VTYX - NASDAQ

Good day, and thank you for standing by. Welcome to the Ventyx Biosciences First Quarter 2022 Financial Results Conference Call. [Operator Instructions] 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. Thanks for joining the call today. Welcome to Ventyx Biosciences conference call and webcast 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 & 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 commencement, enrollment and completion of clinical trials, the anticipated timing of release of clinical trial data and the expected timeframe for funding operations with current cash, cash equivalents and marketable securities. These statements are subject to risks and uncertainties that could cause actual results to differ. Please note that these forward-looking statements reflect our opinions only as of the date of this call, and we undertake no obligation to revise or publicly release the results of any revisions to these forward-looking statements in light of new information or future events. 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 & Exchange Commission, including our Form 10-Q for the first quarter of 2022, which we expect to file again this afternoon. With that, I will hand the call over to Dr. Raju Mohan, Ventyx’s Founder and CEO. Raju, please go ahead.

Thanks, Marty, and thanks to everyone for joining our call this afternoon. So, let me briefly run through the conference agenda. We’ll start with a business update and then present an overview of the company’s pipeline, followed by recent highlights. I’m then going to hand the call back to Marty for a brief overview of our first quarter financial results before we open the discussion and the call for Q&A. Before we begin, however, I want to take a minute to formally introduce Bill Sandborn, and we announced his news earlier this week, 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, particularly inflammatory bowel disease or IBD. Bill has been closely involved in the development of a number of approved therapies in the I&I space, 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, but more importantly for us as a CMO. He will lead the team [ph] our clinical development team as we advance our portfolio to target multiple immune-mediated diseases. So welcome to the Ventyx team, Bill. I’d appreciate if you would say a few words before we move ahead with the rest of the agenda. Bill?

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 adviser 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. I’m thrilled to be joining Ventyx and dedicating my full attention to our portfolio of innovative oral medicines, most – foremost of which is VTX958, our potential best-in-class allosteric TYK2 inhibitor for the treatment of immune-mediated diseases, including psoriasis, psoriatic arthritis, Crohn’s disease and lupus. 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.

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 TYK2, 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. So for now, I’d like to briefly address each of these programs, including recent progress and upcoming milestones. So let me begin with VTX958, our novel allosteric TYK2 inhibitor. Based on its preclinical profile that we have disclosed earlier, VTX958 is highly selective for TYK2. It shows no measurable inhibition of all other JAK isoforms. So from the outset, our goal with VTX958 has been very clear, to develop a potential best-in-class highly selective allosteric TYK2 inhibitor with a wide safety and tolerability window that allows us to achieve clinical exposure that cover TYK2-driven target, not just IC50 levels, but pushing up to IC90 levels for these TYK2 targets. So again, the key to achieving this potentially best-in-class target profile really comes back to the design of our molecule to what I call our chemistry craftsman, who built 958 to be highly selective for the allosteric domain of TYK2, and our preclinical work has demonstrated that 958, VTX958 inhibits key TYK2 pathways, such as IL-12, IL-23 and interferon-alpha, while eliciting virtually no, I repeat, no detectable inhibition of JAK1 pathways or any other JAK pathways, and JAK1 pathways, in particular, cytokines, such as IL-6, IL-10, IL-22 and others. So we believe this profile will allow us to dose VTX958 with high exposures while avoiding JAK-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 1 single-ascending dose trial for VTX958 in healthy volunteers. This is a trial with seven dose cohorts. We began at subtherapeutic doses, low doses, and we escalated up to significantly higher doses. As we have stated before, we are very pleased with these results that we saw, both in terms of drug exposure, the PK – what we call PK and the pharmacodynamic effects, what we call PD on target engagement. Our multiple – our Phase 1 multiple-ascending dose trial, also called the MAD trial, which is part of our Phase 1 trial has five dose cohorts. Here, we begin at a dose level that is around the low end of the expected therapeutic range, and again, dose escalate to much higher doses and exposures. We plan to complete dosing by the end of the second quarter and provide a Phase 1 data update in early Q3. Our plan is to show full safety data from our Phase 1 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 solid oral dose or tablet formulation that we expect in our Phase 2 trial. As we have previously guided, we expect to commence Phase 2 trials in the second half of 2022, beginning with psoriasis, followed by psoriatic arthritis and Crohn’s disease. We believe that the profile of VTX958 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 may expand utility of TYK2 into other disease areas beyond psoriasis and psoriatic arthritis, including indications like Crohn’s disease, in particular, which may require higher exposures to achieve therapeutic benefit. And as a reminder, these are very large markets, all currently dominated by biologics, including a $20 billion annual market in psoriasis, a $4 billion-plus annual market in psoriatic arthritis and a $13 billion annual market in Crohn’s disease. We believe there’s an opportunity for a safe and effective oral therapies to capture significant share within these markets, including a new addition to the TYK2 validation, which is lupus. Next is VTX002, our 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 the profile of potentially best-in-class S1P1R modulator. 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 important effective titration regimen that we used effectively in Phase 1 that minimizes on-target first-dose heart rate effects also known as bradycardia. Our Phase 1 trial 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 put the dose an 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 in previous UC trials with other S1P1 drugs. In the fourth quarter of 2021, we initiated a Phase 2 randomized, placebo-controlled clinical trial for VTX002, our S1P1 drug in moderate-to-severe UC patients. This trial is planned to enroll around 180 patients, 180 patients includes two VTX002 active dose cohort as well as a placebo group with the 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. Finally, we designed this Phase 2 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 enrollment status as the trial progresses, and we look forward to announcing top line Phase 2 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. For this molecule, VTX2735, a Phase 1 SAD/MAD trial is ongoing in healthy volunteers. This trial has recently completed dosing, and we expect to report top line 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 VTX2735 into one or more proof-of-concept, proof of mechanism trials – clinical trials in the second half of this year, with additional details to be disclosed at a later time. I’d also like to mention another exciting addition to this portfolio, and that is VTX3232, our potent selective CNS brain-penetrant, CNS or brain-penetrant, NLRP3 inhibitor, which we nominated as a development compound, DC in the fourth quarter of last year. So VTX3232 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 VTX3232 into IND-enabling studies and plan to file the IND for VTX3232 in the fourth quarter of this year – in the fourth quarter of 2022. 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 neuro-inflammatory neurodegenerative conditions, with high unmet need that address large markets, including Parkinson’s disease, Alzheimer’s and ALS. The pace at which this program, the CNS-penetrant program is 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 Nuss as accessing brain-penetrant NLRP3 inhibitors 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 is set to be a transformative year for Ventyx. 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 1 data for VTX958, our TYK2 inhibitor in early Q3, initiating three potential Phase 2 trials for VTX958 in the second half of the year, top line Phase 1 data for 2735 later in Q2, continued execution on Phase 2 trials for VTX002, and an IND filing for VTX3232 by year’s end. So, I’d like to emphasize that all our pipeline is internally discovered. We own 100% all IP rights and commercial rights to all our compounds and 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. Marty?

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 in 2021. The first quarter 2021 R&D expense did include a $21.7 million noncash in-process R&D expense related to Ventyx’s acquisition of the Oppilan and

[Operator Instructions] Our first question comes from Yasmeen Rahimi of Piper Sandler. Your line is open.

Good afternoon and thank you for taking my questions. Dr. Sandborn, welcome onboard, and thrilled and excited to work with you. If I may, I have two questions for you. The first one is, if you could shed some light on why you decided to join Ventyx at this junction? And why Ventyx? I am 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 etrasimod Phase 3 abstract was recently published. And the placebo responses in the maintenance space were significantly lower than in the induction phase. So, I would love to hear maybe some thoughts on what the reasons for that could be? And what is Ventyx doing in regard to their Phase 2 study and mitigating placebo response, especially during the induction period? And again, thrilled to have you onboard and be working with you closely.

Well, thank you for the questions. First, why Ventyx? As I mentioned in the prepared remarks, I’ve worked with Raju and John and Chris Krueger for about five years. And I have just been involved with seeing these molecules progress and I’m persuaded that there will be a transition in the coming years from biologics to small molecules. We’re seeing that progressively happen across dermatology, rheumatology and inflammatory bowel disease space. And we see sort of the first-generation molecules and then what I think are the follow-ons that will be best-in-class. And from my view, both the TYK2 and the S1P1 modulator molecules, 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. So happy to join. With respect to etrasimod, the data have not yet fully been presented. They’ll 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 interpret what you said slightly differently. Essentially, there was a 52-week trial that was treat 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. So this just shows that in large multicenter trials, that there can be variations in conduct that have effect on placebo rates. And so without getting into all the details, what I would say, it’s really just doing adequately powered trials at experience centers, closely monitoring them, paying close attention to the entry and exclusion criteria. The central reading of endoscopy to qualify the patients, aiming for the right mixture of biologic naive and biologic experience patients, the right mixture of moderate and severe patients, and all of that just takes a really hands-on clinical development team and a closest collaboration with CROs and 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 drug to show efficacy.

Thank you, Dr. Sandborn. I’ll jump back in the queue.

And our next question comes from Josh Schimmer of Evercore ISI. Your line is open.

Good. 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? Thank you.

Yes. Thanks, Josh. Good question. So as Marty commented in his prepared remarks, right? We’re in a strong financial position currently with over $270 million in cash primarily extent that into first half of 2024 at current operating plan. So we’re committed to driving value across the clinical pipeline regarding our lead asset, the TYK2 and 958, obviously expect to generate meaningful proof-of-concept efficacy data with a drug across psoriasis, psoriatic arthritis, Crohn’s disease and even possibly lupus with Phase 2 trials kicking off. As you know, we talked about this before in the back of 2022 and the data from psoriasis is expected in the second half of 2023, right? So I think our goal right now is laser-focused on executing our proof-of-concept trials. We’re well capitalized to reach really key POC readouts. And in terms of the future, we own all commercial rights through our compounds. And so we’ll have the flexibility to have a number of options, including partnering as we move forward to generate the best value across our portfolio. So a lot of optionality here, right? 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.

Got it. Thank you.

Yes, thanks Josh.

And our next question comes from Michael Yee of Jefferies. Your line is open.

Hey guys thanks for the update and thanks for the questions. We had two questions, both related to TYK2. When you spoke last, you said you were dosing up very nicely in the Phase 1. I think you had said you were up past three or four cohorts out of five, hopefully, that’s going well. And I just wanted to ask about your expectations for differentiation, including things on 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 IL-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 Stelara and will we be able to draw those conclusions from the Phase 1? Thank you.

Great, Mike. Thanks again, and thanks for being on the call. And I think the two questions are sort of tied to each other. And so look, in terms of specifics of where we are in terms of covering IC50 and IC90 stay tuned. We’re 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 MAD to continue to dose escalate throughout five cohorts, and I would say we’re sort of in the endgame here. The goal really for the MAD part of this trial is to be maximized exposures. And you can only do it if you have the safety window to do it, right? So first, we have to demonstrate after these exposures, this compound is extremely well tolerated. And then if we can reach our exposures, provide evidence of target coverage on TYK2 pathways, as you call, which is IL-12, IL-23 and more recently gained trust in lupus, so interferon-alpha. And our thesis is that 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 maximize exposures. Again, safety is key. And with these exposures, we hope to cover not just IC50, but IC94. Hopefully, better part of a QD dosing cycle. So 12, 14 hours or more, and that will bear out from our total Phase 1 readout that we’re looking forward to sharing with folks again in early third quarter.

And as it relates to IL-12 and IL-23, can you comment on your relative potency on that at the higher doses? And just remind us if we can draw conclusions to stuff like Stelara?

Yes. We have disclosed our IL-12, IL-23 human whole blood numbers; they’re pretty comparable of those numbers. And we hope – again, we hope to cover IL-12 and IL-23 and interferon-alpha, IC90s, as we talked about, IC50s, I think is a really low bar for us. We think to reach the efficacy or by largest, including Stelara, 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 the IC90 coverage. What that coverage is. We’re looking forward to sharing with folks in early 3Q. But again, the focus here is not just an IC50, but to achieve the efficacy comparable to biologics, we’re targeting IC90 for each of the individual targets for the respective disease indications, IL-12/23 for psoriasis, psoriatic arthritis and Crohn’s disease and then interferon-alpha for lupus.

Got it. Thank you guys.

Yes, thanks Mike.

And our next question comes from Tiago Fauth of Credit Suisse. Your line is open.

Hey, thanks for taking the question. Just perhaps to hone in a little bit more on the safety side. I’m curious how to interpret the exposure you’re going to have from the multi-ascending dose portion of the study in terms of the risk and the safety profile of the molecule, given what we’re seeing on the AE manifestation profile for other drugs in the class? So basically, how informative is it going to be for the use of interest, how early those usually come up, and how will this inform your path forward? Thank you.

Yes. Thanks, Tiago. Great question. So again, we guide you to published data out there and there’s obviously a lot more data for deucravacitinib than there is for some of the other molecules there. So clearly AEs, such as skin findings, acne, rash, urticaria, lab abnormalities, such as neutropenia, generally reveal themselves within a 14-day dose period, which is the period we are looking at. So if you look across some of the detailed AEs deucrava 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 within the 14-day period and sometimes as early as day five in the case of deucrava outcomes. So again, so our MAD program is looking at this 14-day dosing cycle with, as I mentioned before maximizing exposures to cover these new targets. So on one hand, high exposures. On 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, I’ll defer back to the profile of our compound where from ground zero, we built 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, a very careful look at a non-clinical safety profile. So first, the molecular profile layered with the non-clinical safety profile and going into our Phase 1 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 TYK2 as is VTX958.

Okay, very helpful. Thank you so much.

Yes, thanks Tiago.

And our next question comes from Sam Slutsky of LifeSci 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 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 is necessary to see a clinical benefit?

Yes. So – and I’ll let Bill on this, but we’ll be looking at some of the standard markets that have been disclosed for not just NLRP3, but also for these pathways in general. Certainly, IL-1beta, there’s some serum markers such as SAA, Serum amyloid A marker, other biomarkers associated with some of these factors as well. So we’ll look at – careful 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 NLRP3 compound 2735. Bill?

Yes, not much to add. I think you’ve picked out some of the mechanism-specific markers, although SAA is a little more generic. But then there’s 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 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, but that range of biomarkers, we’ll 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 1 trial as well.

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 NLRP3 compared to IL-1 beta blockade alone?

Yes. Again, I’ll just lead off by saying that NLRP3 is not just IL-1 beta, it has a pronounced effect on [indiscernible] as you know, and the results of [indiscernible] doses are some kind of – is more sort of a mini cytokine storm, a lot of pathologies come out. So it’s not simply IL-1 beta, right? You’re in inhibiting [indiscernible] doses, you’re inhibiting IL-18. So it goes beyond sort of the classic IL-1 beta and the results we’ve seen with our biologic, but perhaps Bill will add more color to this. Bill?

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 [indiscernible]. So the IL-1 inhibitors all have labeled warnings around infection, and that has limited the – and you’ll recall the history and things like gout and stuff of IL-1 receptor antagonism where you have to sort of look at the benefit and the risk and where the risk has played into the acceptability of various indications. And we have a hypothesis that the more narrow spectrum of coverage of an NLRP3 and IL-18 may not have the same infection risk that the more broad acting IL-1 inhibition will have.

Thank you. I appreciate the time.

Thanks, Oliver.

And our next question comes from Jeff Jones of Oppenheimer. Your line is open.

Thank you. Appreciate you guys taking the call. I think the TYK2 have been pretty well covered. So I’ll step back to the S1P for the moment. In light of the etrasimod data that’s out there, the Phase 2 data and the soon to be full data at DDW as well as the recent results that 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 efficacy or other measures to your mind? Thanks.

Yes. Thanks. So let me start out, and of course, let the expert here pick up. So from our perspective, the validation of S1P1 in UC and the pharma – the value of the pharma places on a safe and effective S1P1 drug, is really continue to build first with the approval of ozanimod, the launch of ozanimod Pfizer Arena deal. And most recently, we just talked about with the disclosure of the etrasimod, so Phase 3 data, right? So from our perspective, this is again a good scenario for this class of drugs and in particular, for our compound, VTX002, which really has the potential to positively differentiate from etrasimod, in particular, both on efficacy and safety. But let me hand it over to Bill for his thoughts a 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 had phosphorylated metabolites with very long half-life. So for instance, something like 93% of administered ozanimod quickly becomes the phosphorylated metabolites that 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, 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? It’s a short half-life drug in the range of 24 hours. Our product has a 23-hour half-life, no phosphorylated metabolites, you get the full drop in the lymphocyte count within a week or so. And then if you need to stop it, you can come off quickly. You want to do dose titration so that you’re able to really push to a plateauing of the lymphocyte reduction during Phase 1. And I think that’s quite important, not just to find a higher dose that gets a larger linear dose response, but to see a 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 achieved the lymphocyte reduction that you set out to achieve, and some of the examples you were giving, you can see some slippage between Phase 1 and Phase 2 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 2 with our Phase 1 with dose titration that really maximizes that. So I think we’ve been very thoughtful about the dose titration regimen taking a dose forward with the highest dose that we believe will really solidly reduce the lymphocyte count in the disease setting, have a fast onset and fast off rate. And then the other thing, just harkens back to what I said earlier, the meticulous conduct of clinical trials, you want an 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 pharmacokinetics and the sort of expected disease response in that particular ethnic background. And so there were a lot of trial design issues that could contribute to the inconsistency of the results. 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.

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, look forward to sharing clinical updates as we’ve guided you in the appropriate time. And again, look forward to connecting with you folks in the near future. So thank you all. Thanks, team.