Accropeutics Inc. is advancing its RIPK2 inhibitor, AC-101, for the treatment of ulcerative colitis (UC), a chronic inflammatory bowel disease affecting the large intestine. The U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for AC-101, enabling a Phase II multi-regional clinical trial (MRCT). Simultaneously, a Phase Ib study of AC-101 has been initiated in China.
The Phase II trial will be a 12-week, multi-regional, randomized, double-blind, placebo-controlled, parallel-group study. It aims to evaluate the safety and efficacy of AC-101 in patients with moderate-to-severe UC. The Phase Ib study in China is a 12-week, multi-center, open-label, parallel-group trial focusing on safety, tolerability, preliminary efficacy, and pharmacokinetics in Chinese patients with moderate-to-severe UC.
AC-101's Development and Preclinical Data
AC-101 was developed using Accropeutics' platform targeting regulated cell death and inflammation. Preclinical studies suggest that AC-101 effectively inhibits the release of NOD-RIPK2-dependent inflammatory factors and protects against tissue damage in IBD models. Prior Phase Ia clinical trials in Australia and China demonstrated a favorable safety and pharmacokinetic profile in healthy volunteers.
Executive Commentary
"We are thrilled to receive FDA clearance of IND for AC-101, which is one of the leading RIPK2 inhibitors worldwide," said Dr. Xiaohu Zhang, co-founder and CEO of Accropeutics. "We look forward to evaluating AC-101 for more safety and efficacy data in UC patients in the Phase II study. We will work diligently to move the program forward, in the hope that it would one day benefit IBD patients worldwide with safe and efficacious oral treatment options."
Ulcerative Colitis and the Role of RIPK2
Ulcerative colitis is characterized by inflammation of the large intestine, leading to significant morbidity and an increased risk of colorectal cancer. Current treatments often have limited remission rates (20-30%) and can result in a loss of response over time. RIPK2, or Receptor Interacting Protein Kinase 2, is a serine/threonine kinase implicated in inflammatory diseases, including IBD. Dysregulation of the NOD/RIPK2 signaling pathway is associated with these conditions, making it a potential therapeutic target.
Accropeutics is also developing AC-003, a RIPK1 inhibitor, currently in Phase Ib trials for acute graft-versus-host disease (aGVHD), and AC-201, a TYK2/JAK1 inhibitor, in Phase II trials for psoriasis in China.
