Ventyx Biosciences, Inc.

Thank you for standing by, and welcome to the Ventex Final Science's second quarter 2022 earnings conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you'll need to press star 11 on your telephone. As a reminder, today's program may be recorded. And now I'd like to introduce your host for today's program, Marty Oster, Chief Financial Officer.

Please go ahead, sir. Thank you, Jonathan. Good afternoon, everybody. Thanks for joining the call today. Welcome to Ventex Biosciences conference call and webcast. We'll be discussing top-line results from the Phase I trial of our TIK2 inhibitor, VTX958. As a reminder, you can find press releases issued today covering the Phase I results from VTX958, as well as our second quarter financial results on our website at www.ventexbio.com under the Investor tab of the News and Events section. Before we begin today, I'd like to remind everyone the conference call webcast will contain forward-looking statements, including statements about the potential and positioning of 958 and related market opportunities, the timing of commencement, enrollment, and completion of clinical trials, the anticipated timing of release of clinical trial data, and the expected timeframe for funding operations and current cash equivalents and marketable securities. These statements are subject to risks and uncertainties that could cause actual results to differ, and please note that these forward-looking statements reflect our opinion only as the date of this call. Factors that could cause actual results or outcomes to different material from those expressed or implied by such forward-looking statements are discussed in greater detail in our filings with the SEC, including our Form 10-Q for the second quarter of 2022, which we do expect to file this afternoon. Today's call will feature a presentation hosted by our CEO, Dr. Raju Mohan, and our President and Chief Medical Officer, Dr. Bill Sanborn. Following the presentation, we will open the call to your questions, and at that time, Raju and Bill will also be joined by our Executive Chairperson, Sheila Kudrati, and our Chief Business Officer, Chris Krueger. We're also joined today by a special guest, Dr. James Krueger. In addition to serving on the Ventix Scientific Advisory Board, Dr. James Krueger is the Director of the Milstein Medical Research Program and the D. Martin Carter Professor in Clinical Investigation at Rockefeller University in New York. Dr. Krueger is a board-certified dermatologist and is recognized as a world-renowned research expert on the pathophysiology and treatment of psoriasis. With that said, I will hand the call over to Dr. Raju Mohan, our CEO and Ventix's founder, to walk you through the slides. Thanks.

Richard, go ahead. Thanks, Marty, and good afternoon, everybody. It's a pleasure to be able to have the opportunity to present the phase one results. Slide three, please. Before we talk about BGX958, which is the focus of the call today, 958 is going to go into phase two trials, and Bill will talk more about this later in the discussion. initiating three phase three trials in Q4 of 2022. Really want to highlight our portfolio of small molecule compounds, differentiated molecules, all internally discovered, and we owned all IP rights to these compounds. So in addition to 958, we have BTX002 S1P1 modulator. This compound is currently in phase two studies in ulcerative colitis, and we will report top line data for this compound in 2023. Then for our NLRP3 portfolio, our peripheral compound, VTX2735, it's a potent inhibitor of NLRP3, and we've announced phase one results in July of this year. We plan to initiate phase two trials in CAPS patients in Q4 of 2022. In addition, we'll be disclosing additional opportunities for developing this compound also later this year. And finally, VTX3232. This is also in the NLRP3 class. This, however, is a brain penetrant, a CNS penetrant NLRP3 compound. This compound is currently in IND enabling studies. We plan to initiate phase one trial in Q1 of 2023. So that is a portfolio of small molecule compounds. Let's move to the next slide, please. Why the excitement on TIK2? So TIK2 is a clinically validated target from two angles. One is the established efficacy of biologics, IL-23 and IL-1223, all targeting clinical efficacy in IBD, in psoriasis, in psoriatic arthritis, and the other target of TIK2 is interferon-alpha and now validated in lupus. So in addition to the biologics that also validate this target, allosteric TIK2 inhibitors also target the same pathways, IL-1223 and NF-1-alpha, and thus TIK2 is clinically validated in these targets, not just by the biologics that target these pathways, but also by a small molecule, Ducravacitinib, that has shown efficacy now in psoriasis, psoriatic arthritis, and most recently in lupus. As you know, These are large, the disease that we've talked about here are large markets in the autoimmune disease space, totaling close to $50 billion worldwide. And there's clearly a high unmet need for oral agents because this market, as you know, is currently dominated by biologics. So where does that position VTX958? It is a highly selective TIK2 inhibitor, an allosteric inhibitor. And what we will show you today and what Bill will share with you is the high Selectivity of this compound will differentiate this compound from compounds that are less selective that have shown that profile is borne out in the clinical trials. And the positive phase one data that we'll show you today will establish the therapeutic window of this profile, demonstrate the excellent safety profile, and this all leads to class-leading target coverage of cytokines of interest and positions VTX95A for success across multiple indications that we are planning to start in the second half of this year. Next slide, please. Slide five. So, right from the beginning, our chemistry strategy has focused on the allosteric domain of TIK2, classic JAT inhibitors target the kinase domain. This domain is highly conserved within the JAT family. And while it's easy to get potent compounds, These compounds generally have very poor selectivity. They cross over into all the entire JAK family. They had JAK1, JAK2, and JAK3. By targeting the Allosteric domain, which is much less conserved, one can actually get very high selectivity from this approach. And that's exactly what we have done with VTX958 shown in the panel here. And thus, VTX958 had selectivity for TIG2 in the Allosteric domain versus JAK1. It's about 4,000-fold selective. It has almost no affinity for JAK2 and JAK3. There is no binding to any JAK2 or 2 allosteric domains. There's absolutely no activity via the kinase domain, and no kinase enzyme inhibition has been shown in our assays for any JAK family members. So as a TIK2 inhibitor, targeting the allosteric domain of TIK2 affords inhibitors of high selectivity against other JAK isoforms and inhibitors Very important here, avoids potential safety risks that are associated with compounds that either hit JAK1 or 2 or 3, or compounds that are not as selective as VTX9, 5, 8. Slide 6, please. So if you look at, so both the prolacitinib and VTX9, 5, 8 are both bona fide allosteric TIK2 inhibitors. Where the difference comes up is in the binding of VTX958 to the allosteric domain of TIK2 versus binding to the allosteric domain of JAK1. Now, if I can focus you on the table below, going to the VTX958 column, VTX958 has 4,000-fold selectivity for TIK2 versus JAK1 in the allosteric binding. In contrast, the KRAVA system has only about a 50-fold selected profile for TIG2 versus JAK1. And just a little bit of a structural lesson in here. And the reason why we've been able to do this is that we both, 958 and the KRAVA, both exploit the valine, which is present in the TIG2-JH2 domain. They both bind to it. What we have done with 958 is build a compound such that it has an negative interaction with the isoleucine, which is now a substitute for valine in the JAK1 domain, and whereas ducravacitinib can still bind to this isoleucine, and this binding difference between VTX958 and its steric repulsion with the isoleucine versus ducravacitinib that can bind to it results in this very high selectivity that we've shown for this compound. So this is the binding differential for 958, 4,000-pole selector for TIK2 versus JAK1. Next slide, seven, please. Where this has the biggest impact is now on the functional selectivity of 958. Functional selectivity in its ability to now selectively hit TIK2-driven cytokines, IL-12, IL-23, and if you're on alpha, you can see that there with the pralacitinib, they're both bona fide allosteric compounds. They both hit IL-12, 23, and alpha. Where the difference is most striking is in the right-hand column, where VTX958 has no affinity for these pleiotropic cytokines. These are protective cytokines that you do not want to block. So VTX958, in all the assays that we have run across a panel of cytokines, has no inhibition of IL-22, no inhibition of IL-10, no inhibition of interferon gamma, no inhibition of IL-4, no inhibition of IL-6. So a composite of cytokines, all with a single message. We are highly selective PIK2 versus JAK1. And then the Kravacitinib, which has some interaction with JAK1, then ends up inhibiting the entire panel of cytokines, IL-22, 10, gamma, 4, and 6. So coupled with the high selectivity of PTX958, And the safety profile that we've now seen, first from non-clinical safety assessment, and now from the safety data that Bill will present to you in the subsequent slides, really allows us to reach this broad therapeutic window. In addition to hitting the potent cytokines, we talked about IL-23 cytokines that have been implicated in psoriasis, in psoriatic arthritis, in Crohn's disease. It really allows this therapeutic window, the safety profile of this compound, this Unmatched target coverage allows us to attain safely assumed exposures, higher exposures in phase two and phase three studies to then elicit maximum efficacy in these disease indications. Slide eight, please. So with that, I'm going to hand over to Bill to walk you through the phase one results.