PureTech Health (PRTC) Status Update summary

Disease background and treatment landscape

• Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease with unknown cause, affecting over 232,000 patients in the US and EU5, and has a poor prognosis without treatment.

• Standard-of-care drugs slow disease progression but have significant side effects, leading to low treatment initiation and high discontinuation rates; only about 25% of US patients are on FDA-approved drugs, with over 40% discontinuing therapy due to tolerability issues.

• Deupirfenidone is a deuterated form of pirfenidone, designed for slower breakdown and improved tolerability.

ELEVATE Phase 2b trial design and methodology

• ELEVATE was a global, multicenter, randomized, double-blind, active- and placebo-controlled, dose-ranging Phase 2b trial with 257 participants across 87 sites in 14 countries.

• Patients were randomized 1:1:1:1 to deupirfenidone 550 mg, deupirfenidone 825 mg, pirfenidone 801 mg, or placebo TID for 26 weeks.

• The primary endpoint was rate of decline in forced vital capacity (FVC) over 26 weeks; key secondary endpoint was change in FVC % predicted.

• Both Bayesian and frequentist analyses were used, with a prespecified Bayesian approach allowing augmentation of the placebo arm with historical data.

• Median age was 72 years, with 71.2% male and diverse ethnic representation.

Key trial results and efficacy

• Deupirfenidone 825 mg TID significantly slowed lung function decline in IPF, meeting both primary and key secondary endpoints, with a reduction in FVC decline to -21.5 mL over 26 weeks and an 80.9% treatment effect versus placebo.

• The 825 mg dose demonstrated approximately 50% greater effect size versus pirfenidone in FVC improvement.

• Dose-dependent efficacy was established, with both 550 mg and 825 mg doses showing benefit, but 825 mg providing the most pronounced effect.

• The trial demonstrated robust statistical significance, with a 98.5% posterior probability for the primary endpoint.

• Preliminary open-label extension data indicate durable effects for patients remaining on treatment up to 79–81 weeks.