Trevi Therapeutics, Inc. (TRVI) 2025 Q4 法說會逐字稿

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. We feel very fortunate that we were able to add him to our leadership team at this important time of execution and growth. Welcome, Dave.

I will make some comments on the business. 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 read-outs in both the CORAL trial in patients with idiopathic pulmonary fibrosis or IPF-related chronic cost; 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. The team at Trevi has been moving aggressively to initiate our Phase 3 program.

Let me provide you with an update on where we stand in each of our chronic crop 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. 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 confirm the primary endpoint using the objective cough monitor; and discuss the proposed key secondary endpoints and the evaluation of these end points. Based on the FDA's input, the company plans to conduct two pivotal Phase 3 clinical trials and obtained agreement on the remaining Phase 1 clinical studies to support an NDA submission. The company plans to conduct these two Phase 3 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 3 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 two 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 read-out to support durability of effect in at least one 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 3 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. We believe this pivotal program provides robust safety and efficacy data for a potential NDA submission.

In the US, there are approximately 150,000 IPF patients, two-thirds 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 1 studies: These are all standard label-enabling studies, which we had already been planning for in our development program. 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 2b trial to confirm dose and powering assumptions, prior to rolling into one pivotal Phase 3 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 coughs. This more than doubles the market opportunity of IPF chronic cough. These patients are primarily seen by the same pulmonologists at cIPF patients. This keeps our clinical and commercial efforts efficient and create synergies.

Finally, for refractory chronic cough, we are planning to conduct a Phase 2b parallel-arm dose-ranging trial, with three doses and placebo. The protocol is drafted and being submitted to regulatory authorities. 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 re-estimation read-out, 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 US. We are excited to initiate these trials and begin enrolling patients.

Before I close, I want to note there will be two 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 AM to 12:00 PM, 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 timelines in more detail; share recent commercial learnings that Farrell has been busy at work on, based on our recent data; hear from KOLs on their perspective. 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.

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. Good afternoon, everybody.

First, I just want to say I'm thrilled to be participating in my first earnings call as CFO of Trevi. 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. I'm excited about the opportunity to contribute.

Now, turning to our key financial metrics, which are cash or 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 2b clinical trial in RCC; our Phase 2b clinical trial in non-IPF related chronic cough; and, importantly, top-line data in our 12-week pivotal Phase 3 clinical trial in IPF-related chronic costs.

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 read-outs the company has in front of us.

With that, I'll now turn the call back over to the operator to open the call for Q&A. Operator?

(Operator Instructions)

Roanna Ruiz, Leerink Partners.

A couple for me. I wanted to check on the remaining Phase 1 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?

Roanna, this is Jim. Thanks for the question.

These are pretty much label-informative-studies. Specifically, the FDA has asked us to look at (inaudible) 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. We were kexpecting that 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 (inaudible) or vice versa -- the PK of -- on (inaudible). That's the first one. That was expected, given that we just completed those other ones.

The other one was related to our mechanism of drug metabolism. We are metabolized, in part, by cytochrome P450 liver enzymes; specifically, were metabolized by cytochrome 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 it affects RPK. The FDA wanted to just step one more -- step further -- and look at inducers of those enzymes.

Again, it's routine. We'll be able to inform on the physicians through the label on 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. 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 3. We'll be performing those, as we go along.

Great. That's helpful. 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? 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?

Yeah. 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. IPF is a form of ILD, interstitial lung disease. We're really looking at the other part of that ILD population.

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. 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.

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 2-, Phase 3-adaptive design, as Jen mentioned.

The Phase 2 part is really -- this is a slightly different population. There will be other comorbidities associated with this non-IPF ILD population. We're going to do some dose-ranging in the Phase 2 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 3 study. There will be a data read-out in between there.

We're basically going to lay out that concept with them in the Type C meeting that we plan on having with them.

Judah Frommer, Morgan Stanley.

Congrats on the progress. Dave, congrats on joining the team.

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?

Also, in the end of Phase 2, can you help us with any color on discussion of one trial versus two? I know you had always assumed that you'd be doing two trials here. But was there any discussion around that?

Yeah. 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.

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. We did not have any direct conversations about that.

I'll let Jen chime in on the second part .

Yeah. The one versus two, Judah, I think we got good comments from the agency and had good dialogue with them in the meeting. As you know, there's this in-between phase now where there's this New England Journal articles 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. This will be our first indication approved.

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 in any changes around view there.

It was really a decision we made as a company. There's a lot of confidence that we can run a successful study. These are not big trials because of our drug effect size. I would say it was room to move, probably either way there, and we opted to protect our lead program and move forward with two studies.

That makes sense. And then, just one on refractory chronic off. It sounds like you have a plan there. Just curious on any read-through you'll be looking for in the p2x3 read-out around midyear; and if that could impact the program?

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, what did their placebo effect look like? I think we hope the trial works -- 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.

Annabel Samimy, Stifel.

This is [Jayant], on for Annabel. Congrats on the progress. I had two questions.

The first one is just related to cash runway. It is sufficient for Phase 2b in RCC -- the Phase 2b (inaudible) and a 12-week readout of (inaudible). Does that mean 24-week data (inaudible) covered four-week (inaudible) [read-out]?

Yeah. That's correct. This will get us through, obviously, those key clinical milestones you outlined.

As I mentioned, look, it's important that the company is always appropriately capitalized. We'll make sure that the funding will be there for all our key clinical studies.

Dave, can I just add one thing from 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. We have to keep our placebo arm on and placebo for 52 weeks, which means we can't read out that 24-week end point until the end. 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 got to leave that study blind and go all the way to the end, that's where a little bit of the cap shows up.

Having said all that, we're still nailing down exactly the non-IPF ILD plan and all that.

Yeah. Also, I'd just like to add, strategically, we could deploy cash differently, right? But I think expanding indications is important, as well. 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.

It's very important in this program that we get the patient perspective. The primary endpoint is objective cost 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 3 program. These are primarily centered around patient perception of cost frequency, cost severity.

We also had 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. Of course, it's a very important measure because patients do feel breathless after these coughing period.

We think that's a very important endpoint. It's something that the patients are very concerned about.

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

(multiple speakers) --

Yeah. We have some great data to share at ATS. Spilling the beans a little bit.

Just only a little bit.

(multiple speakers) --

Alexa Deemer, Cantor Fitzgerald.

Congrats on the great year. This is Alexa, on for [Josh]. Two quick questions from me.

The first being, do you expect the label dose in RCC to be the same as in IPF? 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?

Yeah. I'll take that, Alexa. Hi, by the way.

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 cross-over data, it appears that that whole effect is there at the lowest dose, very early and in by one week, the first time we measured it. I think there's a mechanistic reason of why that may be true that you need less drug. And so Jim is going to be really the lower end of that dose range, along with the QD dose we're going to look at, actually.

We've told Jim, once he figures out what's the appropriate dose, we'll figure out the strategy. 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.

That was good.

Your second question, I'm sorry, what was that?

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

Oh. RCC. Yeah. Sorry, I didn't -- I only wrote the (inaudible) as part of that. And then, I couldn't remember what that meant.

Yeah. We have built in the sample size re-estimation. We would not get all the way to the end of the RCC trial this year. We are targeting getting to that sample size re-estimation read-out by later this year. 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 read-out.

Serge Belanger, Needham.

A follow-up regarding the secondary endpoints: I think, in your prepared comments, you mentioned the larger of the Phase 3 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.

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.

It's really a strategic question, Serge, because the FDA is looking for 52 weeks of controlled data, safety data. In that study, because it has to run longer, it's most efficient that we build in a little bit more into that study.

Obviously, that's a study that campaigns our 24-week primary endpoint of fixed dosing. Also, because we have -- we will meet our, basically, 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. They're not quite as clean as signal. They have a little bit more variability and a little bit more end to the study. It was most efficient to build all that into the larger Phase 3 study.

And then, the second study is really just confirmatory with the 12-week end point.

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. They agree 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 (inaudible) IPF, which is largely viewed as one of the most difficult chronic cost conditions.

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.

We will file. We'll ask the question. We wanted to get aligned with the FDA on our program first. Now that we've done that, we'll work to submit that application and get an answer to that question.

(Operator Instructions)

Ryan Deschner, Raymond James.

You had any recent feedback since your big 2025 data read-outs 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 one more question.

Yeah. Ryan, this is Farrell.

We've been doing a lot of work over the summer in terms of just understanding physicians' behaviors and key drivers of just liking. What really comes up to the top of the list is the efficacy that was shown.

We've seen an increase in physician understanding. We've also been really active with the patient advocates in the US and ex-US 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. 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.

Yeah. I would say, as you know, Ryan, we are going to be entering the US with these trials. We've been staying close to that group.

While we've hosted receptions, we have a lot of these physicians show up and lobby. Jim and myself are getting entry into the (inaudible). We've had good response time, right, on all our sites?

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 (multiple speakers) --

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

Got it. 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 [basin] trial design, or even recent turnover at the department?

I would say no. That's what the beauty of this -- Jim, you chime in.

But, at the end-of-Phase 2 meeting, we have a very clear path forward. 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. 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 under that branch. I don't foresee that really affecting what we do because we're going to have our heads down for the next two years, executing the plan that was agreed to.

I don't know, Jim, anything you want to add?

No. Other than -- 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 patient.

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 that we're going to work towards.

Brandon Folkes, HC Wainwright.

Congrats on all the progress. Maybe just two for me, if that's all right.

How do you think about moving forward into a Phase 3 in RCC in terms of timing, post the Phase 2b? Do you expect to make a decision just in terms of the second indication to market where perhaps, post that Phase 2b 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?

That's not the motivation. I would say, obviously, our lead indication is IPF. 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. They would be fast follow-on.

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. It makes a lot of sense with IPF.

Yeah. I think we think about the priorities, internally. It's IPF; ILD, it's close cousin.

RCC, we will move along urgently, though. That is a big unmet need. I think our drug has shown good data there. 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 3 trial to run on the heels of our 2b. We'll be prepared to keep this moving.

Great. And then, secondly, coming back to the Phase 3 in IPF chronic cough, can you just remind us or h1elp 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 (inaudible) cough. We saw the response in our subjects come in within the first couple of weeks. And then, it was a pretty steady respond over that time for the active drug.

Placebo was 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 (inaudible) 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 unknow,n at this point. We're going to find that out, both in the 12-week trial and then, in the longer trial.

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. We built in some safety net there, as you would for a Phase 3 trial. But I think we're going to all find that together.

[Steven Jonathan] (inaudible), [Jones].

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 3 (inaudible) trials?

I have a follow-up.

Yeah. We have good solid data from our CORAL study to lay out some expectations for recruitment. Given the size of the first Phase 3 -- 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.

I think with those kinds of parameters, the vast majority of those centers will be focused in the US, which I think offers all these (inaudible) -- excellent care centers, where there are large numbers of patients.

I think the one-year expectation is reasonable for a trial like that.

Okay. Assuming the one year to recruit and then, you have to follow patients for 52 weeks for safety reasons, by the time this is potentially approved, there could be other IPF drugs, such as United Therapeutics' (inaudible) or [BMS'] (inaudible) that's potentially out there, will you need to do additional, like, Phase 1 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 drug-drug interaction there. I think it will be a matter of timing.

If we're done with our recruitment phase and we're continuing the running of the study, then, obviously, we would not need to bring in any more patients.

I think it's a matter of timing, (inaudible). We'll see what happens.

But it's not a big deal to do a Phase 1 study, a DDI study. I wouldn't see that as a barrier.

William Wood, B Riley Securities.

Two for me, one upfront.

Just thinking about in terms of your ILD study, you've mentioned that you're going to do an adaptive design. 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? Should we really expect that to look into all ILDs, including differential forms of pneumonia, just discuss how we should think about that, if you would?

And then, I have a follow-up.

Yeah. We actually had a very insightful meeting with a group of KOLs last year. It comes down to 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. They all have cough, whatever percentage that is.

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 gpoing to base it on the fibrosis that they have and the amount of cost that they have.

I think it really minimizes it to the core essentials. We think that the fibrosis is probably leading to the cough, anyway. It really does get to the fundamental issues.

Now, that doesn't mean we won't have to deal with comorbid conditions and (inaudible) and things like that. We'll work out those details. But I think that's the essence of the trial.

Got it. Makes sense. And then, in terms of -- the FDA is 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 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 (inaudible) the end of the study. There just isn't much there.

I've been living this ride from the beginning. I would say I just continue to have stronger and stronger conviction that this drug will stay on schedule 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 that it was addiction.

I don't know, Jim, anything you want to add?

Yeah. 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 combination at the NDA time. There's clearly very good day sets 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, then withdrawal.

Just for a point of reference: That's a label issue, not a scheduling issue.

Again, there's two different aspects of this that they're interested in; not that we expect to see any of that but that would be label, as opposed to scheduling.

Kaveri Pohlman, Clear Street.

Hi. This is [Christian]. I'm on for Kaveri today. Thanks for taking our question.

You've mentioned that the one-year IPF Phase 3 safety data set could start to teach you things about things like this [neo-exacerbation], hospitalizations, and maybe even lung function trends, over time.

Will any of those be pre-specified analyses? What data would actually change how you think about the label or launch strategy?

Yeah. 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 one thing that we mentioned previously is that cough patients really do have concerns about shortness of breath. 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 [FECs]. We do other things. We'll look at hospitalizations.

These are going to be patients -- living with their disease is a terminal condition. We'll be tracking those things, as well, over the course of the year.

Got it. I appreciate the color. I just have one more regarding, Phase 3 IPF population. You've previously mentioned that you would like the population to be as real world as possible and that it will be like the Phase 2b 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 2 CORAL study?

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.

We are broadening that. We're making it 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. It 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. There was an arbitrary cut-off, around 10 coughs per hour.

There was some concern about maybe capping those. We are going to cap the number of costs coming in under 10 coughs per hour. That came out of the CORAL study.

We're learning the CORAL study but, really, it's a very similar population to that study.

Got it. Thank you so much.

Thank you, Christian.

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.

Thank you. This concludes today's conference call.

Thank you for attending. You may now disconnect.