The Annual International SBMA Research Conference sponsored by Kennedy’s Disease Association (KDA) will be held online during October 22-25, 2021. Dr. Michael Y Chan, Ph.D., VP of the Research and Translational Medicine in AnnJi Pharmaceutical Co., Ltd. (AnnJi), is invited to present AnnJi’s research and clinical development plan of AJ201 for the treatment of SBMA.  Clinical safety profile of AJ201 in a recently completed Phase I study in healthy subjects will be presented.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s Disease, is one of the polyQ diseases characterized by abnormal expansion of the CAG trinucleotide repeat in the gene encoding of the androgen receptor (AR), resulting in the aggregation of mutant AR. SBMA is a X-linked rare disease and predominantly affects the lower motor neurons and muscles with slow progression and late onset of >30-40 years of age. The pathophysiology of SBMA is complex and thought to associate with toxicity mediated by the polyQ-expanded AR, dysregulation of protein quality control, increased oxidative stress and inflammation, and disturbance in axonal transport. There are no approved treatments for SBMA currently.

AJ201 is an effective Nrf2 activator shown to induce antioxidant gene expression in response to oxidative stress. Previous study in an SBMA mouse model demonstrated that AJ201 activated Nrf2 and Nrf1 pathways, improved motor functions and reduced mutant AR aggregates in muscles (Bott et al 2016). AnnJi’s own research showed that AJ201 suppressed proinflammatory cytokines and exhibited neuroprotective effect through free radical scavenging. Our study suggested AJ201 activates Nrf2 by disrupting its interaction with KEAP1, similar to other reported Nrf2 activators. Interestingly, AJ201 induced a robust response in heat shock protein pathway, which was not reported for other Nrf2 activators.

In a recently completed Phase I study in healthy subjects, AJ201 was well-tolerated with a dose-proportional PK properties over a broad range of oral dose and no accumulation in systemic exposure after 7-day repeated dosing.

The overall scientific evidence, preclinical data and clinical results indicate AJ201 is an attractive and pleiotropic therapeutic approach for the treatment of SBMA. A first-in-patient Phase II study in the US is planned in 2022.