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spk00: Good afternoon, ladies and gentlemen, and welcome to the Vintex Biosciences second 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 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. Marty Oster, Bintex's Chief Financial Officer. Sir, you may begin.
spk04: Thank you, and good afternoon, everyone. Welcome to Ventex Biosciences Conference Call and Webcast, where we'll be discussing our second quarter 2023 financial results and providing a business update for you. As a reminder, the company's most recent investor presentation can be found on our website at www.ventexbio.com in the Investors News and Events section. Before we begin today, I'd like to remind everyone that 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, anticipated timing of release of clinical trial data, the market opportunity for our product candidates, and the expected timeframe for funding operations with our 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 recent periodic reports filed with the SEC, including our Form 10Q for the quarter ended June 30, 2023, which filed just a few minutes ago. 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, except as required by law. With that, I'll hand the call over now to Dr. Raju Mohan, Dentix's founder and CEO. Raju, please go ahead.
spk07: Thanks, Marty, and good afternoon, everyone. Thank you for joining our second quarter 2023 financial results conference call. It's hard to believe that we're already in August and how the first half has flown by. As you may have recalled from the R&D discussions in January and from our recent press releases, it's been a tremendously productive first half of the year for Rentex, and I am very proud of our team's execution across the entire pipeline. So let me run through this afternoon's agenda. I will begin by providing a high-level business update And then I'll hand the call over to Bill Sanborn, our President and Chief Medical Officer, who will provide updates across our drug development programs. And finally, Marty will present an overview of our second quarter of 2023 financial results before opening the call for Q&A. So let me start by saying at DENTX, we've always believed that novel oral therapies are poised to play a significant long-term role in the treatment of numerous immune diseases indications that are currently dominated by injectable biologics, including indications such as psoriasis, inflammatory bowel disease, psoriatic arthritis, lupus, and others. These large but under-penetrated markets currently exceed over $50 billion in annual sales, and we believe that as clinicians and patients are offered the choice of using a pill, an oral drug, instead of an injectable therapy, there is the potential for a meaningful shift in market share, as well as a general expansion of the treated populations in each of the diseases I referenced earlier. We have seen an overall increase in excitement around the promise of oral therapies, encompassing different targets and indications. And we believe that our portfolio of internally discovered compounds positions us at the forefront of this revolution in oral therapies. And I am proud we are currently conducting five phase two trials across our wholly owned pipeline of novel small molecules. Let me begin with the compounds. As you know, our allosteric TIK2 inhibitor VTX958 is in phase two development for plaque psoriasis, Crohn's disease, and psoriatic arthritis. All diseases where TIK2 plays a direct role in modulating IL-23, a key cytokine implicated in the pathology of disease progression. As previously discussed, We are aiming to achieve sharp coverage of TIK2-IC90 at the highest Phase II dose across all the trials. In June, we announced that we completed patient enrollment in the Phase II serenity trial of PTX958 and moderate to severe plaque psoriasis. This is an important milestone for Ventix, and I'd like to thank our entire team for all their efforts. With enrollment now complete, We look forward to reporting top-line data from the Phase 2 serenity trial in the fourth quarter of this year. On the development of an extended release tablet, ER tablet for VTX958, we continue to make progress towards the target product profile and remain confident that we will have an optimized, once-daily tablet to advance into Phase 3 trials in 2024. As previously discussed, our development strategy incorporates an iterative process that allows us to sequentially evaluate multiple prototype formulations in humans. We look forward to providing a detailed update in the fourth quarter. In June, we announced that we completed enrollment in the ongoing phase two trial of VTX002 in patients with moderate to severely active ulcerative colitis. I'd like to again congratulate the Ventix team on this important milestone. We look forward to reporting top-down results from this trial early in the fourth quarter of this year. We believe we are the first company to demonstrate a greater magnitude of reduction in absolute lymphocyte counts, or ALC, relative to adrazumab and ozonamab in similar Phase II trials. We believe we are exploiting the full potential of this mechanism by a greater reduction of ALC validated by a marker and believe that this may translate into differentiated efficacy relative to other drugs developed for ulcerative colitis. Our aspirations for this asset have always been very clear, which are to demonstrate efficacy in moderate to severe UC patients that is 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 UC. And Bill will provide more color on progress of this trial. Beyond these lead programs, we continue to advance our novel NLRP3 inhibitor portfolio, including our peripheral compound VTX2735, which is now in phase two trials in CAHPS patients, and our CNS penetrant NLRP3 inhibitor VTX3232, for which we recently announced initiation of dosing in phase one trial in healthy volunteers. So in summary, I'm very proud of our team's execution during the first half of the year. and we look forward to generating important Phase II data for both VTX002 and VTX958 in the fourth quarter. So with that, I'll hand the call over to Bill for a more detailed pipeline discussion. Bill?
spk06: Thank you, Raju, and good afternoon, everyone. I'm excited to provide a brief pipeline update today and to highlight recent progress across our portfolio. I'll begin with our allosteric TIK2 inhibitor, VTX958. you will recall that we have three ongoing Phase II trials for VTX958, the Serenity trial in moderate to severe plaque psoriasis, the Harmony trial in moderately to severely active Crohn's disease, and the Tranquility trial in active psoriatic arthritis. As Raju mentioned, we announced in June that we completed a patient enrollment in the Serenity trial in plaque psoriasis. The Serenity trial includes a target enrollment of approximately 200 patients randomized to one of four VTX958 doses or two placebo, and the primary efficacy endpoint is the proportion of subjects achieving PASI75 at week 16. As previously disclosed, we are exploring multiple dose cohorts in this phase two trial ranging from an anticipated minimally therapeutic dose at the low end to a high dose that is expected to achieve TIK2-IC90 coverage at trough as measured by IL-12 and 23. Our team did an excellent job enrolling this trial in around six months, with enrollment now complete, and we are very excited to report top-line data from the Phase II serenity trial during the fourth quarter. In addition to the Serenity trial, we continue to make progress in rolling the Harmony trial in Crohn's disease and the Tranquility trial in psoriatic arthritis, and we expect to have more to say about our progress on these trials before the end of the year. Now moving to VTX002, our potential best-in-class S1P1 receptor modulator in development for ulcerative colitis at the Phase II stage. Recall that we have previously shared data from Phase II open-label extension demonstrating that our high dose of 60 milligrams is achieving steady-state absolute lymphocyte count reductions in the approximately 70% or more range as compared to approximately 50% for a Trasomod and a Xanamod. And our thesis remains that this differentiated pharmacodynamic effect may translate into improved efficacy in ulcerative colitis based on our analysis of consistent observed efficacy-driven dose response across both ulcerative colitis and multiple sclerosis trials evaluating S1P1 receptor modulators. As Raju mentioned, we announced in June that we completed enrollment in the ongoing Phase II study of BTX002 in patients with moderately to severely active ulcerative colitis. This trial includes a target enrollment of approximately 180 patients randomized to one of VTX002 doses or placebo for a 13-week induction treatment period followed by a 39-week blinded long-term extension period. The primary endpoint is the proportion of subjects achieving clinical remission at week 13 as defined by the modified Mayo score. I want to join Raju in congratulating the team on this accomplishment. It is no small feat to enroll a large Phase II ulcerative colitis trial in a challenging and dynamic environment, and I'm grateful for the dedication and perseverance of our team. We are now looking forward to reporting top-line data from this trial early in the fourth quarter. We expect to report Phase II top-line data for VTX002 and ulcerative colitis ahead of the Phase II top-line data for VTX958 and psoriasis. Finally, I'll touch briefly on our portfolio of novel NLRP3 inhibitors. We announced in June that we had initiated dosing in a phase one trial of our CNS penetrant, NLRP3 inhibitor, VTX3232, in healthy volunteers. This is a two-part, single ascending and then multiple ascending dose trial designed to evaluate the safety, tolerability, and pharmacokinetics, and pharmacodynamics of VTX3232, including serial cerebrospinal fluid sampling to assess CNS exposure. We have a Phase II proof-of-concept trial underway with VTX2735 our peripheral NLRP3 inhibitor, and familial cold autoinflammatory syndrome, or FCAS, which is the most common subpopulation of cryopyrin-associated periodic syndromes, or CAPs. I'll reiterate that with both of our NLRP3 inhibitors, our goal is to establish a potential best-in-class profile in terms of safety, pharmacokinetics, and pharmacodynamics, and to ensure that these compounds are Phase II ready. We believe that this approach will create strategic optionality and will unlock the value of these programs in a wide range of indications for future development. With peripheral NLRP3 inhibition, this includes large cardiovascular, dermatologic, and rheumatic disease indications. And with NLRP3 inhibition in the CNS, this includes neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, among others. In conclusion, this is a very exciting period for Ventex with important top-line Phase II data for VTX002 and VTX958 just around the corner in the fourth quarter of this year. I'd like to thank our team again for their efforts during the quarter. Before moving on to question and answer, I'll hand the call back to Marty for a brief discussion of our financial results. Marty?
spk04: Thanks, Bill. So you'll find more detail on our financial results in the press release issued after the bell today, as well as in our 10Q, which filed also after market closed today. um i'll summarize the second quarter results briefly here though r d expenses in the quarter were 48.6 million compared to 14.7 million in the second quarter of 2022 and this reflects the advancement of our pipeline into later stages of clinical testing including the execution of the ongoing phase 2 trial of vtx02 and ulcerative colitis and the broader phase 2 program for vtx 958 with phase 2 trials being conducted in psoriasis crohn's disease and psoriatic arthritis G&A expenses were $8.6 million for the second quarter of 2023 compared to $5.7 million in the year-ago period, reflecting growth of the company, and net loss of $53.3 million for the second quarter of 2023 compared to a net loss in the second quarter of 2022 of $20.0 million. Cash, cash equivalents and marketable securities were $332.3 million as of June 30th, 2023. This compares to $376.9 million in cash, cash equivalent and marketable securities on March 31st of 2023. We continue to believe our current cash equivalents and marketable securities are sufficient to support our planned operations into 2025. This concludes our prepared remarks for the afternoon's call, and I'll now turn the call back over to the operator to begin the Q&A session. And I'll be joined by our CEO, Richie Mohan, President and CMO, Bill Sanborn, and our CBO, Chris Krueger. Operator?
spk00: Thank you, sir. At this time, the floor is now open for questions. 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. And our first question will come from Michael Yee with Jefferies.
spk11: Hey, guys. Thanks for the question, and thanks for the updates today. Maybe a two-part question on the upcoming TIK2 results for you. I know a lot of people kind of point to Bristol's data, BID dosing, you kind of get to 67, 69% positive 75. You look at some of the Nimbus data, I guess they were in that range and then at 33% positive 100. How do you think about where you want to be relative to the profile of some of those? I guess higher the better, of course. But what would you want to see there to say, hey, look, we're better at cross-talk person? And then the second part of that is what does that lead you to believe for Crohn's, which would then follow that? And maybe it's the PD marker of IL-13. So maybe Bill could walk through what you see in psoriasis and then how does the IL-13 data play into that to give you confidence on Crohn's. Thank you.
spk07: Yeah, thanks, Mike. So, yeah, Bill, why don't you walk? You can take both of those.
spk06: Yeah, so I think in terms of where we would like to arrive, really if we get into the zone that the Nimbus Decatur product achieved, especially where you see the PASI 100 up into the 30s, that's really getting up into a solid area of efficacy for an oral agent, and that's generally the zone that was seen recently with the protagonist, Janssen, oral IL-23 antagonist as well. So, and then every, but all of these are somewhat short of what you see with the monoclonal antibodies to IL-23. And so I think, you know, that the aspirational floor has been set with some of these other oral sort of second-generation agents, and you want to hit into that zone, and above that would be further differentiating. So that's sort of how we see it and where we would hope to land as a low-water mark.
spk11: And then how about what the read-through data is to Crohn's, and is it the PD data that you see, or maybe just clarify that. That gives you the confidence.
spk06: Yeah, I mean, you know, we're, of course, speculating on read-through to Crohn's, so what we know is that with Ducravacidinib, doses of six twice a day or 12 once a day have not been effective in for ulcerative colitis and Crohn's disease. And of course, those total daily doses or regimens are both twice the six milligrams once a day dose that's approved for psoriasis with sort of moderate efficacy. And then we know with biologics, with inhibition of either interleukin-12-23 with Stelara or inhibition of interleukin-23 alone with Guy Razier, Kempfaya, and Mirakishimab and others, that the doses that have been required to optimize efficacy in Crohn's disease are higher than the doses that sort of plateaued efficacy for psoriasis. So it's reasonable to speculate that you would need that more intense target coverage for Crohn's disease as well, with blocking interleukin-23 and interleukin-12 with TIK2 inhibition. We, of course, need to generate primary data to show that, and our trials are designed to do that. So while we have four different active dosing groups in the psoriasis trial across a wide range of doses and exposures, as I described a few minutes ago, in Crohn's disease, we have just two active doses, and they're the two highest active doses from the psoriasis trial, so we're emphasizing high exposure with the hypothesis that greater exposure will be required in Crohn's disease, and we anticipate being able to read that Crohn's trial out next year. Thank you.
spk00: Thank you. Our next question will come from Alex Thompson with Stiefel.
spk08: Great. Thanks for taking my questions, and congrats on the progress. I guess Two for me. Firstly, on the QD formulation, I wonder if you could comment on what has been driving the delay here from the mid-year update to Q4 and how much more buffer you have to get a QD formulation for phase three studies next year. And then for the two phase twos for ulcerative colitis and psoriasis, I wonder if you could comment on whether discontinuation rates are tracking within your expectations. Thanks.
spk07: Yeah. So, you know, I'll say the disclosure of the data are Goal will always be to complete, develop by the end of the year, Alex, and leave ample buffer. So you've got ample buffer to complete the prototype development. The real actual selection of Phase 3 QD tablet happens after the data comes out from Phase 2 to understand exactly where we line up with the doses and the dose for Phase 3. So we've always built that in. There's plenty of buffer. Now, as we outlined in the R&D day, when we introduced the program to you guys, we had a strategy that sort of iterative process, you build and test in humans, establish a relationship between the ER dose, ER prototype and the IR dose, plus multiple formulations that we're doing and testing them in human studies. It's really important for us to get it nailed, to have the right final formulation before we begin to make disclosures as we expect. This formulation will be the drug that we take into phase three, and that's the goal. And submit for reg approval, clinical trial work's all worked out. First of all, there's plenty of buffer. We always plan to get this done by the end of the year in time of the Phase 2 data coming out and then use that prototype to then actually get the actual tablet made, manufactured, regulatory stability, ready for Phase 3 start. So there's no impact on Phase 3 start. And so, you know, we're really confident in the process. We believe we made real progress towards achieving the target profile. But honestly, we recognize that our earlier timings of data release was probably a little over-optimistic. So we're looking forward to sharing more details with you in Q4. But the key emphasis is there's no impact to Phase 3. We've always built in the buffer, and that includes manufacturing, regulatory, stability, packaging, and mailing. So just, you know, stay tuned for an update somewhere between now when we have the phase two data, probably closer to more of the, when the phase two comes out.
spk09: Yes. Um, so I think we,
spk06: It wouldn't be appropriate to give granular, really clinical trial data, which is what a specific conversation about that would be. What I would say is these are both sort of shorter-term or induction trials, if you will, but the ulcerative colitis trial is 13 weeks in duration to the primary endpoint. And the psoriasis trial was 16 weeks. From an interpretability standpoint, what is typical from a statistical standpoint is if you have patients that discontinue therapy prematurely, and typically both ulcerative colitis trials and Crohn's psoriasis trials, we'll have some of those. For the dichotomous outcome measures, the patients with missing data are treated as failures, so you actually don't lose any statistical power in the analyses with any patients that do require discontinuation. So I think we're well set up in a very conventional fashion to manage any patients that would discontinue, but we I won't make any comments beyond that. Great. Thank you.
spk00: Thank you. Our next question will come from Vikram Truitt with Morgan Stanley.
spk02: Hi. Good afternoon. Thanks for taking our questions. Two from our side. First, we'd just love to get your thoughts on particular commercial performance to date and how it's impacted, if it has your view of the commercial opportunity for a therapy like 9582-ISIS. And then secondly, maybe a question for Marty. Could you just remind us what level of pipeline development is contemplated in your current cash guidance and runway and how far the runway gets you for the current set of new programs? Thanks.
spk07: So maybe Marty can take both questions and start with the commercial SITC2 sort of thing and then go back to the second one.
spk04: Yeah, this is a rare treat to get both of them. Thanks, Vikram. So in terms of SITC2 commercial performance, I think we're quite encouraged by the early days of SITC2. Obviously, Bristol has been providing services quarterly updates about their commercial performance in the space. They're getting substantial significant market share relative to the other approved oral therapy on the market in psoriasis. They're continuing to kind of see share coming from all different avenues, which is highly encouraging. That includes sort of treatment-naive to systemic therapy patients in psoriasis. conversions from the other oral therapy at Tesla, conversions from patients currently taking BioObject who are seeking to get off of injectables and over to oral, We think long-term about the market opportunity here. This is a $25 billion global class of therapeutics. We think that oral agents overall are going to play a very significant and substantial meaningful portion of that market. Currently, the oral portion of that market is just about 10% or so. We think that's going to grow meaningfully from here. We think TIK2 is going to be a major player within that class, obviously, with the and then obviously our own development and other TIC2 patterns we think look attractive that are coming online in the next several years. So I think it all looks pretty favorable. Shifting over to the cash guidance question, Vikram. So our cash guidance is forecast to bring us into 2025. And what that includes then is sort of phase three prep work and the ability for us to kind of be able to be on track for phase three launches in 2024 for both the VTXO2 ulcerative colitis program as well as for VTX958 and psoriasis. It includes completion of the VTX958 phase two programs in Crohn's disease as well as in psoriatic arthritis, both of which we're expecting to report data in 2024. It includes completion of the phase one SADNAV that Bill described earlier for VTX3232, our CNS-directed NLRP3 inhibitor, as well as our phase two proof-of-mechanism trial in CAPS patients with 2735. It does not, you know, obviously then get us through completion of those phase three trials for psoriasis or UC, but allows us to kind of being positioned to commence and allows us to complete all the other ongoing clinical work that's happening now. If we continue to kind of advance, obviously, we'll have additional capital needs eventually. Understood. Thank you.
spk00: Thank you. Our next question will come from Yasmeen Rahimi with Piper Sandler.
spk05: Hi, this is Jungu speaking in for Yasmeen Rahimi at Piper. Thank you for taking our questions. Our first question is, as we will be eager to do our comparisons of serenity to other oral psoriasis agents, which PAGI score, in your view, is the most reflective of drug activity and dose ranging? Second, what type of activities have been completed in regards to Phase III PrEP across VTX958 and VTX002? Thank you so much.
spk07: Yeah, I'll deal with the second question, and I'll have Bill address the first one. So as we guided in the last earnings call, we've initiated all necessary activities around phase three prep for both programs. So this includes CMC work, drug substance, drug product, regulatory preparation for end of phase two meetings, all of the clinical studies that are needed to support that certain domain pk study so all that has been well planned and it's been on track again uh you know we're planning for uh data release in the fourth quarter and then moving on seamlessly to phase three starts so yes all all all necessary activities there'll be no delay due to anything that was not planned or executed both on the cmc side the right side the clinical side and all the other planning of those goes to these trials So, Bill, why don't you address the first one, first question?
spk06: Sure. So, what is the utility of the different PASI outcome measures for Phase II dose finding? You know, we have both Phase II data fully published with, so TIC-2 and in abstract form with the TICATA Nimbus product. But we also have Phase II trial data with a number of the anti-IL-23 antibodies. And what you see across both the TIK2 inhibitors and the antibodies is that, first of all, we know that psoriasis is exquisitely sensitive to IL-23 inhibition. So you see relatively high levels of, respectively, of PASI 75, 90, and 100 inhibitors. as you go up on dosing. But I would say the most sensitive outcome measure seems to be PASI-75. And you will sometimes see sort of a blending of several dose groups across a range of three or four doses for PASI-75. And then as you go up PASI 90 and especially PASI 100, that seems to be more specific or differentiating. So the absolute rates of achieving PASI 100 in particular will be lower, often half or less of what it is with PASI 75, and that tends to separate groups better, and that was seen both with TIC-2 at the 12-milligram once-a-day dose in Phase II and with the Nimbus Decata product at the 30-milligram dose that each of the highest doses and highest exposures had the greatest achievement of PASI-100. So that's sort of how we see it.
spk05: Very helpful. Thank you so much.
spk00: Thank you. Our next question will come from Derek Arcilla with Wells Fargo.
spk03: Guys, thanks for taking the questions and congrats on the progress here. Just two quick ones from us. I guess first, can you just remind us how we should be thinking about the geographical diversity from the Phase 2 trial with BTX002 in terms of like number of U.S. sites versus ex-U.S. sites? And then maybe I missed this in the prepared remarks, but I guess when are we going to see the data for VTX2735 and how are you thinking about prioritizing either indications or potentially partnering that asset in the future? Thanks.
spk07: Bill, why don't you take both of them and then maybe I can add to the future of VTX2735. Why don't you begin?
spk06: Yeah. For geographic diversity, inflammatory bowel disease trials, whether it's ulcerative colitis in the case of VTX002 or Crohn's disease in the case of VTX958, you really require a lot of clinical trial sites as you get into phase two and you're requiring anywhere from 132 patients target enrollment for Crohn's disease or 180 patients target enrollment for the now enrolled ulcerative colitis trial. So those end up being multiple countries and worldwide development programs. It's typical to have greater enrollment in Eastern Europe, but to have enrollment in Western Europe and North America as well. we are in all of those jurisdictions in the ulcerative colitis trial. I think we won't get into details about exactly the distribution of the trial sites, except to say it's pretty conventional for a Phase II trial, and I feel very comfortable with the geographic mix that we achieved, and we'll report that when we report the data in the fourth quarter. And then for For VTX2735, our peripheral NLRP3 inhibitor, we reported a year ago in June the phase 1 SAD and MAD data, and then we have an ongoing sort of phase 2A trial in CAPS, as I mentioned. We do have patients that are now enrolled in the trial. And, you know, remember, this is an ultra-rare disease. There's a couple hundred patients in the U.S. So, you know, if you had two patients, that's 1% of the prevalent population. So this is not easy to recruit. And the fact that we have patients enrolled, we're pleased with. I won't, you know, get into the granular detail about where we are in that, but I think we're pleased with the level of screening and enrollment that's going on, and I feel confident that we'll be able to have some data by late in the year with that program.
spk07: Good. And then, and this is Raju, so on, you know, development strategy for 2735, you know, as we said on R&D Day, and we've sort of continued to reiterate that, We want to get both compounds phase two ready. So 2735 is finished. Phase one. We're in the middle of some starting some chronic talk studies and with 32 32 again, we're finishing up phase one expect to have that wrapped up early first half of next year. And, again, there, again, we're CMC ready. We're planning on FOX work. So we'll have both compounds Phase II ready in the early first half of next year. And, you know, we'll have the data readouts on the two Phase II trials ongoing for 958 and 002. And, you know, we'll just look at the strategy across the portfolio as where we pursue these two molecules. But no matter where – where these go in terms of whether we do it alone or whether we have a partner, we are ready for the phase two start. And, you know, and we've outlined the opportunities for both drugs. So the peripheral molecule has indications, broad indications that Bill outlined, both in cardio, cardiometabolic areas, as well as some very specific darn indications. And then for 32, 32, there's a huge excitement in neurodegenerative diseases, including Parkinson's. So, you know, our goal has always been focus the phase two trials, get ready for phase three with the two compounds and get the NLRP3 portfolio phase two ready late this year or early first half. And then we can sort of look at the entire portfolio and decide where we take these two molecules.
spk06: Excellent. Thank you.
spk00: Thank you. And once again, if you do have a question, please press star one on your telephone keypad at this time. And our next question will come from Chris Shibutani with Goldman Sachs.
spk10: Thank you. Two questions, if I may. On the psoriatic arthritis opportunity, the Kata Nimbus is expected to have Phase IIb data that reads out this year. Can you share with us what your expectations are for this trial and any potential for a read-through in terms of what your ongoing psoriatic arthritis trial is? And a question on Crohn's. as far as enrollment in the Phase 2. Have you observed any changes in particular since Bristol's compound failed its Phase 2 study? I did note that in Bill's prepared remarks about the S1P UC study, the word perseverance was used. Thank you.
spk06: Yeah. Bill, go ahead. Yeah, I think the saw the totality of effect at the higher doses with the nymphisticated product in psoriasis as being, you know, a bit greater than what was seen with Ducrapacitinib, particularly with where you end up at the final approved dose. And so given really a meaningful signal with both the 3-milligram BID, as I recall, and 6-milligram QD and 12-milligram QD doses with Ducravacitinib. And to my eye, I thought there was a bit of dose response, particularly as you got into ACR 50 and 70 doses. for the 12 milligram once a day dose with Ducravacitinib. So I anticipate that there would be a positive and meaningful effect across ACR 20 and 50 and 70 for the Nimbus, Takeda drugs. I don't know that we know exactly what doses they are doing, but it's reasonable to speculate or anticipate that they would include some of the higher doses from the already completed psoriasis trial. So, we do think that the concept of TIK2 inhibition being an effective therapy for psoriatic arthritis is likely to be further confirmed with the domesticated data. And we wouldn't be surprised to see an effect that's at least as good and possibly a little better than what was seen with Ducravacitinib. And we think that opens up the opportunity for other TIK2 inhibitors with excellent target coverage like VTX958.
spk10: And on the Crohn's enrollment piece?
spk06: Yeah, I mean... You know, we've always resisted being too granular about that as we've gone along. You know, we had a lot of learnings around, and in my view, we were quite successful in the ulcerative colitis program with, you know, getting the right CRO, the right country mix, the right number of sites, effectively interacting with the investigators and getting the trial enrolled on a timely basis. And we've taken all those learnings as a young company and applied to the Crohn's program. There are many common sites between the ulcerative colitis and the Crohn's programs, which allowed us to leverage contract negotiations. We had relationships with the sites, with the investigators, with the study coordinators, and all those things. So, you know, we have all those synergies going for us in the Crohn's trial, and I'll just say, you know, from my standpoint, the site activation rates that we had planned were, you know, on track. The patient enrollment rates are on track, and I feel confident that we can deliver the results next year. I'm going to wait another quarter or two before we start to narrow the band around when exactly next year. But for our internal metrics, we're absolutely on track for where we intend to be right now, and the trajectory is strong to stay on track.
spk10: Great. Thank you.
spk00: Thank you. Our next question will come from Emily Bosnar with Wainwright.
spk01: Hi, thanks for taking the questions. Maybe just to follow up on the previous question on psoriatic arthritis, if you can kind of talk about how you think about the bar for you internally versus CITIC2 phase 2 data so far. And then also, Bristol has talked about evaluating CITIC2 for other indications like SLE and alopecia. Are those indications that you think might make sense for a CITIC2 inhibitor, and are those ones that you'd maybe consider for VTX958? Thank you.
spk06: Well, until we have more data with the Nimbus Takeda products, we have sort of another data set with the implied target coverage and things across the range of doses. I think right now the more benchmark should probably really be what was seen with Ducrapacitinib and maybe say that it's what was seen with the 12 milligram dose as opposed to the 6 milligram dose. If you do cross mechanism of action comparisons, those data with the 12 milligram dose actually look pretty favorable to other agents, and even JAK inhibitors. So let's see as we get some more data in that field how high the floor can raise, but that's probably how we would think about it. For other indications, I'm not aware that there are any data yet for alopecia. It's interesting. There is some logic to it. And, you know, we're, of course, thinking about different indications, including whether there are any beyond psoriasis and dermatology. We haven't pulled the trigger to go into that space yet, but we're watching that with interest. For lupus, you know, you'll recall that really interleukin-1223 inhibition with Stelara is was ultimately not effective, and so I'm a little bit skeptical about for IL-23 inhibition with that, but of course you have the interferon alpha side, and that looks good, so I think you know, for TIK2 inhibition, that's certainly an opportunity for us and one that is differentiated from the IL-1223 and IL-23 antibodies where, you know, lupus cannot be a target. These are large trials. The endpoints are sort of squishy. If you'll remember the Phase II study, Ducravacitinib and lupus, As I recall, it was 360 patients, about 90 patients per arm for three doses plus placebo. It took about three and a half years to recruit that trial and read out six-month results. So it's really a long slog. The effect sizes are often in the 10% to 15% range relative to placebo, so you need to a lot of patients per group. And we haven't pulled the trigger on that yet because we think it's a big undertaking. But, of course, you know, pending successful and robust data in some of our other ongoing Phase II trials, that could be revisited at any time.
spk01: Very noble. Thank you.
spk00: Thank you. Our next question will come from Sam Slutsky with LifeSide Capital.
spk09: Hey, good afternoon, everyone. Thanks for the questions. Quick question for Bill. Just on the S1P class, you know, obviously the posy of sales in UC, I think, has so far underwhelmed versus earlier expectations. That said, Pfizer obviously believes that atrazumab is going to be a blockbuster in IBD, and they obviously paid a good amount of money to get the drug. I guess as the IBD position, it would be good to get your view on what factors could have contributed to the slow launch of SUPPOSIA, and then what potential profile for a next-gen S1P1 could lead to better uptake or does ultimately result in blockbuster potential like expected for the class?
spk06: Go ahead, Bill. I'll opine a little bit, and then maybe Marty, given all of his life experience, could talk a little bit about the launch as well for SUPPOSIA. I think whenever there's a new mechanism of action, robust physician and provider engagement and education is required. Therapies usually don't sell themselves. They require an educational and ultimately marketing campaign. I think the sense that I get from all of my colleagues in the field is that that just hasn't happened in any robust way with Ziposia. So I think that plays a lot into it. The drug has also been priced for the multiple sclerosis market. So it's in the $80,000, $90,000, $100,000 range. So as a starting price for an IBD drug, that's kind of high, and that really then sets barriers to access. I think it's heavily those things. I do have the sense that there is a rising experience with using the drug, and it would be interesting to see where that Pfizer sets their pricing. I would anticipate that they're going to put a lot more marketing and education muscle behind it and that the launch of Atrasimod will really start to grow the class. What are physicians and ultimately patients looking for I think it's really heavily about efficacy, and most of our legacy drugs were about 10% better than placebo, so 10% placebo-adjusted remission rates for induction. Some of the newer entrants, Renvoke is, you know, 20% to 25% placebo-adjusted Delta. Some of the Phase II data with TL1A antibodies, both the Prometheus and Prometheus, Roy Vant Pfizer molecules had 25 and 20% respectively remission deltas. The tracemod, depending on how you look at it, phase two was 25%. Phase three was 20% in one trial and about 10% in the other trial. Blended average is probably high teens pushing 20%. So I think the next generation drugs that would be really differentiated and exciting, you probably want to see at least the 15 and ideally 20% or more placebo-adjusted remission rate. And, you know, if that's what we're aspiring to, and if we land in that zone, not only the primary endpoint, but with consistency and the secondary endpoints and some of the differentiating things like getting, you know, complete endoscopic remission and stuff like that. You know, that's going to be very interesting to people. Our drug is not aimed at multiple sclerosis, so it could be appropriately priced for an ulcerative colitis market. We think all of that will be a real opportunity. Marty, did you want to add anything about the sort of long trajectory of Ziposia as you see it?
spk04: Yeah, Bill, I think you hit on a lot of the things that we see and we talk about internally when we hear from KOLs and folks we engage with in the field. I think it's a combination of the factors you cited along with also as you sort of talked around the efficacy there. Sam, I suppose you was in a sort of very low double digit, so it wasn't particularly sort of groundbreaking or exciting efficacy. It's perceived as a slower onset of action drug as well, which is You know, it's better to have a fast onset of action, of course, with the active metabolite that the drug works through. So I think we've got some benefits with VTXO2 that I think are, you know, hopefully more attractive attributes for the market. And obviously we'll be watching closely as you and our investors will on how Pfizer's regulatory outcome and commercial launch goes with the plasma this year.
spk09: Super helpful. Thanks.
spk00: Thank you. And at this time, there are no further questions in the queue. So I'd like to turn the floor back over to Dr. Mohan for additional or closing remarks.
spk07: Yeah, great. And thank you all again, all your analysts, all the investors for your continued interest in Ventex. Hopefully we'll connect with you, with many of you at one of the upcoming conferences we plan to attend in the third quarter. And we're really excited, you know, For the fourth quarter approaches, looking forward to sharing our phase two top line results with you for both starting with OO2 in UC and then followed by VTX958 in Soraya. So thanks. Thank you all once again.
spk00: Thank you. This concludes today's Vintex Biosciences second quarter 2023 earnings conference call. Please disconnect your line at this time and have a wonderful day.
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