Acetylon Pharmaceuticals presents positive preclinical data for selective HDAC1/2 inhibitors at ASH meeting

Acetylon Pharmaceuticals, Inc.Dec 11 2013

Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, announced that positive preclinical data for its selective HDAC1/2 inhibitors for the treatment of sickle cell disease (SCD) and β-thalassemia (bT) were presented at the 55^th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, LA. An oral presentation given today and a poster presentation on December 8 describe the mechanism of action of selective HDAC1/2 inhibition in the induction of fetal hemoglobin (HbF) and report that Acetylon's selective HDAC1/2 inhibitor compounds may provide a novel treatment option for SCD/bT.

"Inhibition of Class I HDACs is known to induce HbF, however, significant toxicity, potentially through the inhibition of HDAC3, has limited the development of non-selective HDAC inhibitors for the treatment of SCD/bT," said Matthew Jarpe, Ph.D., Senior Director of Biology at Acetylon. "In the data presented at ASH, Acetylon's selective HDAC1/2 inhibitors induced HbF through the downregulation of known repressors of fetal globin synthesis and the upregulation of proposed activators of fetal globin synthesis with minimal effect on cell viability. Together, the data suggest that HDAC1/2 inhibition may provide a novel, targeted treatment option for patients with SCD and bT."

Highlights of the Presentations at ASH

Pharmacological Inhibition of Histone Deacetylase (HDAC) 1, 2 or 3 Have Distinct Effects on Cellular Viability, Erythroid Differentiation, and Fetal Globin (HbG) Induction (oral presentation, Abstract # 564)

• Selective HDAC1/2 inhibition resulted in a 3-fold increase in HbG
• Inhibition of HDAC 1, 2 and 3 resulted in a 20-fold decrease in cell viability, whereas selective inhibition of HDAC 1 and 2 resulted in a minimum reduction of cell viability (1.2-fold)

Mechanistic Insights into Fetal Hemoglobin (HbF) Induction through Chemical Inhibition of Histone Deacetylase 1 and 2 (HDAC1/2) (poster presentation, Abstract # 2253)

• Selective HDAC1/2 inhibition resulted in the downregulation of genes known to repress fetal globin synthesis (Bcl11A and Sox6) and upregulation of genes proposed to activate fetal globin synthesis (Klf2 and Gata2)