Preclinical Results for Acetylon Pharmaceuticals' Selective HDAC1/2 Inhibitor for the Treatment of Sickle Cell Disease and Beta-Thalassemia Presented at ASH 2012

BOSTON--(BUSINESS WIRE)--

Acetylon Pharmaceuticals Inc., a leader in targeted epigenetic drug discovery and development for enhanced therapeutic outcomes, today announced results from a preclinical study of a selective histone deacetylase (HDAC) 1/2 inhibitor for the treatment of sickle cell disease (SCD) and beta-thalassemia (bT) at the 54^th Annual Meeting of the American Society of Hematology (ASH), taking place in Atlanta, Georgia. The study results suggest that selective inhibition of the epigenetic regulators of gene expression, HDACs 1 and 2, could represent a refined and targeted approach for the treatment of SCD and bT through the induction of disease-corrective fetal hemoglobin (HbF) in human red blood cell progenitors.

“The data presented at ASH demonstrate the potential for selective HDAC1/2 inhibition in hemoglobinopathies, including the two most prevalent severe human genetic diseases, sickle cell disease and beta thalassemia, for which treatment options are severely limited,” said Walter C. Ogier, President and Chief Executive Officer and co-founder of Acetylon. “This program adds to our broadening pipeline of targeted epigenetic drugs and is yet another example of the wide array of human disease indications for which selective HDAC inhibitors hold promise.”

The induction of HbF is an established therapeutic strategy for SCD and could potentially also be an effective therapeutic strategy for bT. Previous studies suggested that non-specific HDAC inhibitors were successful in inducing HbF, however, their development has been delayed due to concerns over variable efficacy and off-target side-effects. Acetylon scientific founders James E. Bradner, MD, and Ralph Mazitschek, Ph.D., of Harvard Medical School first demonstrated the potential for selective HDAC1/2 inhibition in inducing HbF (Bradner et al, PNAS, July 13, 2010, vol. 107, no. 28, 12617-12622). Subsequently, Acetylon sought to discover and develop novel, orally bioavailable, selective HDAC1/2 inhibitors which were later tested for HbF induction. In the study presented at ASH, the HDAC1/2 inhibitors had highly favorable oral pharmacokinetic profiles. Furthermore, in cultured human red blood cell progenitor cells, HDAC1/2 inhibitors induced a dose-dependent increase in HbF expression. The HbF induction observed was similar to that of either a non-selective HDAC1/2/3 inhibitor or decitabine, both of which have been in clinical trials for the treatment of SCD. These results suggest that Acetylon's selective HDAC1/2 inhibitor compounds are capable of inducing HbF expression with a pharmacokinetic profile suitable for clinical development for the potential treatment of SCD and bT. The study results are being presented by Jeffrey Shearstone, Ph.D., of Acetylon during an ASH poster session today in a poster titled, “Induction of Human Fetal Hemoglobin Expression by Selective Inhibitors of Histone Deacetylase 1 and 2 (HDAC1/2).”

About HDAC1/2 Inhibition

The induction of fetal hemoglobin (HbF) is an established therapeutic strategy for sickle cell disease that also holds potential for the treatment of beta-thalassemia. HDAC inhibition has been shown to induce HbF, however, clinical development of non-selective HDAC inhibitors has been limited due to the number of off-target side effects. Selective HDAC1/2 inhibition represents a novel treatment approach that could represent a safer and more effective treatment option for patients with SCD and bT.

About Acetylon Pharmaceuticals Inc.

Acetylon Pharmaceuticals Inc. is a leader in the development of novel small molecule drugs targeting epigenetic mechanisms for the enhanced therapeutic outcome of cancer and other critical unmet medical needs. The Company's epigenetic drug discovery platform has initially yielded a proprietary library of optimized, orally-administered Class I and Class II histone deacetylase (HDAC) selective compounds. Alteration of HDAC regulation through selective HDAC inhibition is thought to be applicable to a broad range of diseases, including cancer, sickle cell disease, beta-thalassemia, and autoimmune and neurodegenerative diseases. Acetylon's lead drug candidate, ACY-1215, is a selective HDAC6 inhibitor in clinical development for the treatment of multiple myeloma.