Contact    |    Site Map    |    Careers

News & Publications

Acetylon Pharmaceuticals Presents Positive Preclinical Data on Selective HDAC1/2 Inhibition for the Treatment of Sickle Cell Disease/β-thalassemia


-- Data Presented at the 56th ASH Annual Meeting in San Francisco --

Boston – December 8, 2014 – Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, today announced positive preclinical data further detailing the mechanism of action and potential therapeutic use of selective HDAC1/2 inhibitors in the treatment of sickle cell disease (SCD) and beta-thalassemia (bT). The data were presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition in San Francisco, California.

“In the data presented at ASH, we extended our HDAC1/2 inhibition proof-of-concept preclinical findings in the treatment of SCD/bT to ex vivo patient blood cell samples, where we observed an induction of fetal hemoglobin, an established therapeutic strategy for these patients,” said Matthew Jarpe, Ph.D., Associate Vice President of Biology at Acetylon.

“In addition, we have gained a greater understanding of the mechanism of action of HDAC1/2 inhibition in the induction of fetal hemoglobin. We believe selective HDAC1/2 inhibition could provide an effective mechanism to treat patients with SCD and bT,” said Jeff Shearstone, Ph.D., Senior Scientist at Acetylon who gave the presentation at ASH.

Highlights of the data presented at ASH

Pharmacological Inhibition of Histone Deacetylases 1 and 2 (HDAC1/2) Induces Fetal Hemoglobin (HbF) through Activation of Gata2 (oral presentation, Abstract #335)

  • Selective HDAC1/2 inhibition induces fetal hemoglobin in SCD ex vivo patient blood cell samples
  • Selective HDAC1/2 inhibition downregulates repressors of fetal hemoglobin, Bcl11a and Sox6, and upregulates Gata2, thought to activate fetal hemoglobin
  • A novel role for Gata2 was discovered in the activation of the fetal beta-like globin gene (HbG)
  • Selective HDAC1/2 inhibition induces HbG, in part, through acetylation-induced activation of a Gata2 auto-regulatory loop

About HDAC1/2 Inhibition for SCD and bT

The induction of fetal hemoglobin (HbF) is an established therapeutic strategy for sickle cell disease and could also potentially be effective for beta-thalassemia. HDAC1/2 inhibition has been shown to induce HbF, however, clinical development of non-selective HDAC inhibitors has been limited due to the frequency of side effects from non-selective acetylation of nuclear histones resulting in broad dysregulation of gene expression. Selective HDAC1/2 inhibition represents a novel treatment approach that could represent a safer and more effective treatment option for patients with sickle cell disease and beta-thalassemia.

About Acetylon

Acetylon Pharmaceuticals, Inc., based in Boston, Massachusetts, is a leader in the development of novel small molecule drugs targeting epigenetic mechanisms for the enhancement of therapeutic outcomes in cancer and other critical human diseases. The Company’s epigenetic drug discovery platform has yielded a proprietary portfolio 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 and beta-thalassemia, and autoimmune and neurodegenerative diseases. Acetylon’s lead drug candidate, ricolinostat (ACY-1215), is a selective HDAC6 inhibitor currently in Phase 2 clinical development for the treatment of multiple myeloma. The Company recently announced a strategic collaboration agreement with Celgene Corporation, which includes an exclusive option for the future acquisition of Acetylon by Celgene. Acetylon’s scientific founders are affiliated with Harvard University, the Dana-Farber Cancer Institute, the Massachusetts General Hospital, and Harvard Medical School. www.acetylon.com


Walter C. Ogier
President and Chief Executive Officer
(617) 435-1300

MacDougall Biomedical Communications
(781) 235-3060

Kari Watson

Michelle Avery