Climb Bio Phase I Data Backs 12-Week Dosing Plan for IgA Nephropathy Drug

Climb Bio presented phase I data for CLYM116, an anti-APRIL “sweeper” antibody being developed for IgA nephropathy, and said the results support advancing the program into an ongoing phase II study in China. The company said CLYM116 is designed to bind circulating APRIL, bring the target into cells for degradation and recycle back into circulation to bind additional APRIL molecules. Climb Bio believes this mechanism could enable deeper and more durable APRIL suppression than first-generation therapies while allowing less frequent dosing. Aoife Brennan, Climb Bio’s president and CEO, said the company’s objective is to develop a differentiated APRIL inhibitor that combines efficacy, convenience and safety. “APRIL is now a clinically validated target in IgA nephropathy,” Brennan said, adding that CLYM116 could potentially support a 12-week dosing schedule without sacrificing biological activity.

The data came from an ongoing Australian phase I study in healthy volunteers evaluating single CLYM116 doses of 25 mg, 80 mg, 160 mg, 320 mg and 480 mg, along with a multiple-dose cohort receiving 320 mg on days one and 15. Participants were followed for 12 weeks after treatment or placebo. As of the presentation, Climb Bio had 12-week data through the 320 mg single-dose cohort, while data from the 480 mg single-dose and 320 mg multiple-dose cohorts were still emerging. Edgar Charles, Climb Bio’s chief medical officer, said CLYM116 showed dose-proportional exposure, an approximately 29-day half-life and low, steady clearance. He said the company did not observe target-mediated drug disposition at concentrations above 1 microgram per milliliter, which it views as evidence supporting the antibody’s sweeper mechanism. Following a single 320 mg dose, free APRIL was suppressed by more than 90% through week 10 and by more than 75% at week 12, according to the company. Climb Bio also reported downstream reductions of approximately 60% in IgA, more than 70% in galactose-deficient IgA1, or Gd-IgA1, and approximately 75% in IgM at the 320 mg dose level. Charles noted that APRIL suppression is the more direct measure of drug activity, while downstream IgA measurements can show greater variability in small healthy-volunteer cohorts. The company said baseline IgA levels varied across some dose groups, which may have affected percentage reductions in IgA.

Climb Bio reported no dose-limiting toxicities, serious adverse events, grade 3 or higher adverse events, or treatment discontinuations related to adverse events. All reported adverse events were mild or moderate. The most frequently reported treatment-emergent events were headache, upper respiratory tract infection and injection-site reactions. Injection-site reactions occurred in five participants, were all grade 1 and resolved without intervention, the company said.