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spk07: Good 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. If you would like to ask a question at that time, please press star 1 on your telephone keypad. If at any point your question has been answered, you may remove yourself from the queue by pressing star 2. 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. Marty Oster, Vintex's Chief Financial Officer. Please go ahead.
spk00: Thanks, Angela. Thank you, everyone, for joining us today, and good afternoon. Welcome to Vintex 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.ventexbio.com and the Investors tab in the News and Events section. Before we begin the call today, I'd like to remind everyone this conference call and webcast will contain forward-looking statements about the company, including, without limitation, statements about the anticipated timing of commencement, enrollment, and completion of clinical trials for our product candidates, the anticipated timing of release of clinical trial data, and other information about our product candidates. the market opportunity for our product candidates, and the expected timeframe for funding operations with current cash, cash equivalents, and marketable securities. These statements are subject to risks and uncertainties that could cause actual results to differ. Factors that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward-looking statements are discussed in greater detail in our most periodic reports filed at the SEC, including our Form 10-Q for the first quarter, 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 revise or publicly release the results of any revisions to these forward-looking statements in light of new information or future events, except as required by law. With that said, I'll hand the call over now to Dr. Rajiv Mohan, Ventex's founder and CEO. Rajiv, please go ahead.
spk14: Yeah, thanks, Marty. So good afternoon to all again, and thank you for joining Ventex's first quarter 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-level business update. Bill Sanborn, our President and Chief Medical Officer, will then provide updates across our pipeline programs in a bit more detail. Finally, Marty will present an overview of our first quarter 2022 financial results before we open the call for Q&A. As I always like to remind our audience, the foundation of VENTIX 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're off to a great start. Our team is executing across the board with five, and I repeat, five phase two clinical trials now ongoing across our wholly owned pipeline of internally discovered small molecule drug candidates. So with BTX958, we remain confident that we are developing a potential best-in-class allosteric TIK2 inhibitor. Based on class-leading target coverage and safety that we observed in phase one, we see great potential to not only establish a differentiated profile in psoriasis and psoriatic arthritis, but also to be a first mover among TIK2 inhibitors in Crohn's disease, where we believe our ability to achieve TROF IL-23 IC90 coverage will be particularly important. We have three Phase II trials now underway in black psoriasis, 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, the TPP, and we remain confident that we will have optimized once-daily tablet to advance into Phase III trials in 2024. As we have previously disclosed and discussed, our development strategy for this path incorporates an iterative process that allows us to sequentially evaluate multiple prototype formulations in humans. We look forward to providing a more detailed update in the early part of, early second half of 2023. With our S1P1 modulator, VTX002, We believe we will be the first to truly explore the full potential of this mechanism in ulcerative colitis, and our aspirations for this asset have always been very clear, which are to demonstrate efficacy in moderate to severe UC patients, ulcerative colitis patients, that is unambiguously differentiated from both atrazumab and zeposia, and is competitive with or superior to levels achieved by biologics. This efficacy profile, if achieved, should position VTX002 as a potential class-leading safe oral agent in ulcerative colitis. And again, Bill will provide more color on the progress of this trial. Beyond these lead programs, we continue to advance our novel NLRP inhibitor portfolio including our peripheral NLRP3 inhibitor VTX2735, which is now in Phase II trials in CAHPS patients, and a CNS-penetrant NLRP3 inhibitor VTX3232, which is expected to advance into Phase I studies this quarter. So with that, I'll hand the call over to Bill Sanborn for a more detailed pipeline update.
spk11: Bill? Thank you, Raju, and good afternoon, everyone. I'm excited to provide a brief pipeline update today and to highlight recent achievements across our portfolio. I'll begin with BTX958. As you are all aware, we are now well underway with three Phase II trials of VTX958, including the Serenity trial in moderate to severe plaque psoriasis, the Harmony trial in moderate 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 TIK2 pathways, with the top dose in each of the three trials expected to achieve approximate TROF IC90 coverage of interleukin-12 and interleukin-23. So we are really pushing towards biologic-like suppression of the interleukin-23 pathway, and we expect this to translate into differentiated efficacy closer to that observed with the anti-IL-23 antibodies. This is our expectation not only in plaque psoriasis and psoriatic arthritis, but also in Crohn's disease, where we continue to see a tremendous unmet need for a safe and effective oral therapy and where we believe our class-leading therapeutic window may afford us a strong position relative to competitors. Looking more closely at the psoriasis market, we remain very excited about the commercial opportunity for orally delivered small molecules to gain both market share versus legacy biologic therapies, as well as to continue to drive expansion of the treated population within the 28 billion projected 2023 global psoriasis market. We are particularly optimistic for the potential of the TIK2 inhibitor class and point to strong signs of early uptake for SOTIK2, the first approved TIK2 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 TIK2 inhibitors specifically to continue to expand in the coming years with the potential for greater TIK2 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 TIK2 class. As Raju mentioned, the team has done an excellent job getting the VTX958 Phase II program up and running over the past six months, and we have made tremendous progress in enrolling the Serenity Plaque Psoriasis trial. As we've stated previously, we are on track to report top-line data in the fourth quarter. We are looking forward to carrying this operational momentum into the other VTX958 Phase II trials, including the Tranquility trial in psoriatic arthritis and the Harmony trial in Crohn's disease, and we continue to expect top-line results from both of these trials in 2024. Shifting to VTX002, our S1P1 receptor modulator in Phase II development for ulcerative colitis. I think Raju put it well when he said that the goal here is to be the first to truly explore the full potential of this mechanism in ulcerative colitis. This is similar to the story with VTX958, where we talk about achieving differentiated coverage of the target pathway. You will recall that we previously shared data from our Phase II open-label extension trial demonstrating that our high dose of 60 milligrams is achieving steady-state absolute lymphocyte concentration or count reductions in the range of 70-plus percent compared to approximately 50 percent per atrazomod and supposia. 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 achieve placebo-adjusted clinical remission rates of around just 10% or slightly higher, and the anti-TNF alphas, the alpha-4, beta-7, endocrine inhibitors, and so on, all share this characteristic. There is a significant opportunity for a safe and oral therapy that can exceed this efficacy benchmark. Based on our conversations with physicians, we fully expect the S1P class will grow robustly as Supposia continues to build volume. Meanwhile, the potential approval of Atracimod is expected later this year. If we can achieve our target product profile with BTX002, which is placebo-adjusted clinical remission of around 20% or better, then we believe there's an opportunity for VTX002 to become a class leading drug in ulcerative colitis. And as we mentioned in the press release, enrollment in the phase two trial of VTX002 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 2023. Finally, briefly touch on our portfolio of novel oral NLRP3 inhibitors. On our last earnings call, we announced that we have initiated a Phase II proof of concept study of our peripheral NLRP3 inhibitor, VTX2735, and familial cold autoinflammatory syndrome, or FCAS, which is the most common subpopulation of cryopyrine-associated periodic syndromes, or CAPs. With our CNS penetrant compound, VTX3232, we expect to initiate a phase one trial in healthy volunteers this quarter. Our goal is to position both of these NLRP3 inhibitors as phase two ready clinical candidates by establishing a differentiated profile in terms of safety, pharmacokinetic, and pharmacodynamic activity. We believe that there is a wide range of high value indications for future development of both our peripheral NLRP3 inhibitor, VTX2735, and our CNS penetrant molecule, VTX3232. On the peripheral side mechanism, such indications include cardiovascular, dermatologic, and rheumatologic diseases. With regard to NLRP3 inhibition in the CNS, there's a strong biologic rationale to potentially address devastating neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, among others. In summary, this is a very exciting period for Ventix and our portfolio of novel small molecules. Execution has been strong across the pipeline. and we are very much looking forward to announcing top-line data for VTX 958 and VTX 002 in the second half of this year. Before we move on to Q&A, I'd like to hand the call back to Marty for a brief discussion of our financial results. Marty?
spk00: Thank you, Bill. You'll find details from our financial results for the first quarter ended March 31st in our press release, and I believe the 10-Q filing was also hit on the website. And I'll summarize those results here. R&D expenses were $35.4 million for the first quarter of 2023 compared to $17.4 million in the first quarter of 2022. This increase reflects the advancement of our pipeline in the later stages of clinical testing, including execution of the ongoing Phase II trial of VTX-002 and ulcerative colitis and the Phase II programs for VTX-958 and psoriasis, Crohn's disease, and psoriatic arthritis. As we previously mentioned, we continue to expect R&D expenses to increase directionally throughout 2023, with some quarter-over-quarter variability expected as our Phase II trials progress and as we conduct our CMC activities in preparation for the potential launch of Phase III trials on 002 and 958 in 2024. G&A expenses in the quarter were $7.1 million versus $5.3 million in the first quarter of 2022, and the net loss in the first quarter of 2023 was $38.9 million compared to $22.7 million for the first quarter of 2022. Cash, cash equivalents, and marketable securities totaled $376.9 million as of March 31st. This reflects an increase from our end-of-year cash and equivalents balance of $356.6 million and reflects proceeds from the sales stock on our ATM facility, which occurred during Q1, offset by our first quarter cash spend. And we continue to believe that our current cash, cash equivalents, and marketable securities are sufficient to support planned operations into 2025. With that, we conclude our prepared remarks for this afternoon's call. I'll turn the mic back over to Angela to begin the Q&A session, where I'll be joined by Raju and Bill. Operator?
spk07: The floor is now open for questions. At this time, if you have a question or comment, please press star 1 on your telephone keypad. 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.
spk05: Hey, guys. Thanks for the question. Thanks for the updates. We had two areas we wanted to ask on. The first was actually on the S1P1. I know you have data coming up later this year. There have been some studies that I've read out recently, you know, had no placebo. 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. Can you just remind us, are you testing multiple different technologies in that or is that one technology at different doses? Thank you.
spk14: Yeah, excellent. Thanks, Mike. Good to hear from you. Let me have Bill talk about the S1P1 and trials and placebo, and then I'll come back with the ER tablet.
spk11: Yeah, so it's a good question, Mike. You know, I think that trials without placebo arms that are not controlled are not easy to interpret, and so, you know, you just have to take those data with a grain of salt. Placebo rates can vary. The average placebo rate in moderate to severe ulcerative colitis trials is about 7.5% or 8%. It can sometimes be as low as 2% or 3%, and it can be as high as the low teens. More or less, the way you try to manage for this is to keep good control of the trial, to monitor the disease characteristics of the patients that are coming into the trial, and we do that robustly. You can also sort of monitor the outcomes and pool blinded data to see 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 the trial very carefully as it has progressed.
spk14: Good.
spk05: Anything else on that, Mike? They're helpful. They're helpful. And then on the ER tablet, shed some light on that, what's going on with different technologies.
spk14: Yeah, so on the ER tablet, yeah, 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. So what we do is we use one technology to make sure we're sort of using biorelevant dissolution methods, which is what's happening in the dissolution absorption phase in humans. And then we complement this with a technology that actually simulates what's actually going to happen, the 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 a better word, checking a box 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've simulated what you see both in terms of dissolution fluids and and dissolution rate, and also absorption distribution in terms of what actually happens in a system where you've got, you know, bile salts and motility, all of those factors. 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 III. Thank you. You're welcome.
spk01: Thank you. Our next question comes from Yasmin Rahimi with Viber Sandler.
spk09: Good afternoon, team, and thank you so much for all the great updates. Two questions for you. Maybe the first one is to start off on S1P1. I know most of the analysts and investors are very familiar on what the bar is in regards to efficacy into that data readout in the second half, but maybe what would be helpful is Dr. 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 one. And then question number two is, you know, tomorrow morning we're going to see, you know, some Phase 1 data from the IL-23 oral product and And would love to, you know, as we're looking at that data, think about how you guys are, like, I guess, could we look at that and being able to predict sort of what the, I guess, the comparisons or the TIC-2 class versus the IL-23 class could offer, obviously, just based on phase one data. And I'll jump back into the queue.
spk14: Yeah, so let me address the the protagonist question. Yes, and again, good to hear from you. So, yes, the phase one 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. I think the PKPD itself might be illustrative to some extent. But the real meat is going to be in the Phase II data and how it compares to what we've seen with, you know, drugs in this class, the biologics, and the orals that have come out recently. So, you know, it's really, you know, difficult to speculate on something we have no idea about. And you and I have talked about the press release that came out early on. So I think let's wait for this data. Let's look at the EKPD. 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 add it over to Bill for the S1P1 question.
spk11: Yeah, so just to frame the perspective, remember that the S1P class of medications has had regulatory approval in the United States since 2010 when Gilenya was approved for multiple sclerosis. And there's about a million patient years of exposure with Gilenya and their marketed dose has lymphocyte reductions in the low 70s, which is exactly where we are targeting for the higher of our two 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-understood class of drugs with respect to all the potential safety issues. The second thing is to say is that, you know, we'll be releasing 13 weeks of safety data, and so, you know, that's a limited period of time. So, you know, it's not typical that you see a lot of important, what I would say are big-ticket adverse events anyway in an early trial, but, you know, the data will be what they are. As you look specifically, what you like to see for drugs that are effective, typically and well-tolerated, you typically will 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. 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 investigator. So we'll look at all those things. And then narrowly in the S1P1 class, you can see heart rate reductions and AV blocks, and those can be substantially mitigated with dosing titration regimens, and we think we have a good dosing titration regimen. So seeing what the rates of bradycardia is in the first 13 weeks by treatment group and seeing if there are any cases of AB block and those sort of things, those will be of interest and would allow comparing and contrasting with other products which may or may not be The other things that you see with S1P drugs are generally, you know, rare and you're not likely to see in a Phase II induction study.
spk09: Thank you so much, Dr. Sandberg, for your comments.
spk07: The next question comes from Derek Archillo with Wells Fargo. Please go ahead.
spk10: 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 TIK2 class, even at IC90 coverage. I guess, you know, some folks point to this Pfizer molecule, which allegedly had IC90 coverage for 24 hours, and their 12-week data looking fairly similar to Ducrava and and Decatur's drug at POSI-75 and POSI-90. 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? And any color on the split you would expect for advanced therapies versus naive would also be helpful. Thanks.
spk14: Yeah, Derek, good question. And, you know, we've seen some of that analysis out there. So, you know, 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 in terms of coverage or model coverage in IC70s, 80s, and 90s that people have put out there in particular. And let's get outside the Pfizer compound. Let's focus on some of the analysis that's been done for CITIC2 and for the two Takeda doses that have been done. And look, cross-trial comparison with CITIC2. small number of folks is really challenging. But, you know, the data are what they are, right? I think our belief is that within those three examples, again, we'll leave Pfizer out of there. So the CITIC-2 12-milligram dose that people are using to model out the IC50 coverage for about 18 hours, I think, and the TAC-279, which is the IC70 for for 24 hours, and this is data that's been put out there. I think it's pretty consistent with what you can read from the various NIMBUS disclosures. Thirty milligrams is IC80, right? Now, what we've said is we are going into our Phase II trial, in particular for psoriasis, with trough coverage of IC90 at our top doses. and then significant coverage 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 fourth quarter, and we'll see, you know, an 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. So that really is the crux of the argument. We're going in with maximal coverage, and we hope to show differentiated efficacy from what you've seen here. So again, yes, I've seen the analysis. We've seen the analysis, and this sort of always leads to this flattering effect, in particular when people are sort of myopically focused on PASI-75. 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?
spk11: Yeah, 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 75, 90, and 100. And in Phase II trials, you can have outliers sometimes. So, for instance, if you look at the highest dose of the Takeda product in Phase II, the PASI 100 is in the zone that you would see with full biologic coverage, but the PASI 75 and 90 were not. 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 an antibody-like efficacy because with antibodies, as you dose down, you will see left shifts of all the efficacy across the PASI 75, 90, and 100. And if 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 the expected relationships for PASI 75, 90, and 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 II trial. We've conducted it relatively quickly, and that's what it looks like. From a monitoring perspective, what we do will be, as we have pooled blinded data, we you can stratify patients for high enrolling sites versus non-high enrolling sites, specific high enrolling countries versus rest of world, advanced therapy naive versus advanced therapy failure. 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 the rest of the world. So I think we're conducting a robust trial. 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 perspective, I'm very pleased with the consistency of the data.
spk10: Got it. Understood. Super helpful. Thank you, guys.
spk11: Yeah, thanks, Derek.
spk07: The next question comes from Alex Thompson with Stiefel. Please go ahead.
spk06: Yeah, great. Thanks for taking my questions. For timelines for the rest of this year, I think previously you had mentioned that you expected 002 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 spend. Thanks.
spk12: Yeah, so for S1P1, we probably guided people to –
spk14: 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, fourth quarter. So late fourth quarter, I would probably guide people.
spk00: Hey, Alex. It's Marty. Yeah, so our cash run was expected to carry us into 2025, and what's included in those assumptions then is completion across all the Phase II studies that Bill spoke about today on the call. So that's the CAPS trial for 2735, the psoriasis, psoriatic arthritis, and Crohn's trials for 958, as well as the UC trial for 02. We anticipate being able to complete the Phase I trial for VTX3232, our CNS-directed NLRP3 inhibitor, and we expect to be able to produce materials and conduct necessary kind of like pre-Phase III trial costs around CMC and things like that. Getting into 2025 obviously does not necessarily get us through completion of any of the Phase III trials we might be running. Based on data we get out of our Phase II readouts later this year.
spk06: Great, thanks.
spk13: Yeah, thanks Alex.
spk07: The next question comes from Chris Shibutani with Goldman Sachs. Please go ahead.
spk04: Thank you very much. Two questions, if I may. The first, I believe on clintrials.gov with the Phase II 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? And if so, what drove this decision? Or is it just an updated aspect of the posting and the study has always been designed this way? And then secondly, reflecting on the TIK2 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 two. This has played out. Can you talk about your impressions and if this has any influence on your thinking going forward on Crohn's? And then secondly, with Sir TIK2's commercial performance, They recently talked about how that's done relative to Otesla. I think they talked about a 40% versus 60% share. How has this performance compared with your expectations? And maybe share with us your views updated on the commercial opportunity as a result of how Sotictu is delivering thus far. Thank you.
spk14: Chris, those are three questions, not two. Two A, two B. Yeah. Let me have Bill comment on the CLIN trials and
spk11: For the study design, when we initially did the regulatory filings, we had toxicity coverage, tox study coverage for up to 16 weeks of therapy. The trial was designed with that in mind and the primary endpoint was and remains week 16. Subsequent to that, we have had sufficient long-term or chronic tox data to extend the duration of treatment beyond the 16 weeks, and we went through the regulatory filing process for that, and the clinicaltrials.gov update indicates that we'll do another year of therapy. So it was just availability of supporting data. With respect to Crohn's disease and TIK2, I don't think that we always expected that the outcome of the study would be negative. We know that with IL-23 antibodies that you need doses that will plateau at a high level, PASI 75 and the 85 to 90 percent range, you need at least those doses, if not higher, to see efficacy in Crohn's disease. And, of course, the SOTIC2 dose that was studied was well below that and had estimated IC50 coverage of about 16 hours and IC90 coverage of zero hours. 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 show strong efficacy in Crohn's disease as well. So it doesn't change our thinking at all. We completely factored that in.
spk04: And on the commercial?
spk14: Yeah, on the commercial side, we'll keep it brief. So, of course, we've just recently hired a head of commercial here with our forward thinking across our trials and you know, looking beyond the psoriasis trial and other indications as well.
spk13: I think this, you know, Tesla analysis for what it is, first, the analyses always lag, and now we've begun our own discussions as part of our commercial planning with prescribers and KOLs. You know, there's a huge amount of excitement in this class of drugs, right? Big, big market. It's you know, an oral, which is clearly differentiated from a Tesla, I think the market will grow. It's going to benefit us as we come into the market, as we move along our trials. And I think with the drug, with TIC-2 class, with safe drugs, with efficacy that's comparable but certainly better than what's been shown with TIC-2, I think the market would appreciate that. So we continue to feel very bullish about this class, and the prescribers that we're talking to now are bullish about the TIK2 inhibitors. So I think we just have to, you know, it's still relatively early days from the launch, and I think we have to just appreciate what's happening in terms of not just Otesla, but what's the whole prescribing ratio in terms of biologic patients, naive patients, and folks that are switching from Otesla.
spk04: Anything else to add, Bill? Great. Thank you for sharing your thoughts.
spk14: Of course.
spk07: The next question comes from Emily Bodnar with HC Wainwright. Please go ahead.
spk08: 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 VTX958. And then maybe also if you can comment on VTX2735, how you kind of plan on determining which indications you might want to take that asset into following the phase two cap study. Thank you.
spk13: Yeah. So, again, I think Bill has addressed, he's discussed this before in terms of the TIC-2 and UC, the second trial they're running. Why don't you take that first, and I'll come back to it.
spk11: You know, it's not public to my knowledge exactly what the dose is. You know, 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 zero hours of IC90 coverage, and I'll remind all of us that 78% of patients had skin organ class toxicity on that dose, so it was really not tolerable. So, there have been rumors that they're studying 8BID or 10BID or even 12BID. It's difficult to imagine it's 12BID 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 just to remind us, what you also see is that the effect size with anti-L23 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.
spk02: So the Lilly Phase III program showed that 10% gain over placebo with mirakizumab and both AbbVie with risin-kizumab and Janssen with gasecumab have recently reported 14% better than placebo in their Phase III studies in ulcerative colitis for induction studies.
spk13: As I recall, the
spk11: the, quote, high-dose Ducravacitinib studies, 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 tick-2 inhibitor inhibitor that has IC90 for 24 hours, you'd be trying to show a 14% difference with 40 patients per arm. That's not going to work. So I predict it will fail.
spk13: All right. There you have it. So for MLRP3, As we said in our R&D day, you know, our goal for this year, for 2023, is to position both molecules, 2735, 3232, as phase two ready compounds.
spk14: With respect to 2735, this is a peripheral compound. We believe this is the best in class NLRP3 peripheral molecule out there. So we've done the phase one, we announced the phase one data last year, we've done the TOCS work, we've done the CMC work to support the phase two trial. What we also are very clear about this last discussion was with our focus on driving the phase two trials for TIK2 with 958, with our focus on the UC trial for 002, we would sort of shift the focus from 2735 towards the end of the year
spk13: Again, this will be a phase two ready molecule. We have previously shared the excitement across a number of disease indications where IL-1 beta and IL-18 have been implicated in a lot of sort of validation from different trials out there, in particular from the biologics. So we'll make a decision towards the end of the year with this phase two. 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 just in these as phase 280 compounds, focus on delivering on our promise with both trials for UC and for OO2.
spk03: So just stay tuned for 2735. Great. Thanks so much. Yeah, you're welcome.
spk07: The next question comes from Sam Slutsky with LifeSci Capital. Please go ahead.
spk02: Hey, good afternoon, everyone. Thanks for taking my questions. Two quick ones for me. One, on the oral IL-4 response, 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 receptor alpha to be effective?
spk13: So, again, we are not going to go into too much detail on that program, Sam. As you know, it's we're one of the few folks that has sort of embarked upon this challenge. We've disclosed our lead, just sort of a little, little data on our lead compound in terms of the excitement we have. Obviously we're going against a extremely successful drug out there, dipilumab, dipixent. I would say just stay tuned. We're moving along the lead-up program here. We've got 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.
spk02: And then just lastly, for the phase one study with VTX3232, since you plan to take that into neuroinflammatory indications, just curious on how you're thinking about measuring the PD effect and then what you would want to see with that for a CNS drug.
spk03: Yeah, good.
spk13: Great question. So, You know, there's really no precedent for, or there's no data for any LRP3 that's been taken into a Phase I or a Phase IB trial. There was indication that the inflasome compound had been taken. 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. It has a really good CNS penetrant profile in terms of, you know, KPUs, the KPU
spk14: Profile in terms of, you know, KPUs, the distribution across the CSF, what we expect to be the free fraction in the tissue fluid in the brain. So our goal for the phase one study, it's a two-part goal. First is to do a phase one 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. So that's part one.
spk13: What we're actually looking at now, and we will disclose our final intent, is looking at potentially looking at biomarkers in a phase 1B trial, as well and as you know that it's very complicated and we have to make sure we understand what we're looking for and calibrate that before we do something like that. But again, we feel very confident that a phase one standalone with efficacy PK in particular looking at exposure in the CSF is a very relevant path forward for the eventual development of this compound in longer Phase II studies.
spk14: Again, the precedent for looking at CSF levels and calibrating those to brain levels as well.
spk13: I think in terms of biomarkers, of course, the ultimate biomarker for NLRP3 activity is IL-1 beta, but again, we're also be conscious 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 the duration of these trials. They're really meaningful in terms of what would guide us through a phase two trial. So stay tuned for 3-2-3-2 news coming out. Of course, we're, you know, as we said, we're going to dose the phase one healthy volunteers in this quarter. We'll talk more about that future of the Phase I trials and 1B trials in later discussion.
spk02: Got it. Thanks. Yep, you're welcome.
spk07: Thank you. I would now like to turn the call back to Dr. Raju Mohan for some closing remarks.
spk13: Yeah, well, again, thank you all. You know, we just spoke a few weeks back. It's always great to get together with you all and address the questions. Very thoughtful and appreciate the interest in our programs. And so, you know, we'll see you guys again in a few months. So thanks again. And thanks to the team.
spk07: This concludes today's Ventex Biosciences first quarter 2023 earnings conference call. Please disconnect your line at this time and have a wonderful day.
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