C103-11 PK/PD Modelling of the Anti-AREG Antibody PMG1015 Enabled Its Dose Selection in the Phase 2b Study in Patients With Idiopathic Pulmonary Fibrosis

Rationale PMG1015 is a humanized monoclonal antibody targeting Amphiregulin (AREG), a key profibrotic factor in organ fibrosis and a newly identified prognostic biomarker for patient survival in pulmonary fibrosis. PMG1015 is currently in clinical development for the treatment of Idiopathic Pulmonary Fibrosis (IPF) among other indications. In a recent multiple-ascending dose (MAD) study in IPF participants, PMG1015 demonstrated a well-tolerated safety profile and favorable efficacy signals in both Forced Vital Capacity (FVC) and Ground Glass Opacity (GGO) by quantitative High-Resolution Computed Tomography (HRCT) analyses following a treatment of 3 months (Maher et al, 30Sep2025, Late Breaking Abstract - PMG1015 demonstrates well-tolerated safety and favorable FVC changes after 12 weeks of treatment in IPF Patients, ERS Congress 2025, Amsterdam, Netherlands). To enable dose selection for a Phase 2b study, a population pharmacokinetic (PK)-pharmacodynamic (PD) model was developed for PMG1015 to inform optimal dose based on target engagement and early efficacy signals. Methods A population PK model of PMG1015 was developed using data from 3 completed clinical studies (two single-ascending dose (SAD) studies in healthy volunteers [n = 84], one MAD study in IPF participants [n = 29]). Subsequently, an integrated PK/PD model was built to characterize target engagement of PMG1015 in both blood and lung. Finally, an exposure-response analysis was conducted between PMG1015 doses and changes in FVC and GGO. Results The PK of PMG1015 was well described by a 2-compartment model with linear clearance. Body weight was a significant covariant on all clearance and volume parameters, and participant population (healthy volunteers vs IPF) was also an important factor. Following MAD administration of PMG1015 in IPF participants, robust target engagement >90% was predicted across all tested dose levels (5, 15, 30 mg/kg) in both blood and lung (Figure 1). High level of target saturation across these dose groups was in alignment with the dose response and exposure-response relationships for FVC and GGO. Conclusions The current PK/PD model reliably characterized the observed data and demonstrated robust target engagement of PMG1015 in IPF participants, aligning with early efficacy signals observed in the MAD study across all doses. These PK/PD results supported dose selection for PMG1015 in the planned multi-regional Phase 2b clinical trial in IPF participants. This abstract is funded by: Pulmongene