Q1 2024 Ventyx Biosciences Inc Earnings Call

Operator: Please stand by, your program is about to begin. If you need operator assistance today, press star zero. Good afternoon, ladies and gentlemen, and welcome to the Ventyx Biosciences first quarter 2024 earnings conference call.

Graham is about to begin could you need operator assistance today's press star in theory.

Operator: Good afternoon, ladies and gentlemen, and welcome to the vintage Biosciences first quarter 2024 earnings conference call. At this time all parties parties have been placed in a listen only mode and the floor will be opened for your questions. Following the presentation, if you'd like to ask a question at that time. Please press star one on your telephone keypad if at any point.

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Speaker Change: Your question has been answered you may remove yourself from the queue by pressing star too. So others can hear your questions. Clearly we ask that you pick up your handset for best Sound quality Lastly, should you 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 Auster been Texas Chief financial.

Operator: Lastly, should you 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 Auster, Ventyx's chief financial officer. Please begin.

Speaker Change: Officer. Please begin.

Martin Douglas Auster: Thank you, operator, and good afternoon to everyone joining us today. Welcome to the Ventyx Biosciences conference call webcast, where we'll be discussing our first quarter 2024 financial results and providing a corporate update. Before we begin, I would like to remind everyone that today's presentations will include foreseeing statements. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected. The description of these risks can be found in our Form 10-Q for the quarter ended March 31st, 2024, which was just recently filed this afternoon.

Martin Douglas Auster: Thank you operator, and good afternoon to everyone. Joining us today welcome to <unk> Biosciences Conference call webcast will be discussing our first quarter 2024 financial results and providing a corporate update before we begin I would like to remind everyone that today's presentation will include forward looking statements. These statements are subject to risks and uncertainties that may cause actual results to differ.

Martin Douglas Auster: Materially from those projected a.

Martin Douglas Auster: A description of these risks can be found in our Form 10-Q for the quarter ended March 31, 2024, which was just recently filed this afternoon.

Martin Douglas Auster: Any forward-looking statements are made only as of today's date, and we assume no obligation to update any forward-looking statements made on today's call. With that, I'll hand the call over now to Dr. Raju Mohan, Ventyx's founder and CEO. Raju, please go ahead.

Martin Douglas Auster: Any forward looking statements are made only as of today's date and we assume no obligation to update any forward looking statements made on today's call with that I'll hand, the call over now to Doctor would you Mohan <unk> founder and CEO would you. Please go ahead, yes, thanks, Martie and thank you everyone for joining us for our first quarter 2024 earnings call and corporate update.

Raju S. Mohan: Thanks, Marty, and thank you, everyone, for joining us for our first quarter of 2020 earnings call and Corporate Update. As we recently provided a full pipeline and strategic update at our March Investor Day, I will be brief with my remarks today. Let me take a few minutes to provide some high-level comments on the status of our pipeline programs, and then I'll hand the call back to Marty to review our first quarter financial results.

Raju S. Mohan: As we recently provided a full pipeline its strategic update at our March Investor Day.

Raju S. Mohan: I will be brief with my remarks today.

Raju S. Mohan: Let me take a few minutes to provide some high level comments on the status of our pipeline programs and then I'll hand, the call back to Marty to review, our first quarter financial results. We'll then open the floor to Q&A, where I'd be I can't joined by marking and also with John <unk>, Our Chief Scientific officer.

Raju S. Mohan: We'll then open the floor to Q&A, where I'll be again joined by Marty and also by John Nassar, Chief Scientific Officer. So I'll begin with our portfolio of potential best-in-class NLRP 3 inhibitors. In March, we announced positive top-line results from a Phase 1 single and multiple ascending dose trial of VTX3232, our novel CNS-penetrant NLRP3 inhibitor, in adult healthy volunteers. As you may recall, repeat VTX3232 doses as low as 3 mg once daily achieved steady-state IL-1 beta-IC50 coverage in both plasma and the CSF, and repeat doses of 20 mg all the way up to Based on these data and our dose projection modeling, we estimate that BTX3232 doses as low as 12 milligrams once daily may be adequate to achieve IL-1 beta-IC90 target coverage in the CSF and in plasma.

Raju S. Mohan: Yeah.

Raju S. Mohan: We also observed robust dose-dependent pharmacodynamic or PD effects in a whole blood ex vivo IL-1 beta stimulation assay, and VTX3232 also showed an excellent tolerability profile in this phase one study. We thus believe that these data establish VTX3232 as a potential best-in-class drug candidate for the treatment of neuroinflammatory diseases and conditions. This includes excellent target coverage in plasma and CSF, a favorable safety profile, and a convenient once-daily oral dosing regimen with our tablet formulation.

Raju S. Mohan: So I'll begin with our portfolio our potential best in class analog <unk> three inhibitors.

Raju S. Mohan: In March we announced positive topline results from a phase one single and multiple ascending dose trial of <unk> three to our novel CNS Penetrant analog Petri inhibitor in adult healthy volunteers.

Raju S. Mohan: As you May remember repeat VCX 3222 doses as low as three milligrams once daily achieved steady state IL, one beta IC 50 coverage in both plasma and CSF and repeat doses of 20 milligrams, all the way up to 40 milligrams QD.

Raju S. Mohan: Well exceeded IL, one beta IC 90 coverage in both plasma and CSF.

Raju S. Mohan: Based on these data and our dose.

Raju S. Mohan: Most projections modeling, we estimate that <unk> doses as low as 12 milligram once daily maybe adequate to achieve IL, one beta IC 90 target coverage in the CSF and in plasma.

Raju S. Mohan: We also observed robust dose dependent pharmacodynamic or PD effects, and a whole blood ex vivo IL, one beta stimulation assay <unk>.

Raju S. Mohan: <unk> also showed excellent color showed an excellent tolerability profile in this phase III study.

Raju S. Mohan: We believe that these data established <unk> as a potential best in class drug candidate for the treatment of neuro inflammatory diseases and conditions.

Raju S. Mohan: This includes excellent target coverage in plasma and CSF favorable safety profile and a convenient once daily oral dosing regimen without tablet formulation.

Raju S. Mohan: VTX3232 is a Phase 2 ready compound. As we also communicated in March, we plan to rapidly advance VTX3232 into Phase II trials in high-value indications with substantial unmet need, beginning with a Phase IIa trial of VTX3232 in patients with early Parkinson's disease, which we will initiate in the second half of this year. As we discussed, a growing body of preclinical evidence has implicated LRRP-tremiated inflammation as a key driver of Parkinson's disease pathology by impacting neuronal death and degeneration.

Raju S. Mohan: <unk> two is a phase two ready compound.

Raju S. Mohan: As we also communicated in March we plan to rapidly advance <unk> into phase III trials in high value indications with substantial with substantial unmet need beginning with the phase Iia trial of <unk> in patients with early Parkinson's disease, which we will.

Raju S. Mohan: Initiate in the second half of this year.

Raju S. Mohan: As we discussed our growing body of preclinical evidence is implicated in Iraq Petri me at inflammation is a key driver of Parkinson's disease pathology impacting neuro death and degeneration we.

Raju S. Mohan: We therefore believe that NLRP3 inhibition represents a promising, potentially disease-modifying therapeutic approach in this devastating neurodegenerative condition. More recently, NLRP3 has also created much buzz and discussion as a potentially important target for obesity and obesity-related metabolic diseases, much of it due to data published last February showing central NLRP3-mediated weight loss in obese mice. We have initiated our own studies with Ventyx 3232 in murine models of diet-induced obesity, similar to the published model we just talked about.

Raju S. Mohan: We therefore believe that Enernoc Petrie inhibition represents a promising potentially disease modifying therapeutic approach in this devastating neurodegenerative condition.

Raju S. Mohan: More recently and then RPT has also created much buzz and discussion as a potentially important target for obesity and obesity related metabolic diseases much if it due to data published last February showing central Enernoc between me added weight loss in obese mice.

Raju S. Mohan: We have initiated our own studies with <unk>, 3% to three two in murine models right.

Raju S. Mohan: Alright models of diet induced obesity similar to the published modeled we just talked about and.

Raju S. Mohan: In addition to assessing weight loss induced by VTX3232 and with the GLP-1 agonist samaglutide in a monotherapy study, we're also evaluating VTX3232 in combination with samaglutide. These are exciting studies, and we look forward to providing an update on these studies later in the second quarter. Now, moving from mice to humans.

Raju S. Mohan: In addition to assessing weight loss induced by <unk> and with the <unk> one agonist semi good tight in our monotherapy study.

Raju S. Mohan: Also evaluating <unk> in combination with sound like the tide.

Raju S. Mohan: These are exciting studies and we look forward to providing an update on these studies later in the second quarter.

Raju S. Mohan: So now moving from mice to humans, we plan to initiate a phase II trial of <unk> hundred two <unk> during the second half of 2024, and obese participants with certain additional cardiovascular risk factors.

Raju S. Mohan: We plan to initiate a Phase 2 trial of VTX3232 during the second half of 2024 in obese participants with certain additional cardiovascular risk factors. Now, moving on to VTX2735, a peripherally restricted NrRP3 inhibitor. In March, we announced positive top-line results from a Phase II trial of VTX2735 in patients with cryoprine-associated periodic syndromes, or CADS. In this trial, VTX2735 demonstrated efficacy comparable to that observed with IL-1 biologics, the current standard of care.

Raju S. Mohan: VTX2735 also demonstrated consistent and robust reductions in inflammatory biomarkers such as HSCRP, high-sensitive CRP, IL-6, serum amyloid A, and fibrinogen. There was also a mean reduction of 85% in the key symptom score for these CAHPS patients during the initial treatment period, with a very favorable safety profile, with all treatment-related adverse events graded as mild.

Raju S. Mohan: Now moving on to <unk> 27 35.

Raju S. Mohan: Peripherally restricted enernoc be three inhibitor.

Raju S. Mohan: In March we announced positive topline results from our phase II trial of Etfs 2735 in patients with <unk> associated periodic syndromes or caps.

Raju S. Mohan: In this trial <unk> 27, 35 demonstrated efficacy comparable to that observed with I have run biologics the carbon standard of care.

Raju S. Mohan: <unk> thousand 735 also demonstrated consistent and robust reductions in inflammatory biomarkers, such as HFC ERP high sensitive CRP IL six zero amyloid.

Raju S. Mohan: Fibrinogen.

Raju S. Mohan: There was also a mean reduction of 85% in the key symptom score for these <unk> patients during the initial treatment period with a very favorable safety profile with all treatment related.

Raju S. Mohan: Adverse events graded as mild.

Raju S. Mohan: These phase 2 data in CAHPS patients is therefore compelling proof of mechanism for VTX2735 for our peripheral inhibitor and for systemic inhibition of NLRP3 and NLRP3-related biomarkers in general, including HSCRP and IL-6. And as we communicated in March, we plan to evaluate VTX2735 for future development in cardiovascular and potentially other indications, with an initial focus on recurrent pericarditis and also Both recurrent pericarditis, or RP, and MACE prevention represent indications of large addressable markets and substantial unmet medical needs.

Raju S. Mohan: These phase II data in <unk> patients is therefore, a compelling proof of mechanism for <unk> thousand 735 for our peripheral inhibitor and for systemic inhibition of <unk> related Biomarkers in general, including Hs CRP and IL six.

Raju S. Mohan: And as we communicated in March we plan to evaluate <unk> T X 20.

Raju S. Mohan: <unk> thousand 735 for future develop in cardiovascular and potentially other indications with an initial focus on recurrent pericarditis and also in the secondary prevention of major adverse cardiovascular events or mace.

Raju S. Mohan: Recurrent pericarditis, RP and mace prevention represent indications with large addressable markets and substantial unmet medical need. So we plan to update I'll provide an update on our cardiovascular development plans later in this year.

Raju S. Mohan: So we plan to update or provide an update on our cardiovascular development plans later in this year. Beyond our NNRP3 inhibitor portfolio, the team continues to make progress advancing our IBD assets, including VTX002, our potential best-in-class S1P1 receptor modulator for ulcerative colitis, and VTX958, our allosteric T2 inhibitor in phase 2 development for the treatment of Crohn's disease. For VTX002, you'll recall that we announced positive phase 2 data in October of 2023, demonstrating what we believe is a potential best-in-disease profile for an oral agent in ulcerative colitis.

Raju S. Mohan: Beyond our <unk> inhibitor portfolio. The team continues to make progress advancing our IBD assets, including <unk> 002, our potential best in class <unk> receptor modulator for Austria colitis, and Gtx 958 are allosteric <unk> inhibitor in phase II.

Raju S. Mohan: <unk> for the treatment of Crohn's disease.

Raju S. Mohan: For <unk> 002, you'll recall that we announced positive phase II data in October of 2023, demonstrating what we believe is a potential best in disease profile for an oral agent and ulcerative colitis.

Raju S. Mohan: This includes a highly differentiated rate of complete endoscopic remission and a potential best-in-class safety profile. At the March event, we also showed preliminary data from the open-label extension part of the Phase 2 trial, further reinforcing the endoscopic remission data and the differentiated profile. We anticipate that the data from the 52-week long-term extension part of this Phase 2 study will continue to show sustained or perhaps even improved data for endoscopic remission from that observed in the 13-week induction period. This program is fully Phase 3, and our teams continue to make preparations for a pivotal Phase 3 trial. It's ongoing.

Raju S. Mohan: This includes a highly differentiated rate of complete complete endoscopic remission and a potential best in class safety profile.

Raju S. Mohan: At the March event. We also showed preliminary data from the open label extension part of the Phase II trial.

Raju S. Mohan: Further reinforcing the endoscopic remission data and a differentiated profile we.

Raju S. Mohan: The data from the 52 week long term extension part of this phase II study will continue to show sustained or perhaps even improved data for endoscopic remission from that observed in the 13 week induction period.

Raju S. Mohan: This program is fully phase III ready and our teams continue to make preparations for a pivotal phase III trial.

Raju S. Mohan: It's ongoing.

Raju S. Mohan: Last month, we completed a productive end-of-Phase II meeting with the FDA, and we expect to conduct a scientific advice meeting with the EMA later this quarter. We continue to have confidence that our completed Phase 2 trial may be sufficient to support approval of VTX002 with the successful completion of a second pivotal 52-week trial in ulcerative colitis. And, as we have previously indicated, efforts are underway to identify a partner or other source of non-deleted financing to support this pivotal Phase 3 trial.

Raju S. Mohan: Last month, we completed a productive end of phase II meeting with the FDA and we expect it.

Raju S. Mohan: Dr Scientific advice meeting with the EMA later this quarter.

Raju S. Mohan: We continue to have confidence that our completed phase II trial may be sufficient to support approval of <unk> with successful completion of our second pivotal <unk>.

Raju S. Mohan: 52 week trial in ulcerative colitis, and as we have previously indicated.

Raju S. Mohan: Efforts are underway to identify a partner or other source of non dilutive financing to support this pivotal phase three trial.

Raju S. Mohan: Finally, our Phase II trial of VTX958, our allosteric TIK2 inhibitor, in moderately to severely active Crohn's disease continues to progress. As we've mentioned, in the first quarter of this year, we implemented a protocol amendment to streamline detection of a potential efficacy signal in this trial. As a result of the protocol amendment, target enrollment was revised from approximately 132 patients to approximately 93 patients, and the trial's sole primary endpoint is now the change from baseline in the main Crohn's disease activity index, or CDAI, score at week 12.

Raju S. Mohan: Finally, our phase II trial of <unk> 95, eight are allosteric <unk> inhibitor and moderately to severe active crohn's disease continues to progress as.

Raju S. Mohan: As we've mentioned in the first quarter of this year, we implemented a protocol.

Raju S. Mohan: Implementing a protocol amendment to streamline detection of a potential efficacy signal in this trial as a result of the protocol Amendment target enrollment was revised from approximately 132 patients to approximately 93 patients in the trials. So primary endpoint is now the change from.

Raju S. Mohan: Baseline and the main Crohn's disease activity index or <unk> score at week 12.

Raju S. Mohan: We completed enrollment in the trial in March, and we look forward to reporting top-line results in the early second half of 2024. So, in conclusion, I would again thank all of our Ventyx team members for their continued efforts and contributions across the pipeline, our investigators and collaborators, and, of course, all the patients that have enrolled in our trial. We are very much looking forward to a productive year for Ventyx and to continue to provide these exciting updates. I'll now hand the call back to Marty for a brief review of our financial results for the first quarter. Marty? Yeah, thank you.

Raju S. Mohan: We have completed enrollment in the trial in March and we look forward to reporting top line results in early second half of 2024.

Marty: So in conclusion I would like to again, thank all of <unk> team members for their continued efforts and contributions across the pipeline.

Marty: Joy investigators collaborators and of course, all the patients that enroll in our trials. We are very much looking forward to a productive year for vertex and to continue to provide these exciting updates I will now.

Raju S. Mohan: Ill hand, the call back to Marty for a brief review of our financial.

Raju S. Mohan: First quarter financial results Marty. Thank you Rajeev, our financial results for the first quarter ended March 31, 2024 are presented in our press release issued at market close and I'll briefly summarize those results here now R&D expenses in the quarter were $33 $7 million compared to $35 4 million in the first quarter of 2023.

Martin Douglas Auster: Yeah, thank you, Raju. Our financial results for the first quarter ended March 31st, 2024, are presented in our press release issued at market close, and I'll briefly summarize those results here now. R&D expenses in the quarter were $33.7 million, compared to $35.4 million in the first quarter of 2023. G&A expenses in the first quarter of 2024 were $8 million, compared to $7.1 million for the first quarter of 2023. And our net loss in the first quarter of 2024 was $38.6 million, compared to a $38.9 million net loss in the first quarter of 2023.

Martin Douglas Auster: G&A expenses in the first quarter 'twenty four were <unk> 8 million compared to $7 1 million for the first quarter of 2023, and our net loss in the first quarter of 2024 was $38 6 million compared to $38 9 million net loss in the first quarter of 2023, our cash cash equivalents in marketable securities.

Martin Douglas Auster: Our cash, cash equivalents, and marketable securities balance was $302.6 million as of March 31st, 2024. Net cash used in operating activities during the first quarter of $47.6 million was higher than the reported operating expenses of $41.8 million and is primarily due to an increase in prepaid expenses and a decrease in accrued expenses during the quarter. We expect both our operating expenses and our operating cash flows on a quarterly basis to decrease as we get into the second quarter of 2024 and remain lower for the rest of 2024 as we complete the wind-down activities related to our Phase II trial programs in psoriasis and psoriatic arthritis for VTX 958.

Martin Douglas Auster: <unk> was $302 6 million as at March 31, 2024, net cash used in operating activities. During the first quarter of $47 6 million was higher than the reported operating expenses of $41 8 million and is primarily due to an increase in prepaid expenses and a decrease in accrued expenses during the quarter we expected.

Martin Douglas Auster: Both our operating expenses and our operating cash flows on a quarterly basis to decrease as we get into the second quarter of 2024 and remain lower for the rest of 2024 as we complete the wind down activities related to our phase III trial programs in psoriasis and Psoriatic arthritis for VTS 95 eight.

Martin Douglas Auster: We continue to believe that our current cash, cash equivalents, and marketable securities are sufficient to support our planned operations into at least the second half of 2026. This concludes our prepared remarks for this afternoon's call, and I'll now turn the call back to the operator to begin the Q&A session. In the Q&A session, I'll be joined by Dr. Raju Mohan, as well as our Chief Scientific Officer, John Nuss. Operator, please go ahead.

Martin Douglas Auster: We continue to believe that our current cash cash equivalents in marketable securities are sufficient to support our planned operations into at least the second half of 2026.

Speaker Change: This concludes our prepared remarks for this afternoon's call and ill now turn the call back to the operator to begin the Q&A session on the Q&A session I'll be joined by Dr. <unk> Mohan as well as our Chief Scientific Officer John Us.

Martin Douglas Auster: Later, please go ahead.

Operator: Thank you. If you would like to ask a question, press star 1 on your telephone keypad at this time. It is star 1 if you would like to ask a question. And to remove yourself from the queue, you may press star 2. Our first question today comes from Michael Yee with Jeff.

Martin Douglas Auster: Thank you if you'd like to ask a question press star one on your telephone keypad at this time. It is star one if you'd like to ask a question and to remove yourself from the queue. You May press star two.

Operator: Okay.

Operator: Our first question today comes from Michael Yee with Jefferies.

Kyle: Hey, guys. Thanks for the question. This is Kyle from Michael.

Operator: Hey, guys. Thanks for the question this is Kyle for Michael.

Raju S. Mohan: So on the CNS-NLRP3 program, what do you think is promising for a 28-day study in humans for an oral like this? And what do you think is the bar? And how do you think it stacks up against other injectables and oral options under investigation?

Michael Jonathan Yee: So on the CNS Penetrant <unk> III program, what do you think is promising for our 28 day study in human.

Raju S. Mohan: Oral <unk>.

Raju S. Mohan: And what do you think is the bar and how do you think it stacks up they're injected Barton our options under investigation.

Raju S. Mohan: And a quick one on your mouse data. Where do you think you're going to present the data? Is it going to be in the format of a press release, or are you going to report it at a conference? Thank you. Well, thanks.

Speaker Change: Rick what your mouse data, where do you think youre going to present, the data is there going to be.

Raju S. Mohan: In the format.

Raju S. Mohan: Press release or are you going to report it helicopters. Thank you.

Raju S. Mohan: Yeah.

Raju S. Mohan: Well, thanks. So now we will, as I mentioned before, we plan to report this data in the late second quarter. And, you know, we're in the process of compiling the data. And, you know, once we have all that together, we'll decide on the right forum for presenting it. So just stay tuned.

Speaker Change: So let me let me address the second question first so now we.

Raju S. Mohan: As I mentioned before we plan to report this data in late second quarter and the <unk>.

Raju S. Mohan: Process of compiling the data and once we have all that together will decide.

Raju S. Mohan: What the right forum for presenting at so just stay tuned.

Raju S. Mohan: In terms of your questions about what we expect to see in 28 days, I think there are plenty of studies out there, not just with GLP-1 agonists but other modalities as well, showing measurable weight loss in 28 Days in Human Trials, anywhere from single digits, 2% to, you know, higher weight loss. So again, it remains to be seen what the competitor data will show if and when that data is put out. You know, in our minds, we have two things happening.

Raju S. Mohan: In terms of your questions about sort of what we expect to see in 28 days I think there's plenty of.

Raju S. Mohan: Studies out there not just with <unk> agonists with other modalities as well showing measurable weight loss.

Raju S. Mohan: In 28 days in <unk>.

Raju S. Mohan: <unk> trials.

Raju S. Mohan: Anywhere from single digits, 2% to higher weight loss. So again it remains to be seen.

Raju S. Mohan: What's the competitive data will show if and when that data is put out.

Raju S. Mohan: Our mind, we have two.

Raju S. Mohan: One is obviously something we've done; we're repeating the study that was published in Diet and Use of Beast Mice. As we mentioned, it's a monotherapy study with the compound and a control, and it's a combination study with semaglutide. And we're looking forward to reporting these results. We have also, as you've said, committed to doing our own trial, a 20-day trial in patients. And we think there's biology out there now that certainly links NLRP3, NLRP3 activation or inhibition to hypothalamic control of obesity parameters or mechanisms, such as feeding behavior, and I think that that body of evidence will continue to grow as folks try to link the dots just like it's happened in Parkinson's disease.

Raju S. Mohan: Two things happening one is obviously we have done.

Raju S. Mohan: We are repeating the study that was published in diet induced obese mice as we mentioned, it's a monotherapy study with with compound in our control and it's a combination study with some of the tide.

Raju S. Mohan: And we're looking forward to reporting these results. We also as we've said committed to doing our own trial 22 trial in patients and we think there is.

Raju S. Mohan: Biology, there now that suddenly links NLRB, three and RMB three activation or inhibition too.

Raju S. Mohan: Hypo Tallamy controllers of.

Raju S. Mohan: Obesity.

Raju S. Mohan: Hum parameters or mechanisms.

Raju S. Mohan: Such as feeding behavior.

Raju S. Mohan: I think that that body of evidence will continue to grow as folks try to link the docs just like it's.

Raju S. Mohan: Linked the dots just like it's been happening for Parkinson's disease. So we're committed to doing this trial and we look forward to seeing the data from the competitor if and when it's put out there, but our own path here as planned which is again put out the mouse data and then.

Raju S. Mohan: So we're committed during this trial. We look forward to seeing the data from the competitor if and when it's put out there, but our own path here is planned, which is, again, putting out the mouse data and then planning for our phase 2a study in obese patients in the latter half of the year.

Raju S. Mohan: Planning for our Phase Iia study in obese patients latter half of the year.

Speaker Change: Alright. Thanks.

Liam Heaster: Thank you. Our next question comes from Yasmeen Rahimi with Piper Sandler.

Raju S. Mohan: Thank you. Our next question comes from Yasmin Rahimi with Piper Sandler.

Liam Heaster: Hi, This is Liam Easter on for you guys. So I guess my first question is related to what is the current tox package available for VTS 232, and then moving on to the expected phase III trials.

Raju S. Mohan: Hi, this is Liam Heaster on behalf of YAS. So I guess my first question is related to what's the current tox package available for VTX3232? And then when moving on to the expected phase two trials, what work still needs to be done in order to initiate them in obese patients with additional CV risk? And then moving to 2735, with those phase two trials, what are the rate-limiting steps in initiating a MACE or a current pericarditis trial there?

Raju S. Mohan: Work still needs to be done in order to initiate and obese patients with additional PV, Brad and then moving to 275.

Raju S. Mohan: With those safety trials, what are the rate limiting steps and initiating a mace Eric alright, great data on trial there.

Raju S. Mohan: All right, so let me start with the first one. So our first study is a 28-day study in obese patients. It's a similar study we are planning, a 28-day study in early Parkinson's disease. And then we will initiate the longer-term studies, particularly the obesity study, if that merits phase two in the latter half of the year. So, right now, the TOSS package will support a 28-day study, and then we'll have the talks coverage to do chronic studies in the latter half of the year. The second question was: Briefly, if you don't mind repeating the second one.

Speaker Change: Alright, So let me let me start with the first one so our first study is a 28 day study.

Raju S. Mohan: Obese patients. It's a similar study we are planning for <unk>.

Raju S. Mohan: <unk> study in early Parkinson's disease, and then we will initiate the longer term studies particular.

Raju S. Mohan: Obesity study if that merits.

Raju S. Mohan: <unk> II.

Raju S. Mohan: Latter half of the year.

Raju S. Mohan: So right now on the Tox package will support a 28 day study.

Raju S. Mohan: And then we'll have the tox coverage to do chronic studies in the latter half of the year.

Speaker Change: Second question was on.

Speaker Change: Briefly if you don't mind repeating the second one.

Raju S. Mohan: Oh yeah, so I guess like for... The 2735 asks, what are the rate-limiting steps for the initiation of the Phase II MACE trials and recurrent pericarditis?

Speaker Change: Yes, so I guess like footwear.

Raju S. Mohan: The two 735 asset what are the rate limiting steps for that.

Raju S. Mohan: Initiation of the phase <unk> trial in recurrent pericarditis.

Raju S. Mohan: Every trial has to have its own individual planning, the teams have to get together, the protocols have to be written, and the contracting has to be done. We've laid out our timelines for the Parkinson's obesity trial, and we have laid out the timelines for the cardiovascular trials. Once those have been formed up, there's no rate-limiting step. It's just a part of the planning process from going from a Phase I study to a Phase II study. So it's just a standard process that we have here. But we're pretty excited about the cardiovascular opportunities for 2735, both in recurrent pericarditis and also in the secondary prevention of MACE.

Don: This is Don.

Raju S. Mohan: Every trial has to have its own individuals planning the teams have to get together the protocols have to be written.

Raju S. Mohan: And the contracting has to be done we've laid out our timelines for the Parkinson obesity trial, and we lay out the timelines for.

Raju S. Mohan: Cardiovascular trials.

Raju S. Mohan: Once those have been firmed up but it's not rate limiting step is just a part of the planning process from going from a phase one study to a phase II study. So it's just standard.

Raju S. Mohan: Process that we have here, but we're pretty excited about the cardiovascular opportunities for 2735, both in recurrent pericarditis and also in the secondary prevention of Mace.

Raju S. Mohan: And then actually, just one more question. So, with VTX002, I was wondering if you could provide any more detail on the level of partnership interest and then also any details from the end of phase two meeting.

Speaker Change: Great and then actually just one more question. So with <unk>. Just wondering if you could provide any more detail on that level of partnership interests and then also.

Raju S. Mohan: So any details from the end of phase two meeting.

Raju S. Mohan: Yeah, so at the end of phase two, we had a really good meeting with the FDA and, you know, we laid out our justification for a phase three trial with a single dose and we believe this should serve as a pivotal trial as should the first one and you know we'll have to continue to have the discussion with the agency as this trial progresses so you know our mind was a very successful meeting with the FDA. In terms of partnerships We think this compound continues to show a very strong endoscopic remission.

Speaker Change: Yes, so on the end of phase two meeting we had a really good meeting with the FDA and we laid R. R.

Raju S. Mohan: Depreciation for <unk>.

Raju S. Mohan: Phase III trial with <unk>.

Raju S. Mohan: Single dose and we believe this.

Raju S. Mohan: We believe this should serve as a.

Raju S. Mohan: <unk> pivotal trial as should the first one.

Raju S. Mohan: And we will have continue to have this discussion with agency as this trial progresses. So online a very successful meeting with the FDA.

Raju S. Mohan: In terms of partnerships, we're not going to get into specifics. We think this compound continues to show a very strong endoscopic remission as we showed from the open label. We believe the long term extension data will continue to support both the durability of this and perhaps even improved scores such as a precedent with.

Raju S. Mohan: As we showed in the open label, we believe the long-term extension data will continue to support both the durability of this and perhaps even improved scores, such as the precedent with S1P1 modulators. And, you know, as we said, we are aggressively in the midst of gaining interest from pharma partners across a wide range of people. And, you know, stay tuned, and we'll update you guys once those things progress to something that we can talk about.

Raju S. Mohan: <unk> modulators, and whereas we said.

Raju S. Mohan: We are aggressively in the midst of.

Raju S. Mohan: Getting interest from pharma partners across wide range of folks.

Raju S. Mohan: And stay tuned and we'll update you guys. Once those things progressed as something that we can talk about.

Emily Claudia Bodnar: Thank you. Our next question comes from Emily Bodnar, with HC Wainwright.

Raju S. Mohan: Thank you. Our next question comes from Emily Wagner with HC Wainwright.

Raju S. Mohan: Hi, thanks for taking the question. For Parkinson's disease, I'm curious if you can comment on what kind of neurodegenerative markers you're planning to evaluate and if you're looking at any disease rating scores or any kind of impacts on motor symptoms. And maybe if you could provide a bit more on study design for obesity in terms of like how many patients you're planning to evaluate and are you planning to exclude diabetes patients in that study? Thanks.

Emily Claudia Bodnar: Hi, Thanks for taking the question.

Raju S. Mohan: For Parkinson's disease, and I'm curious if you can comment on what kind of narrowed the general guys Margaret Youre planning to evaluate <unk>.

Raju S. Mohan: If youre looking at any disease rating score that impacts on motors and John.

Raju S. Mohan: And then maybe if you can provide a bit more on the design for my.

Raju S. Mohan: Like how many patients you are planning to evaluate.

Raju S. Mohan: And.

Raju S. Mohan: Thanks.

Raju S. Mohan: Excluding the diabetes patients in that study.

Raju S. Mohan: Yeah, good questions. So again, on specifically the trial, and we're not trying to be cagey here, you know; we don't necessarily disclose every aspect of this trial. Once we have it, it'll be on clintrials.gov, but again, just to bring it in context, you saw the competitor's 28-day trial with an NRPT compound a few months back. They published a biomarker trial. We are planning not just a biomarker trial, but we also have an imaging component of this trial to see the effects of this molecule on glial content and activation as it translates into eventual effects on astrocytes and eventually neural death.

Speaker Change: Yeah. Good questions. So again on specifics of the trial and we are not trying to be cagey here.

Raju S. Mohan: Let's see you disclose every aspect of this trial once once we have it it will be on Clinton trials Dot Gov, but again just to bring it in context.

Raju S. Mohan: You saw our competitors 28 day trial with an NR between compound.

Raju S. Mohan: A few months back they published.

Raju S. Mohan: Biomarker trial, we are planning not just a biomarker trial, but we also have an imaging component of this trial to see effects of this molecule.

Raju S. Mohan: Unclear content and activation as it translates into eventual effects and astrocytes and eventually narrow that don't.

Raju S. Mohan: I don't expect much effect on motor symptoms in these short trials, but we certainly expect to see effects on... Number one, the NLRP3-related biomarkers, such as IL-1 beta, HSCRP, IL-6, Ravinogen, we've shown them now convincingly in multiple trials, even in early phase one. We've seen some movement in these markers, even in healthy volunteers. We certainly showed a robust response to an NLRP3 compound, albeit the peripheral one, in HSCRP, and again, IL-1 beta, and IL-6.

Raju S. Mohan: Don't expect much effect on on motor symptoms in the short trials, but we certainly expect to see effects on.

Raju S. Mohan: Number one the and then on <unk> related Biomarkers, such as IL, one beta HFC ERP IL six <unk>, we've shown them now convincingly in multiple trials even in early phase one <unk>.

Raju S. Mohan: We've seen some movement in these trials and these markers even in healthy volunteers. We certainly showed a robust response often in rfps III compound, albeit the peripheral one in HFC ERP and again IL, one beta and <unk>.

Raju S. Mohan: IL six.

Raju S. Mohan: And in the phase one trial with 3232, we also showed effects on these biomarkers, even in healthy volunteers and in the CSF, right? So those are NLRP3-related biomarkers. And then you have the other side of neurodegenerative markers, in particular, with Parkinson's patients, such as neurofilament light chain and and others, and again Thoughtfully explore a range of biomarkers. There is nothing that precludes us from having a much broader set in our in our measuring strategy.

Raju S. Mohan: In the phase one trial with three to three two we also showed effects on on these biomarkers even in healthy volunteers and in the CSF right. So those are those.

Raju S. Mohan: Those are <unk> related Biomarkers and then you have the other side.

Raju S. Mohan: Neurodegenerative markers and.

Raju S. Mohan: In particular with with.

Raju S. Mohan: In Parkinson's patients, such as neuro filament light chain and others and but again.

Raju S. Mohan: Tactfully explore a range of Biomarkers there is nothing that precludes us from having a much broader set in our in our.

Raju S. Mohan: And our measuring strategy.

Raju S. Mohan: But again, we're not setting any expectation of seeing any sort of meaningful effects in this short trial. And that's why we have a longer trial that we are contemplating towards the end of the year, which will be much more in line with what you've seen recently or published for much longer treatment in Parkinson's patients, and these are 12 months or longer trials.

Raju S. Mohan: But again, we're not setting an expectation of seeing any sort of meaningful effects of the short trial and thats why we have a longer trial that we are contemplating towards the end of the year, which will be much more in line with what <unk> seen recently are published for much longer treatment in Parkinson's patients and these are 12 months or longer trials.

Speaker Change: Okay that makes sense. Thank you.

Raju S. Mohan: Okay.

Vikram Purohit: Okay, excellent. Thank you. Thank you. We will take our next question from Vikram Purohit with Morgan Stanley.

Raju S. Mohan: Thank you and we will take our next question from Vikram <unk> with Morgan Stanley.

Vikram Purohit: Yeah.

Vikram Purohit: Hi, everyone. This is Scott on for Vikram. We have one question regarding your CD program, what is it harder for continuing Gtx 958 in Crohn's disease.

Vikram Purohit: Based on the.

Vikram Purohit: I expect that in the second half of the year.

Raju S. Mohan: Yeah, thanks, Vikram. And perhaps I'll let Marty address this. Marty?

Vikram Purohit: Yes, Thanks, Rick.

Vikram Purohit: Perhaps ill, let Marty address this.

Martin Douglas Auster: Yeah, thanks for the question, Gospel. For that trial, the primary endpoint is a change in CDI score, and then we're looking at key secondary endpoints that include things like endoscopic response and things like that. If you look across sort of approved drugs in the Crohn's disease space, you're looking at some of the biologics as well as more recently developed products like Gupatacinib. You'll see CDI changes in phase two in the range of the upper double digits to kind of the low hundreds as sort of a meaningful type of response on that marker.

Marty: Yes, thanks for the question Gospel.

Marty: For that trial. The primary endpoint is the change in <unk> score and then we're looking at key secondary endpoints that include like endoscopic response, and things like that if you look across sort of approved drugs in the currency space Youre looking at some of the biologics as well as recent.

Martin Douglas Auster: More recently developed products like <unk> Nib Youll.

Martin Douglas Auster: Youll see changes in the phase two in the range of the upper double digits kind of low hundreds as sort of a kind of a meaningful type of response on that marker.

Martin Douglas Auster: We're adequately powered to sort of detect statistical significance at that type of response. And then on the endoscopic side, that's a secondary endpoint given the size of the trial, but we'd be looking to see sort of, again, something competitive there would be in the high teens to low 20s endoscopic response relative to delta versus placebo. So that's sort of kind of where I think the bar is for recently approved drugs to be attractive in this setting. So we're looking forward to reporting those results to you in the next several months.

Martin Douglas Auster: We're adequately powered to detect this is still I think events.

Martin Douglas Auster: Type of response, and then on the endoscopic side Thats, a secondary endpoint given the size of the trial.

Martin Douglas Auster: But we'd be looking to see sort of again something competitive there would be in the high teens to low twenties and.

Martin Douglas Auster: And as Scott Burk response versus relative to delta versus placebo. So that's sort of kind of I think where the bar is for a recently approved drugs to be attractive in the setting. So we're looking forward to reporting those results out to you in the next several months.

Speaker Change: Thank you very much.

Alexander Thompson: Thank you. We will take our next question from Alex Thompson with Stiefel.

Martin Douglas Auster: Thank you we will take our next question from Alex Thomson with Stifel.

Raju S. Mohan: Hey, great. Thanks for taking my questions. I guess the first one on 3.2.3.2, to follow up a little bit on the DIO mouse experiment, can you talk a little bit about sort of the human dose equivalence you're going to be testing relative to what you're looking for in the Phase 2 and what you want to see in both the monotherapy and combo studies to get more confident in the human trial? And then for 27.35, just curious about your thoughts on peripheral Thanks.

Alexander Thompson: Hey, great. Thanks for taking my questions I guess first one on <unk> to follow up a little bit on the DIR masks experiment could you talk a little about sort of the human dose equivalents, you're going to be testing relative to what you are looking for in the phase two and what you want to see in both the monotherapy and combo studies to get more confident in the human trial.

Raju S. Mohan: And then for 2017 35, just curious your thoughts on peripheral and RP three inhibition in the context of what we saw from Buda Kids and that then at AAD and whether you would consider an indication like Hs in the future. Thanks.

Raju S. Mohan: Yeah, so first on human dose equivalent in a mouse study. So the mouse, we don't do these studies in rodents, whether it's for NLRP3 or anything else.

Raju S. Mohan: Yeah, So first on human dose equivalent in the mouse study.

Speaker Change: The amount we don't do these studies.

Raju S. Mohan: Roden proteins, whether it's for <unk> or anything else, it's really a proof of concept and you appropriately dosed the animals based on the profile of the compound.

Raju S. Mohan: It's really a proof of concept, and you appropriately dose the animals based on the profile of the compound in mice, for example, right? So the exposure in mice, the potency of the compound against, for example, mouse NLRP3, and that's the goal. It's not to determine the human dose.

Raju S. Mohan: <unk> mice for example, right so the exposure in mice.

Raju S. Mohan: Occupancy of the compound and for example against mouse analog be three and Thats. The goal its not determined the human dose remember we've done a phase one trial with <unk>.

Raju S. Mohan: Remember, we've done a phase one trial with biomarkers in plasma and in CSF. We've calibrated that trial with what we expect to have the exposure to cover IL-1-IC50 and IL-1-IC90. And if IL-1 is the driver or IL-18, But IL-1beta and IL-18 are the drivers of the disease pathology, so that's the calibration.

Raju S. Mohan: With Biomarkers in plasma and CSF, we've calibrated that trial with what we expect to have the exposure to cover IL, one beta IC 50, iron one based on 90, and if IL, one beta as a driver or IL 18.

Raju S. Mohan: But all one beta and highlight the drivers of the disease pathology and Thats. The calibration. So what doses do we need in humans to that.

Raju S. Mohan: So what doses do we need in humans to then have complete abrogation, a complete inhibition of the IL-1beta produced by NLRP3 in the periphery or in the CNS, and the CSF is a good surrogate. So just to make it clear, the mouse studies are not meant to find doses for... the obesity trial of a Parkinson's trial for any other phase 2 trial. So in terms of mice, again, the doses are now set to make sure that we have adequate coverage in the mice to see effects on weight loss, and to see effects on other endpoints. And it, again, depends on the compound.

Raju S. Mohan: Fleet obligation of complete inhibition of the.

Raju S. Mohan: IL one beta produced by NLRB three in periphery ore in the CNS in the CSF as a good surrogate so just to make it clear. The most studies are not meant to find.

Raju S. Mohan: Find doses four four.

Raju S. Mohan: The obesity trial of a Parkinson's drive for any other phase II trial.

Raju S. Mohan: So in terms of mice again, the doses are now set to make sure that we have adequate coverage in the mice too.

Raju S. Mohan: To see.

Raju S. Mohan: Effects on weight loss to see effects on other endpoints and it again depends on the compounds. So we don't take any sort of guidelines from the competitor dosing paradigm in which case. It was three times a day in mice, we have our own dosing regimen and that's what we've done in both trials the monotherapy and the combo therapy.

Raju S. Mohan: So we don't take any sort of guidelines from the competitor dosing paradigm, in which case it was three times a day in mice. We have our own dosing regimen, and that's what we did in both trials, the monotherapy and the combo therapy. I think the question you had is, what do we expect to see in a combination trial? First of all, this whole trial, the whole study, I shouldn't call it a trial, in mice was really to calibrate our compound, which is a really well-behaved CNS drug, I think the best-behaved CNS penetrant compound out there in the NLRP3 class. And so our goal was to set our own calibration in terms of...

Raju S. Mohan: I think the expectation that the question you had is what do we expect to see.

Raju S. Mohan: And a combination trial first of all we this whole trial the old study I shouldn't call. It a trial in mice was ready to have our own calibration.

Raju S. Mohan: Our compound, which is a really well behaved CNS drug the best behaved CNS penetrant compound out there in the <unk> class and so our goal is to set our own calibration in terms of these.

Raju S. Mohan: These mice models, which we believe are, are, in different parameters, predictive of human disease. So it's not a one-to-one match between the mouse model and the human model. It's different aspects and different readouts from the study recapitulate what you expect in human studies, right, in this case, obesity. So, you know, having no expectation but having competitive data, we designed this trial with our compound, with the somaglutide control, with adequate controls, and with a placebo. First things to see whether you see any weight loss with our compound. You obviously have weight loss from semaglutide. That's been published many times.

Raju S. Mohan: These mice models, which we believe are.

Raju S. Mohan: Are in different parameters predictive of human human disease. So it's not a one to one.

Raju S. Mohan: Mouse model is the human model, it's different aspects and different readouts from this study recapitulate, what you expect in and human studies right in this case obesity.

Raju S. Mohan: So having.

Raju S. Mohan: Having no expectation, but having the competitive data we designed this trial without compound with some of the tight control with added with adequate controls with the with a placebo.

Raju S. Mohan: First thing is to see whether you see any weight loss.

Raju S. Mohan: With our compound obviously.

Raju S. Mohan: <unk> that's been published many times is a published in the competitor compound data that you saw next thing is to understand.

Raju S. Mohan: It was published in the competitor compound data that you saw. The next thing is to understand the effect of weight loss, the effect of food intake. And then once the study is completed, what happens to other parameters, lipid parameters? What happens to diabetes parameters like glucose, insulin, OGTT, HOMA-IR? What's happening to steatosis?

Raju S. Mohan: Effective weight loss effect of food intake and then once that study is completed what happens to other parameters lipid parameters what happens to dive diabetes parameters like glucose insulin ogtt homa IR, what's happening to steatosis, so as we know obesity or.

Raju S. Mohan: So, you know, as we know, obesity or reduction in obesity results in benefits on a number of parameters. So we look for that. In the combo study, obviously, we would look for not just effects of monotherapy, but what is the effect of NMRP3 inhibition on weight loss vis-a-vis semaglutide alone or a GLP agonist alone? Is it additive?

Raju S. Mohan: Or reduction in obesity results and and benefit on a number of parameters parameters. So we look for that in the combo study. Obviously, we would look for not just effects of monotherapy, but what is the effect of <unk> inhibition on weight loss vis vis <unk>.

Raju S. Mohan: Semi protide alone our <unk> agonist alone is that is it additive as a synergistic.

Raju S. Mohan: Is it synergistic? Eventually, we'd like to understand that this mechanism is orthogonal. So again, the mouse studies are really a way to build, like the in vitro studies, a lot of links in understanding this pathway. So we've done some work with microglial cells. We'll get data from the mouse studies, and then obviously, you know, we're committed to doing the human study, but this is, you know, a pretty exciting stage in this part of the NNRP3 pathways.

Raju S. Mohan: Eventually we'd like to understand this mechanism is our cardinal. So again. This is the mouse studies are really up.

Raju S. Mohan: To build like the in vitro studies a lot of <unk>.

Raju S. Mohan: <unk> links.

Raju S. Mohan: And understanding the pathway right. So we've.

Raju S. Mohan: We've done some work in the microbial cells will get data from the mouse studies.

Raju S. Mohan: And then obviously, we're committed to doing the human study.

Raju S. Mohan: Pretty exciting stuff.

Raju S. Mohan: Stage in this.

Raju S. Mohan: Part of the <unk> III pathway. So we've always been interested in Parkinson's, but this has opened up whole new area and I think we're sort of in the forefront of this with our molecule to be able to sort of connect the dots and we're looking forward to sharing the <unk>.

Raju S. Mohan: I've always been interested in Parkinson's, but this has opened up a whole new area. And I think we're sort of at the forefront of this with our molecule to be able to sort of connect the dots. And I'm looking forward to sharing that mouse data with you guys in a few weeks, at the end of the second quarter. I think the third question was...

Raju S. Mohan: Most data with you guys.

Raju S. Mohan: A few weeks.

Raju S. Mohan: And the second quarter.

Raju S. Mohan: I think a third question was potential for price of 35, NHS potentially for 2735% in Hs, yes. So we think this potential clear potential for.

Raju S. Mohan: Potential for 2735 in HS? Yeah, so you know, we think there's potential, clear potential, for a 2735 mechanism in HS. I just caution you that the results from the AbbVie study were very, very encouraging. But there isn't a real one-to-one correspondence between an IL-1 beta antibody, such as canicunumab, and an RP3 mechanism versus the ADVI. It's an IL-1 alpha beta antibody, as well as, for example, an IL-1 alpha beta trap, such as rilonacep. So there's a little bit of an area there that has to be explored, but yeah, certainly there is enough rationale for looking at the NLRPT molecule in HS.

Raju S. Mohan: 20, 735 mechanism in Hs.

Raju S. Mohan: Just caution you that.

Raju S. Mohan: The results from the <unk> study were very very encouraging.

Raju S. Mohan: But there isn't a real one to one correspondence between a.

Raju S. Mohan: IL, one beta antibodies, such as <unk> such as.

Raju S. Mohan: Kind of Kitimat, and <unk> mechanism versus <unk>.

Raju S. Mohan: Abbvie.

Raju S. Mohan: It's an IL one alpha beta antibody.

Raju S. Mohan: As well as for example.

Raju S. Mohan: Alpha beta trap, such as rollout of set price so there's a little bit of a.

Raju S. Mohan: Area that it has to be explored but yes, certainly there is.

Raju S. Mohan: Yes.

Raju S. Mohan: And Thats rationale for looking at.

Raju S. Mohan: And at RPT molecule in Hs.

Derek Christian Archila: Thank you. We will take our next question from Derek Archila with Wells Fargo.

Speaker Change: Thank you we will take our next question from Derik call Sheila with Wells Fargo.

Derek Christian Archila: Okay.

Raju S. Mohan: Thanks for taking our questions. I guess, just a couple on... Given what you've seen in your Phase 1 data for Northero's NT796 positive outcome and their Phase 1B, 2A, do you think getting to the Phase 2B trial is now a deep risk? And then also, do you expect 32, 32 to differentiate from NT796 in Parkinson's view?

Derek Christian Archila: Hey, Thanks for taking our questions I guess couple of hours.

Speaker Change: Thank you.

Raju S. Mohan: Given what you've seen in your phase one data in North Trs 80, 996 positive outcome in phase <unk> do you think getting into two phase two b trial risks and then also we expect to continue to differentiate from <unk>.

Raju S. Mohan: 706 in Parkinson's.

Raju S. Mohan: Sorry, you were fading a little bit. Not Terra in there.

Raju S. Mohan: Yeah, so I'll fight.

Speaker Change: Yes, so fight sorry, you were fading a little bit to your question was.

Raju S. Mohan: Has the data from.

Raju S. Mohan: Not terror in there.

Raju S. Mohan: Parkinson's Phase 2a de-risked our trial? That was the question. Yeah, so let me assume that's the question. So, so.

Raju S. Mohan: <unk> phase Iia Derisked, our trial that was the question.

Raju S. Mohan: Yes, So let me assume thats a question so so.

Raju S. Mohan: You know, it's always good to see, yeah, it's always good to see data from any drug in the class where there hasn't been a lot of data out there showing effects on biomarkers in the study. But again, for us, we believe from our phase one study, everything we've seen, this is an extremely well-behaved compound. It's suitable for QD dosing at low doses. We expect to have coverage of IC90 at doses starting at 10 to 12 milligrams.

Raju S. Mohan: Sure.

Raju S. Mohan: Always good to see.

Raju S. Mohan: Yes, it's always good to see data from our <unk>.

Raju S. Mohan: Any drug in the class.

Raju S. Mohan: It hasnt been a lot of data out there showing effects on biomarkers in this study right.

Raju S. Mohan: But again for US we believe from our phase one study everything we've seen this is our extremely well behaved compound suitable for QD dosing at low doses, we expect to have coverage.

Raju S. Mohan: Coverage of IC 90 doses, starting at 10 to 12 milligrams and it's a real clean single order kinetics dosing profile. So we're looking forward to this 28 day study and generate our own data like I said I don't have any.

Raju S. Mohan: And, you know, it's a real clean, single-order kinetics dosing profile. So we're looking forward to this 28-day study and generating our own data. Like I said, I don't have any doubts that we'll see effects on IL-1 beta downstream markers, NLRP3, again, IL-1 beta, IL-6, HSCRP, and, you know, and we'll establish our own biomarker profile, both in blood and in CSF, with respect to things like neurofilament light chain and other biomarkers as well.

Raju S. Mohan: Doubts that we will see effects on IL, one beta downs.

Raju S. Mohan: Downstream markers and in RMB, three again, IL, one beta IL six HSC ERP.

Raju S. Mohan: And.

Raju S. Mohan: And we will establish our own.

Raju S. Mohan: Biomarker profile, both in blood and CSF with respect to things like narrow filament light chain and other biomarkers as well and then there was some data from Natera, but do not compound is so well behaved we hit the target so hard.

Raju S. Mohan: Now, there was some data from Lottera. But, you know, our compound is so well-behaved, we hit the target so hard, that we'll have to set our own calibration for Phase IIa before we go into a longer Phase II study.

Raju S. Mohan: That will have to set our own calibration for the phase Iia before we go into a longer phase II study.

Raju S. Mohan: Yes.

Samuel Evan Slutsky: Thank you. We will take our next question from Sam Slutsky with LiveSci.

Raju S. Mohan: Thank you we will take our next question from Sam Slutsky with life Science.

Raju S. Mohan: Hey, good afternoon, everyone. I hopped on a tad late, so if you answered any of my questions previously, just let me know. On the obesity preclinical study with 3232, just kind of generally speaking, how similar or different is the methodology to what NADARA did in their preclinical study? And then do you anticipate that there will be any bigger conclusions that can be drawn from it other than just kind of the binary of whether it looks good or not on weight loss?

Samuel Evan Slutsky: Hey, good afternoon, everyone I hopped on a tad laid since you answered any of my questions. Previously just let me know.

Raju S. Mohan: On the RBC preclinical study with <unk>, just kind of generally speaking, how similar or different methodology to why not derogate in their preclinical study and then do you anticipate that there'll be any bigger conclusions that can be drawn from it other than just kind of a binary of it looks like it or not on weight loss.

Raju S. Mohan: Good to hear from you, Sam. I'm happy to repeat the answers for you. I don't think I've ever in my 30 years spent so much time talking about my studies, but I'm happy to do so. So there are really no learnings from the mouse study that the competitor did. Again, it was a pretty standard DIOS study, so in the olden days, you had to generate these mice by feeding them a high-fat diet for 15 weeks or longer. Nowadays, these are off the shelf. You can buy them.

Speaker Change: Yes, good to hear from you salmon happy too.

Raju S. Mohan: Repeat the answer for you I don't think Andrew.

Raju S. Mohan: Never in my 30 years spent so much time talking about my studies, but happy to do so.

Raju S. Mohan: It's so there's really no learnings from from the mouse study that the competitor did.

Raju S. Mohan: Again, it was a pretty standard Dio study so you have.

Raju S. Mohan: Obese mice in the Olden days, you had to two <unk>.

Raju S. Mohan: Generally these mines by feeding them, a high fat diet for 15 weeks or longer Nowadays. These are off the shelf you can buy.

Raju S. Mohan: You can buy obese mice diet induced obese mice.

Raju S. Mohan: In terms of.

Raju S. Mohan: You can buy a BeastMice diet and use a BeastMice. In terms of, So we have done these trials before, perhaps looking at different endpoints. In this case, the primary endpoint, obviously, is weight loss, and we look at secondary endpoints, as I mentioned before, like effects on liver weight, body weight, and body skin. We're also doing DEXA in this study, looking at lipids, we look at liver steatosis, we do staining in the liver, so everything that you would want to read out post-weight loss there as well.

Raju S. Mohan: So we have done these trials before perhaps looking at different endpoints in this case the primary endpoint, obviously weight loss and we look at secondary endpoints as I mentioned before like effects on.

Raju S. Mohan: Liver weight body weight.

Raju S. Mohan: <unk> body scan, we also doing <unk>. This study look at lipids, we look at the rest of the doses, we do staining in the liver.

Raju S. Mohan: So everything that you would want to read out post the weight loss there as well.

Raju S. Mohan: <unk>.

Raju S. Mohan: Really, again, like I said before, you need to look at individual readings from this study to understand, you know, how it translates or potentially translates into what you expect in humans. It's not a one-to-one correlation, right?

Raju S. Mohan: Really again like I said before you need to look at individual readings from this study.

Speaker Change: I understand.

Raju S. Mohan: How it translates to potentially translates into what you expected humans is not a one to one correlation I just model. This model to use for a number of things. So you will see them being used for developing drugs for diabetes have been used for DPP four inhibitors happy news for ICF <unk>, they've been used for <unk> one agonist.

Raju S. Mohan: These models are used for a number of things. You'll see them being used for developing drugs for diabetes; they've been used for DP4 inhibitors, SGLT2, and GLP-1 agonists. Now we're looking at an RP3, so it's really a broad model, and you can take individual pieces from this model and then reconstruct what you would want to see in a human study. And again, we're excited about not just this model.

Raju S. Mohan: Now we're looking at an RP three so it's really a broad model and you can take individual pieces from this model and and then reconstruct what you would want to see in a human study right.

Raju S. Mohan: And again, we're excited about not just this model. This model is just a path for us to go into the humans.

Raju S. Mohan: This model is just a path for us to go into the human. And so, you know, we'll complete the models. We'll get you the data in a few weeks. And then on to the human study. And in the meantime, our biologists are actively trying to link the dots and understand hypothalamic interaction within an RP3 and, you know, effects downstream. So just try to build a picture.

Raju S. Mohan: And so we will complete the models, we'll get you the data in a few weeks and then onto the human study.

Raju S. Mohan: In the meantime, our biologists are actively trying to link the dots and understanding hypertonic interaction with within an RP three effects downstream. So just trying to build a picture.

Raju S. Mohan: Yes.

Raju S. Mohan: Okay, that's helpful. And just real quick on 2735, the potential prevention of MACE and pericarditis study. As you think about that landscape on that knee, the current treatment paradigm, where do you see the profile 2735 kind of best slotting in?

Speaker Change: Okay. That's helpful and just real quick on 735 on the potential prevention of nascent Pericarditis study.

Raju S. Mohan: As you think about that landscape unmet need current treatment paradigm, where do you see the profile to 73, five kind of best slotting.

Raju S. Mohan: Okay.

Martin Douglas Auster: Yeah, let me, let me have Marty, you know, we've thought a lot about this, let him articulate this for you, Marty. Yeah, sure, Sam.

Speaker Change: Yeah, Let me, let me have Marty.

Marty: A lot of other things.

Marty: Let him articulate this for you.

Martin Douglas Auster: Yeah, sure, Sam. So obviously, there's some, you know, evolution in some of the management of cardiovascular disease, and so that'll sort of mature over the time course that we're developing. 2735. I think on the recurrent pericarditis side, you have a pretty classic sort of niche orphan indication with limited therapeutic options. You know, currently Rolanaceps is really your go-to for difficult-to-manage refractory patients. It's obviously You may be less than less than perfect for some patients due to its nature as an injectable therapeutic.

Marty: Yes, sure Sam So obviously, there's some evolution in some of the management of cardiovascular disease, and so that will sort of mature over the time course that we're developing 2735 I think in the recurrent pericarditis side, you have a pretty classic sort of niche orphan indication with limited therapeutic options.

Martin Douglas Auster: <unk>.

Martin Douglas Auster: Currently relentless that's really your sort of your go to for difficult to manage refractory patients since obviously.

Martin Douglas Auster: It's also a very expensive therapeutic So there's some opportunities certainly to to I think put forth an oral option for patients who are suffering with recurrent pericarditis symptoms I think that disease is often managed now with sort of you know, sort of a bit more of a scattered approach without necessarily a lot of consistency in Treatment guidelines and people use things like aspirin and steroids and colchicine and things like that and I think a very nice targeted NLRP3 inhibitor Such as 2735 could play an important role and obviously the clinical pathway is heavily de-risked by the success of IL-1 driven biologics in the setting, so excited to kind of develop that, find the right slotting for that in the tree paradigm.

Martin Douglas Auster: You may be less and less than perfect for some patients due to its nature as an injectable therapeutic. It's also a very expensive therapeutics theres. Some opportunities certainly two to I think put forth an oral option for patients who are suffering with recurrent pericarditis symptoms I think diseases, often manage now with sort of.

Martin Douglas Auster: Sort of.

Martin Douglas Auster: A bit more of a scattered approach without necessarily a lot of consistency and treatment guidelines and people use things like aspirin and steroids and colchicine and things like that and I think a very nice targeted <unk> inhibitor.

Martin Douglas Auster: Such as 2035 could play an important role and obviously the clinical pathway is heavily derisked by the success of idle one.

Martin Douglas Auster: Driven biologics in the setting.

Martin Douglas Auster: So excited to kind of develop that in.

Martin Douglas Auster: Find the right slotting for that treat paradigm.

Speaker Change: Alright, alright, thanks, everyone.

Martin Douglas Auster: Yes.

Raju S. Mohan: Thank you. We have no further questions at this time. I now turn the presentation back over to Dr. Raju Mohan for any additional or closing remarks.

Raju S. Mohan: Thank you we have no further questions at this time I would now turn the presentation back over to Dr. Rajiv Mohan for any additional or closing remarks.

Raju S. Mohan: Yeah, yeah, thank you, everybody. Thank you to all on the call. So we thank you for your continued interest in Ventyx. Obviously, a very exciting period for us. We look forward to connecting with you at the investor conference in the coming months, discussing the MICE data. We're looking forward to talking about our efforts with O2 partnerships, moving towards the Phase 3 trial, and then, you know, hopefully reporting on, and coming back and reporting on the ongoing Crohn's trial. So, a lot to talk about, but again, for today, thank you all, and thank you to the team.

Raju S. Mohan: Yes, Thank you everybody and thank you to all on a call.

Raju S. Mohan: Thank you for your continued interest in <unk>, obviously, a very exciting period for US we look forward to connecting with you at investor conferences coming months connecting with you on the mice data we.

Raju S. Mohan: Looking forward to.

Raju S. Mohan: Talking about our efforts with over two partnerships moving towards the phase III trial, and then hopefully reporting on.

Raju S. Mohan: And coming back and reporting on the ongoing Crohns trials, so lots to talk about but again for today. Thank you all and thank you to the team.

Operator: Thank you, everyone. This concludes today's teleconference. We appreciate your participation. You may disconnect at any time.

Speaker Change: Thank you everyone. This concludes today's teleconference. We appreciate your participation you may disconnect at any time.

Operator: Mhm.

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