Q1 2022 Ventyx Biosciences Inc Earnings Call
Yeah.
Okay.
Good day, and thank you for standing by.
Operator: Good day, and thank you for standing by. Welcome to the Ventyx Bioscientists First Quarter 2022 Financial Results Conference call. At this time, all participants are in a listen-only mode.
Welcome to the vintage Biosciences first quarter 2022 financial results conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one on your telephone if you require any further assistance. Please press star zero I would.
Operator: After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Mr. Martin Auster. Please go ahead. Thank you, operator. Good afternoon, everyone.
Now like to hand, the conference over to your Speaker today, Mr. Marty Arthur Please go ahead.
Thank you operator, and good afternoon, everyone and thanks for joining the call today welcome to <unk> Biosciences Conference call and webcast, we will be discussing our first quarter 2022 financial results and providing a business update as a reminder, the company's most recent investor presentation can be found on our website at www diabetics dot com under the Investor tab in the news and events.
Martin Auster: Thanks for joining the call today. Welcome to Ventyx Biosciences' conference call and webcast, where we'll be discussing our first quarter 2022 financial results and providing a business update. As a reminder, the company's most recent investor presentation can be found on our website at www.ventyxbio.com under the investor tab of the news and events section. Before we begin today, I'd like to remind everyone that this conference call webcast will contain forward-looking statements about the company, including statements about the timing of the commencement, enrollment, and completion of clinical trials, the anticipated timing of release of clinical trial data, and the expected timeframe These statements are subject to risks and uncertainties that could cause actual results to differ.
Sure.
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 statements about the timing of commencement enrollment and completion of clinical trials.
The anticipated timing of release of clinical trial data and your expected time frame for funding operations with current cash cash equivalents in marketable securities.
These statements are subject to risks and uncertainties that could cause actual results could differ. 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 future events.
Martin Auster: 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 at future events. Factors that could cause actual results or outcomes to differ materially from those expressed or implied by such forward-looking statements are discussed in greater detail in our filings with the Securities and Exchange Commission, including our Form 10-Q for the first quarter of 2022, which we expect to file later this afternoon. With that, I will hand the call over to Dr. Raju Mohan, Ventyx co-founder and CEO. Raju, please go ahead. Thanks, Marty.
Factors that could cause actual results or outcomes to differ materially from those expressed or implied by such forward looking statements are discussed in greater detail in our filings with Securities and Exchange Commission, including our Form 10-Q for the first quarter of 2022, which we expect to file this afternoon.
With that I will hand, the call over to Dr. Rajiv Mohan.
<unk>, who is founder and CEO of our Zhu. Please go ahead.
Raju Mohan: And thanks to everyone for joining our call this afternoon. So, let me briefly run through the staff notes agenda. We'll start with a business update and then present an overview of the company's pipeline, followed by a recent highlight. And then I'm going to hand the call back to Marty for a brief overview of our first quarter financial results.
Thanks, Marty and thanks to everyone for joining our call. This afternoon.
So let me briefly run through the darkness agenda.
We'll start with a business update and then present, an overview of the company's pipeline.
Followed by recent highlights.
And then going to hand, the call back to Marty for a brief overview of our first quarter financial results.
Raju Mohan: Before we open the discussion, the call for Q&A. Before we begin, however, I want to take a minute to formally introduce Bill Sanborn, and we announced his news earlier this week that he joined the Ventyx leadership team as president and chief medical officer. As many of you know, Bill is a highly accomplished clinician and a renowned expert in the field of autoimmune and inflammatory diseases, but specifically inflammatory bowel disease, or IBD
Before we open the discussion to call for Q&A.
Before we begin however, I wanted to take a minute to formally introduce bill Sandborne and we announced his.
Raju Mohan: Bill has been closely involved in the development of a number of approved therapies in the I&I space and in the immunology space, both biologics and small molecules. As chairman of our clinical advisory board for the past few years, Bill has played a key role in developing and shaping our clinical strategy and now, in his new role as both president and, more importantly for us, as CMO. He will lead our clinical development team as we advance our portfolio, which targets multiple immune-mediated diseases. So welcome to the Ventyx team, Bill. And I'd appreciate it if you would say a few words before we move ahead with the rest of the agenda. Bill?
News earlier this week joined <unk> leadership team as President and Chief Medical Officer.
As many of you know bill is a highly accomplished clinician and a renowned expert in the field of autoimmune.
And inflammatory diseases.
Alright, inflammatory bowel disease or IBD.
Bill has been closely involved in the development number of approved therapies and the.
Nice space in the immunology space, both biologics and small molecules.
As chairman of our clinical Advisory board for the past few years.
<unk> played a key role in developing and shaping our clinical strategy and now in his new role as both president, but more importantly for us as the CMO. He.
He will lead oxen.
<unk> team our clinical development team.
We advanced our portfolio.
The target multiple immune mediated diseases.
Welcome to the Ventas team Bell.
I appreciate if you would say a few words before we move ahead with the rest of the agenda Bill.
bill Sanborn: Thank you so much Raju for the warm welcome and good afternoon everyone. Over the past five years I've worked closely with Raju and the Ventyx team as an advisor and chair of the clinical advisory board And it's been remarkable to see the team's progress over that time now with three differentiated products in the clinic, thrilled to be joining Ventyx and dedicating my full attention to our portfolio of innovative oral medicines, of which is VTX958, our potential best-in-class allosteric TIK2 inhibitor for the treatment of immune-mediated diseases, including psoriasis, psoriatic arthritis, Crohn's disease, and lupus.
Thank you so much Russia for the warm welcome and good afternoon, everyone over the past five years I've worked closely with <unk> and <unk>.
Gentex team as an adviser and chair of the clinical Advisory Board and it's been remarkable to see the teams progress over that time now with three differentiated products in the clinic and thrilled to be joining <unk> and dedicating my full attention to our portfolio of innovative oral medicines.
Most foremost of which is <unk> 95 day, our potential best in class I will steer uptick two inhibitor for the treatment of immune mediated diseases, including psoriasis, psoriatic arthritis, crohn's disease and lupus.
bill Sanborn: I strongly believe that our clinical candidates have the potential to address important unmet medical needs and to disrupt large immunology markets, which are currently dominated by biologics. I look forward to sharing more details on our program in the coming months, including an important Phase 1 update for the VTX958 program early in the third quarter of this year. I'll now turn the call back to Raju.
I strongly believe that our clinical candidates have the potential to address important unmet medical needs.
So just rough large immunology markets, which are currently dominated by biologics.
Look forward to sharing more details on our program in the coming months, including an important phase one update for the <unk> 95 to eight program early in the third quarter of this year ill now turn the call back to Russia.
Raju Mohan: Thanks, Bill, and once again, welcome to the... So I'll now move on to the pipeline and a business update. So the first quarter of 2022 was a really important period for us, both in terms of execution and as we continue to advance our three clinical programs targeting TIC-2, S1P1, and NLRP3. I'm really proud of our team's continued efforts, and we look forward to sharing a number of key updates, as Bill said, with you all over the next few months.
Thanks, Bill and once again welcome to the team.
So I'll now move to the pipeline and a business update.
So the first quarter of 2022 was a really important period for us.
Both in terms of execution and as we continue to advance our three clinical programs targeting take two <unk>, one and <unk> three.
I'm really proud of our team's continued efforts and we look forward to sharing a number of key updates as Bill said with you all over the next few months.
Raju Mohan: So for now, I'd like to briefly address each of these programs, including Recent Progress and Upcoming Milestones. So let me begin with VTX95, a novel allosteric inhibitor, based on its preclinical profile that we have disclosed earlier. VTX958 is highly selected for TIC2. It shows no measurable inhibition of all other JAK isoforms.
So for now I would like to briefly address each of these programs, including recent progress and upcoming milestones. So.
So let me begin with Gtx 958, our novel Allosteric <unk> inhibitor.
Based on its preclinical profile that we have disclosed earlier.
<unk> 95, eight is highly selective kick to.
It shows no measurable inhibition of all other JAK isoforms.
Raju Mohan: So from the outset, our goal with VTX958 has been very clear, to develop a potential best-in-class, highly selective allosteric TIK2 inhibitor with a wide safety and tolerability window that allows us to achieve clinical exposures that cover TIK2-driven targets, not just IC50 levels, but pushing up to IC90 levels for these TIK2 targets.
So from the outset, our goal with VTS 95 base has been very clear.
To develop a potential best in class highly selective allosteric <unk> inhibitor.
Safety and Tolerability window allows.
Allows us to achieve clinical exposure that cover take two driven target not just IC 50 levels, but pushing up to IC 90 levels for these two targets.
So again.
Raju Mohan: The key to achieving this potentially best-in-class target profile really comes back to the design of our molecule, to what I call a chemistry class, who built 958 to be highly selective for the allosteric domain of TIK2, and our preclinical work has demonstrated that 958, TX958, inhibits... The key TIK2 pathways, such as IL-12, IL-23, and interferon-alpha, while eliciting virtually no, and I repeat, no detectable inhibition of JAK1 pathways or any other JAK pathway, and Jacqueline Pathways, in particular, cytokines such as IL-6 and IL-10. IL-22, and others. So we believe it.
The key to achieving this potentially best in class target profile.
It really comes back to the design of our molecule.
So what I call a chemistry craftsmen.
Who built 95% <unk> highly selective for the allosteric domain uptick too.
And our preclinical work has demonstrated that 95 <unk> 95, eight inhibits key take two pathways such as IL 12.
'twenty three and interferon alpha.
Illustrating virtually no in a row.
Pete No no detectable inhibition of JAK, one pathways or any other JAK pathways and Jack one pathways in particular.
Cytokines, such as IL, six IL 10 IL.
<unk> 2002 and others.
So we believe.
Raju Mohan: This profile will allow us to dose PTX958 at high exposures while avoiding Jack mediated pathways and safety and tolerability issues associated with these JAK pathways that have been seen with other JAK inhibitors, including adverse laboratory findings that are either clinical or dermatological. So last year, we completed a phase one single ascending dose trial for VTX958 in healthy volunteers. This was a trial with seven dose cohorts. We began at sub-therapeutic doses, low doses, and we escalated up to significantly higher doses.
This profile will allow us to dose VTS 95, eight at high exposures.
While avoiding Jack mediated pathways.
And safety and Tolerability issues associated with these JAK pathways and that has been seen with other JAK inhibitors.
Including adverse laboratory findings.
That are either clinical or dermatological aes.
So last year, we completed a phase one single ascending dose trial for <unk> 958 in healthy volunteers.
This was a trial with seven dose cohorts.
Again at sub therapeutic doses low doses and we escalated up to significantly higher doses as we have stated before we are very.
Raju Mohan: As we have stated before, we are very pleased with these results that we saw, both in terms of drug exposure, P.K., what we call P.K., and the pharmacodynamic effects, what we call P.D., on target engagement, are multiple are phase one multiple ascending dose trials, also called the MAD trial, which is part of a phase one trial. 5-Dose Cohort Here we begin at a dose level that is around the low end of the expected therapeutic range, and again, those escalate to much higher doses and exposure.
Pleased with these results that we saw.
Both in terms of drug exposure.
The PK.
What we called PK.
And the Pharmacodynamic effects there'll be called PD.
Target engagement.
Our multiple.
Our phase one multiple ascending dose trial.
Also called the Mad trial, which is part of a phase one trial.
Five dose cohorts.
Here, we begin at a dose level that is around the low end of the expected therapeutic range.
Again dose escalate too much higher doses and exposures.
Raju Mohan: We plan to complete dosing by the end of the second quarter and provide a phase one data update in early Q3. Our plan is to show full safety data from our phase one program at this time and also data characterizing our exposure levels and target and engage. In addition to these data, we will also present data on a selected solid oral dose or tablet formulation that we expect in our phase 2 trial. As we have previously indicated, we expect to commence phase 2 trials in the second half of 2022, beginning with psoriasis, followed by psoriatic arthritis. Kronstein.
We plan to complete dosing by the end of the second quarter and provide a phase one data update in early Q3.
Our plan is to show full safety data from Las Vegas on program at this time.
And also data characterizing our exposure levels and target engagement.
In addition to these data we will also present data on our selected <unk>.
Solid oral dose tablet formulation that we expect in our phase two trial.
As we have previously guided we expect to commence phase II trials in the second half of 2022.
Beginning with psoriasis, followed by Psoriatic arthritis, and Crohn's disease.
Raju Mohan: We believe that the profile of PTX 958, in terms of safety, exposure, and target coverage, may allow us to achieve superior efficacy for an oral agent in all our target indications, potentially closer to the efficacy seen with biologicals. We also believe this profile may expand utility of TIK2 into other disease areas beyond psoriasis and arthritis, including indications like Crohn's disease, in particular, which may require higher And as a reminder, these are very large markets, all currently dominated by biologics, including a $20 billion annual market for psoriasis, a $4 billion plus annual market for psoriatic arthritis, and a $13 billion annual market for Crohn's disease.
We believe that the profile of <unk> 95, eight in terms of safety exposure and target coverage may allow us to achieve superior efficacy for an oral agent.
In all our target indications.
Potentially closer to the efficacy seen with biologics.
We also believe this profile mix spans utility uptick to into other disease areas.
Beyond psoriasis, and Psoriatic arthritis, including indications like Crohn's disease and <unk>.
Particular, which may require higher exposures to achieve therapeutic benefits.
And as a reminder, these are very large markets. All currently dominate their biologics, including a $21 billion annual market psoriasis, a $4 billion plus annual market in Psoriatic arthritis, and a $13 billion annual market in Crohn's disease.
Raju Mohan: We believe there's an opportunity for safe and effective oil therapies to capture a significant share within these markets, including a new addition to the TIG-2 validation, which is Blueprint. Next is VTS002, a novel S1P1 receptor modulator currently in phase 2 development for moderate to severe ulcerative colitis, or UC. So this is another clinically validated mechanism, and we believe VTX002 has all the characteristics and profile of a potentially best-in-class S1P1R module. This compound has high selectivity for S1P1R and has a rapid and robust suppression of PD biomarkers, in this case, circulating lymphocytes in healthy volunteers, no known active metabolites, and an important effective titration regimen that we used effectively in phase one that minimizes on-target first dose heart rate effects, also known as radicardia.
We believe there's an opportunity with a safe and effective oral therapies to capture.
We can share within these markets.
Including a new addition to.
TIK, two validation, which is Lucas.
Next is <unk> 002 on.
Our novel <unk> receptor modulator currently in phase II development for moderate to severe ulcerative colitis or UC.
So this is another clinically validated mechanism and we believe <unk> has all the characteristics and the profile of potentially best in class <unk> <unk> modulator.
This compound is high selectivity for <unk>.
<unk>.
And robust suppression of <unk>.
PD Biomarkers in this case circulating lymphocytes in healthy volunteers no.
No known active metabolites and.
Potent effective titration regimen that can be used effectively in phase one.
Minimises on target first dose heart rate effects also known as Lady cardio.
Raju Mohan: Our phase one trials for VTX002 explored a wide dose range, a broad dose range, and demonstrated excellent safety and tolerability, as well as allowing us to push the dose, to maximize both the dose and exposure, to maximize pharmacodynamic or PD activity, which again, as I mentioned before, is a reduction in absolute lymphocyte count. This PD effect has been shown to correlate with key efficacy outcomes, including achievement of clinical remission in previous UC trials with other S1P1 drugs.
Our phase one trials for <unk> to explore a wide dose range, a broad dose range and demonstrated.
Excellent safety and <unk>.
Tolerability as well as allowing us to push the dose to maximize split the dose exposures to maximize pharmacodynamic or PD activity, which again as I mentioned before is reduction in absolute lymphocyte counts.
This PD effect has been shown to.
Correlate with key efficacy outcomes, including achievement of clinical remission and PBS you'll see trials with other <unk> drugs.
In the fourth quarter of 2021, we initiated a phase II randomized placebo controlled clinical trial for <unk> <unk>, one drug in moderate to severe UC patients.
Raju Mohan: In the fourth quarter of 2021, we initiated a Phase II randomized placebo-controlled clinical trial for VTX002, an S1P1 drug, in moderate to severe UC patients. This trial is planned to enroll around 180 patients. 180 patients include two VTX002 active-dose cohorts, as well as a placebo group, with a primary efficacy endpoint of clinical remission at the 13-week time point, followed by 39 weeks of open-label extension, an open-label treatment period. We will also be evaluating numerous other efficacy measures, along with safety and tolerability.
This trial is planned to enroll around 180 patients 180 patients.
<unk> two <unk> 002 active dose cohorts as well as the placebo group with a primary efficacy endpoint of clinical remission at the 13 week time point, followed by 39 weeks of open label extension open label treatment period.
We will also be evaluating numerous other efficacy measures along with safety and Tolerability.
Raju Mohan: Finally, we designed the Phase II induction trial to potentially serve as the first of two pivotal trials required by the Agency for Registration in QC. We plan to have more specific updates on this program, on the enrollment status as the trial progresses, and we look forward to announcing top-line phase two data in 2023. Finally, I'll turn to our NLRP3 inhibitor profile, beginning with VTX2735, which is our selective and peripherally restricted NLRP3 inhibitor designed to target systemic inflammatory diseases, such as cardiovascular, hepatic, renal, and rheumatological diseases.
Finally, we design this phase two induction trial to potentially serve as the first of two pivotal trials required by the agency for registration in UC.
We plan to have more specific updates on this program on the <unk>.
<unk> status as the trial progresses, and we look forward to announcing topline phase II data in 2023.
Finally, I'll turn to our MLR between <unk>.
A profile beginning with VTS 2735, which.
Which is a selective peripherally restricted <unk> three inhibitor designed to target just cemex inflammatory diseases such as diseases.
Cardiovascular.
Renal Andrew metallurgical diseases.
So this molecule <unk> 2735 phase one.
Raju Mohan: So this molecule, VTX2735, a phase one SADMED trial is ongoing in healthy volunteers. This trial has recently completed dosing, and we expect to report top-line data at the end of Q2, which will include a summary of safety and probability, as well as details on target engagement. We plan to advance VTS 2735 into one or more proof of concept, proof of mechanism trials, and clinical trials in the second half of this year, with additional details to be disclosed at a later time.
Sad Mad trial is ongoing in healthy volunteers. This trial as recent recently completed dosing and we expect to report topline data by the end of Q2, which will include a summary of safety and probability as well as details on target engagement.
We plan to advance <unk> thousand 735.
Into one or more proof of concept proof of mechanism trials clinical trials in the second half of this year with.
Additional details can be disclosed at a later time.
I'd also like to mention another exciting addition to this portfolio and that is VTS $32 32, our potent selective CNS brain penetrant CNS, our brain penetrant <unk> inhibitor.
Raju Mohan: I'd also like to mention another exciting addition to this portfolio, and that is VTX3232, our potent selective CNS or brain penetrant NLRP2 inhibitor, which we nominated as a development compound, DC, in the fourth quarter of last year. So VDX-332 is a novel chemical scaffold different from the peripheral 2735 series. It shows good CNS penetration and good CNS exposure in early preclinical studies. We have now advanced VTX 3.2.3.2 into IND-enabling studies and plan to file the IND for VTX 3.2.3.2 in the fourth quarter of this year or in the fourth quarter of 2022.
Which we nominated as a development compounds DC in the fourth quarter of last year.
<unk> is a novel chemical scaffold.
From the peripheral 2700 35 series it shows good CNS penetration.
And good CNS exposure in early preclinical studies.
We have now advanced <unk> two into IND, enabling studies and plan to file the <unk>.
<unk> 32 in the fourth quarter of this year in the fourth quarter of 2022.
Raju Mohan: We believe that VTX3232 could be the first truly CNS-penetrant, truly brain-penetrant NLRP3 inhibitor to enter the clinic, with potential to target a range of neuroinflammatory neurodegenerative conditions with high unmet need that address large markets, including Parkinson's disease, Alzheimer's, and ALS.
We believe that <unk> could be the first truly CNS penetrant truly brain penetrant <unk> inhibitor to enter the clinic.
With potential to target a range of neuro inflammatory neurogenic degenerative conditions with high unmet need.
That address large markets.
In Parkinson's disease, Alzheimer's and ALS.
Raju Mohan: The pace at which this program, the CNS Benefit Program, has advanced is a significant achievement for our discovery team, what I called our chemistry craftsman here at Ventyx, led by our chief scientific officer, John Nassar, as accessing rain penetrant NLRP3 inhibitors has historically been very challenging. John's group continues to remain very active in the discovery of new candidates, and we look forward to providing updates on our discovery efforts in future quarters. So, in summary, 2022 is set to be a transformative year for Ventyx.
The pace at which this program.
CNS benefit program has advanced as.
As a significant achievement for our discovery team, what I called our chemistry Craftsman here Atlantic's led by our Chief Scientific Officer, John Us as.
As accessing brain penetrant <unk> inhibitors have been store has been historically very challenging.
John's Group continues to remain very active in the discovery of new candidates and we look forward to providing updates on our discovery efforts in future quarters.
So in summary, 2022 set to be a transformative year for <unk>. Our team is off to a great start and we look forward to a number of milestones over the remainder of the year, including top line phase one data for VTS 95 day Arctic two inhibitor in early Q3.
Raju Mohan: Our team is off to a great start, and we look forward to a number of milestones over the remainder of the year, including top-line phase one data for VTX958, our TIC2 inhibitor, in early Q3, initiating three potential phase two trials for VTX958, in the second half of the year, and top-line phase 1 data for 27.35 later in Q2. Continued execution at the phase 2 trial for VTX002 and an IND filing for VTX3232 by year's end.
Initiating three potential phase II trials for Etfs 95 eight.
In the second half of the year.
Top line Phase <unk> data for 2017 35 later in Q2.
Continued execution of phase III trial for <unk>.
And an IND filing for <unk> three to three two by years end.
So I'd like to emphasize that all our pipeline is internally discovered.
Raju Mohan: So I'd like to emphasize that all our pipelines, Charlie, Discovered, We own 100% of all IP rights and commercial rights, all are compounds, they're all wholly owned by Ventyx. Before we move to Q&A, I'd like to hand the call back to Marty Auster for a brief discussion of our financial results.
We own 100%.
All IP rights and commercial rights.
All our compounds all wholly owned by <unk>.
Before we move to Q&A I'd like to hand, the call back to Marty Officer.
For a brief discussion of our financial results Marty.
Martin Auster: Thank you, Raju. I'll briefly summarize our financial results here for the first quarter of 2022. R&D expenses in the quarter were $17.4 million compared to $24.6 million for the first quarter of 2021.
Thank you Roger I'll briefly summarize our financial results here for the first quarter of 2022.
R&D expenses in the quarter were $17 4 million compared to $24 6 million for the first quarter in 2021. The first quarter of 2021 R&D expense did include a $21 $7 million noncash in process R&D expense related to <unk> acquisition of <unk> and Joe mentioned subsidiaries, we expect R&D.
Martin Auster: The first quarter 2021 R&D expense did include a $21.7 million non-cash in-process R&D expense related to Ventyx's acquisition of the Opelon and Zomagen subsidiaries. We expect R&D expenses to generally trend upwards over 2022 as we prepare and launch three phase two trials for VTX958 in the second half of the year that Raju had previously detailed. G&A expenses were $5.3 million for the first quarter of 2022 compared to $0.7 million in the first quarter of 2021, and the net loss for the first quarter of 2022 was $22.7 million compared to $37.6 million in the first quarter of 2021.
<unk> expenses to generally turned upwards over 2022, as we prepare to launch three phase III trials for <unk> in the second half of the year that Regina previously detailed.
G&A expenses were $5 3 million for the first quarter of 2022 compared to <unk> 7 million in the first quarter of 'twenty one.
Net loss for the first quarter of 2022 was $22 7 million compared to $37 6 million in the first quarter of 2021 importantly, cash cash equivalents and marketable securities were children $73 1 million as of March 31, 2022, and we believe our current cash equivalent and marketable securities are sufficient to fund operations into the <unk>.
Martin Auster: Importantly, cash, cash equivalents, and marketable securities were $273.1 million as of March 31, 2022, and we believe our current cash and marketable securities are sufficient to fund operations into the first half of 2024. We believe this cash runway will provide us with the ability to deliver key proof of concept readouts across our clinical stage pipeline, including the Phase II readouts for psoriasis for VTX95A and the Phase II ulcerative colitis readout for VTX02, both of which we expect to report in 2023. That concludes our prepared remarks for this afternoon's call, and I can now turn the call back to the operator to open up the Q&A session, where I'll be joined by Raju and Bill. Operator?
Half of 2024.
We believe this casual mobile provides us with the ability to deliver key proof of concept readouts across our clinical stage pipeline, including the phase III Readouts for <unk> since <unk> five agencies to also replace readout for <unk> two both of which we expect to report in 2023.
That concludes our prepared remarks for this afternoon's call and I can now turn the call back to the operator to open up the Q&A session, where I'll be joined by Rodrigo and Bill operator.
Operator: Certainly. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please limit yourself to one question.
Certainly as a reminder to ask a question you will need to press star on your talent Star one on your telephone to withdraw your question press the pound key please limit yourself to one question for additional questions. Please re enter the queue.
Yasmeen Rahimi: For additional questions, please re-enter the queue. One moment. Our first question comes from Yasmeen Rahimi of Piper Sandler. Good afternoon, and thank you for taking my questions. Dr. Sanborn, I'm thrilled and excited to work with you. If I may, I have two questions for you.
The moment.
Our first question comes from yes mean.
Rahimi of Piper Sandler Your line is open.
Good afternoon, and thank you for taking my questions. Dr. Sandborne will come on board and thrilled and excited to work with you.
bill Sanborn: The first one is if you could just shed some light on why you decided to join Ventyx at this point and why Ventyx? I'm certain it was a tough decision to pause on many of the other activities that you have ongoing. And then the second question is, as you might be aware, the Atresimod Phase III abstract was recently published, and the placebo responses in the maintenance phase were significantly lower than in the induction phase.
If I may I have two questions for you. The first one is maybe you could just shed some light on.
Why you decided to join <unk> at this junction and Wideband takes I'm certainly was a tough decision too.
To pause on many of the other activities that you have ongoing and then the second question is as you might be aware the <unk> phase three abstract was recently published.
And.
The placebo responses in the maintenance space were significantly.
Lower than in the induction phase.
Would love to hear maybe some thoughts on.
What the reason for that could be and what is then takes doing in regards to their phase II study in mitigating placebo response, especially during the induction period.
They are also happy with board be working with you closely.
bill Sanborn: So I would love to hear maybe some thoughts on what the reasons for that could be and what Ventyx is doing in regards to the Phase II study and mitigating placebo response, especially during the induction period. And again, thrilled to have you on board and be working with you closely.
Well, thank you for the questions.
First.
bill Sanborn: As I mentioned in the prepared remarks, I've worked with Raju and John and Chris Krueger for about five years, and have just been involved with saying these molecules progress. I'm persuaded that there will be a transition in the coming years, from biologics to small molecules. We're seeing that happen gradually across dermatology, rheumatology, and inflammatory bowel disease. And we see sort of the first generation of molecules and then what I think are the follow-ons that will be best in class.
<unk> as I mentioned in the prepared remarks worked with.
<unk> and John .
Chris Krueger for.
About five years.
And had just been involved with seeing the.
These molecules progress and I'm persuaded that.
There will be a transition in the coming years from biologics to small molecules were seeing that progressively happened across dermatology rheumatology.
Inflammatory bowel disease space, and we see sort of the first generation.
Molecules and then what I think are the follow ons that we will be best in class and from my view.
bill Sanborn: From my point of view, both the TIK2 and the S1P1 modulator molecules at Ventyx really have the potential to be best in class, and that interested me very much, along with joining a great chemistry discovery group and a great team. I'm so happy to join.
Both.
Two in the <unk> modulator molecules dentex really have the potential to be best in class and that interested me very much along with joining.
Great Chemistry discovery group and a great team so happy to join with respect to.
bill Sanborn: With respect to Etrasamad, the data has not yet fully been presented. They'll be presented in a little less than two weeks, at Digestive Disease Week. So, you know, we probably can't talk too much about it. But I think I would interpret what you said slightly differently.
<unk>.
Data is not yet fully been presented there will be presented in a little less than two weeks at digestive disease week. So we probably can't talk too much about it.
But I think I would.
<unk> and <unk>.
What you said slightly differently.
bill Sanborn: Essentially, there was a 52-week trial that was treated straight through, and the placebo rate was reported by some other analysts this week as being less than 10%. And then there was a shorter 12-week trial, just an induction trial, where the placebo rate was higher in the mid-teens. So it's not so much that it's a lower placebo rate in maintenance; the 12-week placebo rate in the 52-week trial was also in the single digits.
Essentially there was a <unk>.
52 week trial that was treat straight through.
And the placebo rate.
It was reported by some other analysts this week as being less than 10% and then there was a shorter.
Short 12 week trial, just an induction trial, where the placebo rate was higher in the mid teens. So.
It's not so much that it's a lower placebo rate in may and maintenance of the 12 week. Please.
Placebo rate than that in the <unk>.
52 week trial was also in the single digits. So just.
bill Sanborn: So this just shows that in large multi-center trials, there can be variations in conduct that have an effect on placebo rates. And so, without getting into all the details, what I would say, it's really just doing the Adequately Powered Trials at experience centers, closely monitoring them, paying close attention to the entry and exclusion criteria, and the central reading of endoscopy to qualify the patient.
Shows that.
In large multicenter trials that there can be variations and conduct that have affect on placebo rates and so without getting into all the details, but I would say it's really.
Just doing.
Adequately powered trials.
At experienced centers closely monitoring them paying close attention to the entry and exclusion criteria.
Central reading of endoscopy to qualify the patients.
bill Sanborn: Aiming for the right mixture of biologic-naive and biologic-experienced patients, the right mixture of moderate and severe patients, and all of that just takes a really hands-on clinical development team and close collaboration with CROs. Our development team at Ventyx is really committed to executing well on all of those little details that add up to an interpretable trial that gives the best chance for a drug to show up. Thank you, Dr. Sanborn. I'll jump back in the queue. And our next question comes from Josh Schimmer of Evercore ISI. Your line is open.
Aiming for the right mixture of biologic naive and biologic experienced patients the right mixture of moderate Tim.
Severe patients and all of that just takes a really pans on clinical development team and the close collaboration.
With <unk>.
Our.
Element team that Gentex is really committed to.
Executing well on all of those little details that add up to interpretable trial, but that gives us the best chance for drug to show efficacy.
Thank you Dr. Christine I'll jump back in the queue.
Yes.
Josh Schimmer: Great, thanks for taking the question. For each of the clinical stage programs, have you thought about the optimal time to partner each one, or are there ones that you would consider advancing to and through commercialization on your own? Yeah, thanks, Josh. Good question.
And our next question comes from Josh Shimmer of Evercore ISI. Your line is open.
Great. Thanks for taking the question.
So for each of the clinical stage programs have you thought about the optimal time to.
Partner.
Each one or are there ones that you would consider advancing two and through commercialization on your own.
Yeah. Thanks, Josh good question, so as money.
Raju Mohan: So this money comes into this with their remarks, right? We're in a strong financial position currently with over 270 million in cash.
Commented in his prepared remarks, we're in a strong financial position currently with over $270 million in cash.
Raju Mohan: This round may extend into the 1st of April 2024, my current operating plan. So we're committed to driving value across the clinical pipeline, regarding our lead asset, the PIKQ-958. Obviously, expect to generate meaningful proof of concept efficacy data with the drug across psoriasis, cervical arthritis, Crohn's disease, and even possibly lupus, with phase two trials kicking off. As you know, we talked about this before, in the back of 2022, and the data on psoriasis is expected in the second half of 2023, right?
Ron we extend that into first half of 2024 and our current operating plan.
So we're committed to driving value across our clinical pipeline regarding our lead asset <unk> hundred 95 eight.
Obviously, we expect to generate meaningful proof of concept efficacy data with the drug across psoriasis, psoriatic arthritis, crohn's disease, and even possibly with Lucas with face across kicking off as you know we've talked about this before in the back half of 2022 and the data on psoriasis is expected in the second half of 2023 alright.
Raju Mohan: So I think our goal right now is laser-focused on executing our proof-of-concept trials, you know, where we'll capitalize to reach really key POC readouts. And, you know, in terms of the future, we own all commercial rights to our compounds. And so, you know, we'll have the flexibility to have a number of options, including partnering as we move forward to generate the best value across, across our portfolio. So a lot of optionality here, right?
So I think our goal right now is laser focused on executing our proof of concept trials and are well capitalized to reach really cute POC readouts.
<unk>.
In terms of the future.
We own all commercial rights to our compounds and so we'll have the flexibility.
I have a number of options, including partnering as we move forward.
Generate the best value across.
Across our portfolio. So a lot of optionality here right, so, but the key really is to do.
Michael Yee: So, but the key really is to keep executing, keep generating meaningful proof of concept data that we're truly lucky to be in a position that we are capitalized to do so. Yeah, thank you. And our next question comes from Michael Yee of Jeffreys. Your line is open.
Keep executing keep generating meaningful piece of our proof of concept data that were truly lucky to be in a position that we are capitalized to do so.
Got it thank you.
Yeah. Thanks, Josh.
And our next question comes from Michael Yee of Jefferies. Your line is open.
Yes.
Michael Yee: Hey guys, thanks for the updates and thanks for the questions. We had two questions, both related to TIC-2. When you spoke last, you said you were dosing very nicely in Phase 1. I think you said you were up past three or four cohorts out of five. Hopefully, that's going well.
Hey, guys. Thanks for the update and thanks for the questions.
Two questions.
Both related to take two.
When you spoke last you said you were dosing up very nicely in the phase. One I think you had said you were up past three or four cohorts out of five hopefully thats going well and I just wanted to ask about.
Raju Mohan: And I just wanted to ask about your expectations for differentiation, including things related to safety tolerability like acne or neutropenia and how much differentiation you think you could possibly show in a Phase 1. And the second part of the question is related to coverage of the targets and specifically with respect to IL-12 and 23, which are extremely important in IBD. Just remind us what type of coverage you have there at the higher doses and specifically relative to stuff like still air, and will we be able to draw those conclusions from phase one? Thank you. Great, Mike.
Your expectations for differentiation, including things.
On safety Tolerability like acting or neutropenia, how much differentiation do you think you could possibly show in a phase one.
And the second part of the question is related to coverage of the targets specifically.
With respect to IL 12 in 'twenty, three which are extremely important in IBD, just remind us what type of coverage you have there at the higher doses and specifically relative to stuff like still are and will we be able to draw those conclusions from the phase one thank you.
Got it.
Raju Mohan: Thanks again. Thanks for being on the call. And I think the two questions are sort of tied to each other.
Great Mike. Thanks, again, thanks for being on the call and I think the two questions are sort of tied to each other.
Raju Mohan: And so, look, in terms of the specifics of where we are in terms of covering IC50 and 90, stay tuned. I'm really looking forward to disclosing this data in early Q3. And so, just going back to where we are in the trial, so we are, you know, obviously in the final cohorts of our MAD, we continue to dose escalate throughout five cohorts, and I would say we're sort of in the end game here. The goal really is for The MAD part of this trial is to be maximized, and you can only do it if you have the safety window to do it right.
So look in terms of.
Specifics of where we are in terms of covering IC $15 90.
At June .
What are you looking forward to disclosing this data in early Q3.
And so just going back to where we are in the trial. So we are obviously in the final cohorts of our EBIT continued to dose escalate throughout.
<unk> cohorts and I would say, we're sort of in the us and the end.
And game here.
The goal really for the <unk>.
Part of this trial is to be maximized exposures and you can only do it if you will.
The safety window to do it right. So so first we have to.
Raju Mohan: So first we have to... demonstrate that these exposures, this compound is extremely well tolerated, and then if we can reach those exposures, provide evidence of target coverage on TIK2 pathways, as you call it, which is IL-12, 23, and more recently gained trust in lupus. So, in Effie on alpha. And our thesis is that the profile that we have built non-clinically, which we have shared with you, and the exciting profile of this molecule, we hope will allow us to maximize exposures. Again, safety is key.
Demonstrate at these exposures with compound is extremely well tolerated.
And then if we can reach a exposures.
Evidence of target coverage on two pathways as you call it which is which is IL 12, 23 and more recently the interest in lupus So interferon alpha.
Thesis is that the the profile that we have built non clinically that we have shared with you and the exciting profile of this molecule. We hope will allow us to two.
Maximized exposures.
Again safety is key and would these exposures we hope to cover not just IC 50, but I see 94, hopefully better part of a QD dosing cycle, So 12 14 hours or.
Raju Mohan: And with these exposures, we hope to cover not just IC50, but IC90 for hopefully the better part of a QD dosing cycle. So 12, 14 hours or more, and that'll bear out from our total phase one readout. We're looking forward to sharing with folks again at early, early... Third Quarter.
Or more and that will be a lot from our.
Total phase one readout.
Looking forward to sharing with folks again early.
Early.
Third quarter.
And as it relates to IL 12 in 'twenty three can you comment on on your relative potency on that at the higher doses and just remind us if we can draw conclusions just stuff like Stella.
Raju Mohan: And as it relates to IL-12 and 23, can you comment on your relative potency for that at the higher doses and just remind us if we can draw conclusions about stuff like sclerosis? Yeah, so we have disclosed our... IL-12, 23, and 23 human whole blood numbers, so they're pretty comparable. Those numbers. And we hope, again, we hope to cover IL-12 and IL-23 and NFU on alpha. IC90s, as we talked about, IC50s, I think is a really low bar for us.
Yes, so we have we have disclosed our.
IL 12 23.
12 23.
Human whole blood numbers, so they're pretty comparable.
Those numbers.
And.
We hope again, we hope to cover IL 12, and IL 23 antibody.
On Alpha.
You see <unk> as we've talked about IC <unk>, particularly.
Really low bar for us we think.
Raju Mohan: You know, we think to reach the efficacy of biologics, including Stella, you have to be in very high coverage of IC90 numbers. And we believe the safety profile of this molecule should allow us to maximize that coverage. What that coverage is, we're looking forward to sharing with folks in early 3Q.
To reach the efficacy of biologics, including Stella you have to be in very high coverage of IC 90 numbers and we believe the safety profile of this molecule.
Should allow us to maximize the IC 90 coverage what that coverages were looking forward to sharing with folks in early <unk>, but again the focus here is not just an IC <unk>.
Raju Mohan: But again, the focus here is not just an IC50, but to achieve efficacy comparable to biologics, we are targeting IC90 for each of the individual targets with the respective disease indications IL-12, 23 for psoriasis, psoriatic arthritis, and Crohn's disease, and then inofreon-alpha for lupus. Yeah, thanks, bye. And our next question comes from Tiago Fahoud of Credit Suisse. Your line is open.
To achieve the efficacy comparable to biologics, we're targeting pricing 90 for each of the individual targets for <unk>.
<unk> disease indications IL 12, 23 for psoriasis Psoriatic arthritis, Crohn's disease, and then interferon alpha <unk> for lupus.
Got it thank you guys.
Yes, Thanks, Mike.
And our next question comes from Thiago food.
Suisse. Your line is open.
Tiago Fahoud: Hey, thanks for taking the question. Just perhaps to hone in a little bit more on the safety side, I'm curious how you interpret the exposure you're going to have from the multisending dose portion of the study, in terms of the risk and the safety profile of the molecule, given what we've seen on the AE manifestation profile for other drugs in the class. So basically, how informative it's going to be for the purpose of interest, how early those usually come up, and how will this inform your path forward?
Hi, Thanks for taking the question just perhaps to hone in a little bit more on the safety side.
Curious how to interpret the exposure youre going to have from the multi ascending dose portion of the study.
In terms of de risking the safety profile of the molecule given what we've seen they AE manifestation profile for other drugs in the class. So basically how informative is going to be for the use of interest how early those usually come up.
How will this inform your path forward. Thank you.
Raju Mohan: Thank you. Yeah, thanks, Tiago. Great question.
Yes, Thanks, Thiago great question so.
Raju Mohan: So, Again, you know, we guide you to published data out there. And there's obviously a lot more data for proboscitinib than there is for some of the other molecules there. So clearly, AEs such as skin findings, acne, rash, corticaria, lab abnormalities such as neutropenia generally reveal themselves within a 14-day dose period, which is the period we are looking at.
Again, we guide you to.
Published data out there and there's obviously a lot more data for the province than there is for some of the other molecules there.
So clearly aes such as skin findings.
Acne rash quota carrier.
<unk> abnormalities such as neutropenia.
Generally reveal themselves.
Within a 14 day dose.
<unk>, which is the period, we're looking at so if you look across some of the detailed aes.
Raju Mohan: So if you look across some of the detailed AEs that Ducrovo in particular has disclosed and some of the stuff that has come out with newer drugs, again, to emphasize, these findings have revealed themselves, have shown themselves, within the 14-day period, and sometimes as early as day five in the case of some of the Dukrava outcomes. So again, our MAD program is looking at this 14-day dosing cycle, with, as I mentioned before, maximizing exposures to cover these two targets. So on the one hand, high exposures.
In particular as disclosed in some of the stuff that has come up with the newer drugs again to emphasize these findings have revealed themselves have shop.
Within the 14 day period, and sometimes as early as day five in the case of some of the crop outcomes. So again. So our program is looking at this 14 day dosing cycle.
As I mentioned before.
Maximizing exposures to cover these two targets so on one hand.
Raju Mohan: On the other hand, really careful look at what some of the other drugs have shown in this dosing period. So again, these show up in the 14-day period, and we are confident that if we were to see some of these effects that have been in other compounds, they would show up. But again, again, I'll defer back to the profile of our compound, where from ground zero, we build this molecule to have no JAK activity, a very selective allosteric molecule, no hint of JAK1 signaling, not in really relevant functional assays, and then build on top of that with a very, very careful look at a non-clinical safety profile.
Hi, exposures other hand really careful look at what some of the other drugs have shown in this dosing period. So again this show up in the 14 day period, and we are confident that if we were to see some of these.
Effects that have been some other compounds they would show up.
But again again I'll refer back to the profile of our compounds where from ground zero. We built this molecule to have no JAK activity.
Very selective allosteric molecule no hint of JAK, one signaling not really relevant functional assays.
And then build on top of that.
A very.
Careful look at our non clinical safety profile. So of course, the molecular profile led with the non clinical safety profile and going into our phase one trials.
Raju Mohan: So first, the molecular profile layered with the non-clinical safety profile and going into our phase one trials now so that we can take a careful look at some of the effects other folks have seen. And we are confident that without the JAK1 activity that we have managed to avoid with this molecule, we hope to avoid some of those signals that you've seen that you just mentioned with other inhibitors that are not as selective for TIK2 as VTX958. Perfect. No, very helpful.
Now so that we can take a careful look at some of the other folks have seen and we are confident that without the JAK one activity that we that we have managed to avoid with this molecule. We hope to avoid some of those signals.
Signals that you've seen but just mentioned with other inhibitors that are not selective for kick.
As is <unk> 95 eight.
Perfect very helpful. Thank you so much.
Raju Mohan: Thank you so much. Yeah, thanks, Diego. And our next question comes from Sam Slutsky of LifeSky Capital. Your line is open. Hi, this is Oliver McCammon filling in for Sam Slutsky.
Yes, Thanks Heiko.
And our next question comes from Sam Slutsky of Lifescan capital. Your line is open.
Hi, This is Oliver mccammon filling in for Sam Slutsky I. Appreciate you taking the questions I have two but to start as we think about initial clinical data with your MLR <unk> three inhibitor <unk> 273, five what markers and assays should we be most focused on for assessing its pharmacodynamic.
Sam Slutsky: I appreciate you taking the questions. I have two, but to start, as we think about initial clinical data with your NLRP3 inhibitor, VTX2735, what markers and assays should we be most focused on for assessing its pharmacodynamic effect? And is it known how much of an effect these PD markers are necessary to see a clinical benefit? Yeah.
And is it known how much of an effect these PD markers.
It is necessary to see a clinical benefit.
Yeah, So I'll, let bill and this but we'll be looking at some of the standard Mark because that had been disclosed four four.
Raju Mohan: So, and I'll let Bill comment on this, but we'll be looking at some of the standard markers that have been disclosed for not just NLRP3s but also for this pathways in general. Certainly IL-1 beta, there are some serum markers such as SAA, so serum amylodosis A marker, other biomarkers associated with some of these pathways as well. So we'll look at them carefully in terms of proof of mechanism and target engagement. I'll let Bill comment more on sort of what our, you know, near-term and long-term plan is with the NLRP3 compound 2735, Bill. Yeah, not not much to add.
Not just <unk>, but also for this pathway and general search.
The IL one beta does some serum markers such as Apis.
So serum.
Low doses.
Martha.
Other biomarkers associated with some of these factors as well. So we'll look at carefully look at these in terms of proof of mechanism and target engagement, but I'll, let bill.
Comment more on sort of what our.
Near term and long term plan is with.
The NLRB three compound 2735.
No.
bill Sanborn: I think you've picked out some of the mechanism-specific markers, although SAA is a little, you know, more generic. But then there are the old standby simple things like C-reactive protein and erythrocyte sedimentation rate. So, you know, all of those are markers that have been used for various indications. And, as Raju said during the prepared remarks, we look forward to giving a more holistic view of the indication for the proof of mechanism in the second half of the year.
Yes, not much to add I think you've picked out some of the mechanism specific biomarkers, although FCA is a little more generic but then there is the old standby simple things like C reactive protein and erythrocyte sedimentation rate.
So all of those are markers that have been used for various indications.
And as Joe said during the prepared remarks, we look forward to giving a more holistic view of.
The TARP the indication for the proof of mechanism in the second half of the year, but that range of Biomarkers.
bill Sanborn: But that range of biomarkers will certainly be in the development program for the proof of mechanism study. And to the degree that some of those are relevant, we're looking at them in the phase one trial as well. That's very helpful.
Well certainly.
And the development program for the proof of.
Mechanism study.
And to.
To the degree that some of those are relevant we're looking at them in the phase one trial as well.
bill Sanborn: And then, as a quick follow-up, it would be helpful also to get a sense of the potential benefits of inhibiting NLRP3 compared to IL-1 beta blockade alone. Yeah, again, I'll just lead off by saying that NLRP3 is not just IL-1 beta; it has a pronounced effect on PAREP2, as you know. And the results of pyroptosis are more sort of a mini-cytokine storm. A lot of pathologies come out.
That's very helpful. And then as a quick follow up it would be helpful. Also to get a sense of the potential benefits of inhibiting <unk> three compared to IL, one beta blockade alone.
Yeah, again, I'll just lead off by saying that in our Q3, not just one beta it has a.
Pronounced effect on product as you know.
<unk>.
And the results of part of doses are.
As more sort of a <unk>.
Many cytokines storm a lot of the policies to come out so it's not simply IL, one beta right Joe Hinrichs.
Raju Mohan: So it's not simply IL-1 beta, right? You're inhibiting pyroptosis. You're inhibiting IL-18. So it goes beyond sort of the classic IL-1 beta and the results we've seen with the biologics. But perhaps Bill will add more color to this. Bill?
Innovating PARP doses you are in the bidding.
<unk> 18, so it goes beyond sort of the classic IL, one beta and all the results we've seen with our biologics, but perhaps below add more color to that as well.
bill Sanborn: Well, I would say it goes beyond in the sense that there's inhibition of IL-18, but it goes less in the sense that it doesn't have the full spectrum of IL-1 inhibition, whether you do it with a receptor antagonist or an antibody or something like Rolanacept. So, you know, the IL-1 inhibitors all have labeled warnings around infection, and that has limited, and you'll recall the history and things like gout and stuff about IL-1 receptor antagonism, where you have to sort of look at the benefit and the risk, where the risk is weighed into the acceptability of various indications. And we have the hypothesis that the more narrow spectrum of coverage of an LRP3 and IL-18 may not have the same infection risk that the more broad-acting IL-1 inhibition will have. Thank you.
Well I would say it goes beyond in the sense that there is inhibition of IL 18, but it goes less in the sense that it doesn't have the full spectrum of IL, one and tradition, whether you.
With the receptor antagonist antibody.
Something.
Something like Milan us up so.
They are one inhibitors all have labeled warnings around infection and that has limited them youll recall, the history and things like gout and stuff.
The.
<unk>.
Receptor.
Tagging.
Where you have to sort of look at the benefit and the risk.
The risk is play them till the acceptability of various indications.
We should have the hypothesis that the more narrow spectrum of coverage of <unk> and <unk>.
May not have the same infection risks that the more broad acting inefficient.
Thank you I appreciate the time.
bill Sanborn: I appreciate the time. Thanks to all. Hey, Doug.
Thanks Al.
Jeff Jones: Our next question comes from Jeff Jones of Oppenheimer. Your line is open. Thank you. Appreciate you guys taking the call. I think the TIC-2s have been pretty well covered, so I'll step back to the S1Ps for the moment. In light of the Atrazimod data that's out there, the Phase 2 data, the soon-to-be full data DDW, as well as the recent results out of Connect Bio on their S1P program, and obviously the market's reaction to that, what does it take for another S1P program to stand out in this space, be it advocacy or other measures to your mind? Thank you. Yeah, thanks. So, let me start out and, of course, let the expert here pick it up.
Our next question comes from Jeff Jones of Oppenheimer. Your line is open.
Thank you I appreciate you guys taking the call.
The TIK twos have been pretty well covered.
So step back to the <unk> piece for the moment.
In light of the <unk> data Thats out there the phase II data in the soon to be full data tw.
As well as the recent results that is connected by a warm their S. One P program.
And obviously the market's reaction to that.
What does it take for a another <unk> program to standout in the space.
Be it efficacy or other measures to your mind.
Thanks.
Raju Mohan: So from our perspective, in the validation of S1P1 in UC, and the pharma, the value the pharma places on a safe and effective S1P1 drug, slowly continue to build, first with the approval of Zonamod, the launch of Zonamod, then with the Pfizer-Arena deal, and most recently, we just talked about, with the disclosure of the Atrasamod, so Phase 3 data. So from our perspective, this is, again, a good scenario for this class of drugs, and in particular, for our compound, VTX002, which we believe really has the potential to positively differentiate from atrostimide, in particular, both on efficacy and safety. But let me hand it over to Bill for his thoughts, a bit more on this. Bill.
Yes. Thanks, So let me start off of course, let the expert here pick up so from our perspective and the validation of <unk> in UC.
And the pharma.
The value of the pharma places on a safe and effective S&P, one it's really continuing to build.
First with the approval of <unk>, the launch of <unk> and that the Pfizer Arena deal.
And most recently, we just talked about with the disclosure of the across a mod so phase III data.
So from our perspective. This is a again a good scenario for this class of drugs and in particular for our compound Gtx 002, which we believe really has the potential to positively differentiate from across the mod in particular, both on efficacy and safety.
But but let me hand, it over to bill for his thoughts a little bit more on this bill.
Well, if we look at the history of this class of drugs beginning in multiple sclerosis, and then coming into ulcerative colitis, the earlier generation products.
bill Sanborn: Well, you know, if we look at the history of this class of drugs, beginning in multiple sclerosis and then coming into ulcerative colitis, the earlier generation products had phosphorylated metabolites with very long half-lives. So, for instance, you know, something like 93% of administered Ozanimod quickly becomes phosphorylated metabolites that have a half-life of about eight days. So it's essentially a biological condition, and that means it's a slow onset.
Phosphorylated metabolites with very long half life. So for instance.
Something like 93% of administered Hosanna Mod quickly becomes the phosphorylated metabolites would have a half life of about eight days. So it's essentially a biologic.
And that means it's a slow.
Onset if you look at the time course of lymphocyte reduction that doesn't plateau for a month or more and of course when you stop the drug the off rate is similarly.
bill Sanborn: If you look at the time course of lymphocyte reduction, it doesn't plateau for a month or more. And, of course, when you stop the drug, the off rate is similarly slow. So what's the ideal profile?
Slow.
What what's the ideal profile to short half life drug in the range of 24 hours. Our product is has a 23 hour half life no.
bill Sanborn: It's a short-life drug, in the range of 24 hours. Our product has a 23-hour half-life, and it doesn't have any phosphorylated metabolites. You get the full drop in the lymphocyte count within a week or so. And then if you need to stop it, it can come off quickly.
Phosphorylated metabolites.
Full.
Dropping the lymphocyte count with them a week or so.
And.
And then if you need to stop it can come off quickly.
bill Sanborn: You want to do those citations so that you're able to really push for a plateauing of the lymphocyte reduction during phase one. And I think that's quite important, not just to find, you know, a higher dose that gets a larger linear dose response, but to see it kind of plateau and not necessarily choose your final dose right at that inflection point so that you're sure as you switch from healthy volunteers into larger disease trials that you really achieve the lymphocyte reduction that you set out to achieve.
Wanted to do dose titration, so that you're able to really.
Push to a plateauing of the lymphocyte reduction during phase one and I think that's quite important not just to find a higher dose.
Get some larger linear.
Dose response, but to see it kind of plateau and not necessarily choose your.
Your final dose right at that inflection point. So that you are pure issue switch from healthy volunteers into larger disease trials that you really achieve lymphocyte reduction that you set out to achieve.
bill Sanborn: And in some of the examples you were giving, you can see some slippage between phase one and phase two in terms of how much lymphocyte reduction there is, and that's often because the final selected dose backs away from what was seen in phase two with phase one with dose titration that really maximizes that.
Some of the examples you were giving.
You can see some slippage between.
Phase one and phase two in terms of how much lymphocyte reduction there isn't that's often because the final selected dose backs away from.
What was seen in phase II with sort of phase one with dose titration that really maximizes that so I think we've been very thoughtful about.
bill Sanborn: So I think we've been very thoughtful about the dose titration regimen taking, dose forward with the highest dose that we will believe will really solidly reduce the lymphocyte count in the disease setting, have a fast onset and pass off. And with that, you know, and then the other thing, it just harkens back to what I said earlier, the meticulous conduct of clinical trials. So you wanted an adequately well-powered trial, if you think of, you know, the example you gave, a smaller trial, heavily bio-naive patients, heavily Asian patients, about which we know less about the pharmacokinetics and the sort of expected disease response in that particular ethnic background.
The dose titration regimen, taking.
<unk> for that with the highest dose that we will pleased we'll really solidly.
Reduce the lymphocyte count in the disease setting have a fast onset and pass off right.
And with that thank you.
And then the other thing just harkens back to what I said earlier the meticulous.
Conduct of clinical trials. So you wanted to adequately well powered trial, if you think of.
The example, you gave.
Smaller trial.
Heavily bio naive patients heavily Asian patients, which we know less about the <unk>.
Our mccook kinetics in the sort of expected.
bill Sanborn: And so, you know, there were a lot of trial design issues that could have contributed to the inconsistency of the result, although the totality of that trial still showed an effect, and I think it just reiterates that this class of drugs is a solidly effective therapy in ulcerative colitis, and if you want a differentiated effect, you really need to pay attention to the second generation molecules with all the dose aspects that we just talked about. Thank you for that.
Disease response in that particular ethnic back.
Background and so there were a lot of trial design issues that could contribute to the inconsistency of the results, although the totality of the <unk>.
Trials still showed an effect and I think I'd just reiterate.
This class of drugs.
Solidly effective therapy in ulcerative colitis, and if you want a differentiated effect you really need to pay attention to the second generation molecules with all the.
Dose aspects that we just talked about.
Yes.
Thank you for that.
bill Sanborn: And I'm showing no further questions. I would now like to turn the conference back to Raju Mohan for closing remarks. Great. Again, thank you all. We're really excited about where we are with each of these programs and look forward to sharing technical updates as we've provided you at the appropriate time. And again, I look forward to connecting with you folks in the near future. So, thank you all. Thanks, team. This concludes today's conference call. Thank you for participating. You may now disconnect. [music]
And I'm showing no further questions I would now like to turn the conference back to Rajeev Mohan for closing remarks.
Great again. Thank you all we're really excited about where we are with each of these programs and look forward to sharing.
Clinical updates as we guided you at the appropriate time and again look forward to connecting with you folks in the near future. So thank you all thanks team.
This concludes today's conference call. Thank you for participating you may now disconnect.
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