C103-15 Safety and Tolerability of PMG1015, an Anti-Amphiregulin (AREG) Monoclonal Antibody in Development for Idiopathic Pulmonary Fibrosis

Abstract Rationale Amphiregulin (AREG) has been implicated in fibrosis onset and development across multiple organs, including lung, liver, kidney, and skin. PMG1015, a humanized, anti-Amphiregulin monoclonal antibody has been studied in 3 Phase 1 studies, 2 in healthy volunteers and 1 in participants with idiopathic pulmonary fibrosis (IPF). Here, we report the cumulative safety profile. Methods To date, PMG1015’s safety has been studied in 3 Phase 1 studies with treatment durations up to 20 weeks: two single-ascending dose (SAD) studies in healthy volunteers (up to 12 weeks duration), one multiple-ascending dose (MAD) study in IPF participants (up to 20 weeks duration). Results The overall safety population (N = 113; n = 89 PMG1015 and n = 24 placebo) was 61.1% male and 33.6% white, with a median (range) age of 37 (18-79) years and a median (range) body mass index (BMI) of 24.3 (19.8-32.3) kg/m2. In the Phase 1b study in participants with IPF, the population (N = 29; n = 25 PMG1015 and n = 4 placebo) was 96.6% male and 100% Asian, with a median (range) age of 63.0 (45-79) years. The mean time since diagnosis of IPF was 5.3 and 8.6 months in the PMG1015 and placebo groups respectively. The most common reported treatment-emergent adverse events (TEAE with an incidence of ≥ 10%) in the overall safety population (All Treatment PMG1015/placebo) were upper respiratory tract infection (21.3%/20.8%), headache (11.2%/8.3%), and COVID-19 (6.7%/12.5%). For IPF participants in Phase 1b study, the most common TEAE (with an incidence of ≥ 10%) were upper respiratory tract infection (12%/0%) and hyperlipidemia (12.0%/0%). Three Grade 3 TEAE of were reported in 3 participants and all events were deemed not related to PMG1015. One Grade 5 event was reported. No serious TEAE in the Phase 1 studies were related to PMG1015. There were no titratable PMG1015-induced anti-drug antibodies (ADA) in the SAD healthy volunteer studies and no ADAs at any visit in the MAD IPF study. Conclusions PMG1015 was generally well tolerated in 113 study participants in Phase 1 trials to date. The most common TEAE with PMG1015 was upper respiratory tract infection, headache, and COVID-19. Most TEAEs were Grade 1 or 2 and discontinuation rates were low. These findings support the continued development of PMG1015 in IPF. This abstract is funded by: Pulmongene