Abstract: TH-PO0823
CLYM116, a Novel "Sweeper" Anti-A Proliferation-Inducing Ligand Monoclonal Antibody in Development for IgAN: Phase 1 Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) Results in Healthy Volunteers
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Luo, Stacey, Climb Bio, Inc., Wellesley, Massachusetts, United States
- Liu, Xifang, Beijing Mabworks Biotech Co Ltd, Beijing, China
- Wang, Xia, Beijing Mabworks Biotech Co Ltd, Beijing, China
- Li, Feng, Beijing Mabworks Biotech Co Ltd, Beijing, China
- Charles, Edgar D., Climb Bio, Inc., Wellesley, Massachusetts, United States
Background
CLYM116 (MIL116) is an investigational, novel ‘sweeper’ anti-A PRoliferation-Inducing Ligand (APRIL) monoclonal antibody (mAb) engineered with both pH-dependent antigen-binding to enhance APRIL degradation and antibody recycling and Fc mutations to extend serum half-life and diminish its effector function. CLYM116 is in development for IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide. In cynomolgus monkeys, CLYM116 demonstrated a half-life approximately 2-3 times that of sibeprenlimab analog (synthesized from published sequences), deep and durable APRIL suppression, as well as deep and sustained IgA reduction, after a single subcutaneous administration (Beeck, ASN 2025). Translational pharmacokinetic/pharmacodynamic modeling, informed by sibeprenlimab clinical data, supported dose selection for this first-in-human study.
Methods
This Phase 1 study (NCT07248865) is a randomized, double-blind, placebo-controlled, single-center study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of subcutaneous CLYM116 in healthy adult volunteers outside of China. Five single ascending dose cohorts and one multiple dose cohort were enrolled sequentially with sentinel dosing and Safety Review Committee oversight between cohorts. Key pharmacodynamic biomarkers include serum IgA, Gd-IgA1, and APRIL.
Results
As of May 1, 2026, 29 adult healthy volunteers were enrolled across 4 active dose cohorts, with placebo administered within each cohort. CLYM116 was well tolerated with no dose-limiting toxicities, serious adverse events, or discontinuations due to adverse events. Dose-dependent reductions in serum IgA were observed in the available data from the first three dose cohorts, with nadir and recovery kinetics consistent with the pharmacological mechanism of APRIL inhibition. Consistent findings were observed in a parallel Phase 1 healthy volunteer study in China (Mabworks, NCT07375758). Pharmacokinetic, pharmacodynamic, and safety data from all cohorts of the ex-China study will be presented at the meeting.
Conclusion
Initial data demonstrate favorable tolerability and dose-dependent IgA suppression across early dose cohorts in this Phase 1 study, supporting continued clinical evaluation of CLYM116 as a potential best-in-class, disease-modifying treatment for IgAN.
Funding
- Commercial Support – Climb Bio, Inc.