Climb Bio (CLYM) Study result summary

Study background and rationale

• CLYM116 is a next-generation anti-APRIL antibody for IgA nephropathy, featuring a novel sweeper mechanism with pH-dependent binding and FcRn recycling for repeated APRIL capture and degradation, aiming for improved efficacy, durability, and dosing convenience.

• IgA nephropathy is a progressive kidney disease with significant unmet needs, affecting about 200,000 patients in the U.S., with most eligible for disease-modifying therapy.

• The evolving treatment landscape and new guidelines are expected to expand the diagnosed and treated population, with the U.S. market opportunity estimated to exceed $20 billion annually.

• First-generation APRIL inhibitors have validated the target, but CLYM116 aims to improve on efficacy, durability, and convenience.

Study design and objectives

• Phase 1 was a randomized, double-blind, placebo-controlled, ascending-dose study in 46 healthy volunteers, evaluating safety, pharmacokinetics, and pharmacodynamics, with robust assessment around the 400 mg dose.

• Doses ranged from 25 mg to 480 mg, including single and multiple ascending dose cohorts, with subcutaneous administration and 12-week follow-up.

• Cohorts were well balanced in demographics and baseline characteristics, consistent with a healthy volunteer population.

Safety and tolerability

• CLYM116 was generally well-tolerated, with no serious adverse events, dose-limiting toxicities, or hypogammaglobulinemia observed.

• All adverse events were mild to moderate, transient, and self-resolving; injection site reactions were mild and resolved without intervention.

• No AE-related discontinuations occurred, and the most common events were headache, upper respiratory tract infection, and injection-site reactions.