Trevi Therapeutics (TRVI): A High-Potential Biotech Play in Chronic Cough with a Clear Path to Phase 3 and FDA Alignment

Trevi Therapeutics (TRVI) has emerged as a compelling biotech investment, driven by its robust clinical progress, strategic regulatory alignment, and a well-funded path to commercialization. With its lead candidate, Haduvio™ (oral nalbuphine extended-release), the company is addressing a significant unmet medical need in chronic cough associated with idiopathic pulmonary fibrosis (IPF), non-IPF interstitial lung disease (non-IPF ILD), and refractory chronic cough (RCC). The recent Phase 2b CORAL trial results, combined with a clear timeline for Phase 3 initiation and FDA alignment, position TRVI as a high-conviction opportunity for investors seeking exposure to a transformative therapy in a niche but high-impact market.

Clinical Progress: Dose-Dependent Efficacy and Quality of Life Improvements

Trevi's Phase 2b CORAL trial, completed in February 2025, enrolled 165 patients with chronic cough due to IPF and demonstrated statistically significant reductions in 24-hour cough frequency across all dose groups. The 108 mg BID (twice daily) dose achieved a 60.2% reduction in cough frequency (p<0.0001), outperforming the 53.4% and 47.9% reductions in the 54 mg BID and 27 mg BID groups, respectively. Placebo-adjusted differences were even more pronounced, with the highest dose group showing a 43.3% placebo-adjusted improvement.

Beyond cough frequency, the trial highlighted clinically meaningful improvements in quality of life. The Leicester Cough Questionnaire (LCQ) Total Score increased by 3.4 points (p=0.01) in the 108 mg BID group and 3.7 points (p=0.01) in the 54 mg BID group—well above the 1.3-point threshold for clinical significance. Rapid efficacy was observed as early as Week 2, with 65% of patients on the highest dose achieving a 50% reduction in cough frequency by Week 6.

The safety profile was consistent with prior trials, with discontinuation rates due to adverse events (5.6% for Haduvio vs. 5.0% for placebo) and manageable side effects such as nausea and dizziness. These results reinforce Haduvio's potential as a first-in-class therapy targeting the central and peripheral cough reflex arc via its kappa agonist and mu antagonist (KAMA) mechanism.

Regulatory Pathway: FDA Alignment and Phase 3 Readiness

Trevi is on track to request an End-of-Phase 2 meeting with the FDA in Q4 2025 to finalize the design of its Phase 3 program. The company's leadership has emphasized that the CORAL trial's robust dose-ranging data will inform the Phase 3 trial design, with a focus on IPF-associated chronic cough. A Phase 3 initiation is anticipated in H1 2026, leveraging the strong Phase 2b results and prior positive data from the Phase 2a RIVER trial in RCC.

The FDA's feedback, while not explicitly detailed in recent disclosures, is expected to align with Trevi's strategic approach. The company's confidence stems from the statistically significant and dose-dependent efficacy observed in CORAL, as well as the absence of new safety signals. This regulatory clarity reduces the risk of delays or additional requirements, a critical factor for biotech investors.

Financial Strength: A $203.9M Cash Runway to 2029

Trevi's financial position is a cornerstone of its investment thesis. In June 2025, the company completed a $115 million underwritten offering, bringing its total cash, cash equivalents, and marketable securities to $203.9 million as of June 30, 2025. This provides a cash runway extending into 2029, ensuring sufficient resources to advance Haduvio through Phase 3 trials, potential FDA approval, and pre-commercial planning.

The absence of near-term financing needs mitigates the risk of dilution, a common concern in biotech investing. Trevi's leadership has also emphasized its ability to scale operations efficiently, with a lean organizational structure focused on late-stage development and commercial readiness.

Market Opportunity: A $1.5B+ Unmet Need in Chronic Cough

Chronic cough affects up to 85% of IPF patients, with approximately 150,000 individuals in the U.S. suffering from this debilitating condition. Current treatment options are limited to symptomatic relief, with no FDA-approved therapies addressing the underlying pathophysiology. Haduvio's unique KAMA mechanism offers a transformative solution, potentially capturing a significant share of this underserved market.

The IPF chronic cough segment alone represents a $1.5 billion+ market opportunity, with additional potential in non-IPF ILD and RCC. Trevi's data from the RIVER trial in RCC further support the broader applicability of Haduvio, suggesting a multi-indication platform with scalable revenue potential.

Investment Thesis: A High-Conviction Biotech Play

Trevi Therapeutics combines robust clinical data, a clear regulatory path, and financial strength to create a compelling investment case. Key catalysts in 2026 include:
- FDA alignment on Phase 3 design (Q4 2025).
- Phase 3 initiation in H1 2026.
- Top-line results from the RIVER trial in RCC (already positive, but further validation is key).

For investors, TRVI represents a high-potential, high-conviction play in a niche but impactful therapeutic area. The company's ability to advance a first-in-class therapy with a strong safety profile and rapid onset of action positions it to capture market share upon approval. Given the $203.9 million cash runway and the absence of near-term dilution risks, Trevi is well-positioned to deliver outsized returns for those willing to navigate the inherent risks of late-stage biotech development.

Risks and Conclusion

While the investment case is strong, risks remain. Phase 3 trials carry the inherent risk of failure, and regulatory hurdles could delay approval. Additionally, competition may emerge if other companies target the same mechanism or indication. However, Trevi's first-mover advantage, robust Phase 2 data, and financial flexibility mitigate these risks.

In conclusion, Trevi Therapeutics is a high-conviction biotech investment for those seeking exposure to a transformative therapy in a high-unmet-need market. With a clear path to Phase 3, FDA alignment, and a well-funded runway, TRVI offers a compelling opportunity to capitalize on the next phase of its development. Investors with a medium to long-term horizon and an appetite for biotech risk should consider adding TRVI to their portfolios.