Abstract

ORY-2001 - An Epigenetic Approach to Treat Alzheimer's Disease and other Neurodegenerative Disorders

Tamara Maes, Chief Scientific Officer, Oryzon

ORY-2001 is a novel brain-penetrable covalent inhibitor of LSD1 and MAO-B with excellent oral bioavailability and PK profile. The compound has excellent selectivity over other FAD containing amine oxidases like MAO-A and LSD2, and did not inhibit other chromatin modulators nor > 100 targets from a CEREP diversity panel. Long term administration confirmed the feasibility of chronic treatments with ORY-2001 and prevented the cognitive impairment as assessed by NORT in the mouse SAMP8 model for accelerated aging and Alzheimer disease. Microarray analysis of hippocampal samples revealed that ORY-2001 has a limited pleiotropic effect on gene expression. Treatment with ORY-2001 potently down-regulated the expression of a subset of genes related to immune reaction and inflammation including S100A9; and up-regulated genes associated with improved cognitive function, neuroplasticity and memory. Preclinical regulatory toxicology studies with ORY-2001 have finalized successfully and a Clinical Trial Application has been filed to the Spanish Drug Agency (AEMPS) to initiate Phase I studies.