Climb Bio and Mabworks report deep APRIL suppression for IgAN mAb
Climb Bio and its partner Mabworks have presented Phase 1 data for their anti-APRIL monoclonal antibody CLYM116/MIL116 at the American Society of Nephrology Kidney Week 2026 in Denver, reporting sustained near-complete suppression of a key driver of IgA nephropathy and a pharmacokinetic profile the companies say supports once-quarterly dosing.
The data were drawn from two parallel randomised, double-blind, placebo-controlled ascending-dose studies conducted in Australia and China, enrolling 46 and 42 healthy volunteers respectively. Following a single subcutaneous dose of 800 mg, participants showed approximately 70% reduction in galactose-deficient IgA1 (Gd-IgA1) and approximately 60% reduction in total IgA at 12 weeks. Free APRIL suppression exceeded 90% across the full 12-week dosing interval at doses of 480 mg and above.
The antibody recorded an estimated half-life of approximately 33 days, which the companies compare favourably to the reported half-life of sibeprenlimab, a competing anti-APRIL therapy currently in late-stage development. Exposure was linear across the effective dose range with no target-mediated drug disposition observed, findings the companies describe as consistent with the candidate's pH-dependent "sweeper" mechanism, which promotes lysosomal degradation of APRIL and recycles the antibody to extend its functional duration.
Safety data appeared clean: CLYM116/MIL116 was generally well tolerated across doses from 25 mg to 1,280 mg, with no dose-limiting toxicities, no treatment-related serious adverse events, and no hypogammaglobulinemia. Injection-site reactions occurred in five of 88 participants across both studies; all were Grade 1 and resolved without intervention.
Aoife Brennan, President and Chief Executive Officer of Climb Bio, said the two datasets offered "complementary validation" of what the company regards as a differentiated profile. "CLYM116 was engineered as a sweeper antibody, and we've now seen this mechanism translate into superior in vivo potency, extended half-life, and predictable, linear exposure across two, parallel clinical studies," she said.
Trial progress and regulatory path
The NAVIGATE-2 Phase 2 trial is currently enrolling IgAN patients, with initial data expected in the first half of 2027. A global Phase 3 programme is anticipated to start in 2027, subject to regulatory feedback. Climb Bio holds worldwide rights outside Greater China; Mabworks retains rights within Greater China.
IgAN is the most common primary glomerulonephritis globally, affecting an estimated 200,000 patients in the United States alone and carrying a disproportionate burden in populations of Asian descent. Two therapies targeting the disease's pathogenic pathway have recently received regulatory approval: Travere Therapeutics' sparsentan and Calliditas Therapeutics' budesonide formulation Nefecon. Neither directly suppresses APRIL, leaving room for a dedicated anti-APRIL approach if clinical data in patients confirm the biomarker reductions now observed in healthy volunteers.
Competitive landscape
The APRIL pathway has attracted multiple developers. Visterra, acquired by Otsuka, and Vera Therapeutics are among those pursuing APRIL or BAFF/APRIL dual-blockade in IgAN, while sibeprenlimab from Vivisimo/Chinook (now part of Novartis) generated Phase 2 data that helped validate the target class. Climb Bio's emphasis on half-life advantage and quarterly dosing is a deliberate positioning move in a field where dosing convenience has become a meaningful differentiator alongside efficacy. Whether the biomarker reductions reported in healthy volunteers translate proportionally into proteinuria and renal-function benefits in IgAN patients will be the pivotal question for the NAVIGATE-2 readout in 2027.