ALS (amyotrophic lateral sclerosis) is a devastating disease that progressively destroys the nerve cells that control movement, eventually taking away a person’s ability to walk, speak, swallow, and breathe. AcuraStem Incorporated is developing AS-241, an experimental medicine designed to protect motor neurons by correcting a genetic malfunction that occurs in the vast majority of ALS cases. Specifically, AS-241 is an antisense oligonucleotide, a short piece of synthetic genetic material, that restores the normal function of a protein called UNC13A, which is disrupted in ALS patients when a key protein called TDP-43 stops working properly.

During this reporting period, the team achieved several important milestones on the path toward the first in-human clinical trial.

In laboratory studies using stem-cell-derived motor neurons generated from ALS patients of diverse ethnic backgrounds, AS-241 consistently restored normal UNC13A activity across multiple patient lines tested, an important step in demonstrating that the therapy may work broadly across the ALS patient population.

In animal studies, AS-241 was administered to the nervous systems of mice and nonhuman primates to evaluate how the drug behaves in the body and whether it is safe at various doses. The drug was found to persist in the central nervous system for an extended period, which is a favorable property for a medicine targeting brain and spinal cord disease. In a nonhuman primate safety study, AS-241 was well tolerated at all doses tested, with no deaths or serious adverse events.

Finally, in this project the team successfully manufactured an engineering batch of AS-241 drug product at Corden Pharma-a pharmaceutical-grade facility in Italy, meeting all pre-defined quality criteria, a critical step toward regulatory submission for a first-in-human clinical trial.