Trevi Therapeutics 2026 Q3 Earnings Call

Please go ahead. Good afternoon, and thank you for joining us for our third quarter 2026 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. Dave and I will make some initial comments, and then the team is happy to answer any questions you may have. 2026 is a busy year of execution for the company, and the team is heads down on initiating and executing clinical trials in each of our programs. This includes activating sites globally, focusing on ensuring enrollment stays on track, all while staying aligned with the regulatory authorities. It has been fast-paced, but this is the fun part of what we do. Let me provide a brief update on each of our programs. First, our lead program in IPF-related chronic cough.

We have initiated both OCEAN-1 and OCEAN-2 trials. We are now approved by all regulatory authorities in each of the countries in which we are conducting clinical trials, and the clinical team is focused on getting all the sites activated and screening patients. We will give an update once we reach 50% of the patients randomized in each of these trials. The trials are in early stages and progressing, and we continue to believe we are on track with our previously stated guidance for OCEAN-2, the 12-week study reading out in the second half of 2027, and OCEAN-1, the 24-week efficacy endpoint with 52 weeks of safety, reading out in the first half of 2028. In October, we took an important step forward in our non-IPF ILD cough program by aligning with the FDA on the development plan and next study.

The pulmonary division has been very helpful and supportive as we think about how to get the first chronic cough drug approved in the U.S. The discussions have been collaborative and clear. Following this meeting with the FDA, our plan is to conduct a phase II dose-ranging study with approximately 120 non-IPF ILD patients to confirm the optimal dose or doses to take forward into phase III. The protocol is written and will be submitted back to the FDA for any comments. We also have the wheels in motion identifying sites and working with our CRO partner to prepare for study initiation. Recall that these clinical centers will overlap directly with the same sites we are using in our North American IPF phase III program. When we signed a contract and negotiated budgets for our OCEAN trials, we planned for the fact that we likely would conduct an ILD trial.

We are planning to initiate this trial in the first quarter of 2027. We will study two doses of Haduvio for 12 weeks of fixed dosing in patients with interstitial lung disease, excluding patients with IPF. We anticipate top-line data to be available in the first half of 2028. Remember, the ILD opportunity more than doubles the IPF potential, and we continue to hear about the high unmet need in this population from doctors. In parallel to the clinical work, we are looking at prevalence and epi data to help refine our estimates of the commercial opportunity in non-IPF-related chronic cough. Turning now to refractory chronic cough, or RCC, and our late phase IIb trial. With the two competitive drug failures this summer, I have talked more about this program over the past few months than I thought was humanly possible.

Let me try to briefly summarize where things stand in the RCC space and explain the upcoming sample size re-estimation, or SSRE. First, there are no active competitive programs left in RCC, or any of our targeted chronic cough indications for that matter. Peripheral-only mechanisms have not been able to withstand the complexity and heterogeneity of cough triggers. It was always our hypothesis that while the peripheral mechanism plays a role in sensory signaling, the central mechanism is critical in mitigating the hypersensitivity related to cough. Second, I've been asked about the differences in market dynamics between RCC and IPF and non-IPF-related chronic cough. The reality is that RCC is a significant unmet need in which patients' quality of life is deeply affected. We believe that if our drug can offer relief to these patients, we can figure out the commercial dynamics.

We are working on various options around targeting the most refractory patient group, potentially with lower doses, et cetera. In a world where it all starts with the patient, RCC is a severe chronic cough condition with no good treatment options. There have been numerous examples of brands, such as DUPIXENT, successfully navigating payer dynamics in larger follow-on indications. Finally, as you know, drug development has been very challenging in RCC because of the heterogeneity of patients with chronic cough, as well as the placebo effect. We believe we have distinct advantages with our dual central and peripheral mechanism, and the demonstrated evidence that our drug works broadly across cough counts. However, we are mindful that there have been very few positive trials.

So, as we design the phase IIb LAKE study, we built in a sample size re-estimation, or SSRE, to account for variability in the patient population, placebo effect, et cetera. Let's just recap the analysis. Once 50%, or 50 patients, complete the trial, an independent stats team outside of Trevi will look at the unblinded data and confirm powering assumptions at that point in the study. Essentially, we will get one of three answers back with no corresponding data, so as not to unblind the trial. The three potential answers are, one, the trial to date has at least 80% power, and we should continue with the original plan of enrolling 100 patients. Two, the trial is showing a conditional power range of 40%-80%. This means the drug is working, but there is either more variability or less of an effect size than our original assumptions.

We then will upsize accordingly, up to a maximum of 152 patients. It is not all or nothing with the upsize. It is a proportional upsize from four to 52 patients, meant to restore at least 80% conditional power. A little color on what that means. The effect size in this conditional power range represents an effect size of approximately low 20% range to 30%. Just to be clear, effect size is defined as drug effect less placebo. A 20%-30% effect size is clinically meaningful and could have a significant impact in a world where there are no good options. And finally, the third option for the SSRE is futility. The conditional power at the time of analysis for the trial would be below 40% and suggest futility for the fully completed trial.

In light of the fact that the study will likely be close to fully enrolled and there are no competitive programs left, we would plan to finish enrollment based on the original sample size of 100 and look at the data. To wrap up this SSRE discussion, the SSRE design means that a non-futile result is a clinically meaningful benefit in cough reduction, and upsizing the trial slightly is to ensure that clinical meaningfulness is statistically significant at the end of the study. We estimate we will have the results of the SSRE in the early part of the first quarter and have reconfirmed our guidance for full trial results in the second half of 2027.

Finally, last month, a number of chronic cough patient advocacy organizations teamed up to hold an externally led patient-focused drug development, or PFDD, meeting with the FDA to discuss the disease burden of chronic cough. Patients told their stories of the impact on their lives, and their experiences exemplified the burden of chronic cough across IPF, ILDs, and RCC patients. One ILD patient stated, "Cough is the single greatest thief of my quality of life." This meeting represents a meaningful engagement with the FDA in raising the need for effective and safe therapies. The results will be released in 2027 in a Voice of the Patient report. We are pleased by the focus of the FDA on this significant unmet need. In closing, we are focused on executing against our plan of becoming the leader in chronic cough.

With the recent competitive failures in RCC, we are alone in all three of our cough indications and have the potential to be a first-in-class therapy in very big markets. We believe if we are able to execute against our current plan, we can create meaningful value for patients and, in turn, significant value for our shareholders. I will now turn it over to Dave for his remarks, and then we are happy to answer your questions.