Trevi Therapeutics, Inc. (NASDAQ:TRVI) Q1 2024 Earnings Call Transcript May 11, 2024
Trevi Therapeutics, Inc. isn’t one of the 30 most popular stocks among hedge funds at the end of the third quarter (see the details here).
Operator: Good afternoon, and welcome to the Trevi Therapeutics First Quarter 2024 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 quarterly 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 at 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.
Jennifer Good: Good afternoon, and thank you for joining us for our first quarter 2024 earnings call and business update. Joining me today on this call are my colleagues, Lisa Delfini, Trevi’s Chief Financial Officer; and Dr. David Clark, Trevi’s Chief Medical Officer. We reported Q4 earnings just six weeks ago. So Lisa and I will give a brief update then the three of us are happy to answer any questions. This is a busy time at Trevi, advancing our clinical development plans for both refractory chronic cough or RCC as well as cough and idiopathic pulmonary fibrosis or IPF. Let me provide a brief update on our various trials, beginning with our Phase 2a trial in RCC, which is expected to read out later this year. Refractory chronic cough or RCC is a debilitating disease that affects up to 10% of the adult population and is defined as a persistent cough lasting greater than eight weeks despite treatment for the underlying condition.
With the lack of any approved therapies for RCC in the U.S., there continues to be a significant unmet and urgent need for new potential therapies. The key point of differentiation for Haduvio in refractory chronic cough is the mechanism of action, which works synergistically both centrally in the brain and peripherally in the lungs. We believe Haduvio’s mechanism has the potential to work in more patients and potentially have a stronger effect across a broader range of baseline cough counts than peripheral only mechanisms like the P2X3 inhibitors. Our RCC trial RIVER is a Phase 2a double-blind, randomized, placebo-controlled, two-period crossover study, evaluating the reduction of cough in approximately 60 patients. This design is similar to other Phase 2a cough trials run to date but does incorporate a meaningful difference.
These patients will be randomized with a 1:1 stratification between those with 10 to 19 coughs per hour and those with greater than 20 coughs per hour. Each treatment period will last three weeks separated by a three week washout period. Patients on Haduvio will have the dose titrated weekly from 27 milligrams up to 108 milligrams twice daily across the dosing period. The primary efficacy endpoint is the relative change in the 24-hour cough frequency as measured by an objective cough monitor. The study will also explore secondary endpoints, including patient-reported outcome measures for cough and quality of life. We now have all 14 sites activated for this trial and see almost an even split in the enrolled subjects between each arm, the 10 to 19 and greater than 20 cough counts in the study.
Enrollment is progressing, and we continue to expect top line data from this study in the second-half of this year. Next, an update on our lead program in IPF chronic cough. IPF is a serious end-of-life disease. Chronic cough is reported by approximately 85% of patients suffering from IPF and have similar significant physical, psychological and social impacts to that of RCC, but may also be a risk factor that plays a role in the progression of the underlying disease of IPF. The constant lung injury, microtears and potential inflammation caused by persistent coughing may lead to worse health outcomes for patients such as increased respiratory hospitalization, mortality or need for transplant. With no currently approved treatment options for chronic cough and IPF, patients and providers have an urgent need for new therapies.
While there are a lot of ongoing development programs in IPF, current and in-development therapies have not shown an impact on chronic cough, which is one of the most difficult aspects of IPF elevating the unmet need. Our trial, CORAL is a Phase 2b parallel arm dose-ranging study that will study three active doses of Haduvio and placebo. The study is a six week trial in approximately 160 patients. We are conducting this study in multiple countries and sites to be able to complete enrollment in a timely manner. We expect to have the majority of our planned 60 sites activated by the end of June. Enrollment is progressing, and we are working with our sites to ensure our study is top of mind. We reaffirm our guidance for this study in which we expect to read out the results from our sample size reestimation analysis in the second-half of this year, and we continue to expect top line data for the full study in the first-half of 2025.
As a reminder, the SSRE is conducted when 50% of the subjects complete the study. We intend to share the SSRE results once it is complete, which will either confirm our current study sizing assumptions, recommend upsizing within a prespecified range or indicate utility. We have also made good enrollment progress on our human abuse potential study or half this year. This study is now approximately 75% enrolled, and we expect to complete enrollment this summer. The objective of this study is to determine the abuse potential of oral nalbuphine relative to butorphanol and placebo and was designed and agreed upon with FDA input. Recall that parenteral nalbuphine is unscheduled by the DEA and was recently rereviewed by the DEA and left on schedule.
It’s also important to note that the two parts of nalbuphine’s mechanism are also unscheduled, whether it be kappa agonist such as Korsuva or mu antagonists in products such as naloxone and naltrexone. This study will be submitted with our NDA as part of an eight-factor plan, which includes all the preclinical work done to-date, the mechanistic rationale for why this drug is unscheduled. Our clinical data generated in our development programs, the results of this HAP study as well as a public health rationale. Our goal is to have oral nalbuphine ER remain unscheduled as the parenteral form has been all these years. We continue to expect top line data from this study in the second-half of this year as well. Finally, our IND for IPF cough was cleared by the FDA, and we expect to initiate our respiratory physiology study in the third quarter of 2024.
We anticipate this study being conducted in the U.S. and in the U.K. The goal of this study is to systematically measure the impact of nalbuphine ER on respiratory depression in varying levels of disease severity in IPF to determine our Phase 3 patient population. To-date, we have excluded sleep disorder breathing patients in our studies, and we want to better characterize the safety in this group as we move forward. As you can see, it is a busy time clinically for Trevi, and we believe the data from these trials will be important to inform the development path forward for Haduvio across chronic cough conditions. We are excited to begin completing these studies in the second-half of this year and reporting the data. On a final note, our management team will be attending several medical conferences over the next few months, including the American Thoracic Society meeting in San Diego in a couple of weeks, the London Cough Conference in July and European Respiratory Society Meeting in Austria in September.
Please let us know if you plan to attend as we would love to meet with you. I will now turn it over to Lisa to review our financial results, then we will open it up for any questions.
Lisa Delfini: Thank you, Jennifer, and good afternoon, everyone. The full financial results for the three months ended March 31, 2024, 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. The first quarter of 2024 was a quiet quarter for finance as the rest of the company is operationally focused on the enrollment and execution of our four trials that Jennifer discussed today. For the first quarter of 2024, we reported a net loss of $10.9 million, compared to a net loss of $6.4 million for the same quarter in 2023. R&D expenses were $8.8 million during the first quarter of 2024 compared to $5 million in the same quarter of ’23, primarily due to increased clinical development expenses for our Phase 2b CORAL trial, our Phase 2a RIVER trial and our HAP trial.
These increases were partially offset by decreased clinical development expenses for our Phase 2b/3 PRISM trial. G&A expenses were $3.1 million during the first quarter of 2024 compared to $2.6 million in the same period of 2023, primarily due to increases in information technology and finance staffing and activities, as well as professional fees. Other income net was $1 million in the first quarter of 2024, compared to $1.2 million in the same period of 2023. As of March 31, 2024, our cash, cash equivalents and marketable securities totaled $72.8 million, compared to $83 million as of December 31, 2023. We used about $10.9 million in cash in Q1 ‘24, offset by about $700,000 of interest received. This is within the range of our expected cash burn for the year of $9 million to $12 million per quarter.
Our cash runway guidance remains unchanged, and we have cash, cash equivalents and marketable securities into 2026. This concludes our prepared remarks, and I will now turn the call back over to the operator for Q&A.
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Q&A Session
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Operator: Thank you. We will now begin the question-and-answer session. [Operator Instructions] Your first question comes from Leland Gershell from Oppenheimer. Please go ahead.
Leland Gershell: Hi, good afternoon. Thanks for taking our questions. Just two from us. First, in terms of the upcoming ATS meeting, we look forward to, I believe, we’ll be hearing a cough bout analysis from CANAL by Dr. Jacky Smith from the U.K. As we look forward to those data, if you could maybe, Jennifer, kind of discuss what the formal definition of a cough bout would be at least in the setting? And to what extent do cough bouts impact patients with IPF. And then I have a second question.
Jennifer Good: Yes, sounds good. I’ll kind of tee it up, and I’m going to let David give you the specifics because he was deep into the paper. The reality is this whole concept of cough bouts reminds me a lot of itch and that when we talk about average cough, that sort of averaged over time. But there’s a belief that when people have these severe bouts, that’s what’s doing a lot of the damage. So people are starting to get interested in looking at what that looks like. Unfortunately, there’s no agreement in the field as to how you define a cough bout, so that is sort of part of the debate. And there’s two very leading KOLs who have taken our data and done the analysis. So Dr. Smith will present that, and I’ll let David speak exactly just sort of her methodology at this meeting.
And then I think in the fall, one of the other KOLs is going to present it sort of using a different methodology. But David, can you explain sort of Jacky’s methodology and how that will be presented?
David Clark: Absolutely, I can. So the methodology that Dr. Smith prefers is a cough bout is defined by two coughs — a minimum of two coughs, and then you have to have an off period. And the off period is so that a bout is if you have a cough and typically, if the off period is a two seconds duration. So if you have a cough within two seconds, that bout is ongoing. Now in an exploratory way, she likes to look at cough bout off periods of one second, up to 10 seconds. So what you’ll see in the paper is looking at the definition of this cough bout. So there’s cough within this duration that varies between one and 10 seconds. And that sort of cough bout definition, as Jennifer Good said, there’s not complete consensus in the field, but the methodology that Dr. Smith uses is probably amongst the commoner of the cough bout definitions. And then we have — as we say, we have this other methodology will be presented later in the year.
Leland Gershell: Thanks. Very helpful. And then I just wanted to ask with respect to the HAP study, I know you’re looking at a few different doses there, and it’s obviously encouraging to hear recent support for lack of scheduling for nalbuphine from the FDA. If you were to see significant liking at, I guess, any of those dose levels, would that be incremental concern that we could see some form of DEA scheduling? What would be kind of the sensitivity if you have that in any sort of way that you can quantify for us to the risk of scheduling based on the HAP study?
Jennifer Good: Yes. So the scheduling decision will be made. It will be a review decision first by the division that gets deferred to the DEA. They do look at sort of that, Gershell, if you will, of the eight-factor plans. So the mechanism of the drug, what they know about it from epidemiology, what you saw in your own clinical trials, just there’s sort of a whole big picture they look at. Now the HAP is not in — with the preclinical data is also quite important, which has all been done, and that’s all clean. The HAP though is not insignificant. I think it’s not that you can’t see anything in your data. It’s all going to be — in theory, you’re going to be a little more likable than placebo. I think if you’re significantly more likable than butorphanol, it opens up the conversation.
I think it will just depend. We’ll have to look at that data sort of in context of everything else. I will tell you though, when I sat through the original discussions of what the FDA focuses on, it’s not that you can’t have sort of any signs of this. What they really get worried about is a dose response to likability. So if you have some likability at call your low dose and that doubles and then triples with sort of your high dose. That’s where you get into issues because they obviously worry people take kind of your tablets and that’s a problem. So it’s a hard question to answer, Leland. And internally, we’ve been grappling with. I think when we have the data, we’ll put it out as clear as we can and have an expert join the call, so that people can interrogate the data themselves and ask the questions.
Leland Gershell: Fair enough. Thank you for the incremental color.
Jennifer Good: Yes, thank you. And we’ll see you at ATS.
Operator: The next question comes from Jack Padovano from Stifel. Please go ahead.
Jack Padovano: This is Jack on for Annabel. Thanks for taking our questions. So when you arrive at this sample size reestimation for IPF. What might the chances be that the study has already hit statistical significance at that point? And if that occurs, would you just continue as planned until final readout? Or could you potentially halt the trial early in that case? And then kind of a follow-up on that. Just recalling the magnitude of effect that we’ve seen in IPF already, if those kinds of effects persist in upcoming trials, are there any opportunities for you to move straight from POC into Phase 3?
