Tvardi Therapeutics, Inc. (TVRD) Earnings Call Transcript & Summary

Good morning, and welcome to the Tvardi Therapeutics Investor Webcast. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be available on the company website following the conclusion of the event. I will now turn the call over to P.J. Kelleher of LifeSci Advisors. Please go ahead, P.J.

Thank you, Wilson, and good morning, everyone. Earlier today, Tvardi Therapeutics issued a press release announcing data from its Phase II heels of its next-generation STAT3 inhibitor TTI-109. A copy of this press release is available on Tovardi's website at tovarditherapeutics.com. Joining me on today's call is Imran Alibhai, Chief Executive Officer of Tvardi Therapeutics. Before I turn the call over to Imran, I would like to remind everyone that this discussion in the accompanying press release will contain forward-looking statements, including statements concerning the anticipated benefits of Tivarti's product candidates, the potential benefits of TI. -- as compared to TTI-101, Tavares ongoing and planned future clinical trials and anticipated timing of reporting data from such trials. Potential indications for its product candidates, Tovardi's development plans in such indications, discovery and development of its product candidates its anticipated cash runway and other statements regarding management's intentions, plans, beliefs, expectations or forecasts for the future as well as matters that are not historical facts or information. Various risks may cause Devardi's actual results to differ materially from those stated or implied in such forward-looking statements. For a list and description of the risks and uncertainties that Tvardi faces. Please see the reports to already has filed with the Securities and Exchange Commission. including its most recent annual report on Form 10-K for the year ending December 31, 2025, in subsequent filings with the SEC. This conference call contains time-sensitive information that represents management's judgment and intention and is accurate only as of today, July vary undertakes no obligation to update or revise any forward-looking statements, except as required by law. I will now turn the call over to Imran Alibhai, Chief Executive Officer of Tvardi Therapeutics. Imran?

Thank you, [indiscernible], and thank you for everyone for joining this call this morning as we review new and exciting data from our TT development program. Ben, I'd like to point out that the slides that accompany this call are available on our site with an appendix that includes additional materials, including more in-depth data from our preclinical program in model systems that are the backbone of our translational program as well as the data we presented earlier this year from our Phase II IPF study, which we will highlight today. That brings us to step, which is what we are focused on. Satis an incredibly a validated convergent node, if you drop it into PubMed, only 45,000 papers describe its role as a central mediator inflammatory inflatory and proliferative disease. What we have demonstrated over time is that preclinically, we can downregulate activated STAT3, which then leads to down-regulation of immune disregulation, inflammation and proliferation. We can now show you that we've confirmed these findings in patients in that week show target engagement, downregulation of the cellular and humoral responses as well as actual validation of decreases in inflation. That brings us to 109. This is our next-generation STAT3 inhibitor, which is a phosphate prodrug of a first-generation molecule. Today, we will idostrate that TTI109 met the design objectives that in that rapidly converts with predictable dose proportional PK and has improved GI tolerability to our first-generation molecule. Beyond this, we will mechanistic pharmacodynamic data of reductions in disease-associated immune populations, specifically T cells and B cells. Seeing this kind of pharmacodynamic data signal in healthy volunteers, we believe portends well for patients with chronic and inflammatory diseases in the dermatologic GI space, that exhibit State driven immune to circulation, inflammation and proliferative tissue modeling. If you take a step back and think about all the signaling pathways that have been individually targeted in the past, which code growth factors, cytokines, even non-tire smotherinses, all of these convergence step, and induce the protein to become phosphorylated, it then homodimerizes, moves into the nucleus where it drives the transcriptional cascades of immune disregulation, inflammation and proliferation. -- the common hammers we see in dermatologic and GI indications. What we've developed at Divardi, our noncovalent oral small molecule inhibitors that simply inhibits state's ability to become phosphorylated. This prevents homodimerization, it's moving into the nucleus and the transcriptional cascades we associate with disease. What we do not do and what we have published on the bottom left and have demonstrated now in patients has had any impact on STAT3 in the mitochondria. This has been an issue previously for other molecules in the space and from our perspective, not only do we have the in vitro data that suggests that Step 3 is not affected. Now we don't affect motochondostat function. We now have 400 patients worth of data across our 2 molecules that demonstrate we have seen 1 example of a drug-related mitochondrial toxicity. The reason all this is so important is really here in the middle of the page. And then that is that STAT3 has a dual mechanism Intrinsically, we know that STAT3 activation drives the inflammation and proliferation we see in the cellular compartment. But extrinsically and maybe equally important, we know that STAT3 activation also drives immune disregulation. What we have demonstrated in vivo, in vitro and now clinically is that intrinsically in the cell compartment, we can downregulate the inflammatory and proliferative cascades and simultaneously may control you extrinsically in the immune department that we can restore humoral and cellular immune deep. The basis of our program is on our first-generation molecule, TTI101, which is the clinical foundation for the development of TTI. Our first in human study was actually an oncology study in which we demonstrated PK, PD, tolerability and activity. And shown here is that pharmacodynamic effect and that is that we were able to take biopsies for patients pretreatment and on treatment, and we were able to demonstrate that in every patient, we saw a decrease in activated STAT3. The overall decrease was 55% and in patients with clinical benefit, it was almost 80%. And then earlier this year, we presented data from the IPF study called RVI. Trial, which was a Phase II study, in which we demonstrated that in patients treated with TTI-101, we could decrease 1 of the hallmarks of inflammation in fibrosis, and that is -- what you see on the top of this panel is that patients treated with TTI-101 had a great for difference in the slope of the line versus patients on placebo or i6. But the thing that was really encouraging to us is potentially early signs of disease modification in these patient populations. In that, in the bottom of the panel, you can see a difference in fibrosis. We measured by CT fibrosis pretreatment and posttreatment. And what you see is a 7% difference in weighted fibrosis score, an actual decrease in fibrosis, we are unaware of any other trial, whether they be a 12 trial like this or a 52-week trial has actually shown a decrease in fibrosis relative to the starting point of the patient population. And then finally, from an overall safety profile, we've tested TTI101 our first-generation molecule across 300 subjects. And we've demonstrated -- we do not see any of the moderate chondrotoxicity observed with other cat inhibitors like prophanopathy and lactic acidosis. And commonly, we are compared to JAK inhibitors. But Similarly, we do not see the safety signals that we see with [indiscernible]. We don't see serious infections. We don't see major cornivascular events or malignancies. These are all black box warnings, nor do we even see the cytopenias. The most commonly reported adverse event with TTI101 has been diarrhea. So based on this foundation, we wanted to basically maintain this mechanism of action and observed clinical activity of 101. But we want to improve its drug delivery and diminishes GI exposure. And so we built TT100 on the left-hand side, T10 is the phosphate prodrug of TTA101. And interestingly, 109 it is like 101 delivered orally and once it passes through the gut is designed to convert to the active moiety in the blood because of all the phosphatases we have in our blood. And so what that allows us to do is generate a very soluble molecule that's easily formulated, but two, because it has no activity, we're diminishing any of the GI exposure of the active Montan the guy. What we have demonstrated in our GLP results, IND-enabling Jigar results is that like 101, there were no tox mining on. Two, for the prodrug, we show that at equal -- or near equivalent doses of 109 and 101, we had equivalent exposures. And then finally, what we needed to show for this prodrug to be where we expect it to be is that 109 had to rapidly convert to the active Mode-101. And that's exactly what we see. See in the bottom right-hand corner, what you're looking at is the highest dose we tested in a GLP primate study. And what you can see, within 2 hours, 109, which is an orange has now rapidly converted and the vast majority of it is converted into TTL101. To that end, we wanted to replicate these findings in humid banks. And so what we did is we ran a 3-part study. Part A was a sad portion of the study. In this portion of the study, we wanted to demonstrate that like in rats and monkeys, 109 rapidly converted 101. Part B was a pioequivalence crossover study in which we gave patients 101 or 19 to start, wash them out and then gave them the alternative molecule. And we wanted to show that equivalent doses of the molecules gave equivalent exposures, again, like what we had shown in rats and monkeys. Finally, Part C was 3 arms combined. In that, we looked at placebo, TTL109 and TTA101 at the recommended Phase II dose. What this allowed us to do was look at steady-state exposures, safety and tolerability and really then demonstrate pharmacodynamics of 109. So first, from the SAD portion of the study, here on the left-hand side is the data I just showed you. This is the primate study. we saw that 109 rapidly convert to 101. Here is the human data. And what you can see, again, very similar to the animal data is that 109 in human being rapidly converts to 101. And again, at 2 hours, greater than 95% of 109 is converted to 101. The next part of the study was giving near equivalent doses of 109 having a washout period in the gaming or reversing the order and demonstrating equivalent exposure. And that's exactly what we saw when we gave equimolar dosing confirmed equivalent exposure of the active LoDo 101 versus 109. And then the final part of the study was really understanding the exposures. And in the SAD portion of the study, which you can see is the higher the dose of 109 we gave the higher the dose of 101 we got. And at all the active doses, we were well above the IC50. This compares favorably to what we saw at steady state in the MAD portion of the study, which you can see that in green and purple, the same dose, we can see similar pharmacokinetic profiles of day 1 and day 21. We see a predictable dose proportional PK increase at steady state and what's interesting is those exposures are all above the STAT3 IC50. So the next part of the site after we've now checked the boxes for exposure was to really demonstrate a differentiation in a healthy volunteer of the -- from a safety perspective. And so what you can see is the overall profile for these 3 molecules for placebo, for TTI-109 at different doses, and then a head-to-head comparison of 109 to 101. And what you can see, the overall, the safety profile appears favorable. The incidences of TAEs are broadly similar across the groups from placebo to 109 to the recommended Phase II dose of 101. Interestingly, we did see a near molar equivalence of 109 and 101 and potentially improved profile 109. Important to note that the second dose level 101, we observed 1 subject who discontinued due to an episode of isolated transaminitis; however, it's unlikely related to TTI 109 as the lab values begin to improve while she was on treatment and prior to treatment discontinuation. In addition, we saw no changes in bilirubin so there was no indication of dili. It was theorized that an alternative etiology for this could have been a passing of a gallstone as its shared much of the same symptomology. Importantly, the study demonstrated no SAEs no dose-dependent pattern in adverse events and no clinically relevant changes in vital science or ECGs. As detailed in the prior slide, we built TTI 109 to approve on the GI tolerability of 101. This slide highlights that improved tolerability. Overall, the TEA rates were similar, but we absorbed an important distinction between 109 and 101. When diving deeper into the characteristics of diarrhea, -- the duration of diarrhea for TTI-109 was comparable to placebo. It was transient and resolved without treatment, very placebo-like in contrast to T-11 at the recommended Phase II dose of TTL-101 wheat versus TD-019, you can see quite a contrast. TTI109 had a duration last simple actually, and much less than what we see with TTI101. And interestingly, we had 3 patients exhibit diarrhea and 1 patient had a grade 1 in the 101 arm that actually led to discontinuation. So from our perspective, not only have we shown you from a kinetic perspective, we had achieved our goals, but also this data demonstrates to us that we have achieved our goals in improving the GI tolerability with 109 that had placebo-like activity. So the final part of the study was really -- was really understanding pharmakinetics. We had a specific hypothesis rooted in biology. State 3 is essential for Th17 and B-cell function. We know there's some genetic knockout studies where T cell and B cell specific state knockout mice are Th17 deficient or can't produce autoantibodies, respectively. And what we have demonstrated previously, and this is a study done years ago. When you give TTI-101 to a healthy -- what you can see is a 50% reduction in Th17 cells, both in the blood and the spleen, which portends quite well for disease mice. And that when -- again, we know in diseases like -- in [indiscernible], these animals upregulate IL-17. And what you can see is that when we therapeutically treat with our molecule, we can reduce these IL-17 producing cells back to near baseline. So our expectation going into this healthy volunteer study was, can we see the same thing, can we demonstrate in a healthy volunteer a decrease in these immune populations and not only can we see in maybe Th17 cells, can we also see it in other immune cell populations that we know that are related to STAT3. That's exactly what we saw. At the active doses, which are the 250-milligram and up doses, these were the doses as you recollect from the previous slides that were above the [indiscernible], we saw reductions in TH17 cells reductions in T follicular helper cells and in B cells. Now not only did we show it for simplicity, we were just showing these 3 cell types in the core cell types. But actually, we can show you and demonstrated that we saw reductions across 16 cellular in humoral immune subsets recognized as pathologic markers of inflammatory and proliferative dermatologic in GI diseases, all of which were sustained over the active dose range. So from our perspective, what we had demonstrated in a healthy population, is down regulation of cellular and human lumen populations, which portends really well for disease populations. And so the take home from our perspective, as we think about all of the clinical data that we have generated across 101 and 109 is this. With 101, me, we've shown target engagement. We've seen decreases in disease populations of inflammation and proliferation. And now the 109 clinical observations build on this. In that, in the PK portion of the study, we showed rapid conversion with dose proportional exposures above the STAT3 IC50. Beyond that, from a GI tolerability perspective, we saw that 109 was similar to placebo in incidence and duration of diarrhea and improved versus DTA101. And finally, what we were actually exceeded our own expectations is that in a healthy volunteer, we were able to show decreases in cellular and [indiscernible] disease-related immune population, which portends well for variety of STAT3 driven dermatologic and gastrointestinal indications. So over the next 4 slides, I will walk you through why we think these 2 therapeutic areas are key and could be well interrogated by 101 -- 109 excuse me. And that is that both these indications are driven by STAT3. And in these indications, we see immune disregulation. We see inflammation and we see proliferation, all STAT3 driven. And so across -- you'll see this common theme across the next 4 slides. -- is that we'll walk you through both the dermatologic space and gastrointestinal space, preclinical data and then how that preclinical data has translated into clinical data and why this, we think portends well for disease population. So first, let's look at activated sector. And so there are 2 models that we've interrogated in the dermatologic space and 1 is a chemically induced inflammatory skin model in which the animals are delivered bleomycin, and we see inflammatory increase in proliferation in these models. Second, we have a genetically induced on as a Tyskino1 model, and this is a growth factor dependent increase in inflammation and fibrosis. And what you can see is that when we therapeutically treat with our molecules, we retain -- return excuse me, activated Step 3 back to baseline levels. Similarly, when we go to GI models, whether they be models that are focused on the innate immune access or the adaptive immune access, we see the exact same phenotype. That translates to what we've seen clinically. Again, in our oncology study, we saw reductions with cleared biopsies of activated STAT3. Now when we look at immune disregulation, across the -- across the dermatologic and GI space, we see increases in cellular responses. For example, in the dermatologic space, whether it be [indiscernible], systemic therasclerosis or stereoderma or even dermatomyositis, we see inductions of pathogenic Th17 cells. Similarly, when you go to the GI space, when you look at either UC patients or Crohn's disease patients, we see induction of TH17 cells. And then when we go to these models, and we look at TH17, we can see that all of these models like in humans, we see an induction of the Th17 response. And in the presence of our molecule, we can therapeutically return the IL-17 producing cells back to baseline. And our conversion clinically is that we've showed you in a healthy population. We can actually down-regulate this not only TH17 response, but even the humoral response in a healthy population, which portends well for disease population. Now when looking at inflammation, that hallmark, the second hallmark of dermatologic disease. You can see across the chemically induced model and the genetically induced model, we return inflammation, looking at IL-6 back to near baseline levels. Similarly, the way we measure inflammation in an animal in the GI models is to look at colonic inflammatory scores. And again, you see reductions with therapeutic treatment back to baseline levels. And that ties with what we've seen clinically in our IPF study where we actually showed reductions in IL-6, which is the key cytokine involved not only in inflammation, but later-stage proliferation. And then the final commentary here is on proliferation and that in both of these models, and I don't show all the data, it's in the back of this deck, you can see that when we therapeutically treat, we cannot only show reversals of this proliferative or fibrotic step, but we can also show you that we downregulate all of the indices related to this inflammatory profibrotic transcripts and this includes everything from CTG up to TGF beta to fibronectin [indiscernible] across the board, not only are we seeing reductions in the fibrosis, but we're seeing those in the markets that we associate with these populations. Similarly, when we look at GI models, we see the same thing. -- with therapeutic treatment, we can see we -- and this is an example from the innate immune axis that we can actually retain colon length and morphology in these animals. And again, the final step of this is that we see we can reduce fibrosis in a human. That's how we've translated that in -- from our IPF study. So to wrap up here, I think what we've learned from our perspective is that we know STAT3 as a transcription factor is genetically validated. And what we've demonstrated preclinically as we can down regulate this in both the inflammatory and proliferative spaces in both the dermatologic and GI space. And we've confirmed that not only in a healthy volunteer, but also in disease populations. And we believe 109 is now well suited to interrogate these populations where we know they're stat to be driven. And those -- that drives both the cellular humoral immune response, inflammation and proliferative tissue remodeling. And so -- that leads us to my last slide, and that is that today, we've reported out our top of the data. We anticipate incumbent on filing our INDs and funding for these indications. We can initiate these studies in the first half of 2027. And depending on the size and scope of the data, we expect to be able to quickly wrap these studies and provide proof of further validate and drive more proof of concept for our data so that we can eventually move to confirmatory spaces. And also at the end of the year, in the second half of this year, we will also provide the top line data from our initial oncology study in HCC, which will report across lines. And so we believe we've developed a diversified pipeline with multiple data catalysts, which we can drive long-term value for our investors. So with that, I thank you for all of your time, and I'll open the door for questions from the audience.

[Operator Instructions] So our first question comes from Yasmeen Rahimi with Piper Sandler.

Okay. Wonderful. Sorry for the Manan. -- collapsing on the data, and thank you for really connecting the data, the product profile and also the opportunity of expansion in dermatology and gastroenterology. I think my question for you is just sort of maybe a little bit more granular in terms of how soon can you get the IND filed. Dermatology and gastroenterologists quite wide spaces? And at what point will you be in a position to kind of fine-tune as you think about which indications you're interested in pursuing? And then also a reminder, like if you do move forward to a Phase II study, with these, given your tax coverage, I'm assuming you could rapidly expedite going into a Phase IIb study or Phase IIa. So you could just crispen out a little bit the way you envision the next step. That would be really helpful. Sorry, there will be many multipart costs.

No, no, no. These are all great questions. And so from our perspective, now that we have -- we've completed the 9-month monkey tox studies 109. We are -- anticipate that there are no other preclinical experiments to do here. We've now wrapped up with Phase I. We'll have the complete study report within the next few months. And then that allows us to rapidly move into D. And we -- we believe we can file an IND for a Phase II program in 1 or both of these spaces by the end of the year. And so we could get, as I mentioned, a study advanced or initiated in the first half of the year. Now for a lead indication, there beyond the therapeutic areas is that selection remains ongoing. And it's really informed by kind of a number of important inputs and those include our Board the KOLs, our external consultants and importantly, our investors and the broader competitive landscape. We expect to announce the indication once we have completed that alignment process, and have the appropriate funding in place to support this future development. Our priority is to select an indication where we know there's an unmet need. The competitive environment is there and we have a capital efficient clinical trial design that allows us to create meaningful value for patients and shareholders. And I think we actually identified some of those indications in this [indiscernible] in the dermatologic space and you could pick very small indications where we've seen like dermatomyositis, right? Two very large indications like hydride anticipative, all of which share the clinical features of STAT3 driven disease, which then meets information and proliferation in the modulation. Similarly, in the GI space where you could pick very small indications or smaller indication small things like fibrosis in crude disease all the way to front-line alter colitis. And what we think is interesting across these spaces is that when you think about all of the drugs that we've that are approved even in these spaces. They hit singular pathways. And where STAT3 is multimodal, we think we'll be able to hit all of these consecutively. So I think -- once we have alignment and support and the funding in place, we think we can rapidly move into these Phase II studies. Is that fair?

Yes. Yes. That's very helpful.

Our next question comes from Steve Seedhouse with Cantor.

Yes. Thanks. Thanks for hosting the call and for the update. I wanted to just first ask if you could clarify like how -- and maybe signal to the market, like how much money do you think you'd need to raise to get to some sort of signing data in 1 or more of these candidate indications. And in different financing scenarios, like are you sort of ideally hoping for a parallel track development in a couple of these? Or are you really going to narrow it down to 1 and update the market at some point before the study initiation.

Yes, absolutely. So let me ask it all depends on the studies, right? And so we could -- because of the parallel nature of both of these therapeutic areas, we think that we could absolutely run these apparel. -- and we have the resources to do so. And I think the funding would be important. I think when we look at these trial designs that if you ran them in parallel, the run Phase II studies that it could be $100 million, but we could also run that or half that cost for 1 indication for smaller trials. And so it really depends on having alignment from investors to the indication or indications that would allow us to move forward across the board so that we could put this data out there, have the ability for people to digest the data and then work on developing indication-specific protocols that will allow us to rapidly enter trials within a short time frame, get interim proof-of-concept data, and then beyond that have clinical evidence of that so that we could rapidly move it to confirmatory trials. Is that fair?

Yes. And just want to also follow up on the grade 3 transaminitis case. So just -- I think you mentioned maybe an alternative hypothesis or a hypothesis for what happened was this patient might have had a gallstone. Was that a formal diagnosis? Or is that just a hypothesis at this point?

It's not real -- yes, no, no. Yes. So I think important to note is that while the patient was on treatment, we saw an increase in her transaminases, but then a decrease while she's still on treatment. And so it is very -- we believe it's very unlikely that it was drug related. And again, there was no change in billing. It wasn't a formal diagnosis, but it did share some of those from some of the same symptomology from that perspective. And so that's why we think this is not related to our compounds.

Our next question comes from Julian Harrison with BTIG.

Okay. Great. Congrats on this update. First, on phosphorylated Step 3, sorry if I missed it, but just wondering how that compares between 100 and 101 on -- and then second, I'm wondering if you could talk more about your decision not to revisit IPF considering just how much the GI tolerability seems improved with 109 versus 101?

Yes. So it's no different. And sorry, it wasn't made clear. So 109 is the prodrug of 101. And the purpose of 109 is to basically -- it is -- 109 is inter. And so once it passes through the gut and into the bloodstream, it converts into the active 101. And we know when we have data that's demonstrated that how 101 works and 101 works by non-covenant binding at and then preventing that phosphor relation step that causes homodimerization, and its movement is the nucleus. So empirically, once is converted to 101, which we demonstrated that, that seems to be occurring quite rapidly. There is no difference on how the -- this prevention of phosphorylation or is occurring. So does that make sense, Julien?

5 Yes, it does.

No. And look, on the IPF, I think -- from our perspective, the IPF study provided important clinical proof of mechanism for STAT3 inhibition, right? And what we've been able to show, as you mentioned, is decreases in the population and step 3. But -- that said, when we look at the IPF trials. These trials are longer trough. And we know that the validated mechanism -- the validated FDA endpoint in IPF is now forced motor capacity. And that even in itself has a tremendous amount of variability. And so it's clear that these studies need to be really 6 months or potentially even a year. And so -- and then also you have to take into account that we have new drugs that are now available in the space beyond what we had with EsperNovev now we have the PDE4 inhibitor and then and potentially inhaled treprostinil. And so that landscape has changed dramatically in the last year or 2, which is great for patients. Now I don't -- we don't believe that these mechanisms or disease monitoring, but they are -- they have changed FVC values. And so running a trial like that in the U.S. or even ex U.S. is -- will take a lot of time. and to be quite costly because we would have to fund the background in these indications in ex U.S. studies, where here in the United States, that's paid for because of interest. But ex U.S., you fund all of the components of these indications. And so -- and the final component of this is that with GI studies in derm studies, we are allowed to -- we take biopsies quite common and so that allows us to have interim data to provide that initial step that allows us to show, hey, we're hitting these kinoonical cascades by looking at activated STAT3 and looking at inflammatory and fibrotic markers in the skin and in the GI, whereas you can't do that in IPF. So I think for all those reasons, it's something that we would happily revisit and some of the indications in these spaces have ILD components. But I think in this time, where we want to be capital efficient and move quickly, improve this proof of move to mechanism to profitable is really to pick indications where we can get interim data and then also put out and then move forward with clinical efficacy endpoints and do that in a shorter order than doing what would potentially be a very long-term and expensive study in IPF. Makes sense?

Thank Yes.

Our next question comes from Devin Jonathatergy with Jones Trading.

Thanks for the presentation and congress on the data. So you mentioned that biopsy-driven interim proof of concept would be very interesting. So would you be able to help us frame the expected time line to clinical POC if you're pursuing the derm opportunities versus ulcerative colitis or IBD?

Yes. I think both would be similar, honestly, right, I think we could -- we believe in both indications that we would be able to get started in the first half of we think that interim data can be available in both studies in the first half of '28 and then be able -- now depending on -- this all depends on size and all the other components, but we think that in a modest Phase II trial, we'll be able to have data in '29 from this. And so it would build a nice set of inflection points that would validate what we've seen with 101 using 109 into indications in the derm and space, we haven't interrogated in the past, but have this interim data sets where we know that there are markers that are diagnostic for the disease that we think can move forward in early 28, and then that would validate and really get us the clinical end points. in within the year from that time plan.

Yes. And a quick follow-up. So if you ultimately prioritize a T7 driven derm indication, How should we think about the risk-reward tradeoff between pursuing dermatomyositis, HS or the classic D17 disease like psoriasis.

Yes. So I think it's -- each is interesting. -- each has its own components that we have to think about, right? So dermatomyositis the valid trial really nice data. The drug there is a JAK inhibitor. We saw an increase from 1% to 10% in infections in that population, something we don't see with our molecule it may, as we talk to folks, it may be that prebactually become the standard of care, and so you might have to run your trial on top of that. When you look at other diseases like hydrant Supertiva. Those indications is where patients can fail oil where we see kind of the ceiling about 30% efficacy with either a TNF inhibitor or 1 inhibitor. [indiscernible] once they fail, then you can -- they can [indiscernible] then move to another therapy. So you don't have to have background therapy in this space. Again, in both of those indications, you're able to take biopsy to validate your findings and then move forward. I think the larger indications like a psoriasis and others, Those are big trials. They're in our feeling those are more inflammatory in nature, The where we are interested is really lean in disease populations where there is not only an inflammatory component but a proliferative impotent. -- that's where [indiscernible] is critically vol. We know that step drives both inflammation and the proliferative steps. And so I think when we think about where we can make the biggest impact in the res time frame, That's how we think about the overall cascade and then being able to run these trials efficiently in the U.S. but also ex U.S. and making sure that we can hit our regulatory time lines. as well as our clinical and interim data points.

Thank you. I'll hop back in the line.

Thank you, Dan. Our next question comes from Ryan Deschner with Raymond James.