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

Key Points

• Phase I results supported CLYM116’s potential for less frequent dosing: A single 320 mg dose suppressed free APRIL by more than 90% through week 10 and over 75% at week 12, with an approximately 29-day half-life.
• Safety findings were favorable: No dose-limiting toxicities, serious adverse events, severe adverse events or treatment-related discontinuations were reported; observed adverse events were mild or moderate, and no hypogammaglobulinemia occurred.
• Climb Bio is advancing the drug in the phase II NAVIGATE-2 study in China, testing 400 mg every 12 weeks or every eight weeks after an 800 mg loading dose. Initial data are expected in the first half of 2027, with a phase III study potentially beginning that year.

Climb Bio NASDAQ: CLYM 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.

Phase I pharmacokinetic and pharmacodynamic findings

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.

Safety and dosing plans

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. No participants developed hypogammaglobulinemia, a condition involving low immunoglobulin levels that can increase infection risk. Anti-drug antibody data are not yet available because the assay remains under development.

Climb Bio said it has developed a 200 mg/mL formulation intended to deliver a 400 mg dose in a single 2 mL injection, compatible with both prefilled syringes and an autoinjector. The ongoing phase II NAVIGATE-2 study is using a 160 mg/mL formulation, but the company plans to use the higher-concentration formulation in future registrational studies.

Using its integrated pharmacokinetic and pharmacodynamic model, the company said it projects that an 800 mg loading dose followed by 400 mg every 12 weeks could maintain drug exposure above its estimated APRIL EC75 threshold and provide durable APRIL suppression over repeated dosing intervals.

Phase II and registrational outlook

NAVIGATE-2 is enrolling patients with IgA nephropathy in China through Climb Bio’s partner Mabworks. The study is evaluating 400 mg every 12 weeks and 400 mg every eight weeks, each following an initial 800 mg loading dose, with an optional third arm intended to help select a regimen.

The company expects initial NAVIGATE-2 data in the first half of 2027 and said it aims to advance the every-12-week regimen into phase III. Climb Bio anticipates beginning a registrational phase III study in 2027, subject to regulatory feedback.

Brennan said additional data from the Australian phase I study and Mabworks’ China phase I study are expected at a major medical meeting in the fourth quarter. Mabworks is studying an 800 mg dose in its phase I trial, Climb Bio said.

Climb Bio also cited an evolving IgA nephropathy market, including the November 2025 accelerated U.S. approval of Otsuka’s sibeprenlimab, marketed as Voyxact. The company estimates that about 200,000 patients in the U.S. are living with IgA nephropathy and that the annual domestic market opportunity could exceed $20 billion, based on its assumptions regarding diagnosis, treatment rates and pricing.

About Climb Bio (NASDAQ:CLYM)

Climb Bio Therapeutics, Inc is a clinical-stage biotechnology company focused on the discovery and development of engineered protein therapeutics for the treatment of cancer and immune-mediated disorders. The company's mission centers on designing biologics with enhanced specificity and functional activity to engage key cellular targets and improve patient outcomes in areas of high unmet need.

At the heart of Climb Bio's approach is its proprietary protein engineering platform, which combines mammalian cell display, directed evolution and computational modeling.

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