TRVI - NASDAQ

Good afternoon and welcome to the Trevi Therapeutics First Quarter 2025 Earnings Conference Call. At this time, all participants will be in a listen-only mode. [Operator Instructions] After today's presentation, there will be an opportunity to ask questions. [Operator Instructions] Please note this event 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-Q, 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 over to Jennifer Good, Trevi's President and CEO. Please go ahead.

Good afternoon and thank you for joining us for our first quarter 2025 earnings call and business update. Joining me today on this call is my colleague Lisa Delfini, Trevi's Chief Financial Officer; Dr. James Cassella, our Chief Development Officer; and Farrell Simon, our Chief Commercial Officer. Lisa and I will make some comments on the business and financial results, then the team is happy to answer any questions that you may have. The strong momentum of 2024 at Trevi continued into the first quarter of 2025 with the positive data readout from the Phase 2a RIVER Trial in RCC patients and the completion of enrollment in the Phase 2b CORAL trial in IPF chronic cough patients. I will discuss both of these programs in a bit more detail, but needless to say, it has been an exciting few months for us. In March, we announced the data from our Phase 2a RIVER trial in patients with refractory chronic cough, or RCC, which includes those with unexplained chronic cough. RCC is a debilitating disease that affects approximately 2 to 3 million US patients and has no approved therapies in the US. Importantly, there have been many drugs studied for this condition which have failed, all primarily peripherally acting agents with only one drug still in late-stage development, GSK's camlipixant. Our hypothesis heading into the RIVER study was that our central and peripheral mechanism could change the outcome for RCC patients by having a larger effect, as well as working across a broader range of cough counts than other peripheral only therapies in development. RCC is believed to result from cough hypersensitivity at the brain level and why we believe the central activity of our mechanism is important and differentiating. In the Phase 2a RIVER study, Haduvio met the primary endpoint with a statistically significant reduction in 24-hour objective cough frequency achieving a P value of less than 0.0001. There was a 57% placebo adjusted reduction in cough from baseline and importantly, showed the same strong effect across a broad range of cough counts including patients with moderate and severe cough frequencies. In our top line announcement, we also showed two patient reported secondary endpoints in both cough severity and cough frequency that were highly statistically significant and corroborated the primary endpoint of the objective cough monitor. Since reporting those data, we have received the full data set and can confirm that all prespecified secondary endpoints in the study were statistically significant at the end of treatment. The RIVER data were important not only for potential therapeutic value to patients but scientifically as well. Haduvio is the first mechanism to work in both patients with RCC and in IPF patients with chronic cough. We believe this is evidence of the importance of the central mechanism underlying neurogenic chronic cough conditions and lays the groundwork for not having to do the enrichment strategies others have employed to show statistical significance in RCC. Turning now to our lead program in IPF patients who suffer from chronic cough. During the first quarter, we also completed the enrollment of the Phase 2b CORAL trial for the treatment of this condition. And in April, the last patient completed their last visit. This study enrolled approximately 160 patients in 10 countries and across 60 sites. The team is now cleaning the data and preparing for database lock, so we remain on track for top line data this quarter. We are excited to get the data from this dose ranging study and advance the development program in both chronic cough conditions of IPF and RCC. Speaking of the FDA, there's a lot going on there that all of us collectively are worrying about. I do want to convey our recent experience as I think it is important for all of us to monitor the current state of this important regulation regulatory body. We asked for guidance through a Type C request with written responses only on a technical matter in our program. I am pleased to report that the FDA met their goal date this month and provided us responses with clear guidance. We recognize the FDA staff has a lot going on and appreciate their ability to keep companies moving forward with their development programs. FDA feedback is critical during development and we hope that the new leadership will prioritize this aspect of the FDA's role. So, to wrap up all eyes here on the IPF chronic cough data. This is a patient group that has had very little innovation in treatment options over the past 10 years, especially when it comes to improving their day to day lives of living with IPF. As a side note, we are planning on being quite active at ATS in San Francisco in a couple weeks. I will be there with several of my colleagues, so if you plan to attend, please let me know. We are hosting a KOL panel featuring both IPF experts and an RCC doctor for investors and analysts and already have quite good attendance. We plan to share new insights from the full RCC data set which we will release online after as well. We will also be participating in a dinner with investors and will be actively attending sessions at the conference. Unfortunately, our RCC data came too late to make it into the late breaker timelines for this conference. However, we plan to submit abstracts for analyses from both the RIVER and CORAL studies for the European Respiratory Society meeting in September. I will now turn it over to Lisa to review our financial results. Then we will open it up for any questions you may have.

Thank you, Jennifer and good afternoon, everyone. The full financial results for the three months ended March 31, 2025 can be found in our press release issued ahead of this call and our 10-Q which was filed with the SEC today after the market closed. For the first quarter of 2025, we reported a net loss of $10.4 million compared to a net loss of $10.9 million for the same quarter in 2024. R&D expenses were $7.8 million during the first quarter of 2025 compared to $8.8 million in the same quarter of 2024. The reduction was primarily due to decreased costs related to our Human Abuse Potential study which was actively enrolling in the first quarter of 2024. This was partially offset by an increase in personnel related expenses due to increased headcount. G&A expenses increased to $3.7 million during the first quarter of 2025 compared to $3.1 million in the same period of 2024, primarily due to an increase in personnel related expenses. As of March 31, 2025, our cash and investments totaled $103.3 million, which gives us runway into the fourth quarter of 2026. We plan to use this cash to complete our ongoing Phase 2b CORAL trial of Haduvio for chronic cough in patients with IPF. And based on this data, we'll determine the development path forward in our programs and the related financing needs. During the first four months of this year, we had a total of 7.9 million common stock warrant exercises. We currently have about 1.9 million common stock warrants that remain outstanding. Our current fully diluted shares outstanding are approximately 137 million, which includes 101.7 million shares outstanding. Those 1.9 million common stock warrants about 23.2 million prefunded warrants and approximately 10 million stock options. This concludes our prepared remarks. I will now turn the call back over to the operator for Q&A.

Thank you. We will now begin the question-and-answer session. [Operator Instructions] Our first question comes from Faisal Khurshid of Leerink. Please go ahead.

Hey, thank you for taking the question. Just wanted to ask, can you remind us for the CORAL readout, what would you see as a kind of encouraging or positive readout both on the efficacy side and on the safety side? And is that like meeting the statistical bar? Is there anything kind of beyond that as well? And I have a follow up as well.

Thanks, Faisal for the question. I think for this trial because there's been so little, it's been such a difficult condition and there's really nothing for these patients. We powered this study fast and to be able to move forward. And I think unlike RCC, when there were other programs, we had to consider as far as moving forward. For this program a statistically significant positive trial, we will keep moving forward in development. So that's the bar for us for success. I think on the safety side, just continuing, no sort of unusual adverse events that we didn't see, no safety signals which we would already know at this point. So, I'm comfortable we sort of crossed that bar. We've also shared before that our discontinuations are less than 10%. So, I think level perspective, I think, we'll look at, obviously, sort of the AE profile and things, but we've seen a lot of that so far, and there's nothing jumping out as unusual here. So really, I think it's just a matter of having positive data here and what it looks like.

Got it. Great. And then, can you remind us what did the next catalyst for the company look like sort of in like the year or so, like coming out of the CORAL readout.

So, Faisal, I'm going to a little bit kick that can down the road, because once we get the IPF data, I think we'll be in a better position to lay out the catalyst path forward. I mean, we've talked about -- we've got to get to the FDA and see them based off the IPF results, assuming they're successful. And Jim and Farrell are doing some work around gearing up for running a basket trial in interstitial lung disease, which we can talk more about. And I think once we get the IPF data and we're clear sort of on the path forward, we'll lay out a good catalyst track coming out of our IPF data.

That's great. Thank you for taking the questions and look forward to seeing you in San Francisco.

Great. Thanks, Faisal.

Our next question comes from Annabel Samimy of Stifel. Please go ahead.

Hi. Thanks for taking my question. Just following up on the discontinuation rate you mentioned. It was less than 10%. Can you just remind us what you powered for? And was this powering based on overall discontinuations or just discontinuations based on adverse events? And then just to follow on that, just after the positive data in CORAL and RIVER and positive SSRE, what is it that in your mind still presents the biggest challenge for you or uncertainty going into this ILD study -- I'm sorry, IPF study.

I'll let Jim answer the statistical question.

Yeah. So, we had powered for a 30% discontinuation rate for the study, and obviously, we came in a lot less than that.

Yeah. And I think, Annabel, to your point, I think, really, which is how much risk is left? I think all of us never stop worrying about these trials. I do think we had good Phase 2a results. RCC was obviously corroborating. The SSRE, I think was comforting. But this is a complicated trial. They're tough patients. It's in 60 different sites across 10 countries. I think Jim never stops worrying about every aspect of this trial. So, it'll be nice when we turn over the card, for sure. And it's such an important indication that I think we all feel the burden of that. But no, we're feeling good about it heading into the readout.

Okay. Great. Thank you.

Yeah, thank you.

Our next question comes from Leland Gershell of Oppenheimer. Please go ahead.

Hey, good afternoon. Thanks for taking our questions. I will keep myself to one question. Curious, Jennifer, it's been about maybe a bit over a year since you saw the publication of data from the PACIFY study of low dose-controlled release morphine and IPF chronic cough, which had shown, I think, a fairly modest 20% improvement in cough counts. Just wondering, since Simon's left, any feedback or reflection you've had from the physician community on those data and any potential role of that substance for use in IPF chronic cough? Thanks.

Yeah, no, it's a great question, Leland. So, the PACIFY study was a single site study run in the UK by Dr. Phil Molyneaux. He's also the lead investigator in our IPF trial. Very well-respected guy. It basically showed a 40% drug effect from a MU agonist essentially, but a zero-placebo effect, which was probably artificial. That's sort of a function of single side in his patients, I think. As you know, in our data sets we've seen between a 67% and 74% drug effect. So, a bigger effect, I think the community feels like we do, which is the CAPA side of our mechanism is important here. Clearly, it's sort of almost doubling the effect size. I think morphine also has other issues. You have to keep the dosing low. It's got respiratory depression. It's got addiction potential with it. And so, I've heard people ask this question at various panels. I think for all these doctors, any ability to move people to something that's not a Schedule 2 substance and doesn't have the issues around respiratory depression is going to be a better alternative for them. The fact that it's got very much better efficacy is just a bonus. So, I think while morphine was interesting, it validates the mechanism. I think that our drugs continue to perform better. Jim, you're a CNS guy. Anything you would want to add to that?

No, I think that summarizes it. I think it really maybe shows -- maybe the limitation of that particular drug in this space. And I think the comment of a 0% placebo response always raises questions about maybe the trial design or the single center nature of that.

Yeah, fair enough. Thanks for the question, Leland.

Our next question comes from Serge Belanger of Needham & Co. Please go ahead.

Hi, good afternoon. This is John on for Serge today. Thanks for taking our question. Just regarding the respiratory physiology study. Just curious if it's still on track to finish in the second half this year. And I believe you guys have been contemplating implementing a 108-milligram dose in the study. Just curious if any updates have been made since March. Thanks.

Hi, this is Jim. So, I think we're on track to keep that timeline. I think the study is ongoing and we should be okay with that timeline.

Yeah. And we're covering our clinical doses and that, John, we're comfortable. This will answer the question. Okay. Thank you. And just a reminder to everyone on that point, we really need this data when we go to talk to FDA next about the program forward. So that's kind of what we're working against here and we feel comfortable we'll be able to do that. Go ahead, Ariel.

Our next question comes from Deepa Njama of Jones Trading. Please go ahead.

Hi. Thanks for taking my question. So, could you provide us any additional color on what data points we can expect at ATS from this additional data from RIVER that we are getting?

Yeah. Happy to do that. Hi, Deepa. We're still kind of finalizing the presentation, but I think we're going to talk a little bit about some of the questions we've been getting from the sell side and also investors, which is a little bit around sort of the time period. So, a little more analyses around the timing of AEs, when they occurred, the discontinuations, what drove those. We're going to show a few patient vignettes from the trial. So, people came in, how long they'd had cough, what happened during the trial. We're going to show data around the Leicester cough questionnaire, which is a QOL questionnaire. And then I think if we can pull this together, we're going to show the treatment period effect of the crossover. So, we're doing some work around that. Now we know there was no treatment period effect, but we do get questions about what the effect size looked for both in each treatment period. So that's our current plan. Jim and I don't want to take up too much of the time. We'll probably talk for 15, 20 minutes. But we have an amazing panel which is -- thank you, Leland, who's going to Moderate it with Dr. Toby Mayer, who's probably the world's leading expert in ILD, Nazia Chowdhury, who's actually an investigator in our IPF trial. Amazing woman as well. And then Dr. Dispeningidis [ph], who many of you have heard speak, is sort of the leading authority in the US on RCC. So, we'll have a nice open discussion with them and sort of open up the room and Leland will moderate through that. So that's the plan for that time and we've gotten very good response to that. So, it should have a nice full room for that.

Thank you so much. Very helpful and look forward to seeing you in SS.

Yes, thank you, us too.

Our next question comes from Mayank Mamtani of B. Riley Securities. Please go ahead.

Yes, good afternoon team. Thanks for taking a question and congrats on the progress. On the RIVER data follow up. You're trying to figure out for the next steps some additional dose exploration work. Could you maybe talk your latest thinking on that, Jennifer? And then, I guess, a related question on the ILD study. Have you planned the protocol, the crossover versus parallel arm design, how that would look like? And is there anything we can learn from the IPF chronic cough data set that would be helpful to also think about the ILD study probability of success?

Yeah. So, I'll take the first part. Jim, maybe you can take the second part and decide if you want to fold Farrell in. I think on the dose exploration, the next step for us, Mayank, we're waiting on that IPF data. It's an important data set. It's parallel arm. We do think there's synergies between RCC and IPF. So, Jim's team has been busy doing some planning and sort of synopses and things like that. But we're going to wait and see the IPF data set and then decide the path forward sort of for both programs forward. I think. Jim, Farrell, I'll turn it over to you guys to talk about ILDs and sort of where you're at on thinking about that.

I'll talk about briefly what we're thinking about for the trial design. Farrell to fill in some of the other commercial side of things and patient side of things. But I think the key is there's a lot of learnings from the crossover design that have been really used in these types of cross studies. We're definitely going to take advantage of that crossover design. We're going to follow the footpath of the IPF work that we've done. And so, I think you can anticipate that we're going to run a similar type of trial. I think the major question here is not really about the trial design or endpoints or things like that. It's really about the nature of the population. And Farrell and I have been looking at this from a couple different dimensions and talking to KOLs and Farrell has been looking at it from the commercial side, so I'll let him chime in on that piece too.

Yeah. Thanks Mayank, for the question. When we look at the non-IPF ILD population, there is one distinction that we're making different than the anti-fibrotics. The anti-fibrotics mainly look at this from a progressive pulmonary fibrosis. So, they need to see a progressive phenotype to see a difference in FEC over time. That's different with a chronic cough therapy in this space. So, we really need two measures. As Jim was saying, we need a patient with ILD with fibrosis and we need one with chronic cough and the overlap of the two. And so that does expand that population. We're just better defining that and we hope to provide more details on the data call for oral.

Yeah. And Mayank, if I would just add. IPF is obviously a big trigger for that as well. So, assuming the IPF trial is positive, hopefully we can give a little more color around that.

Yeah, super helpful. And just a quick follow up to your comment on the recent FDA Type C meeting. Are you able to share the details of what it was about. And also obviously if your plans for next set of FDA engagement, I believe that would be the end of Phase 2 meeting for IPF chronicles. Thank you for taking that question.

Sure. On the technical matter, Mayank, it just has to do with validate -- the whole validation around the primary endpoints. Same issue everybody knows around cost counting, clarifying what we need to do. So, fortunately, the FDA's thought about that and is clear I think. Jim, I'll let you comment on sort of your thinking forward on FDA.

Yeah. I think it's very encouraging that, this was again a very specific question. The FDA came in on time, they gave appropriate answers or clarifying answers for us. So that's a very encouraging sign for us. We will plan on having the appropriate meetings. We expect that the FDA is going to be engaged with us as we need to go to them for follow up on both the RCC and the IPF programs. So, fingers crossed that things remain stable there for all of us.

Thank you, Mayank.

[Operator Instructions] Our next question comes from Kaveri Pohlman of Clear Street. Please go ahead.

Yeah. Good evening. Thanks for the updates and for taking my question. I'm curious about your thoughts on long-term patient outcomes and safety findings. The current plan does not seem to include FDA required long-term patient safety monitoring protocols even for the Phase 3 trial. Have you received any feedback on that from the agency? Could decades of this safety data from the existing formulation serve as an acceptable proxy?

Hi. This is Jim. So, we actually have pretty good clarity around what the requirements are going to be for long-term safety. The FDA has not only told others in the RCC space that 52 weeks is an important time point as far as they're concerned. So, we had planned on having 52 weeks worth of safety when we submit the NDA. There's ways to do that in the Phase 3 program with separate long-term extension trials. So, our intention is to make sure that we include 52 weeks of safety. And, of course, in that trial we're also able to look at continued effects on cough. So, I think it's in our plans and we'll be looking for that.

Okay. That's very helpful. And maybe going forward ahead of running big Phase 3 trials. What are your current perspective on potential US or ex-US partnerships? Thanks for taking my question.

Yeah. I mean, we're always in strategic conversations. I would say we are -- I think we're equipped and preparing for handling this ourselves in the US sort of absent just to straight out buying the company. Farrell is always talking to various partners potentially for commercialization in Europe and Japan. And I think depending on the data and sort of timing, that's certainly on the table.

Got it. Thank you.

Yeah. Thank you.

Our next question comes from Ryan Deschner of Raymond James. Please go ahead.

Hi. Good afternoon. This is Anthony filling in for Ryan. We wanted to ask, have you seen any trends in the RIVER study in terms of patient baseline characteristics such as like background therapies or initial disease etiology?

It's probably too early to ask that, but I'll defer you.

We are digging in on all of the data. I can't tell you that I have an answer for that right now. It's clearly some of the analyses that we'll be putting together and preparing for presentations at some future meeting.

I mean, this drug, as you probably remember, Anthony, worked in literally everyone in a big way. So, it's hard to see trends of maybe where it didn't work. But they are going sort of patient by patient trying to understand what we can see here.

All right. Thank you very much.

Yeah, thank you.

Thank you. We look forward to the upcoming results of our Phase 2b CORAL trial this quarter and appreciate all of you joining today's call. We are available after the call for any follow up questions that you may have. Thank you for joining.