Gossamer Bio (GOSS) Study result summary

Study design and patient population

• PROSERA was a global, randomized, double-blind, placebo-controlled phase III trial in PAH patients on background therapy, enrolling 390 patients (197 seralutinib, 193 placebo) treated up to 48 weeks.

• The primary endpoint was change in six-minute walk distance (6MWD) at week 24; key secondary endpoints included NT-proBNP, clinical improvement, and REVEAL Lite 2 risk score.

• The study population was heavily pretreated, with 55% on triple/quadruple therapy, 61% on background prostacyclin, and most on two or more background PAH therapies.

• Baseline demographics were balanced between arms, with mean age ~50 years and ~86% female; patients were WHO Functional Class II or III.

• Enrollment criteria included REVEAL Lite 2 risk score ≥5, with a prespecified subgroup analysis at risk score ≥6 (intermediate/high risk), representing about two-thirds of the population.

Efficacy results

• At week 24, seralutinib showed a placebo-adjusted improvement in 6MWD of 13.3 meters (p=0.032), not meeting the prespecified alpha of 0.025.

• In intermediate/high-risk patients (REVEAL Lite 2 ≥6), seralutinib achieved a 20-meter placebo-adjusted improvement (p=0.0207), with three of four key secondary endpoints also showing p<0.0125.

• The CTD-PAH subgroup had a 37-meter placebo-adjusted improvement at week 24 (p=0.0104), outperforming other studies in this population.

• NT-proBNP at week 24 showed a -120.4 ng/L shift versus placebo (p=0.0002) in the overall population, with even greater reduction in higher-risk patients (-265.8 ng/L; p=0.0002).

• At week 48, the seralutinib arm showed a ~30-meter improvement (p=0.02, ANCOVA), with continued separation from placebo over time.

Placebo response and regional heterogeneity

• The placebo arm showed an unexpectedly large improvement (13.5 meters), especially in Latin America and Asia/Middle East, compressing the treatment effect.

• In North America, the placebo response was minimal (-3.9 meters), and the drug effect was more pronounced (26 meters).

• Regional differences in placebo response were a key factor in not meeting the primary endpoint.

• Over time, placebo effects normalized, and drug-placebo separation increased, especially at week 48.