AcuraStem, a patient-based drug discovery platform company developing novel therapeutics for amyotrophic lateral sclerosis (ALS) and neurodegenerative diseases, has received an Amyotrophic Lat-eral Sclerosis Research Program (ALSRP) Therapeutic Development Award from the Department of Defense, Congressionally Directed Medical Research Programs (CDMRP) totaling $1 million. Through CDMRP’s award mechanisms and funding rec-ommendations, the ALSRP highlights innovative and impactful research targeting the development of new therapeutics for ALS. The CDMRP award nomination under-scores the significance of AcuraStem’s drug candidate AS-202, which has potential to be a disease-modifying therapeutic for the vast majority of patients who do not harbor a genetic mutation known to cause ALS, often referred to as “sporadic” ALS. Currently there are few disease-modifying treatments in development for sporadic ALS.

AcuraStem’s most advanced therapeutic candidate, AS-202, lowers levels of the lipid kinase PIKFYVE. The disease-modifying potential of PIKFYVE for ALS was discovered by AcuraStem’s co-founder and close collaborator, Justin Ichida, Ph.D., in a landmark study appearing in Nature Medicine in 2018 (Shi Y et al Nature Med 2018). Reducing PIKFYVE levels has been highly effective in animal and patient-derived models of sporadic ALS.

“The studies in my lab at the University of Southern California that discovered PIKFYVE as a therapeutic opportunity in ALS were funded in part by the CDMRP,” said Dr. Ichida. “We welcome CDMRP’s continued support of AcuraStem to rapidly advance this treatment towards the clinic.”

AcuraStem’s Head of Research, Dr. Wen-Hsuan Chang, will lead the project. Dr. Chang has been instrumental to the preclinical development of AS-202 and, prior to that, led the team that established and validated AcuraStem’s proprietary iNeuroRx^® technology platform. The iNeuroRx^® platform uses ALS-patient derived neurons to model ALS with high fidelity. Machine-learning driven, unbiased screens in these neurons have discovered novel therapeutic targets that, because they were discovered using neurons from patients, should have a higher probability of becoming disease-modifying treatments. Because the platform includes neurons from patients with sporadic ALS, AcuraStem is able to identify novel therapeutic approaches that could be disease-modifying for all ALS patients.

“The iNeuroRx^® platform enables us to discover and develop treatments that will work for the vast majority of patients, including sporadic ALS,” said AcuraStem Co-founder and Chief Executive Officer Sam Alworth. “This is a game-changing approach to treating neurodegeneration. Our methods are well validated in ALS, and we are extending iNeuroRx^® into other neurodegenerative indications.”

Supported by the National Institutes of Health and the Muscular Dystrophy Association, AcuraStem has developed several best-in-class PIKFYVE-targeting drug candidates that achieve high levels of on-target exposure in the central nervous system. The CDMRP funds will be used to advance the development candidate AS-202 into GLP toxicity studies to support the IND filing, which is expected in 2022. This work was supported by the Department of Defense through the Congressionally Directed Medical Research Programs under Award No. W81XWH2110355. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.