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

Positive Phase 1/2a Results for AJ201 at AnnJi Pharmaceutical

AnnJi Pharmaceutical Co., Ltd., a Taiwanese clinical-stage biotechnology company, recently announced promising outcomes from its Phase 1/2a clinical trial of AJ201, designed for patients suffering from Spinal and Bulbar Muscular Atrophy (SBMA). This study aims to address unmet medical needs in diseases that currently lack effective treatments.

Overview of the Clinical Trial

The double-blind, randomized, placebo-controlled study was conducted at six clinical sites across the United States. The primary focus was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AJ201 (ClinicalTrials.gov identifier: NCT05517603). Although the trial wasn't adequately powered to assess efficacy, exploratory endpoints presented significant treatment-related improvements, warranting further investigation.

Safety and Pharmacokinetics

Results indicated that both safety and pharmacokinetic profiles in SBMA patients aligned with previous findings in healthy volunteers. AJ201 was well-tolerated, with no observed systemic drug accumulation, which is a positive sign for its continued development.

Remarkable Clinical Signals Detected

Upon completing 12 weeks of oral treatment, patients receiving AJ201 showed clinically significant improvements in physical and muscle function compared to the placebo group. For instance, there was an average increase of 17.6 meters in the six-minute walk test (6MWT) and a mean improvement of 0.8 points in the SBMA functional rating scale (SBMAFRS). In contrast, the placebo group exhibited slight declines in these measures, suggesting that AJ201 may promote physical capabilities in SBMA patients.

Moreover, AJ201 treatment also correlated with reduced serum levels of creatine kinase and myoglobin, indicating potential therapeutic benefits. Impressively, a large majority of AJ201 recipients demonstrated responses in key metrics: of the 15 participants assessed via the 6MWT, 11 showed benefits, along with 6 out of 7 in the SBMAFRS. Notably, all 14 subjects evaluated for creatine kinase levels and 11 out of 12 for myoglobin recorded favorable reductions, enhancing the case for AJ201.

Quality of Life Improvements

Participants reported significant enhancements in the physical functioning component of the SF36v2 quality of life questionnaire, where the AJ201 group experienced increases while the placebo group faced declines (p=0.026).

Exploratory Biomarker Findings

The study also investigated mutant androgen receptor (mAR) levels as a potential biomarker for SBMA. Muscle biopsies revealed that AJ201 treatment led to decreases exceeding 50% in mAR nuclear levels among 53% of participants, contrasting with only 17% in the placebo group. This reduction hints at a possible therapeutic mechanism of action.

Additionally, RNA sequencing of muscle biopsies from those treated with AJ201 demonstrated the activation of the Nrf2 pathway and the modulation of several signaling cascades associated with the disease, both of which were absent in the placebo cohort.

Expert Commentary

The continuous improvement witnessed in functional, biochemical, and molecular markers during this study supports the ongoing development of AJ201 for treating SBMA. Dr. Christopher Grunseich, the principal researcher of the study, shared his optimism: "The study results are incredibly promising. AJ201 exhibited clinical benefits, marked by enhancements in functional assessments, favorable changes in serum biomarkers, and RNA sequencing data supporting Nrf2 pathway activation. Collectively, these outcomes highlight the therapeutic potential of AJ201."

Dr. Grunseich currently leads the hereditary neuromuscular disorders unit at the National Institute of Neurological Disorders and Stroke, part of the NIH.

Wendy Huang, Ph.D., the CEO and Chair of the Board at AnnJi, expressed similar enthusiasm regarding the trial results, emphasizing the company's dedication to advancing the program into Phase 3 clinical trials. "Our goal is to provide a safe and effective treatment option for SBMA patients, for whom there is currently no FDA-approved therapy available," she noted.

About SBMA and AJ201

SBMA, also known as Kennedy's disease, is a rare hereditary neuromuscular disorder linked to the X chromosome, caused by an expansion of CAG repeats in the androgen receptor (AR) gene. The resulting mutant AR protein is known to contribute to muscle and neuron degeneration via mechanisms involving cell toxicity, oxidative stress, and neuroinflammation. Globally, SBMA affects roughly 1 in 40,000 men, accentuating the urgent need for effective treatments.

AJ201, or JM17, is an experimental compound demonstrated to reduce the mutant AR toxicity and enhance motor function in preclinical models of SBMA. At the molecular level, it promotes the degradation of the pathological mAR protein and induces the expression of antioxidant enzymes and proteasome subunits, which may help slow disease progression.

About AnnJi Pharmaceutical

Founded in 2014, AnnJi Pharmaceutical Co., Ltd. is a clinical-stage biotechnology company focused on developing first-in-class small molecule therapies for serious and neglected diseases. With a pipeline that encompasses neurology, dermatology, and rare diseases such as SBMA, AnnJi is committed to translating cutting-edge science into differentiated treatments and advancing them through global collaboration and commercialization. For more information, visit www.ajpharm.com.