Trevi Therapeutics (TRVI) investor relations material

Program overview and market opportunity

• Single-asset focus on chronic cough across IPF, other ILDs and refractory chronic cough (RCC); phase III IPF trials underway, with data expected later in 2026 and H2 2027.

• IPF prevalence estimated at 140,000; 85% have cough and two-thirds of those have uncontrolled cough, representing ~100,000 patients.

• Other ILDs could roughly double the IPF opportunity; RCC represents an estimated 2 million-3 million patients, with a specialty focus on the most refractory patients.

• Existing IPF care centers primarily use antifibrotics to slow disease; cough treatment would address patients’ daily symptoms and quality of life.

Nalbuphine, safety and intellectual property

• Nalbuphine blocks the mu opioid receptor and acts at kappa; its peripheral lung and central brain activity targets the cough reflex arc.

• Human abuse-potential and respiratory-depression studies were described as clean; nalbuphine has been unscheduled as an injectable, and management expects it to remain unscheduled.

• Issued method-of-use patent broadly covers nalbuphine for chronic cough and IPF cough through 2039; additional label-related claims are being pursued to extend protection toward 2046-2047.

IPF phase II evidence and phase III design

• CORAL showed a ~36% differential from placebo; 54 mg BID was selected over 108 mg BID, which offered no added benefit on patient-reported cough severity or frequency.

• Safety profile was characterized mainly by transient, generally mild CNS and GI events. Phase III uses one week of nighttime 27 mg QD, then one week of 27 mg BID titration.

• FDA-aligned primary endpoint is 24-hour objective cough monitoring; OCEAN-1 has 24 weeks of fixed-dose efficacy assessment and 52 weeks of placebo-controlled safety, while OCEAN-2 assesses efficacy at 12 weeks.

• OCEAN-1 is a 300-patient trial, powered for key secondary endpoints; OCEAN-2 is a 200-patient confirmatory trial, powered for primary and key secondary endpoints. OCEAN-2 was due to start this quarter.

• Phase III assumes a 30% reduction in objective cough; CORAL showed 36%. Cough severity is the key secondary endpoint, with FDA agreement that significant change from baseline is meaningful.