Laekna presented encouraging Phase I clinical trial results for LAE102, its ActRIIA-selective antibody for obesity treatment, at the 85th American Diabetes Association Scientific Sessions in Chicago. The first-in-human study demonstrated a favorable safety profile and robust target engagement, supporting continued development of this novel therapeutic approach.
Phase I Trial Results Show Favorable Safety Profile
The single ascending dose study enrolled 64 healthy volunteers across two administration routes: 40 participants received intravenous doses (Part A) and 24 received subcutaneous injections (Part B). All participants completed the study as designed, with mean ages of 29.0 and 31.2 years and mean BMI values of 23.32 kg/m² and 23.08 kg/m² for the IV and SC cohorts, respectively.
LAE102 demonstrated excellent tolerability following single IV or SC administration. No serious adverse events or treatment-emergent adverse events leading to discontinuation were reported. The majority of adverse events were mild laboratory test abnormalities that were asymptomatic and required no medical intervention. Notably, no cases of diarrhea were reported, distinguishing it from some existing weight-loss therapies.
Sustained Target Engagement Indicates Therapeutic Potential
The study revealed dose-dependent pharmacodynamic effects, with Activin A levels significantly increasing within 24 hours of LAE102 administration. High-dose groups (8 mg/kg IV, 16 mg/kg IV, and 8 mg/kg SC) maintained 2-to-3-fold increases above baseline levels through 28 days post-administration, indicating prolonged pathway blocking.
LAE102 exhibited nonlinear clearance saturation at concentrations of approximately 2-4 μg/mL, a threshold that coincided with sustained pharmacodynamic effects. This robust pharmacokinetic-pharmacodynamic correlation suggests potential efficacy and supports further clinical development in overweight and obese populations.
Preclinical Studies Demonstrate Muscle-Preserving Weight Loss
Complementary preclinical research presented at ADA showed LAE102's unique mechanism of action. In mouse models, LAE102 alone significantly induced muscle growth and reduced fat mass. When combined with LAE103 (an ActRIIB-selective antibody), synergistic effects on muscle increase and fat loss were observed, achieving maximal effects comparable to the dual-specific antibody LAE123.
The findings indicate that ActRIIA serves as a major regulator of muscle growth and fat loss in mice. LAE102, LAE103, and LAE123 function as high-affinity functional antagonists, completely inhibiting signaling from ligands including activin A, B, AB, and myostatin, which contribute to muscle atrophy. They also inhibit activin E and GDF3, which promote lipid accumulation in adipose tissue.
Expert Commentary Highlights Clinical Significance
Professor Xuening Li from Zhongshan Hospital affiliated to Fudan University, the trial's principal investigator, emphasized the achievement: "As the Principal Investigator of this trial, I am delighted to see this First-in-class research achievement being presented at the scientific sessions of the 2025 ADA. Based on the clinical data of LAE102 in overweight and obese populations, we endorse further clinical development of this innovative drug candidate."
Professor Linong Ji from Peking University People's Hospital, Chairman of Laekna's Expert Advisory Committee, noted the broader implications: "Even more exciting is the emergence of novel pathways and targets like ActRII, which can be the next generation of high-quality weight-loss therapies following GLP-1. We look forward to more comprehensive and diverse data from its global study in the next phase, which may address current clinical challenges – including concurrent muscle loss during fat reduction – seen with existing therapies."
Strategic Partnership Accelerates Development
Laekna has secured IND approvals from both the FDA and China's CDE for LAE102 in obesity indication. In November 2024, the company entered into a clinical collaboration agreement with Eli Lilly and Company to support and accelerate global clinical development of LAE102 for obesity treatment.
The company has established a comprehensive portfolio targeting ActRII receptors, with LAE103 and LAE123 advancing to IND-enabling studies. Dr. Chris Lu, Chairman and CEO of Laekna, stated: "As a pioneer in research and development of ActRII pathway, we are committed to collaborating with global partners to conduct extensive and in-depth investigations of this target. Through developing novel drug candidates and expanding therapeutic indications, we aim to fully unlock its potential to benefit patients with obesity, sarcopenia, and other severe diseases."
