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ARTICLE | Emerging Company Profile

Thinking about HDAC2

Rodin's safe, selective HDAC2 inhibitors for AD

April 14, 2016 7:00 AM UTC

Rodin Therapeutics Inc. is developing selective HDAC2 inhibitors to treat cognitive impairment in Alzheimer's disease (AD) without causing the serious side effects associated with pan-HDAC - a strategy that netted it a deal with Biogen Inc. in January worth up to $485 million and a buyout option.According to Rodin CEO Adam Rosenberg, HDAC2 is up-regulated in the brains of AD patients, and studies by the company's collaborators at the Broad Institute of MIT and Harvard and others have shown inhibiting HDAC2 overexpression results in cognitive improvement and presynaptic plasticity in animal models.

However, there are no HDAC2-specific inhibitors on the market or in commercial development, and available pan-HDAC inhibitors for neurological diseases - such as valproic acid and its analogs - have toxicity profiles unsuitable for chronic treatment. Pan-inhibitors for cancer have hematopoietic toxicities and are designed for low brain exposure, Rosenberg said. "We believe that a selective HDAC2 approach will have superior efficacy and potency, and potentially much better safety margins as well." ...