STIFEL 2026 HEALTHCARE CONFERENCE - TREVI THERAPEUTICS INC

Financial Performance:

• Company maintains a clean balance sheet with $299 million in cash and zero debt.
• Cash runway is sufficient to fund IPF through approval, complete two Phase II studies in ILD, complete the Phase IIb study in Refractory Chronic Cough (RCC), and support pre-commercial activities.
• No immediate need to fund a full commercial launch; capital is sufficient for clinical inflection points.
• Financial impact of potential sample size re-estimation (SSRE) is deemed minimal, with no impact on the runway or current guidance.

Guidance and Future Outlook:

• RCC (Refractory Chronic Cough): SSRE results expected in January 2025; top-line Phase IIb data anticipated in the second half of 2026.
• IPF (Idiopathic Pulmonary Fibrosis): Two pivotal trials ("Ocean 1" 24-week efficacy/52-week safety and "Ocean 2" 12-week efficacy) scheduled to read out in the first half of 2028; Ocean 1 may read out late 2027.
• ILD (Interstitial Lung Disease): Phase II dose-ranging data expected in late 2026/early 2027; Phase III data anticipated in the first half of 2028.
• Commercialization: Aiming for launch in IPF in late 2029, targeting a $2 billion revenue vertical per indication (IPF, ILD, RCC) with a potential total market value of $6–$8 billion.
• Growth Strategy: Company positioned as a standalone specialty commercial entity targeting pulmonologists, rather than seeking early-stage licensing.

Business Segments and Product Lines:

• Core Strategy: Sole remaining operator in the chronic cough market following competitor exits (e.g., GSK/Bellis); approach focuses on central nervous system (brain) modulation rather than peripheral lung targeting.
• IPF Segment: Lead indication; targeting ~2/3 of patients with moderate-to-severe cough. Dosing confirmed at 27mg/54mg BID; "Ocean 1" is a 300-patient study powering all seven secondary endpoints, while "Ocean 2" is a 200-patient study confirming primary/secondary endpoints.
• RCC Segment: Phase IIb trial in progress; investigating lower doses (27mg QD/BID vs. 54mg BID) due to potentially higher efficacy at lower levels compared to IPF.
• ILD Segment: Expansion strategy aims to leverage IPF data to file an SNDA (Supplemental New Drug Application) after one confirmatory Phase III study if IPF results are positive, potentially doubling the market opportunity.
• Formulation: Overcoming low oral bioavailability (15%); exploring lower dose formulations for RCC which could enable brand splitting or per-milligram pricing strategies.

Market and Competitive Landscape:

• Competitive Vacuum: GSK's Bellis acquisition failed in two Phase III trials, leaving Trevi as the only player in the space; other major pharma (Roche, Merck, Bayer, etc.) remain interested but are cautious.
• Market Dynamics: IPF anti-fibrotic innovations (e.g., BMS Jaskade, United Therapeutics) are expected to increase patient diagnosis and awareness, benefiting Trevi's market size.
• Commercial Target: For RCC, targeting the most refractory 40% of patients (approx. 650k–1M seen by pulmonologists) to avoid diluting a specialty model; pricing strategy aims for ~$100,000/year similar to IPF.
• Sales Force: Company plans to self-commercialize via a respiratory-focused sales force (approx. 5,200 reps) accessing 90 ILD care centers in the US.

Risks and Challenges:

• Placebo Response: RCC trials face high placebo rates (estimated 25–30%) compared to IPF (18–19%); SSRE designed to mitigate statistical risk if effect sizes are smaller than projected.
• Trial Complexity: Chronic cough is historically difficult to prove with statistically significant results; GSK's failure highlights the high barrier to entry.
• Enrollment Constraints: Exclusion criteria for IPF trials limit inclusion of patients on mu-agonist opioids (due to Trevi's mechanism) or those with <1 year life expectancy, though anti-fibrotic background meds are permitted.
• Commercial Risk: While IPF is a clear specialty target, broad RCC adoption requires overcoming high patient volume in primary care settings; success hinges on proving efficacy in refractory populations.

Management Commentary and Tone:

• Confidence: Management expressed high confidence in the unique central nervous system approach and the "clean" balance sheet, viewing the departure of competitors as a strategic advantage.
• Transparency: CEO Jennifer Good and CFO Dave Hastings were direct regarding the delayed SSRE timeline (slip from Q4 to January) and the lack of data impact.
• Strategic Clarity: Emphasis on maintaining independence to control the commercial narrative, with potential licensing post-Phase III data only if a "big check" is offered that outweighs the value of self-launching.
• Regulatory Relationship: Described FDA interactions as collaborative, accessible, and supportive, particularly regarding the ILD expansion path.

Analyst Questions and Answers:

• SSRE Mechanics: Clarified that SSRE provides no data to the company, only a statistical bucket (continue, upsize up to 52 patients, or stop for futility) to ensure trial success.
• Dosing Strategy: Confirmed IPF will use 27/54mg BID, while RCC requires lower doses; ILD dosing remains under investigation but likely aligns closer to IPF than RCC initially.
• Brand Splitting: Discussed the feasibility of lower doses enabling brand splitting or price differentiation, contingent on formulation limits (lowest feasible dose is 27mg BID currently).
• IPF Innovation Impact: Asked about new anti-fibrotic launches (BMS, United Therapeutics); management views this as net positive for market education and patient identification.
• Phase III ILD Timing: Confirmed that if IPF is successful, a smaller Phase III (200-300 patients) in ILD could follow immediately via SNDA, potentially accelerating timeline if safety data is robust.

Other Key Points:

• Trial Endpoints: IPF "Ocean 1" includes cough frequency (primary), severity, breathlessness, cough bouts, sleep, and QoL; breathlessness reduction is a key secondary driver for labeling.
• Safety Profile: Previous Phase II data showed no waning of effect in long-term derm trials (pruritus), providing confidence in 12-24 week durability for cough.
• Patient Eligibility: Broad inclusion for IPF allowing background anti-fibrotic changes; exclusion primarily for severe comorbidities or active opioid use.
• Market Valuation: Management targets 20,000 patients in RCC to achieve $2 billion in revenue, reinforcing the focus on high-price specialty markets rather than mass primary care.