STIFEL 2026 HEALTHCARE CONFERENCE - TREVI THERAPEUTICS INC

Explicit Guidance:

• Clinical Readout Timing: SSRE results for the Refractory Chronic Cough (RCC) program expected in January (previously guided for Q4, delayed a few weeks).
• RCC Phase 2b Readout: Expected in the second half of next year (2025), even under a maximum sample size increase scenario.
• IPF Program Timeline:
  • OCEAN 2 (12-week study): Scheduled to read out in the first half of 2028.
  • OCEAN 1 (52-week study): Scheduled to read out in the second half of 2027.
• ILD Program Timeline:
  • Phase 2 Confirmation: Ongoing in parallel; results to inform Phase 3 design and potential SNDA filing.
  • Phase 3 Readout: Expected in the first half of 2028 (200-300 patient study, 6-month duration).
• Commercial Launch Target: First indication (IPF) expected to launch in late 2029.
• Financial Runway: Current cash position of $299 million (no debt) extends through key clinical inflection points, IPF approval, completion of ILD Phase 2 studies, and RCC Phase 2b, with funds for pre-commercial infrastructure.

Business-Segment Outlook:

• Refractory Chronic Cough (RCC): Positioned as a single-asset solo operator following competitor failures (GlaxoSmithKline/Bellis). Strategy targets the refractory cohort (approx. 650,000–1 million patients seen by pulmonologists, ~40% of total RCC population) rather than the total addressable market immediately.
• IPF Segment: Addresses ~66% of IPF patients with moderate-to-severe chronic cough. Strategy focuses on dual-endpoint trials (frequency and severity/breathlessness) to secure a robust label.
• ILD Segment: Aims to expand the IPF label to the broader Interstitial Lung Disease population (200+ conditions with lung fibrosis and cough) via an SNDA pathway, potentially doubling the market opportunity contingent on IPF success and Phase 2 confirmation.
• Commercial Strategy: No intention to partner for Phase 3 completion. Planning a self-commercialized launch targeting 2,000 specialists across 90 ILD care centers in the U.S., with a projected price point of ~$100,000 annually. Goal: $2 billion in sales from 20,000 RCC patients or similar volume in IPF/ILD.

Market and Competitive Outlook:

• Competitive Landscape: "Nobody left" in chronic cough indications following GlaxoSmithKline's recent Phase 3 failures in RCC.
• Demand Trends: Unmet need remains high; market size projected at $6–$8 billion for a successful product.
• Pricing Dynamics: Anticipated price point of $100,000 based on IPF value; lower doses in RCC could enable a shift to a different pricing corridor (price-per-millogram).
• Market Expansion: Positive IPF anti-fibrotic launches (Bayer's Jaskade, United Therapeutics' Teprastanil) are expected to increase patient diagnosis and follow-up, indirectly expanding the TAM for symptomatic cough treatments.

Macro / Industry Outlook:

• Regulatory Environment: FDA viewed as "accessible, collaborative, and super interested" in cough solutions, supporting a "one-size-fits-most" hypothesis for fibrotic cough (IPF/ILD) and encouraging a streamlined path to market.
• Industry Shift: Post-Glaxo failures, large pharma is expected to demand Trevi's Phase 3 data before considering partnerships, reducing Trevi's exposure to commercial risk during the study phase.
• Pulmonary Market Dynamics: High interest from major pharma (Roche, Merck, Bayer, etc.) due to patent cliffs and the lack of recent approvals in respiratory space; Trevi is well-positioned to complete trials independently before potential M&A discussions post-Phase 3.

Strategic Initiatives:

• OCEAN Program: Two confirmatory Phase 3 trials in IPF: OCEAN 1 (300 patients, 52-week safety, 24-week efficacy) and OCEAN 2 (200 patients, 12-week efficacy).
• ILD Expansion Path: Alignment with FDA to complete Phase 2 dose-ranging, followed by a Phase 3 (200-300 patients) and potential SNDA to expand indication.
• Dose Optimization: Investigating lower doses for RCC (e.g., 27mg QD or BID) vs. IPF (54mg BID) to address bioavailability constraints and enable potential brand splitting or pricing optimization.
• Commercial Infrastructure: Building internal sales force capabilities (respiratory specialists) to support a 2029 launch without immediate reliance on external commercial partners.
• M&A/Partnership Stance: Commitment to advance assets through Phase 3 independently; open to partnerships or out-licensing only after seeing positive Phase 3 data to eliminate clinical risk for potential partners.

Risks and Headwinds to Outlook:

• Placebo Response: High variability in RCC trials (projected 25–30% placebo rate) remains a key uncertainty; SSRE mechanism is in place to mitigate this via potential sample size up-sizing (max +52 patients).
• Dose Formulation: Drug has low oral bioavailability (~15%); finding a viable low-dose formulation for RCC without tablet integrity issues is a technical hurdle.
• Patient Eligibility: Exclusion criteria for IPF trials limit enrollment to patients with >1-year life expectancy and those not on mu-agonist opioids (requiring washout), though anti-fibrotic co-administration is permitted.
• Sample Size Expansion: Max up-sizing in RCC could delay the readout to "later in the year," though financial impact and runway are deemed minimal.
• Competitor Data: Lack of public data from Glaxo's failed RCC trials creates uncertainty regarding the condition's treatability and placebo susceptibility.

Management Tone on the Future:

• Confidence Level: High confidence in the "solo operator" status and the biological plausibility of the mechanism (treating cough via the brain), citing lack of waning effects in similar dermal hypersensitivity trials (pruritus).
• Strategic Certainty: Firm commitment to self-commercialization, citing the ability to build a specialty sales force and the strategic risk of aligning with Big Pharma's shifting priorities.
• Financial Prudence: Optimistic about capital allocation, viewing the $299M cash reserve as sufficient to navigate to approval and pre-commercial launch phases.
• Forward Outlook: "Excited about the future," emphasizing 2027 as a "year with a lot of data ahead" and positioning the company for a high-value inflection point upon Phase 3 completion.

Miscellaneous:

• Market Size Math: Management calculates that capturing 20,000 RCC patients at $100,000/year yields a $2 billion revenue run-rate for that specific indication alone.
• Trial Design Specifics: OCEAN 1 powered for all seven secondary endpoints (including breathlessness and sleep) for a robust label, while OCEAN 2 confirms primary/secondary endpoints for a faster readout.
• Background Medications: No interaction concerns identified with anti-fibrotics (Ofev, Esprit, Jaskade, Teprastanil) or opioids (with washout), facilitating broader enrollment.