AJ201 is a novel, first-in-class asset in development for the treatment of spinal and bulbar muscular atrophy (“SBMA”), also known as Kennedy’s Disease.

It was designed to modify SBMA through multiple mechanisms, including degradation of the mutant androgen receptor protein and stimulation of Nrf1 and Nrf2 pathways, which are involved in protecting cells from oxidative stress that can lead to cell death.

AJ201 is currently being studied in a Phase 1/2a multicenter, randomized, double-blind clinical trial in six clinical sites across the U.S., which aims to evaluate the safety, PK/PD data and clinical response of AJ201 in patients suffering from SBMA. The 12-week, multicenter, randomized, double-blind Phase 1b/2a clinical trial of AJ201 is expected to enroll approximately 24 patients, randomly assigned to AJ201 (600 mg/day) or placebo. The primary endpoint of the study is to assess safety and tolerability of AJ201 in subjects with clinically and genetically defined SBMA. Secondary endpoints include pharmacodynamic data measuring change from baseline in mutant AR protein levels in skeletal muscle and changes in the fat and muscle composition as seen on MRI scans, which are believed to be biomarkers indicating likelihood for longer term clinical improvement. Further details about this study can be found at ClinicalTrials.gov (Identifier: NCT05517603). Enrollment in the trial is expected to be complete by the end of 2023 or early 2024 with potential topline data in 2024.

“We are excited to announce that the first patient has been dosed in our Phase 1b/2a clinical trial evaluating AJ201 for the treatment of SBMA, a progressive and devastating neurodegenerative disease that currently has no approved treatments available,” said Alexandra MacLean, M.D., Chief Executive Officer of Avenue. “We are encouraged by the Phase 1 clinical data of AJ201 that demonstrate the drug’s excellent safety profile in healthy volunteers. Additionally, compelling preclinical data in a mouse model showed efficacy signals, including improvement in motor function, robust degradation of mutant androgen receptors (“AR”), a disease-signaling protein, and activation of the Nrf1 and Nrf2 pathways. In this Phase 1b/2a clinical trial, we aim to demonstrate how AJ201’s novel, multi-fold mechanism of action reduces accumulation of mutant AR aggregates to potentially decrease neuroinflammation, protect cells from oxidative stress, and ultimately improve clinical outcomes for SBMA patients. We look forward to advancing development of this much needed drug, as we continue to deliver on our mission of bringing impactful therapies to people suffering from neurologic diseases.”

AJ201 has been granted Orphan Drug Designation by the FDA for multiple polyQ diseases, including SBMA, Huntington’s disease and spinocerebellar ataxia. Avenue exclusively licensed AJ201 from AnnJi Pharmaceuticals in the United States, Canada, European Union, Great Britain, and Israel.