Trevi Therapeutics, Inc.

To the Trevi Therapeutics fourth quarter and year-end 2023 earnings conference call. At this time, all participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your telephone keypad. To withdraw your question, please press star, then two. 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-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 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 our fourth quarter and year-end 2023 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. Lisa and I have some prepared remarks, then we will open it up for questions. The fourth quarter of 2023 and start of 2024 was a productive time for Trevi with the initiation of three clinical studies. Let me provide a brief update on each of these trials. I will begin with our Phase IIa River trial in refractory chronic cough that was initiated in the fourth quarter of 2023. 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 a treatment for an underlying condition. RCC is caused by cough reflex hypersensitivity in the central and peripheral nerves and has a significant impact on patients physically, psychologically, and socially. With multiple drug failures in the space and a lack of any approved therapies for RCC in the U.S., there continues to be a significant unmet and urgent need for new potential treatments. The key point of differentiation for Hadovio and refractory chronic cough is the mechanism of action, which works synergistically both centrally in the brain and peripherally in the lungs. We believe Hadovio's central and peripheral 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. RCC patients have been stratified for clinical trial purposes into three categories of frequency, very high, greater than 20 coughs per hour, high to moderate, 10 to 19 coughs per hour, and low frequency coughers. The very high and high to moderate frequency coughers are all considered as having severe cough by the KOLs. The P2X3s to date have only demonstrated statistical significance in the very high cough counters and have not shown successful results in the cough frequency of 10 to 19 coughs per hour. We believe that based on the data from our IPF cough trial, which showed a strong drug effect across all baseline cough counts, and the drug central and peripheral mechanism of action, that Heduvio has the potential to work in patients broadly across varying cough frequencies. When you look at the RCC patient distribution, 44% of the patients are estimated to have moderate to high cough frequency, whereas only 29% are estimated to have very high cough frequency. So there's potential Heduvio may address close to three-fourths of the RCC market, whereas P2X3s may only be effective in less than a third of the market. On to the details of RRCC trial, which is the standard design across several cough trials run to date. The RIVER trial is a phase 2A double-blind randomized placebo-controlled two-period crossover study evaluating the reduction of cough in approximately 60 patients. These patients will be randomized with a one-to-one 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 Heduvia 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 at day 21 from treatment period baseline for Hadovio compared to placebo as measured by an objective cost monitor. The study will also explore secondary endpoints including patient reported outcome measures for cost and quality of life. We are excited to have initiated this study and expect to have substantially all the sites activated by the end of this month. 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 idiopathic pulmonary fibrosis or IPF chronic cough. IPF is a serious end-of-life disease. Chronic cough is reported by approximately 85% of patients suffering from IPF and has 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 IPF. The constant lung injury, micro tears, and potential inflammation caused by persistent coughing may lead to worse health outcomes for patients, such as increased respiratory hospitalizations, mortality, or need for transplant. With no currently approved treatment options for chronic cough and IPS, 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, one of the primary complaints of these patients, elevating the unmet need. At the end of 2023, we initiated a Phase IIb study in chronic cough and IPF, the CORAL study. CORAL is a forearm Phase IIb dose-ranging trial that will study three active doses of Heduvia and placebo. The study is a six-week trial in approximately 160 patients. We plan to conduct this study in multiple countries and sites to be able to complete enrollment in a timely manner. Site activations are moving along in multiple countries and enrollment is in early stages. We reconfirm our guidance for this study for top line data in the first half of 2025. assuming no changes from our sample size re-estimation results, which are expected in the second half of this year. And lastly, we initiated dosing of the final part of the Human Abuse Potential, or HAP, study in January of this year. The final portion of the HAP study is a randomized, double-blind, double-dummy, five-way crossover design to determine the abuse potential of three doses of oral nalbufine relative to the selected dose of IV butorphanol and placebo. The primary objective is to evaluate the likability of nalbufine as compared to both placebo and butorphanol, and the primary endpoint is a drug-liking VAS scale. Recall that parenteral nalbufine is unscheduled by the DEA. This study is moving along nicely, and we have passed the 50% enrollment mark. We continue to expect top-line data from this study in the second half of this year as well. 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 Heduvia on chronic cost conditions. We are motivated by the potential to offer an effective treatment to patients with these serious conditions and chronic costs. 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 December 30th, 31st, 2023 can be found in our press release issued ahead of this call and our 10K, which was filed with the SEC today after the market closed. For the fourth quarter of 2023, we reported a net loss of 7.8 million compared to a net loss of 5.5 million for the same quarter in 2022. R&D expenses were 6.5 million during the fourth quarter of 2023 compared to 4.3 million in the same quarter of 2022. The increase was primarily due to increased clinical trial costs in our Phase 2b coral trial and our Phase 2a river trial, both of which were initiated in the fourth quarter of 2023. DNA expenses have remained essentially flat at $2.4 million during the fourth quarter of 2023, compared to $2.3 million in the same period of 2022. We take a very disciplined approach to cash management, and as a result, while R&D expenses increased as we are starting up for clinical trials, G&A expenses have remained consistent. Other income net was $1.1 million in both the fourth quarter of 2023 and 2022, and primarily consists of interest income on our cash balances offset by any interest expense. We paid off our term loan in May of 2023, so interest expense was de minimis in the fourth quarter of 2023. As of December 31, 2023, our cash, cash equivalents, and marketable securities totaled $83 million, compared to $120.5 million as of December 31, 2022. Our cash runway guidance, that we will have cash, cash equivalents, and marketable securities into 2026, remains unchanged and we believe is enough to fund all of the trials Jennifer just discussed and gives us good cash runway after the last readout. In 2024, we expect average cash burn of about $9 to $12 million per quarter, And our fully diluted shares outstanding at December 31, 2023 is $114.5 million. This concludes our prepared remarks. I will now turn the call back over to the operator for Q&A.