10-Q: Trevi Therapeutics Reports Q3 2025 Results, Advances Haduvio Trials

Trevi Therapeutics announced its third-quarter 2025 financial results, highlighting positive Phase 2b CORAL trial data for Haduvio in IPF chronic cough and progress across its clinical pipeline.

Summary

• Net loss for the three months ended September 30, 2025, was $11.8 million, an improvement from $13.2 million for the corresponding period in 2024.
• Net loss for the nine months ended September 30, 2025, was $34.4 million, compared to $36.5 million for the same period in 2024.
• Cash, cash equivalents, and marketable securities totaled $194.9 million as of September 30, 2025.
• Existing cash, cash equivalents, and marketable securities are expected to fund operating expenses and capital expenditure requirements into 2028.
• Positive topline results from the Phase 2b CORAL trial for Haduvio in chronic cough in patients with idiopathic pulmonary fibrosis (IPF) were announced in June 2025, demonstrating statistically significant reductions in 24-hour cough frequency across all dose groups (60.2% for 108 mg BID, 53.4% for 54 mg BID, and 47.9% for 27 mg BID) compared to a placebo reduction of 16.9%.
• Positive topline data from the Phase 2a RIVER trial for Haduvio in patients with refractory chronic cough (RCC) were announced in March 2025, meeting the primary endpoint with a statistically significant reduction in objective 24-hour cough frequency of 67% from Baseline and 57% on a placebo-adjusted basis.
• The Phase 1 drug-drug interaction study, completed in October 2025, concluded no clinically meaningful pharmacokinetic findings for Haduvio when co-administered with pirfenidone or nintedanib, eliminating the need for dose adjustments.
• Positive topline results from a human abuse potential (HAP) study in December 2024 demonstrated a statistically significant lower 'Drug Liking' for oral nalbuphine compared to intravenous butorphanol.
• Research and development expenses decreased to $10.1 million in Q3 2025 from $11.2 million in Q3 2024, and to $27.3 million for the nine months ended September 30, 2025, from $30.0 million in the prior year, primarily due to decreased clinical development expenses for trials actively enrolling in the prior year.
• General and administrative expenses increased to $3.8 million in Q3 2025 from $2.9 million in Q3 2024, and to $11.8 million for the nine months ended September 30, 2025, from $9.2 million in the prior year, driven by increased professional fees (SOX 404(b) preparation) and personnel-related expenses (including severance costs).
• Interest income, net, increased to $2.1 million in Q3 2025 from $0.8 million in Q3 2024, and to $4.6 million for the nine months ended September 30, 2025, from $2.7 million in the prior year, due to higher invested cash equivalent and marketable securities balances.
• The company raised approximately $115.1 million in gross proceeds from an underwritten public offering in June 2025 and approximately $50.0 million in gross proceeds from an underwritten registered direct offering in December 2024.
• The prospectus relating to the 2023 ATM Sales Agreement was terminated on June 2, 2025, with no shares sold under it during the nine months ended September 30, 2025.

Sentiment

Score: 8

Explanation: The company reported strong positive clinical trial results for Haduvio in both IPF chronic cough and refractory chronic cough, which are significant milestones. It also successfully raised substantial capital, extending its cash runway into 2028. While still pre-revenue and requiring significant future funding, the clinical progress and financial stability are highly favorable.

Positives

• Achieved primary efficacy endpoint in Phase 2b CORAL trial for IPF chronic cough, showing statistically significant reductions in 24-hour cough frequency (60.2% for 108 mg BID, 53.4% for 54 mg BID, 47.9% for 27 mg BID vs. 16.9% for placebo).
• Demonstrated rapid reduction in 24-hour cough frequency as early as Week 2 in the CORAL trial.
• Observed a 50% reduction in 24-hour cough frequency at Week 6 vs. Baseline in 65% of patients on 108 mg BID Haduvio, 63% on 54 mg BID Haduvio, and 60% on 27 mg BID Haduvio, compared to 19% of placebo patients.
• Achieved statistically significant improvements in secondary endpoints including the cough-severity numerical rating scale (CS-NRS), E-RS: IPF Cough Subscale, and Leicester Cough Questionnaire (LCQ) Total Score in the CORAL trial.
• The safety profile observed in the CORAL trial was generally consistent with the known safety profile of Haduvio, with low discontinuation rates due to adverse events (5.6% combined Haduvio vs. 5.0% placebo).
• Met the primary endpoint in the Phase 2a RIVER trial for RCC, with a statistically significant reduction of 67% from Baseline and 57% placebo-adjusted in 24-hour cough frequency.
• All pre-specified secondary endpoints in the RIVER trial, including patient-reported outcomes, were statistically significant.
• The safety results of the RIVER trial were consistent with the known safety profile of Haduvio, with no serious adverse events reported.
• The Phase 1 drug-drug interaction study showed no clinically meaningful pharmacokinetic interactions when Haduvio was co-administered with pirfenidone or nintedanib, indicating no dose adjustments are required with these common anti-fibrotic therapies.
• The human abuse potential (HAP) study demonstrated a statistically significant lower 'Drug Liking' for oral nalbuphine compared to intravenous butorphanol, which is a favorable outcome for potential DEA scheduling.
• Net loss decreased for both the three-month ($11.8 million vs. $13.2 million) and nine-month ($34.4 million vs. $36.5 million) periods ended September 30, 2025, compared to the prior year.
• Maintained a strong cash position with $194.9 million in cash, cash equivalents, and marketable securities as of September 30, 2025.
• Existing cash, cash equivalents, and marketable securities are expected to fund operating expenses and capital expenditure requirements into 2028, providing a significant runway.
• Successfully completed substantial capital raises in December 2024 ($50.0 million gross) and June 2025 ($115.1 million gross).

Negatives

• Continued to incur significant net losses, with an accumulated deficit of $321.5 million as of September 30, 2025.
• General and administrative expenses increased due to higher professional fees (primarily for SOX 404(b) compliance preparation) and personnel-related expenses, including severance costs and increased headcount.
• The company has not generated any revenue from product sales since inception and has no products approved for commercial sale.
• Substantial additional funding will be required to complete the development and commercialization of Haduvio for all indications through regulatory approval.
• The prospectus relating to the 2023 ATM Sales Agreement was terminated on June 2, 2025, and no sales were made under it during the nine months ended September 30, 2025, limiting a potential source of future funding unless a new prospectus is filed.

Risks

• Incurred significant losses since inception and expect to continue incurring significant and increasing losses for the foreseeable future, and may never achieve or maintain profitability.
• Will need substantial additional funding; inability to raise sufficient capital when needed on acceptable terms or at all could force delays, reductions, or abandonment of product development programs or commercialization efforts.
• Dependent on the successful development and commercialization of Haduvio, its sole product candidate; failure or significant delays would substantially harm the business.
• Changes in planned trial design or regulatory delays may affect the timing and costs of planned trials and the ability to complete them with existing cash resources.
• The outcome of clinical trials of a product candidate may not be predictive of the success of later clinical trials of such product candidate or of clinical trials for different indications; Haduvio may fail to show desired safety and efficacy despite demonstrating positive results in earlier Phase 2 clinical trials.
• Experienced delays and difficulties in patient enrollment in clinical trials in the past; future delays could prevent or delay necessary regulatory approvals.
• Clinical drug development involves a lengthy and expensive process with an uncertain outcome; the regulatory approval process is uncertain.
• Adverse events or undesirable side effects caused by, or other unexpected properties of, Haduvio may be identified during development, which could delay or prevent marketing approval or limit its use.
• The drug label for nalbuphine, the active ingredient in Haduvio, carries an opioid class label warning for serious, life-threatening or fatal respiratory depression, and Haduvio, if approved, will likely carry a similar opioid class label.
• Many currently approved mu-opioid receptor agonist products are subject to restrictive marketing and distribution regulations (e.g., REMS, controlled substance scheduling) which, if applied to Haduvio, could potentially restrict its use and harm the ability to generate profits.
• If unable to establish sales, marketing, and distribution capabilities or enter into arrangements with third parties, the company may not be successful in commercializing Haduvio if and when approved.
• Faces competition, which may result in others developing or commercializing products before or more successfully.
• Relies on third parties to conduct clinical trials and for the manufacture, storage, packaging, and distribution of Haduvio (including a single supplier for the active ingredient); unsatisfactory performance could harm the business.
• Failure to comply with obligations under existing and future intellectual property licenses with third parties (e.g., with Endo, Inc.) could lead to loss of critical license rights or damages.
• Inability to obtain and maintain sufficient patent protection for Haduvio or if the scope of patent protection is not sufficiently broad, competitors could develop and commercialize similar products.
• The number of shares of common stock underlying outstanding warrants is significant, which could negatively affect the market price of common stock and make future equity financings more difficult.
• Use of patient-reported outcome assessments (PROs) in clinical trials and high placebo response rates may delay or impair development or adversely impact clinical trials.
• The FDA may not conclude that Haduvio satisfies the requirements under Section 505(b)(2) of the FDCA, leading to a significantly longer, costlier, and riskier approval pathway.
• Even if Haduvio receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors, and others necessary for commercial success.
• Expending limited resources to pursue a particular product candidate or indication may cause failure to capitalize on product candidates or indications that may be more profitable or have a greater likelihood of success.
• Product liability lawsuits could divert resources, cause substantial liabilities, and limit commercialization.
• The FDA may not accept data from clinical trials conducted outside the U.S., potentially requiring additional delays and expense.
• Failure to obtain marketing approval in foreign jurisdictions would prevent Haduvio from being marketed in other countries.
• A Fast Track designation, grant of Priority Review status, or Breakthrough Therapy status by the FDA, or receipt of a priority voucher, is not assured and may not lead to faster development or regulatory review or approval.
• Any regulatory approval to market Haduvio in the U.S. will be limited by indication; failure to comply with FDA regulations restricting the promotion of Haduvio for unapproved uses could lead to penalties.
• Any approved product could be subject to post-marketing restrictions or withdrawal from the market, and the company may be subject to substantial penalties for non-compliance.
• Disruptions at the FDA and other government agencies (e.g., funding cuts, personnel losses, government shutdowns) could hinder the ability to obtain guidance, progress development efficiently, and secure timely approval.
• Current and future legislation (e.g., ACA, IRA, OBBBA) may increase the difficulty and cost of obtaining marketing approval and commercializing Haduvio, and may affect prices.
• Relationships with customers, healthcare providers, and third-party payors will be subject to applicable anti-kickback, fraud and abuse, and other healthcare laws and regulations, which could expose the company to penalties.
• Compliance with global privacy and data security requirements (e.g., GDPR, HIPAA, CCPA/CPRA) could result in additional costs and liabilities or inhibit the ability to collect and process data globally.
• Laws and regulations governing any future international operations may preclude development, manufacturing, and selling certain products outside the U.S. and require costly compliance programs (e.g., FCPA, UK Bribery Act).
• Business and operations would suffer in the event of system failures (e.g., cyber-attacks, natural disasters).
• If the FDA or comparable foreign regulatory authorities approve generic versions of future products or do not grant appropriate periods of data exclusivity, sales could be adversely affected.
• Artificial intelligence presents risks and challenges that can impact the business, including security risks to confidential information and an uncertain regulatory environment.
• Future success depends on the ability to retain the executive team and to attract, retain, and motivate qualified personnel.
• If the organization expands, difficulties in managing growth could disrupt operations.
• Employees, independent contractors, and consultants may engage in misconduct or other improper activities, which could cause significant liability and harm reputation.
• The trading price of common stock is highly volatile, which could result in substantial losses for purchasers.
• Changes in and uncertainty surrounding U.S. trade policy (e.g., tariffs) could have a material adverse impact on business.
• Could be subject to securities class action litigation.
• If securities or industry analysts do not publish research or publish inaccurate or unfavorable research, the trading price and volume of shares could decline.
• Future sales of shares of common stock, including by the company, employees, and significant stockholders, could negatively affect the stock price.
• Ownership of common stock is concentrated among executive officers and directors and their affiliates, who have significant influence over the business.
• Do not anticipate paying any cash dividends on capital stock in the foreseeable future; stockholders must rely on appreciation in the price of common stock for any return.
• As a smaller reporting company, reduced disclosure requirements may make common stock less attractive to investors.
• Incurs increased costs as a result of operating as a public company, and management is required to devote substantial time to compliance initiatives and corporate governance practices.
• Failure to maintain proper and effective internal controls could impair the ability to produce accurate financial statements on a timely basis.
• Might not be able to utilize a significant portion of net operating loss carryforwards and research and development tax credit carryforwards.
• Changes in tax laws or in their implementation or interpretation may adversely affect business and financial condition.
• Provisions in organizational documents and under Delaware law may prevent or frustrate attempts by stockholders to change management or hinder efforts to acquire a controlling interest.
• Choice of forum provisions in the certificate of incorporation could limit stockholders' ability to obtain a favorable judicial forum for disputes.
• Failure to comply with the continued listing requirements of Nasdaq could result in delisting and negatively impact the stock price and ability to access capital markets.

Future Outlook

The company expects to request an End-of-Phase 2 meeting with the FDA in the fourth quarter of 2025 for Haduvio for chronic cough in IPF patients and plans to initiate its Phase 3 program for this indication in the first half of 2026, subject to FDA alignment. It also plans to conduct a clinical trial for Haduvio in non-IPF ILD patients and initiate its next clinical trial for RCC as a Phase 2b trial in the first half of 2026. The ongoing Phase 1 TIDAL study data is expected in the fourth quarter of 2025 and will be included in the End-of-Phase 2 meeting request. The company anticipates continuing other NDA supportive studies and expects its existing cash, cash equivalents, and marketable securities to fund operating expenses and capital expenditure requirements into 2028, covering two Phase 3 trials for IPF chronic cough, the non-IPF ILD trial, the next RCC trial, the TIDAL study, and planned Phase 1 NDA supportive studies. However, substantial additional funding will be required to complete the development and commercialization of Haduvio for any indication through regulatory approval, with financing expected through equity offerings, debt, or collaborations. General and administrative expenses are projected to increase due to personnel, infrastructure, and SOX 404(b) compliance preparation.

Management Comments

• Management believes that existing cash, cash equivalents, and marketable securities will enable the company to fund operating expenses and capital expenditure requirements into 2028.
• Management acknowledges the need for substantial additional funding to complete the development and commercialization of Haduvio for any indication or future product candidates through regulatory approval.

Industry Context

Haduvio targets chronic cough in IPF, non-IPF ILD, and RCC, addressing significant unmet medical needs as no therapies are currently approved for chronic cough in IPF or non-IPF ILD, and no therapies are approved in the U.S. for RCC. The market is competitive, with other companies developing product candidates, such as GSK plc's camlipixant for RCC, and past failures like Merck's gefapixant in the U.S. and Boehringer Ingelheim's BI 1839100 for IPF chronic cough. Trevi's strategy leverages nalbuphine's established safety profile as an injectable, aiming to mitigate abuse risk with its KAMA mechanism in an oral extended-release formulation. The regulatory landscape is dynamic, with new EU regulations and ongoing U.S. legislative efforts (e.g., IRA, OBBBA, potential tariffs) impacting drug development, pricing, and market access, which could influence the commercial viability of Haduvio.

Comparison to Industry Standards

• No therapies have been approved for the treatment of chronic cough in patients with IPF or non-IPF ILD, and no therapies have been approved in the U.S. for the treatment of patients with RCC, indicating Haduvio could be a first-in-class therapy in these specific US indications.
• Gefapixant, a P2X3 antagonist developed by Merck & Co., Inc., is approved for refractory or unexplained chronic cough in Japan, United Kingdom, and the E.U., but its application filed with the FDA was withdrawn, potentially opening a market opportunity for Haduvio in the U.S. RCC market.
• Development of BI 1839100 by Boehringer Ingelheim for the treatment of chronic cough in patients with IPF and progressive pulmonary fibrosis was terminated in September 2025, reducing future competition in a similar indication.
• The human abuse potential (HAP) study compared Haduvio with butorphanol, a Schedule IV substance, and demonstrated statistically significant lower 'Drug Liking' for oral nalbuphine, suggesting a potentially favorable outcome for Haduvio's scheduling by the DEA compared to other scheduled opioids.

Management Changes

Corporate Governance

Legal Proceedings

• Not subject to any material legal proceedings.

Related Party Transactions

• On October 18, 2021, the company issued and sold 1,851,852 shares of common stock and accompanying warrants to purchase 3,703,704 shares of common stock to New Enterprise Associates 16, L.P. (NEA), an existing stockholder and related party, in a private placement.
• On April 17, 2025, NEA exercised all warrants that would have expired on April 18, 2025.
• NEA, an existing stockholder and related party, as well as an affiliate of NEA, participated in the April 2022 Private Placement.
• Received $725 thousand in proceeds from the disgorgement of a beneficial owner's short-swing profits during the nine months ended September 30, 2025, indicating a past related party transaction that resulted in disgorgement.

Stakeholder Impact

• Shareholders: Potential for value appreciation from successful clinical development and commercialization of Haduvio, but also potential dilution from future equity offerings. Concentration of ownership among executive officers and directors could limit the influence of new investors.
• Employees: Stock-based compensation plans (2019 Stock Incentive Plan, 2019 ESPP) provide incentives. The severance agreement for Lisa Delfini indicates standard HR practices for separations. Increased headcount and personnel-related expenses suggest growth in the organization.
• Customers (future): If approved, Haduvio could address significant unmet medical needs for patients suffering from chronic cough associated with IPF, non-IPF ILD, and RCC.
• Creditors: The strong cash position and extended cash runway into 2028 reduce immediate credit risk.
• Suppliers/CROs: Continued reliance on third parties for clinical trials and manufacturing indicates ongoing business opportunities for these partners.

Next Steps

• Request an End-of-Phase 2 meeting with the FDA in Q4 2025 for Haduvio for chronic cough in IPF.
• Initiate the Phase 3 program for Haduvio for chronic cough in IPF in H1 2026, subject to FDA alignment on study designs.
• Conduct a clinical trial for Haduvio for the treatment of chronic cough in patients with non-IPF ILD.
• Initiate the next clinical trial for Haduvio for the treatment of patients with RCC as a Phase 2b trial in H1 2026.
• Complete enrollment and expect data from the Phase 1 TIDAL study in Q4 2025, to be included in the End-of-Phase 2 meeting request.
• Continue to progress and advance other NDA supportive studies (e.g., food effect, renal impairment studies).
• Prepare for compliance with Section 404 of the Sarbanes-Oxley Act of 2002 (SOX 404(b)) during the remainder of 2025 and into 2026.
• Obtain substantial additional funding to support continuing operations and pursue development and commercialization of Haduvio.

Key Dates

Recommendation

The company has reported very strong positive clinical trial results for Haduvio in multiple indications, significantly de-risking its primary asset and extending its cash runway into 2028. This progress is highly encouraging for a clinical-stage biopharmaceutical company. However, it remains pre-revenue, faces substantial future funding needs for Phase 3 trials and commercialization, and operates in a highly competitive and regulated environment. The stock has likely already reacted positively to the Phase 2b CORAL and Phase 2a RIVER results announced earlier in the year. A 'Hold' recommendation reflects the significant progress and extended runway, balanced against the inherent risks and substantial capital requirements still ahead before potential profitability. Investors should monitor Phase 3 initiation, regulatory feedback, and further financing activities.

Keywords

Haduvio, chronic cough, IPF, idiopathic pulmonary fibrosis, RCC, refractory chronic cough, non-IPF ILD, interstitial lung disease, clinical trials, biopharmaceutical, drug development, SEC filing, 10-Q, financial results, TRVI, nalbuphine ER, kappa agonist, mu antagonist, KAMA, Phase 2b CORAL, Phase 2a RIVER, Phase 1 TIDAL, drug-drug interaction, human abuse potential, capital raise, liquidity, R&D, corporate governance, risk management