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Acetylon Presents Data on the Pharmacokinetics and HbE/HbG Hemoglobin Induction Following Once Daily Dosing of an Oral HDAC1,2 Inhibitor in Animal Models

--Data to be Presented at the 57th Annual Meeting of the American Society of Hematology –


BOSTON – December 7, 2015 – Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, today announced that it will present preclinical data demonstrating the relationship between in vivo drug exposure and epsilon (HbE) and gamma (HbG) globin mRNA induction following oral dosing of ACY-957, a selective inhibitor of HDAC1/2. These experiments explored the effects of several different dose schedules to induce HbE and minimize suppression of white blood cells in rats. The data demonstrate that optimization of dose and schedule of ACY-957 could be performed in rats by monitoring HbE as a surrogate for HbG in primates. The data will be presented in a poster presentation this evening from 6:00pm to 8:00pm EST at the American Society of Hematology Annual Meeting in Orlando, Florida.

Elevated levels of HbG mRNA in CD34+ red blood cell precursors, leading to the formation of fetal hemoglobin, is known to ameliorate disease severity in sickle cell and β-thalassemia patients. Acetylon has previously demonstrated that potent and selective inhibitors of HDAC1/2 can induce HbE and HbG in cultured human primary CD34+ cells.

The data presented by Acetylon indicate that the duration of in vivo exposure to ACY-957 required to induce HbE and HbG could be met with a single daily oral dose of the compound. Since ACY-957 induced HbE in cultured human primary erythroid progenitors, HbE induction in rat was measured as a surrogate marker for HbG in primates, as rats do not express HbG. These results demonstrated that an HDAC1/2 inhibitor induces HbE in rat and HbG in monkey to a similar extent. ACY-957 appeared well tolerated in both rat and primate, although a reversible suppression of white blood cells associated with Class I HDAC inhibition was observed. Together, these findings suggest that an optimization of dose and schedule could be performed in rats by monitoring HbE as a surrogate for HbG in primates. The optimized regimen could then be validated in cynomolgus monkey. Accordingly, Acetlyon initiated experiments that explore the effects of several different dose schedules on HbE induction and white blood cell suppression in rats during a 4 week dosing and 2 week recovery period, resulting in data which will also be presented.

“This data provides us with a strong strategy and plan for moving forward with an HDAC1/2 inhibitor for clinical development for the treatment of beta-thalassemia,” said Simon S. Jones, Ph.D., Senior Vice President, Preclinical Development at Acetylon. “The results of these studies evaluating dosing schedules in rats and primates will inform the design of potential clinical trials. We have also expanded our HDAC 1/2 inhibitor program into oncology, and we believe that compounds of this class are promising as candidates for utilization in combination with other anti-cancer drugs, for example in AML and neuroblastoma.”


Details of the presentation are as follows:

Date: Monday, December 7, 2015

Time: 6:00 PM-8:00 PM EDT

Location: Hall A, Level 2 (Orange County Convention Center)

Session: 112. Thalassemia and Globin Gene Regulation: Poster III

Abstract Number: 3378

Title: The Histone Deacetylase 1 and 2 (HDAC1/2) Inhibitor ACY-957 Increases Epsilon (HbE) and Gamma (HbG) Globin mRNA in the Peripheral Blood of Non-Anemic Rats and Monkeys


About Epigenetics

Epigenetics is the covalent modification of DNA, protein, or RNA, resulting in changes to the function and/or regulation of these molecules without altering their primary sequences. Epigenetic modifications are often stable and may even be passed on to future generations, but in other instances they are dynamic and change in response to environmental stimuli. Epigenetic changes are a normal part of many biological processes. They allow stem cells to differentiate into more-specialized cell types, but they can also lead to cancer and other diseases. Several different classes of drugs are known effectors of epigenetic changes in the human body. One such class of drugs specifically inhibits histone deacetylase enzymes, or HDACs; those drugs are commonly known as “HDAC inhibitors.”

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. In 2013, the Company 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
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MacDougall Biomedical Communications
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Kari Watson