AnnJi Pharma Reports Positive Phase 1/2a Results for AJ201 in SBMA Patients

AnnJi Pharmaceutical Co., Ltd., a Taiwanese biotech company specializing in dermatology, neurology, and rare diseases, has announced promising results from its Phase 1/2a clinical trial of AJ201 in adults suffering from Spinal and Bulbar Muscular Atrophy (SBMA). This trial, which was conducted at six locations across the United States, aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AJ201, although it wasn’t designed to measure efficacy directly. Preliminary findings, however, suggest positive treatment-related outcomes that warrant further clinical exploration.

The trial revealed that AJ201’s safety and pharmacokinetic characteristics in SBMA patients matched those found in previous studies involving healthy volunteers. AJ201 was generally well tolerated, with no accumulation of the drug observed in the body. After 12 weeks of treatment, participants who received AJ201 exhibited significant improvements in physical and muscle function compared to those given a placebo. Notably, there was an average increase of 17.6 meters in the 6-Minute Walk Test (6MWT) and a 0.8-point rise in the SBMA Functional Rating Scale (SBMAFRS) among AJ201 recipients, while placebo recipients experienced minor declines. Additionally, AJ201 treatment resulted in reduced levels of serum creatine kinase and myoglobin, indicating a beneficial therapeutic effect.

The majority of the participants who showed positive responses were in the AJ201 group: 11 out of 15 showed improvement in the 6MWT, 6 out of 7 in SBMAFRS, 14 out of 14 in creatine kinase, and 11 out of 12 in myoglobin. Furthermore, patients receiving AJ201 reported significant enhancements in the physical function component of the SF36v2 quality-of-life questionnaire, unlike the placebo group which showed a decline.

The study also delved into biomarker findings and RNA sequencing to understand the mechanistic support for AJ201. Muscle biopsies were used to measure mutant androgen receptor (mAR) levels, a proposed biomarker for SBMA. Results indicated that nuclear mAR levels decreased by over 50% in 53% of patients treated with AJ201, compared to 17% in the placebo group, suggesting potential therapeutic activity. RNA sequencing in muscle biopsies from AJ201-treated patients revealed activation of the Nrf2 pathway and modulation of several disease-relevant signaling pathways, changes not seen in the placebo group, further supporting AJ201's therapeutic mechanism.

The consistent improvements observed across the study’s functional, biochemical, and molecular markers provide a strong case for the continued development of AJ201 for SBMA. Dr. Christopher Grunseich, Principal Investigator of the study, expressed optimism about the results, noting the clinical benefits demonstrated through functional improvements and positive biomarker shifts, alongside RNA sequencing data supporting the activation of the Nrf2 pathway. Dr. Grunseich is a Lasker Clinical Research Scholar and leads the Inherited Neuromuscular Diseases Unit at the National Institute of Neurological Disorders and Stroke (NINDS).

Wendy Huang, Ph.D., CEO and Chairperson of AnnJi, echoed Dr. Grunseich's enthusiasm, expressing commitment to advancing AJ201 into Phase 3 clinical trials. The aim is to provide a safe, effective therapeutic option for SBMA patients, addressing the current gap as the disease lacks any FDA-approved treatments.

SBMA, also known as Kennedy's disease, is a rare neuromuscular disorder linked to CAG repeat expansion in the androgen receptor (AR) gene. It is characterized by muscle and neuron degeneration due to cellular toxicity, oxidative stress, and neuroinflammation. Affecting approximately 1 in 40,000 males worldwide, SBMA currently has no FDA-approved treatments. AJ201, identified as JM17, is a novel compound that has shown potential in preclinical models by reducing mutant AR toxicity and improving motor function. It promotes the degradation of pathogenic mAR protein and induces the expression of antioxidant enzymes, proteasome subunits, and heat shock proteins, potentially slowing disease progression.

AnnJi Pharmaceutical Co., Ltd., established in 2014, is a clinical-stage biotechnology firm dedicated to creating innovative treatments for serious, underserved diseases. Their research pipeline spans neurology, dermatology, and rare disorders, including SBMA, with a focus on translating scientific breakthroughs into effective treatments through global collaboration.