TRVI - NASDAQ

Good afternoon, and welcome to the Trevi Therapeutics Fourth Quarter and Year-End 2025 Earnings Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. Various remarks that management makes during this conference call about the company's future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of the company's most recent annual report on Form 10-K, which the company filed with the SEC this afternoon. In addition, any forward-looking statements represent the company's views only as of today and should not be relied upon as representing the company's views as of any subsequent date. While the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so even if its views change. I would now like to turn the conference call over to Jennifer Good, Trevi's President and CEO. Please go ahead.

Good afternoon, and thank you for joining us for our fourth quarter 2025 earnings call and business update. Joining me today on this call are my colleagues, Dr. James Cassella, our Chief Development Officer; Farrell Simon, our Chief Commercial Officer; and David Hastings, our Chief Financial Officer. I want to welcome Dave to his first official earnings call with Trevi. His experience has already been felt in the company, and we feel very fortunate that we are able to add him to our leadership team at this important time of execution and growth. So welcome, Dave. I will make some comments on the business, and Dave will make some brief financial remarks. Then the team is happy to answer any questions you may have. 2025 was a major inflection point for growth at Trevi, driven by our positive data readouts in both the CORAL trial in patients with idiopathic pulmonary fibrosis or IPF related chronic cough and the RIVER trial in patients with refractory chronic cough or RCC. As a result of these data, we were able to raise capital, setting us up nicely for the next round of trials for each of our indications. That momentum has carried into the early part of this year as we have been preparing to initiate the next set of clinical trials. This work recently culminated in a positive End-of-Phase 2 meeting with the FDA for our IPF-related cough program. We believe the path forward for our registration trials is clear, and the team at Trevi has been moving aggressively to initiate our Phase III program. Let me provide you with an update on where we stand in each of our chronic cough indications. Beginning with our lead indication of Haduvio for the treatment of IPF-related chronic cough, at our recently held End-of-Phase 2 meeting with the FDA, we believe we gained overall alignment on the plan for the remaining development program and pathway to NDA. First, I want to share that the meeting was very collaborative and we were appreciative of the preparation and comments from the FDA, especially with all of the changes going on at the agency. We had constructive dialogue around each of our questions and left with a good understanding of the path forward. During our interaction, we confirmed the primary endpoint using the objective cough monitor and discussed the proposed key secondary endpoints and the evaluation of these endpoints. Based on the FDA's input, the company plans to conduct 2 pivotal Phase III clinical trials and obtained agreement on the remaining Phase I clinical studies to support an NDA submission. The company plans to conduct these 2 Phase III trials in parallel and is on track to initiate the clinical program. We plan to initiate the first trial in the second quarter of this year. This trial will be a global 52-week trial with a primary efficacy endpoint following 24 weeks of fixed dosing. We have planned for the trial to include approximately 300 patients. The second confirmatory Phase III trial, which we expect to initiate in the second half of this year will also be a global trial with a primary efficacy endpoint at 12 weeks and is estimated to enroll approximately 130 patients. The 2 studies are almost identical in design, except for the different duration for the primary efficacy endpoints and sample sizes. The reason for these differences is the FDA interest in a 24-week readout to support durability of effect in at least 1 of the trials. As for the end of the trials, the 52-week trial with the 24-week endpoint is powered for all of the key secondary endpoints that we would hope to include in the label and supports an adequate safety database. The second Phase III trial is studying a 12-week endpoint to confirm the primary efficacy outcomes along with providing additional safety through 12 weeks of dosing. IPF-related chronic cough is a new indication for the FDA, and we believe this pivotal program provides robust safety and efficacy data for a potential NDA submission. In the U.S., there are approximately 150,000 IPF patients, 2/3 of which have uncontrolled chronic cough. These cough patients have a high unmet need with no FDA-approved therapies. With our distinct mechanism of action and known safety and tolerability profile, we believe we are well positioned to have potentially the first therapy for the treatment of IPF-related chronic cough. Also a quick comment on the remaining Phase I studies. These are all standard label-enabling studies, which we had already been planning for in our development program, and we're aligned with what we had submitted to the FDA in our briefing document. Jim can give more color in Q&A if you are interested. Following alignment with the FDA on our IPF-related chronic cough program, we now intend to submit a meeting request and protocol to the FDA to request our non-IPF interstitial lung disease or non-IPF ILD-related chronic cough program. We intend to propose an adaptive Phase IIb trial to confirm dose and powering assumptions prior to rolling into 1 pivotal Phase III trial for approval. We are planning to file a supplemental NDA for this indication. We are planning to have this meeting in the third quarter of this year, and if all goes as planned with the FDA, initiate that trial by year-end. This population will include non-IPF ILD patients who suffer from lung fibrosis and chronic cough. We estimate there are approximately 228,000 non-IPF ILD patients with 50% to 60% having uncontrolled cough. This more than doubles the market opportunity of IPF chronic cough, and these patients are primarily seen by the same pulmonologists that see IPF patients. This keeps our clinical and commercial efforts efficient and creates synergies. Finally, for refractory chronic cough. We are planning to conduct a Phase IIb parallel arm dose-ranging trial with 3 doses and placebo. The protocol is drafted and being submitted to regulatory authorities, and we have selected sites to conduct this trial. This trial is interesting scientifically as we explore whether dosing in RCC patients is lower or equivalent to doses we are testing in the IPF chronic cough trial. We plan to initiate this trial in the second quarter of this year as well and have included a sample size reestimation readout when 50% of the patients complete the trial. It has been a busy time at Trevi preparing to launch this next round of clinical trials. Jim and his team have been working very hard to leverage the important learnings and relationships we have already built as well as to expand our clinical footprint into the U.S. We are excited to initiate these trials and begin enrolling patients. Before I close, I want to note there will be 2 important meetings we are preparing for in the second quarter where we hope to see many of you. The first is an in-person Investor and Analyst Day on May 7 from 10:00 a.m. to 12:00 p.m. followed by an optional lunch in New York City to discuss the company's clinical and commercial strategy. We will be joined by both IPF and RCC KOLs. At this event, we plan to lay out clinical trials and time lines in more detail, share recent commercial learnings as Farrell has been busy at work on based on our recent data, hear from KOLs on their perspective, and I also plan to discuss our active efforts around obtaining additional intellectual property. So it should be an informative event. We will also webcast the event live for those of you that can't join us in person. Second, we will also be very active at the American Thoracic Society, or ATS meeting this year with all of our submissions being accepted for either presentations or posters. We will be sharing some new data from our various trials at this meeting. We are planning on holding an investor event at ATS, where Jim and Dr. Philip Molyneaux, the lead investigator on our CORAL trial, will summarize and share the various data being presented at the conference. This meeting is being held in Orlando from May 17 to 19, with our ATS investor event being held on Monday, May 18. If you plan to attend ATS, please reach out to us as we would love to have you join us. So in closing, Trevi is well positioned to execute against our plan of becoming the leader in chronic cough, providing therapy for these patients where there are not good options and in the process, creating meaningful value for our shareholders. I will now turn it over to Dave for his remarks, and then we are happy to answer your questions. Dave?

Thanks, Jennifer, and good afternoon, everybody. First, I just want to say I'm thrilled to be participating in my first earnings call as CFO of Trevi. And before moving to the financial results, I want to take a moment to talk about why I took this role. The company has impressive clinical data in indications of high unmet medical need that offer a significant commercial opportunity. Importantly, given their specialty nature, we can commercially launch our indications effectively. In addition, the company has a proven track record of using its capital efficiently as it progresses with its key clinical programs. Also, after meeting the team, I felt confident in their ability to execute and I'm excited about the opportunity to contribute. Now turning to our key financial metrics, which are cash runway and what that runway funds. We ended 2025 with approximately $188 million in cash, cash equivalents and marketable securities, which gives us an expected runway into 2028. This runway allows us to provide top line data in our key clinical trials. This includes our Phase IIb clinical trial in RCC, our Phase IIb clinical trial in non-IPF related chronic cough and importantly, top line data in our 12-week pivotal Phase III clinical trial in IPF-related chronic cough. So while we're well positioned from a cash runway perspective to reach key clinical milestones, it is important to ensure that Trevi is always appropriately capitalized given the key inflection points and significant clinical trial data readouts the company has in front of us. So with that, I'll now turn the call back over to the operator to open the call for Q&A. Operator?

[Operator Instructions] And our first question comes from Roanna Ruiz with Leerink Partners.

A couple for me. I wanted to check on the remaining Phase I studies that you talked about with the FDA at the End-of-Phase 2 meeting. Could you elaborate a bit on what questions they're meant to answer and how efficiently you think you can complete them in the near term?

Hi Roanna, this is Jim. Thanks for the question. So these are pretty much label informative studies. So specifically, the FDA has asked us to look at nerandomilast as a newly approved antifibrotic agent to see if there's any drug-drug interaction with that, we had previously done that with pirfenidone and nintedanib. So we were kind of expecting this one is going to be coming along. The idea there is to make sure that there's no PK drug interaction that could affect the PK levels of either nerandomilast or vice versa, the PK of nalbuphine ER. So that's the first one. That was kind of expected given that we just completed those other ones. The other 1 was related to our mechanism of drug metabolism. We are metabolized in part by cytochrome P450 liver enzymes, specifically, were metabolized by cytochromes P450, the 2C9 and 2C19 isoforms, we had planned on doing an inhibitor study to look at drugs that inhibit the enzymes to see if the effect -- if it affects RPK, the FDA wanted to just step more -- step further and look at inducers of those enzymes. So again, it's kind of routine, we'll be able to inform on the physicians through the label and what happens when we do that. Now what we had also proposed and was accepted was standard label-enabling studies on renal impairment, hepatic impairment, food effect and things like that. So we're in a good place there. I think we have a very good idea of what we're required to do for the pathway to the NDA. These are not rate limiting in any way. They can be done in parallel with the Phase III, and we'll be performing those as we go along.

Great. That's helpful. And a separate question on non-IPF ILD and talking about the -- going in front of the FDA about that trial design as well. Any design features that you particularly want to align with the FDA most? And is there anything that you expect maybe some questions or things you may have to have more of a discussion about with the FDA on?

Yes, great question. I think the beauty of our timing here is that we're coming off of a very positive End-of-Phase 2 meeting in IPF. And you know IPF is a form of ILD, interstitial lung disease. So we're really looking at the other part of that ILD population. So I think a lot of the learnings that we have from the End-of-Phase 2 meeting directly relate to what we're looking to do in the non-IPF ILD. So everything we learned in the End-of-Phase 2 meeting in terms of study design, what the FDA is looking at for study duration, even our endpoints really will carry over. So what we want to do with that meeting is really introduce them to the concept that we're interested in this other part of the population. We are looking at doing this in terms of a Phase II, Phase III adaptive design, as Jen mentioned. The Phase II part is really -- this is a slightly different population. There will be other comorbidities associated with this non-IPF ILD population. So we're going to do some dose ranging in the Phase II part. The idea of the adaptive design is that we were able to pick our doses, determine what our effect size is, look at the variability in this population, immediately translate that into the Phase III study. There will be a data readout in between there. So we're basically going to lay out that concept with them in the Type C meeting that we plan on having with them.

Our next question comes from Judah Frommer with Morgan Stanley.

Congrats on the progress. Dave, congrats on joining the team. I guess maybe just first from us on non-IPF ILD. Was there any conversation in the End-of-Phase 2 about potentially adding an arm in the pivotal program for IPF that could include non-IPF patients if not, did you feel that it just wasn't the right format. And also in the End-of-Phase 2, can you help us with any color on discussion of 1 trial versus 2? I know you had always assumed that you'd be doing 2 trials here. But was there any discussion around that?

Yes. So in terms of non-IPF ILD -- we -- the IPF program is our lead program. It has a very clear directive. It's a very distinct population. It's what we had actually talked about when we filed our IND. So we really kept it to the IPF part of the ILD population. The idea was that we would take the learnings from that meeting and then apply it to the ILD. So we did not have any direct conversations about that. I'll let Jen chime in on the second part.

Yes. The 1 versus 2, Judah, I think we got good comments from the agency and had good dialogue with them in the meeting. As you know, there's sort of this in between phase now where there's this New England Journal article floating around that hasn't really translated down into FDA guidance. I think that causes a little bit of wondering what to do with that at FDA, especially for us because it's a brand-new indication, a chronic cough drug has not been approved, and this will be our first indication approved. So as our management team stepped away from everything we heard, we made the decision that it was best to really lean in on our lead indication here and conduct a robust trial so that we didn't get caught sort of in any kind of changes around view there. So it was really a decision we made as a company. There's a lot of confidence that we can run a successful study and these are not big trials because of our drug effect size. So I would say it was sort of room to move, probably either way there and we opted to protect our lead program and move forward with 2 studies.

That makes sense. And then just 1 on refractory chronic cough. It sounds like you have a plan there. Just curious, I guess, on any read-through you'll be looking for in the P2X3 readout kind of around midyear and if that could impact the program?

So it's interesting. That should read out in the third quarter. Obviously, important for patients. I do think our strategy is a bit different. We're going after treatment failure patients. The only read through there, I think probably particularly Jim will be interested in is kind of what did their placebo effect look like. I think we hope the trial works, sort of work or not work. I don't think it really impacts what we're doing. We will look at some of the trial details. I don't know that those will all be available in the third quarter. It may come later as they publish the data. But that's probably the most interesting thing. I don't know, Farrell, Jim, anything you'd add? No.

No, I think that's right.

Next question comes from Annabel Samimy with Stifel.

This is Jayed on for Annabel. Congrats on the progress. I had 2 questions. The first 1 is just related to cash runway. It is sufficient for Phase IIb in RCC, the Phase IIb in non-IPF and a 12-week readout of IPFCC. Does that mean 24-week data, it doesn't cover 24-week IPFCC readout?

Yes. So that's correct. This will get us through, obviously, those key clinical milestones you outlined. And as I mentioned, look, it's important that the company is always appropriately capitalized and we'll make sure that the funding will be there for all our key clinical studies.

And Dave, can I just add 1 thing, history because I've been around this. I think what changed here fundamentally from our FDA meeting is that the FDA wants 52 weeks of controlled safety. So we have to keep our placebo arm on and placebo for 52 weeks, which means we can't readout that 24-week endpoint, until the end. So that's been a little bit of shift in the requirement. If we could read it out at 24 weeks, we would be able to cover all this. But now that we've got to leave that study blinded and go all the way to the end, that's where a little bit of this gap shows up. Having said all that, we're still nailing down exactly the non-IPF ILD plan and all that.

Yes. Also, I'd just like to add, I mean, strategically, we could deploy the cash differently, right? But I think expanding the indications is important as well. So that's why getting the non-IPF ILD study going and getting data there is also very important.

My other question was regarding secondary endpoints in the IPF pivotal trial. What are you guys thinking? Or is there any color you can give there?

Sure. This is Jim. So it's very important in this program that we get the patient perspective. The primary endpoint is objective cough monitor. Of course, we use the same thing in the CORAL study. But also some of the PROs that we developed and used in the CORAL study, we'll be bringing forward into the Phase III program. These are primarily centered around patient perception of cough frequency, cough severity. We also have some very interesting data that came out of the CORAL study in terms of potential impact on subject perception of breathlessness, and so we are moving that up into a key secondary category because we have some very interesting findings there. And of course, it's a very important measure because patients do feel breathless after these coughing periods. So we think that's a very important endpoint. It's something that the patients are very concerned about.

And Jim, that's one of the things we'll share at ATS.

Yes, we have some great data to share at ATS. So I'm spilling the beans a little bit.

Just only...

Only a little bit.

Our next question comes from Alexa Deemer with Cantor Fitzgerald.

Congrats on the great year. This is Alexa on for Josh. So 2 quick questions from me. The first being, do you expect the label dose in RCC to be the same as in IPF? And if not, do you expect to procure additional IP for dosing in RCC. And then the last question I have is, do you plan on sharing data from the RCC study this year?

Yes. So I'll take that. Alexa, hi, by the way. So the label dose, that's part of what Jim's mission is. He's going to go off and figure that out. When you look at the crossover data, it appears that, that whole effect is there at the lowest dose, very early. And by 1 week, the first time we measured it. I think there's sort of a mechanistic reason of why that may be true that you need less drug. And so Jim is going to be really exploring the lower end of that dose range along with the QD dose we're going to look at actually. So we've sort of told Jim, once he figures out what's the appropriate dose, we'll figure out the strategy. And if we do end up below this dose range we're in now, there will be additional IP because there will probably be some new formulation work that needs to be done, which we're actually working on in parallel. So that was good. Your second question, I'm sorry, what was that?

Just if you plan on sharing data from the RCC study?

Yes. Sorry, I didn't -- I only wrote the S part of that, and then I couldn't remember what that meant. Yes. So we have built in the sample size reestimation. We won't get all the way to the end of the RCC trial this year. We are targeting getting to that sample size reestimation readout by later this year. So we will hope to do that. When we initiate the study formally, we'll lay out guidance for both -- for that milestone as well as the full trial readout.

Our next question comes from Serge Belanger with Needham.

So a follow-up regarding the secondary endpoints. I think in your prepared comments, you mentioned the larger of the Phase III studies was powered to further with secondary endpoints to be included in the label. Just curious if that was an FDA request or it's a strategic decision by the company. And second question, just whether there was any discussion at the End-of-Phase 2 meeting regarding orphan drug designation or that's a conversation that takes place separately at a later time.

Go ahead, Jim.

I'll take the first part of that question. So it's really a strategic question, Serge, because the FDA is looking for 52 weeks of controlled data, safety data. And in that study because it has to run longer, it's most efficient that we sort of build in a little bit more into that study. So obviously, that's a study that contains our 24-week primary endpoint of fixed dosing. And also because we have -- we will meet our -- basically our safety database requirement for the 52 weeks on drug, it was easier and more efficient to build in all of our key secondary endpoints. Remember, I mentioned these are PROs. So they're not quite as clean a signal. They have a little bit more variability, add a little bit more end to the study. It was most efficient to build all that into the larger Phase III study. And then the second study is really just confirmatory with the 12-week endpoint. So it's really a matter of efficiency and strategy that we did it that way.

Jim, we proposed that, FDA didn't make us do it, right? This is our proposal search, and they agreed with it. As far as the orphan drug question, it's a good question. We are going to file this year an application for orphan drug. As you've heard me say before, I'm skeptical whether we'll be able to get it because we're -- while IPF is orphan, we are looking at chronic cough in IPF, which is largely viewed as 1 of the most difficult chronic cough conditions. So they're probably going to look at that and realize that if it works in IPF chronic cough, it could work more broadly, but that's a question we want to answer. I don't want to assume that. So we will file. We'll ask the question. We wanted to get aligned with the FDA on our program first. So now that we've done that, we'll work to submit that application and get an answer to that question.

[Operator Instructions] Our next question comes from Ryan Deschner with Raymond James.

You had any recent feedback since your big 2025 data readouts from either patients or physicians suggesting increased awareness of Haduvio or your programs in general, which might be able to inform on expectations for enrollment demand for the IPF chronic cough pivotal study and then I have 1 more question.

Yes, Ryan, this is Farrell. So we've been doing a lot of work over the summer in terms of just understanding physicians' behaviors and key drivers of just liking. And what really comes up to the top of the list is the efficacy that was shown. So we've seen an increase in physician understanding. We've also been really active with the patient advocacy groups in the U.S. and ex U.S. environment, so that we understand how we can work with them to better support patients. This all nicely flows into the work that Jim and his team are doing in terms of clinical trial awareness and our team have our sights set on that. But we'll give a lot more details on the insights in the Investor and Analyst Day come May.

Yes. I would say, as you know, Ryan, we are going to be entering the U.S. with these trials. And we've been staying close to that group. And while we've hosted receptions, we have a lot of these physicians show up in lobby. Jim and myself are getting entry into the trial. We've had good response time, right, on all our sites. So there's good awareness of our drug, our program, the unmet need. I think I'm excited about the enrollment curves here. I think we can do a good job.

There's a lot of excitement as we reach out to the sites in the U.S. Clearly, very high interest in participating in this drug trial.

And then maybe quickly from a more general perspective. Are you anticipating meaningful read through your programs regarding the relatively new developments to FDA related to plausible mechanism, increased emphasis on Bayesian trial design or even recent turnover at the department.

I would say no. I mean, that's what the beauty of this, Jim, you chime in. But the End-of-Phase 2 meeting, we have a very clear path forward, and that's the playbook we're going to execute against. I think fortunately, the division -- or the acting Division Director was very active in our meeting. So we know she's bought in and solid with that. There's going to be a lot of churn -- or there is churn going on in the leadership roles, we're not sort of under that branch. So I don't foresee that really affecting what we do because we're going to have our heads down for the next 2 years, executing the plan that was agreed to. So I don't know, Jim, anything you want to add?

No. Other than that, I think you hit the nail on the head. We work with the division. The division was very clear on what the expectations are for the approval of a drug for cough, which they were very enthusiastic about. They see the Division Director really talked about the need here and the burden on the patients. So I think that was very clear. We have clear line of sight with this division on what needs to get done. I think that's the most important step that we're going to work towards.

Our next question comes from Brandon Folkes with H.C. Wainwright.

Congrats on all the progress. Maybe just 2 for me, if that's all right. How do you think about moving forward into a Phase III in RCC in terms of timing post the Phase IIb? Do you expect to make a decision just in terms of sort of the second indication to market, where perhaps post that Phase IIb in RCC, we could see a bigger focus on the non-IPF-ILD as the second indication to market given the commercial overlap and then also the fact that you're probably going to get off-label use in RCC.

So that's not the motivation. I would say, obviously, our lead indication is IPF. And I would say our second indication is ILD because they're attached at the hip. I do think, though, ILD, the non-IPF ILD and RCC are both going to be sNDAs. So they would be fast follow-on. So when IPF got approved, we would look to be in a position to file both of those really very closely together. I think if there was ever a resource issue on time, ILD would get prioritized because we'll be launching into those centers, and it makes a lot of sense with IPF. So yes, I think we think about the priorities internally, it's IPF, ILD, it's sort of close cousin. RCC, we will move along urgently, though. That is a big unmet need. I think our drug has shown good data there. And there's no reason we can't have that ready to go as soon as our IPF drug gets approved. We believe there's only going to be one Phase III trial to run on the heels of our IIb. So we'll be prepared to keep this moving.

Great. And then secondly, coming back to the Phase III in IPF chronic cough, can you just remind us or help us think about what's your thinking on the placebo effect in the longer 24-week duration?

That's a great question. Really that question. I think we -- our CORAL study gave us a really good indication of the placebo response. We had about a 17% placebo response in terms of objective cough. We saw the response in our subjects come in within the first couple of weeks. And then it was a pretty steady response over that time for the active drug. Placebo was sort of bouncing around that range. It's a slightly smaller study. I don't think we think about it any differently going forward. I think that we are something that we need to figure out. I think we're sufficiently powered to find out what the effect is but it really is an unknown at this point, and we're going to find that out both in the 12-week trial and then in the longer trial. So I think it's a stay tuned. I think we're well powered to handle any perturbations around what that placebo response is. I think our primary endpoint -- our trial is powered over 90% for the primary and the key secondary endpoint. So we built in some safety net there as you would for a Phase III trial. But I think we're going to all find out together.

Our next question comes from Debanjana Chatterjee with Jones.

So sorry if I missed this and you've already clarified, but could you comment on the internal expectations around pace of recruitment and enrollment completion in the Phase III IPF cough trial? And I have a follow-up.

Yes. We have good solid data from our CORAL study to lay out some expectations for recruitment. Given the size of the first Phase III, the larger one, we're expecting that enrollment should be about a year to enroll the trial. We're anticipating something between 80 and 100 sites. So I think with those kinds of parameters, the vast majority of those centers will be focused in the U.S., which I think offers all these PFF excellent care centers, where there are large numbers of patients. So I think the 1-year expectation is reasonable for a trial like that.

So are you assuming for 1 year to recruit and then you have to follow patients for 52 weeks for safety reasons. So by the time, this is potentially approved, there could be other IPF drugs such as United Therapeutics' Tyvaso or BMS' admilparant that's potentially out there. Will you need to do additional, like Phase I drug-drug interaction studies to file?

Depends on when those drugs get approved, theoretically, we would probably have to do a DDI study to make sure there's no effects on the PK. We do know from the mechanisms, whether or not we expect to see some kind of drug-drug interaction there. I think it will be a matter of timing. If we're done with our recruitment phase, then we're continuing the running of the study, then obviously, we won't need to bring in any more patients. So I think it's a matter of timing, Deb, and we'll see what happens. But it's not a big deal to do a Phase I study, DDI study. So I wouldn't see that as a barrier.

Our next question comes from William Wood with B. Riley Securities.

So 2 for me, 1 upfront. So just thinking about in terms of your ILD study, you've mentioned that you're going to do an adaptive design. And I believe in the past, you've mentioned that you're going to stay away from sarcoidosis. But apart from that, how should we think about how your inclusion criteria could look? And should we really expect that to look into all sort of ILDs, including differential forms of pneumonia, just sort of discuss how we should think about that, if you would. And then I have a follow-up.

Yes. We actually had a very insightful meeting with a group of KOLs last year. And it comes down to that -- the commonality that all these patients have, even though they may have different comorbid diseases is that they all have interstitial lung disease to a varying degree. They have a certain amount of scarring, that scarring can get worse over time, and they all have cough, whatever percentage that is. So what we came to was that there wouldn't be any basket-type trial where we're picking them based on the diagnosis that they have. We're going to base it on amount of fibrosis that they have and the amount of cough that they have. So I think it really minimizes it to the core essentials, and we think that the fibrosis is probably leading to the cough anyway. So it really does get to the fundamental issues. Now that doesn't mean we won't have to deal with comorbid conditions and conmeds and things like that. We'll work out those details, but I think that's the essence of the trial.

Makes sense. And then in terms of -- the FDA is sort of continually evolving. And so I was just curious if there's been any viewpoint change on how they're seeing nalbuphine potentially scheduling or not scheduling and just sort of if there's been any updates and interpretation there?

I would say, William, we provided our human abuse potential study. We provided our data from our respiratory safety study, we had a consult on the meeting from controlled substance staff. It was a very constructive meeting. I would say, I think all of our interpretation is. FDA is less focused on the molecule because that's already unscheduled and focused on our formulation and whether there is anything unique about it that could change the profile around that. Our data has not showed that. Jim did a really nice job of doing a cut around their various terms. They'll look at the end of the study and there just isn't much there. So I've been living this ride from the beginning. And I would say I just continue to have stronger and stronger conviction that this drug will stay unscheduled. So nothing in the End-of-Phase 2 to change that. I would say very relaxed tenor around that generally and clear guidance about what they're interested, which quite honestly, was more around dependence than it was addiction. So I don't know, Jim, anything you want to add?

Yes. No, but that's a good point. I think we laid out for them to plan on how we would pull together the data to support the conversation at the NDA time. So there's clearly very good datasets that need to be generated with the guidance of VA and CSS, where they put out these terms for adverse events that are related to these abuse terms. But as Jen said, there was a lot of discussion or meaningful discussion around observing whether or not there's physical dependence and withdrawal. Just for a point of reference, that's a label issue, not a scheduling issue. So again, there's 2 different aspects of this that they're interested in. So not that we expect to see any of that but that would be label as opposed to scheduling.

Our next question comes from Kaveri Pohlman with Clear Street.

This is Christian. I'm on for Kaveri today. So you've mentioned that the 1-year IPF Phase III safety data set could start to teach you about things like dyspnea, exacerbations, hospitalizations and maybe even lung function trends over time. Will any of those be prespecified analyses? And what data would actually change how you think about the label or launch strategy?

Yes. So there's a lot of things that we're going to be tracking. We are seeking approval for cough. I think that's first and foremost, we have to support that label. I think the 1 thing that we mentioned previously is that cough patients really do have concerns about shortness of breath. So we are moving breathlessness into the key secondary endpoint, that's clearly related. We are clearly going to be capturing data that would relate to these other things that you're referring to. So we do FVCs, we do other things, we'll look at hospitalizations. These are going to be patients living with their disease is a terminal condition. So we'll be tracking those things as well over the course of the year.

Got it. I appreciate the color. And I just have 1 more regarding Phase III IPF population. You've previously mentioned that you would be -- you would like the population to be as real world as possible and that it would be like the Phase IIb population, but with some broadening efforts. Could you possibly talk about which parts of the patient population you're intentionally broadening into versus the Phase II CORAL study?

So there's a lot of carryover from the CORAL study. The CORAL study was really a great study in setting us up for this, not only in terms of dose ranging, but in terms of understanding the patient population. So we are broadening that. We're making as real world as possible, which is clearly what the FDA wants. There will be patients who are on background antifibrotic medications. That was true in CORAL. This is going to be true here. We don't have a cough count requirement coming into the trial. That was true in CORAL. That is true here. The FDA actually mentioned that nobody expects to find cough monitors in doctors' offices when the patients are going there. We actually have some more data that will be coming out at ATS that looks at minimum cough levels, and there was an arbitrary cutoff around 10 coughs per hour. There was some concern about maybe capping those. We are going to cap the number of coughs coming in under 10 coughs per hour. That came out of the CORAL study. So we're learning the CORAL study, but really it's a very similar population to that study.

Thank you. I'm showing no further questions at this time. This concludes our question-and-answer session. I would now like to turn the conference back to Jennifer Good for any closing remarks.

We appreciate you joining us for today's call. I know for all of you guys, this is getting to the end of your earnings season, so you're tired. We look forward to sharing our continued progress in the second quarter as we initiate clinical trials as well as at our Investor and Analyst Day in May as well as ATS. Thank you.