRP 3 that's been taken into a Phase 1 Our Phase 1b trial. There was an indication that the infrasome compound had been taken and there's no data released from that particular trial. So for us, it's really we think this is a best in class compound.

Speaker 2

On. It has a really good CNS penetrant profile in terms of KPUs, the distribution across the CSF, what we expect to be the free fraction in the interstitial fluid in the brain. So our goal for the Phase 1 study, it's a 2 part goal. 1st is to do a Phase 1 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.

Speaker 2

So that's part 1. What we're actually looking at now and we will disclose our final intent is looking Potentially looking at biomarkers in a Phase 1b trial as well. And as you know, that's it's very complicated and we have to make sure we understand what we're looking and calibrate that before we do something like that. But again, we feel very confident that a Phase 1 stand alone SADMAND 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 2 studies. Again, the precedent for looking at CSF levels and calibrating those to BRAIN levels as well.

Speaker 2

I think in terms of biomarkers, of course, the ultimate biomarker for in the LRP3 activity is IL-one beta, but again, we're also be conscious of if and when we go into a disease population, what biomarkers do we expect to modulate in those patients? And are they really sort of Consistent with the duration of these trials. They are really meaningful in terms of what would guide us through our Phase II trial. So stay tuned for 3,232 news coming out. Of course, we're as we said, we're going to dose the Phase 1 healthy volunteers in this quarter.

Speaker 2

And then we'll talk more about that future of this of the Phase I trials and 1b trials in later discussions. On the call.

Operator

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

Speaker 2

Yes. Well, again, thank you all. We just spoke a few weeks back. It's always great to get together with you all and address the questions, very thoughtful and appreciate the interest in our programs. And so let's we'll see you guys again in a few months.

Speaker 2

So thanks again all and thank you to the team.

Operator

This concludes today's Vintex Biosciences 1st Quarter 2023 Earnings Conference Call. Please disconnect your line at this time and have a wonderful day.

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