Annexon, Inc. reported results from the Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) healthy volunteer study of ANX1502, a first-in-kind oral, selective small molecule inhibitor that targets the active form of C1s responsible for propagating classical pathway activation in association with C1q. ANX1502 achieved target serum levels and demonstrated pharmacokinetic (PK) measures that support advancement into a proof-of-concept clinical study to assess pharmacodynamics (PD) and efficacy in patients with cold agglutinin disease (CAD) in 2024. The completed Phase 1 clinical trial is a randomized, double-blind, placebo-controlled SAD and MAD study to assess the safety, tolerability, PK and PD of ANX1502 liquid suspension formulation in healthy adults.

The study evaluated single ascending doses of ANX1502 ranging from 25 mg to 1050 mg and multiple ascending doses of ANX1502 ranging from 200 mg twice-daily to 525 mg twice-daily. Results of the study were as follows: Dose-proportional PK and targeted levels of active drug were observed across both SAD and MAD cohorts; Single doses of 525-1025 mg ANX1502 suppressed C4d serum levels in healthy volunteers with higher than median baseline C4d; Across all doses evaluated, ANX1502 was generally well tolerated with mild to moderate treatment-emergent adverse events (TEAEs). The most frequent TEAEs were gastro-intestinal, which included nausea, emesis and diarrhea.

serious adverse events were reported, and there were no significant clinical or lab findings. Following the successful completion of the proof-of-concept study in patients with CAD, Annexon intends to evaluate ANX1502 in serious complement-mediated autoimmune diseases with the aim of providing enhanced efficacy and offering convenient dosing administration for long-term treatment of chronic conditions.