Trevi Therapeutics, Inc. (TRVI) Earnings Call Transcript & Summary

Good morning, and welcome to the Trevi Therapeutics Phase II CANAL Interim Analysis Conference Call of Haduvio for the treatment of Chronic Cough in IPF. [Operator Instructions] Please note this event may be recorded. Various remarks that management may make during this 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 reported quarterly report on Form 10-Q for the quarter ended September 30, 2021. 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 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. Participating on today's call from Trevi Therapeutics are Jennifer Good, President and CEO; Bill Forbes, Chief Development Officer; and Farrell Simon, Head of Commercial and Strategy. Also joining this call is Toby Maher, MD, Professor of Medicine and Director of Interstitial Lung Disease at Keck School Medicine, University of Southern California. I would now like to turn the conference over to Jennifer Good, President and CEO of Trevi Therapeutics. Please go ahead.

Good morning, and welcome to Trevi's call to review what we view as very exciting data in the field of idiopathic pulmonary fibrosis, or IPF, and cough from the interim data readout in our Phase II CANAL study. Joining me today on this call from Trevi are my colleagues, Dr. Bill Forbes, our Chief Development Officer, who will review the data and provide more color; and Dr. Farrell Simon, Head of Commercial and Strategy, who will be available during the question-and-answer portion of the call. We are also very pleased to be joined by Dr. Toby Maher, a Professor of Medicine and Director of Interstitial Lung Disease at Keck School of Medicine at USC. Professor Maher is also the Director of the NIHR Respiratory Clinical Research Facility at Royal Brompton in the U.K. He is currently the global Chief Investigator for a number of commercial studies of compounds being tested in trials for IPF and other interstitial lung diseases. Professor Maher and his team have recruited over 1,000 subjects to more than 35 clinical studies in the last 8 years. Dr. Maher's also the lead investigator in our CANAL study and is considered a top thought leader in IPF and interstitial lung diseases around the world. We are grateful he is able to join us at this early hour for him and have asked him to help us understand the seriousness of this disease, the impact of cough and why he was interested in being the lead investigator on this trial. We will go through our slides and prepared remarks, then we'll be happy to answer any questions. I want to summarize, at a high level, the very impressive takeaways from this study. We had built into this trial an interim conditional power analysis to determine 1 of 3 possible outcomes: one, our powering was good, and we should finish the study as planned; two, the trial results were not favorable, and we should discontinue the study; or three, the trial results were more favorable than estimated in the original powering calculations, and proof of concept had been established. I am very pleased to report that the results supported establishing proof of concept. The interim data is strong with a 52% placebo-adjusted reduction in the mean percent change from study baseline for nalbuphine ER as compared to placebo in daytime cough frequency to day 22 of treatment with a p-value of less than 0.0001. I don't think I've ever said that on a p-value. The magnitude of effect was strong and very consistent in almost all subjects that received nal ER. Importantly, this is data as measured by an independent cough monitor and the results are consistent, independent of the baseline cough count frequency. Just a few other points I will share, 42% of the nalbuphine ER-treated subjects achieved a greater than 75% reduction from study baseline and daytime cough frequency as compared to 0 of the subjects in the placebo arm, so 75% reduction in their cough count in just 3 weeks of therapy. Bill will show you additional data on the secondary efficacy endpoint measurements, which include patient-reported outcomes, but they all support the strong results seen in the primary efficacy analysis. Nalbuphine ER was well tolerated in the study and the adverse events were consistent with what we've seen in trials and other indications. As a reminder, we are reporting the interim data now for our CANAL study, but we also are conducting a Phase IIb/III study in chronic pruritus associated with prurigo nodularis. That study completed recruitment on January 31 of this year, and we expect data in the second quarter of this year. We will also report out the full data set from the remaining subjects enrolled in this cough trial this year, subsequent to our interim data cuts early in the third quarter. So it is a busy few months of data readouts for the company. Turning now to the market opportunity in chronic cough in IPF. IPF is a progressive and severe condition in which there is scarring of the lung tissues. One of the leading debilitating symptoms of this disease is chronic coughing, which affects up to 85% of these patients and for which there are no approved therapies. In the U.S., we estimate that there are approximately 130,000 patients with IPF and an equal amount in Europe. Due to the high 5-year mortality associated with IPF, prescribers and patients are not only looking to slow the progression of the disease but also improve the patient's quality of life. Dr. Maher will do a much better job than I can do telling you about the significant role of this disease and that cough plays in the daily lives of IPF patients, but I just want to show you this slide to highlight some of the main takeaways from the literature on the impact of cough. You can see here the median cough for some of these patients is as high as 520 times a day. This is also a marker of this disease, and it's very disruptive to their whole social and daily lifestyles. Cough is serious and it's debilitating in a disease that is terminal. We were interested in studying chronic cough in IPF for 2 reasons. We felt it had a strong mechanistic link to the mechanism of action of our drug. We also knew the underlying disease of IPF was quite severe, and these patients did not have effective treatment options available for one of its leading debilitating symptoms. As you can see on this slide, our drug targets the endogenous opioid system, which works broadly throughout the body, both centrally and peripherally. Importantly, there are several opioid receptors in the lungs, the spinal cord and the brain stem, which mediates coughing and breathing. Because our drug is active at 2 of the 3 opioid receptors, mu and kappa, we hypothesized that we can improve the neurological signaling going on between the lungs and the brainstem that was resulting in cough, dyspnea or breathlessness and, ultimately, fatigue. I also want to remind you that because our drug antagonizes or blocks mu and agonizes or activates kappa, it is currently unscheduled and does not seem to have the same addiction characteristics of pure mu agonist. Finally, chronic cough in IPF is an indication in a much larger opportunity for chronic cough, both in other interstitial lung diseases as well as the growing opportunity in refractory chronic cough with a total global cough market potential of $10 billion. These are opportunities we are considering for expansion of our clinical development efforts based on these very encouraging results. Also, as you can see on this slide, we've been actively working on our patent portfolio and are prosecuting patents worldwide that if issued, we believe, will protect this indication as well as other cough indications listed here until at least 2039. If you've been following the cough space, you will know that most companies are studying refractory chronic cough, which is also a significant unmet medical need. The mechanisms of action for the investigational therapies being studied have all largely revolved around P2X3. We feel our mechanism has broad potential in treating chronic cough across a number of patient populations and the area could benefit from an alternative mechanism. I will now turn it over to Bill to take you through the data.

Thank you, Jennifer, and good morning. Today, I will review Trevi's interim analysis results for our CANAL trial study of nalbuphine ER on chronic cough in IPF. This interim analysis was conducted only on efficacy data, and I am very pleased to be able to share with you these strong and clear results. Given the positive results of the trial, we have decided to end further recruitment and complete screening for subjects that are already in the recruitment process. We expect the last patient to enroll in March and to report our full results of the trial early in the third quarter of this year. On January 5, the company announced an interim analysis to gain insight into whether the study already had established proof of concept or if it should continue to completion. Remember, the conduct of this particular trial ran into the headwinds of COVID. And these patients were under shelter-in-place orders during much of the recruitment period. Regardless, we found ways to safely support these patients in enrolling in this trial during a very difficult time in their lives. And we want to express our thanks to them and to the investigators for all their support to bring this trial to this point. I'm excited to share with you today the positive results from the interim analysis of the CANAL trial and our next steps in development. Slide 12 has a diagram of the study design. CANAL is a proof-of-concept trial that is designed as a double-blind, randomized, placebo-controlled, 2-treatment, 2-period crossover trials assessing the efficacy and safety of nalbuphine ER for the treatment of chronic cough in patients with IPF and is taking place in the United Kingdom. Each treatment period is 3 weeks with a 2-week washout period after each of the treatment. In the nalbuphine treatment period, subjects titrate to a final dose of 162 milligrams administered twice a day in the form of an oral tablet. The primary efficacy is acquired by the use of the VitaloJAK digital cough monitor at baseline and at the end of each treatment. For purposes of the primary endpoint, the study baseline was used. The study baseline is the very first VitaloJAK recording prior to the subject receiving any study medication. Trevi is aware that there are other companies in the cough field that have used this same study design and have reported results using the treatment period baseline. During the conduct of CANAL, we acquired data on both of these baselines and have included supplemental analyses that show changes by each treatment baseline in today's presentation. The EXACT patient-reported outcome data was used as a secondary measurement tool to assess cough, breathlessness and other chest symptoms. Slide 13 provides important inclusion/exclusion criteria for CANAL. Importantly, subjects have to be diagnosed with IPF, have an FVC of greater than 40%, have chronic cough for greater than 8 weeks and, if they were on antifibrotics, had to be on a stable dose for greater than 8 weeks. Slide 14 has some information about the digital cough monitor that we used in this trial. This is a 510(k)-approved device and has been widely used in clinical trials around the world. Slide 15 outlines the patient disposition for this analysis. At the time of data cutoff, we screened 45 subjects. 32 of them had been randomized. 26 subjects completed at least 1 treatment period, and they comprise the full analysis set. And 18 of those subjects actually completed both periods in their turn to completers. The primary endpoint is based on all 26 subjects, but we will show you data on the completers as well. Slide 16 provides baseline characteristics of the patients included in the analysis. Approximately 80% were male with a mean age of 72 and an average awake cough frequency of 31 coughs per hour. You'll also notice that the average cough frequency range from 3 coughs per hour to up to 92 coughs per hour in the patients in this analysis. On Slide 17, you will note the primary endpoint. There is a 77% reduction in the geometric mean percent change in the nalbuphine-treated subjects compared to 26% reduction in the placebo arm. As Jennifer mentioned earlier, this results in a 52% placebo-adjusted change and a p-value of less than 0.0001. We are impressed with the magnitude of the efficacy of the nalbuphine ER and the level of significance seen. While the primary analysis uses the full 26 patients, the results remain consistent when looking at the completers as well, that is, the subjects that have received both nalbuphine and placebo in the trial. When looking at the response on nalbuphine ER versus placebo, 15 of the 18 subjects did numerically better in their reduction on daytime cough on nalbuphine than they did when they received placebo. Slide 18 assesses the effect of treatment on cough broken down by different baseline cough severity. Because there is a great variation in baseline cough count, we decided to perform some analysis looking at different levels of baseline cough count. In this analysis, I have moved from geometric mean to arithmetic mean. There are 3 categories: the entire population, baseline cough count greater than 10 coughs per hour and baseline cough count greater than 20.5 coughs per hour. This corresponds to 100%, 80% and 50% of the intent-to-treat population. First, the magnitude of nalbuphine ER's treatment effect is approximately 70% regardless of baseline severity. Also, there is little change in the placebo-adjusted change in each of these cuts when analyzed based on baseline cough severity. Each group demonstrates an approximate 50% improvement over placebo. Slide 19, we have presented data using the treatment baseline and looked at all subjects and by the same baseline cough severity cutoff as the previous slide I just addressed. I mentioned earlier that the primary analysis uses study baseline, but for those subjects that completed the trial, we also have their period 2 baseline. When using treatment baseline, we cut the data using the same 80% and 50% population of the worst baseline cough count. All groups have an approximate 70% reduction from baseline when on nalbuphine ER, consistent with the prior slide, and an amplified placebo-adjusted change of greater than or equal to 70%. On Slide 20, we looked at our data using a responder analysis. Subjects had demonstrated a 30%, 50% and 75% reduction. And their daytime cough were analyzed, and the results reflect that at every cut, the nalbuphine arm outperformed the placebo-treated arm. And again, as Jennifer mentioned earlier, it's interesting to us that 42% of the subjects treated with nalbuphine ER achieved a 75% reduction in daytime cough whereas 0 patients treated with placebo achieved such a reduction. Slide 21 contains data from the patient-reported outcome questionnaire. I mentioned earlier that we collected daily patient-reported outcome measures from subjects using the EXACT questionnaire. EXACT has 14 questions, each with 5 possible answers ranging from 0, which is typically denoted as none; to 4, which is extreme or almost constantly. As such, lower scores in the EXACT denote improvement. Together, the EXACT measures cost severity, dyspnea and breathlessness. Specifically, we had an interesting question #2, which measures, and I quote, "How often did you cough today," which has responses ranging from not at all to almost constantly. Directionally, the patient-reported outcome results corroborate the data reported by cough count. If you look at the EXACT 2 score, treatment with nalbuphine ER resulted in an approximate 1 point reduction from baseline and corresponding to a score of 1 or a response to the question how often did you cough today with an answer of rarely. This is consistent with the results seen with the VitaloJAK. Simply put, the patients tell us their respiratory symptoms improved and are directionally consistent with the results of the objective cough monitor. Slide 22 covers what we know about safety. And again, as a reminder, this interim analysis was undertaken to specifically assess efficacy from the digital cough monitor as well as to assess whether the PRO, or the patient-reported outcome, measures corroborated any possible changes in daily cough count. We do not assess safety. And at this time, the company remains blinded as to the allocation of specific adverse events to either active or placebo treatment. I would also like to emphasize that since this study began, we have had a very capable DSMB overseeing the safety of the study. They have met routinely and received frequent updates. To date, the DSMB has not indicated any safety concerns to us. However, from a blinded perspective, we do know this about this trial in IPF patients. There have been no reported deaths and 1 reported serious adverse event, which was not considered treatment related. That specific serious adverse event was a pneumonia that occurred in the patient. There have been 5 patients discontinued due to adverse events, which accounts for about 16% of the population that was randomized: 1 had anorexia, 1 about a depression, 1 had nausea and vomiting, 1 insomnia and fatigue and 1 had [ education ] anxiety and dyspnea. I will also note that Trevi has treated over 1,000 subjects ranging from healthy volunteers to end-stage liver and end-stage kidney disease to patients with prurigo nodularis. The safety profile of nalbuphine is well characterized in a broad range of populations. Slide 23 just highlights a few points about key next steps. Once we complete dosing, we will look to report out the full study data in early Q3 of this year before initiating discussions with relevant health authorities to review the next protocol design. I am impressed with the magnitude and consistency of these results and look forward to accelerating development of nalbuphine ER in the treatment of chronic cough in IPF. And with that, I wish to introduce Dr. Toby Maher. Dr. Maher is the lead investigator for CANAL. He counseled the company on how to design this trial. And with his more recent move to the University of Southern California, he remains integral in the conduct of the trial. Dr. Maher?

Thank you. Thanks for the introduction and asking me to say a few words. So just to put the challenge in context, idiopathic pulmonary fibrosis, as I'm sure many of you are aware, is a deadly progressive condition that causes irreversible scarring of the lungs. The median untreated survival for the disease is about 3 years. With the advent of antifibrotic therapy, that's probably improved to 5 years. But even so, patients develop progressive breathlessness that ultimately leads to respiratory failure and death. Importantly, as has been mentioned, the other significant symptom from which patients frequently suffer is cough. And the cough is particularly debilitating, particularly when thought of on a background of breathlessness. The cough will often leave patients very disabled. It will leave them unable to exercise or walk because it often comes on, on exertion. It's socially limiting. As I'm sure everyone recognizes, during the COVID pandemic, if you see someone coughing, you tend to cross the street at the moment because you think they're infectious. And in the same way, patients with IPF often find that they can't go out in public. They can't go to theaters or cinemas. They can't go to restaurants because they're too embarrassed by the coughing. And in research that we've done trying to understand the effects of cough on IPF patients, we found that cough is much more strongly associated with depression and anxiety than even breathlessness is. So of all the symptoms we see, it is the most disabling. And it's worth recognizing that although we now have effective treatment for IPF in the form of pirfenidone and nintedanib, what those drugs do is slow disease progression and improve survival. But what they haven't been shown to do is improve quality of life in any form. And they don't appear to meaningfully affect cough in patients with IPF. So although we have treatments for the disease, we don't have treatments for the symptom of cough. And whilst we've tried to develop therapies in this area, we've seen a number of important failures. And there've been failures of sodium cromoglycate in P2X3. So despite best efforts, we don't, at this present time, have any effective treatments for the cough in IPF. So we're left with our patients having very disabling symptoms. So I think, with that in mind, the data that you've just heard is very exciting. There is a clear reduction in cough frequency in the IPF patients compared to placebo. And I really think that this sets the stage for a pivotal trial in this disease population. And I'm really hopeful that by moving things forward, we can address this massive unmet need in IPF patients and, in doing so, have a treatment that dramatically improves quality of life for the group of patients with disabling cough. I'll stop there. Thank you.

Thank you. Yes, that was a good perspective. I think we're now ready to open it up for Q&A. So Danielle, I'll turn it over to you to work us through that.

[Operator Instructions] The first question comes from Annabel Samimy of Stifel.

This is Nick Rubino on for Annabel. Congratulations on the overwhelming win here with CANAL. We have a few questions, if you'll bear with us. First, I know it would be a small n, but within the completers, do you have the percent change for those specifically who switched from placebo to Haduvio and I guess kind of the treatment period baseline? Second, did you notice that the titration scheme helped ease any nausea side effects? Just because that's kind of a typical signaling you guys see. And then lastly, just for next steps, after a Phase IIb, will you need 1 or 2 Phase IIIs in a pivotal program?

Bill, I think that's all you. You're up. So I didn't quite understand the first question, so maybe you did. But titration and pivotal, I'm sure you can comment on.

Yes. So Nick, bear with me as I try to answer your questions. And if I miss it a little bit, why don't you just let me know, but let me start with completers. If you look at the geometric mean percent change and, again, using log transformation data, when you look at the geometric mean percent change in the completers, there was about a 78% reduction in the active treatment period for the completers and about a 29% reduction in the placebo completers. So if you look at that, that p-value is 0.0006. So it's still highly significant, and there was still a great delta between the two. You asked a question about how many pivotal trials we see going forward. I guess that's a matter of debate as to what really needs to be done. I don't imagine that we need more than 2 adequate and well-controlled trials going forward. So I think getting in front of health authorities, the FDA and the MHRA, to try to make sure that we negotiate through what is acceptable, particularly on the primary endpoint, we anticipate that the cough counts will be the primary endpoint, but we want to make sure that we're clear with that with the health authorities. And then the titration scheme, again, as I mentioned a couple of times in my presentation, I don't have the access right now to the treatment-emergent adverse event tables, and then it's a crossover design. I think the other thing regarding this population that Dr. Maher can speak much more eloquently to than myself because he's an expert in the field, but these patients cough an awful lot. So I've heard from some of the investigators that sometimes the vomiting can be there for some of these patients. They are also on antifibrotics. And I think some of the side effects of the antifibrotics overlap with some of the side effects that we have. I am happy with the number of completers that have come through this trial. It seems that these patients are able to tolerate our product well and get, obviously, a fantastic response from it. So maybe I'll ask Dr. Maher if he has any input on any of these topics because he has a lot of experience, both obviously medically but also from a regulatory perspective.

Yes. Thank you. I think you're right about the overlapping side effect profile. Particularly, both nintedanib and pirfenidone can cause upper GI side effect. So I think one of the things to tease out from the data will be the relative effect of background treatment on some of the assay you reported. I think with regards to the pivotal trial, that is an important question. And I guess we don't fully know the FDA's or EMA's viewpoint on this as yet as there haven't been any approvals for this treatment indication. But I think from what we've seen in this trial is that it certainly ticks the boxes of what the FDA expects in terms of improving how patients feel and function. And it's an area of huge unmet need. So one would hope that the regulators would be reasonably flexible given the challenges of doing studies in patients with cough. And I think the discussions to be had with them will be enlightening and, hopefully, will show us the way forward. But I would be optimistic that it might be possible to do a single pivotal trial.

The next question comes from Serge Belanger of Needham & Company.

Congrats on being able to report such a strong p-value with the interim analysis. First question, I guess, for Bill, and I don't know if you can talk about this given this is an interim analysis, but any idea of the onset of nalbuphine here and also whether the response rate should be expected to continue to improve beyond day 22?

No, I think it's a great question, Serge. Originally, when this trial was designed, we had the VitaloJAK applied to the patients not only at baseline but at 1 week, 2 weeks and 3 weeks. When COVID hit, we had to adjust the protocol to make it somewhat COVID-friendly, I guess. We had to reduce the number of interactions and times where the patients came in. So we had to kind of dance and we had to work closely with our investigators to get that done. So unfortunately, one of the casualties of that exercise was we lost the VitaloJAK at week 1 and 2. So we were able to keep it, obviously, at baseline and end of treatment. So we'll flex into the EXACT data the patient-reported outcomes, and we'll start to take a look week-by-week as to whether or not there's an increase. So when you asked about the onset, the feeling we have, anecdotally, talking to the investigators, is that it appears to come on quickly, that the patients have some relief fairly early on. But of course, they are in the titration phase. As to whether or not they continue to progress, I mean we have data on 3 weeks. So our hope is, in the next trial, that we can do a 3-month study or either a 3- or 6-month study, and we'll be able to make a determination using either PRO data or administering more VitaloJAK or acquiring more of cough data through the VitaloJAK or some cough digital cough monitor. So I hope that answers your question. I guess in a way, I have to kind of dance around whether or not it will continue to improve over time. As you can see, 42% got a 75% reduction from baseline at 3 weeks. So whether or not we continue to treat on, that improves, we don't know yet.

Okay. And then for Dr. Maher, maybe just general thoughts on this level of response and how this stacks up to what they currently use in the clinic, and if you've had any experience with the P2X3 drug class and how nalbuphine stacks up to that so far.

Yes. So I think at the moment, in the clinic, we just use a variety of approaches, including inhaled bronchodilators, corticosteroids, drugs like amitriptyline or occasionally sort of codeine phosphate or opiates. And in general, the response is sort of modest at best and I think probably reflects placebo response. You'll see from the trial that there is an approximate 25% placebo response, which is what has been seen in other trials. And I think in clinical practice, that's ultimately what we rely on because none of the treatments that we use are really that effective, particularly in patients with intractable cough. So I think the results we're seeing here are enormously encouraging given that lack of other therapeutic options. And I think the one thing that the cough count overlooks is that it's not just the number of coughs that are disabling, it's also the intensity of coughing. And actually some patients with relatively few coughs can actually have a bigger impact on quality of life because when they do cough, they have sort of really disabling bouts of coughing. And so I think what's important in the data is we're not only seeing the improvement in cough count, but we're seeing the corresponding improvement in the quality of life too as well because that tells me that the reduction in cough frequency is having a meaningful effect for the patients, that it's not just having an effect on reducing cough count, but it's having an effect on the impact of that coughing, which I think is vital. I only have very, very limited involvement with P2X3. But as you'll know, the trials in IPF patients were negative and the drug was limited in use for patients with long-term cough because of the changes in taste, which a lot of patients in the trial found quite sort of debilitating. And so I think that the side effect profile of some of the P2X3 inhibitors was off-putting for IPF patients. So again, that's something that we're not seeing in this trial.

Okay. One last one. I was just going to ask, the CANAL was designed as a proof-of-concept study for IPF cough. Just curious, with this level of data that we're seeing this morning, if that provides proof of concept for a broader cough usage beyond IPF cough?

So either of us can take this. I'll take a shot at it. I mean that's always been the theory here. Because of the mechanism of how this is signaling up to the brainstem, we always believe that this could work more broadly on cough which, by the way, is sort of known in cough, right? People have used this mechanism before for cough broadly. So we certainly targeted some areas we're interested in. I think there's a good reason to believe. I mean I was sort of laughing with Tom, my co-founder, because when we started looking at IPF cough, the advice we got from a lot of cough experts, not Dr. Maher, by the way, is don't look at IPF cough. It's too hard. These people are diseased. They cough hard. It's a really high bar. And Tom sort of felt strongly this had a really good mechanistic link and it was a serious condition. So with this data and sort of how powerful it is, we'll certainly look at other cough indications and think there is probably a good translation to it. Bill, anything you want to add to that?

No. I think just to emphasize, I mean Tom Sciascia is our Chief Medical Officer and a neurologist by training. So we have these conversations. I have these conversations with Tom all the time. I think the feeling I get in speaking with him and, obviously, looking at this is, certainly, there's great opportunity for that. I'm actually going to punt it over to Toby because I'd be interested in his perspective on this as well.

I would agree. I think it certainly opens the door to studying cough, both in other diseases -- it's a major problem across different forms of interstitial lung disease. It's a major problem in patients with lung cancer. And of course, idiopathic cough is, in itself, a hugely disabling problem with a huge number of affected individuals. And I think we recognize that there are sort of fundamental neurological mechanisms that map across all forms of cough. There are also different mechanisms that seemingly drive cough. And I get the sense with nalbuphine that it probably targets a central mechanism common to all coughs. So I would see this as providing a very strong rationale sort of thinking beyond idiopathic pulmonary fibrosis. And I think as has been said, IPF is arguably a fairly tough nut to crack because you've got a disabling and progressive scarring disorder of the lung that is only getting worse and not better and, therefore, to modify cough in this patient group is often very much harder than doing it in patients with idiopathic cough, for instance. So I think it's a very strong data set to do, as was suggested by the question, to look beyond IPF now as well.

The next question comes from Bert Hazlett of BTIG.

Congratulations from me as well. So with regard to next steps with Haduvio and nalbuphine ER, these results were very strong and certainly established proof of concept. Could you just maybe elucidate a little bit further what element of CANAL you would expect to keep in Phase III? And what may be adjustments, minor or major, you would consider as well as you move to next steps? And congratulations again.

Thanks, Bert. Bill, go ahead. This is your power alley.

Bert, thanks for your question. I think I'll try to flesh it out a little bit more. I mean, obviously, we haven't engaged in the conversations with health authorities. But I would imagine a parallel design. Personally, I have an interest in exploring maybe multiple doses. I think for those that have listened to our story and I've interacted with, you know that I love it when you beat placebo and you show a dose response at the same time. And I think that with these kind of results, we can look for 162 milligrams BID, but we can pick another dose as well and establish efficacy possibly in 2 doses. So that's kind of what's worth thinking right now, but I think a lot of this depends upon our interactions with health authorities. I do believe it will come down to digital cough monitoring. But the EXACT is a powerful questionnaire. And so sometimes we have discussions about whether or not we can use the PRO and the patient-reported outcomes as it relates to cough severity that would get acquired every single day. So that is that is option B perhaps. But I think, obviously, given the objectivity of the cough monitor, that's probably where we'll end up. So hopefully, that answers your question a little bit better, Bert. But if you have any other follow-up, happy to entertain that.

That's great. I'm sure there will be more. But really, congratulations on the solid results, really impressive.

Thank you.

Yes. Thank you, Bert.

[Operator Instructions] The next question comes from Jason McCarthy of Maxim Group.

Congratulations on the data. Can you just talk a little bit about timing for meeting with FDA? I know you've got great data now at the interim and you're going to stop the trial or stop enrollment. But do you wait to move to the Phase III till you get that final data in the third quarter? Or how do you see that playing out?

Bill, go ahead.

Yes. I think obviously, we'll try to move in parallel as best we can and use the calendar to try to get in front of the agency. We would like to go with a full data set when we go to visit with them. I anticipate that we'll move from -- if we just look at completers, we'll probably move from 18 to around the mid-30s on completers. At this point in time, we have 20 completers in our database. So I do anticipate a good tranche more data. But when we go, then obviously, we'll have the treatment-emergent safety tables and things like that, that are helpful to health authorities to take a look at. So going before we have the full data set, we may not be able to answer their questions in a clear and concise manner. So that's kind of the goal of waiting until the third quarter. So we'll try to get in front of the agency as soon as we can once we have the tables and listings and figures in final form.

Got it. And one more question. You had mentioned the range in coughs per hour between 3 and 90, I believe it was. But the severity of somebody with 3 could be really, really bad for that person. Do you intend to show the final data set kind of stratified based on number of coughs and patient-reported outcomes? Can we see those people that were maybe 3, 5 and 10 coughs at baseline, but they were really severe, maybe some of them weren't?

Yes. No, I think that's one of the reasons we did some cuts to the data when we looked at 10 and 20.5 coughs per hour. We wanted to show you that as you started to increase the baseline severity as noted by coughs per hour, as you start to get to that in this data set, it really doesn't matter the improvement. So yes, the 3 coughs per hour is an outlier on the low side. Obviously, we have one that has over 90 coughs per hour on the high side. So we will. Obviously, we'll do some probing and we'll break the data set down into different quartiles or tertiles and report out the results that way. And of course, we'll match it up as we're -- you can start to see that we're doing that already with the PRO.

Sorry, that wasn't the last one. For last, really quick. The 3 weeks of treatment, is that sufficient in terms of safety that FDA would require just given that IPF is such a chronic and it's lifelong, do they want to see you go out a little bit further than that? Or can you talk a little bit about what we might expect around long-term safety?

Yes. As I noted, I mean, we have 1,000 patients that have been exposed to nalbuphine ER at this point in time. And so we've got up to a year of follow-up in patients that have it. Then I guess with IPF, we'll have to just -- I don't want to speculate on what the agency is going to request as far as safety in this particular patient population, but we'll bring all the safety to bear as every company does, as you know.

Thank you, Jason.

I am not showing any further questions. This concludes our question-and-answer session. I would like to turn the conference back over to Jennifer Good for closing remarks.

We would like to thank everybody for participating in today's call. I'd also like to thank the Trevi team, our study investigators and all of the subjects in our clinical trial. We'll be available after this call for any follow-up questions you may have. Thanks so much.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.