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Acetylon Announces Preclinical Anti-cancer Activity of Selective HDAC1/2 Inhibitors in Neuroblastoma and Acute Myeloid Leukemia

--Data to be Presented in Poster Sessions at the American Association for Cancer Research Annual Meeting--

BOSTON – April 20, 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 on selective HDAC1/2 inhibition, demonstrating strong anti-cancer activity in preclinical models of acute myeloid leukemia (AML) and neuroblastoma. In both preclinical models, HDAC1/2 inhibition demonstrated significant anti-cancer activity, both as a single-agent and in synergistic combinations with best-in-class cancer drugs. The data will be presented in two poster sessions at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 18-22, 2015, in Philadelphia, PA. 

HDACs are known to cause changes to gene expression through their interactions with histones, the structures around which DNA is tightly wound. These changes are a part of epigenetic modifications, which normally allow the body to rapidly respond to one’s environment. However, many epigenetic changes contribute to disease states and are of particular interest as therapeutic targets in cancer.

In particular, HDAC1/2 inhibition has recently been shown in the literature to induce a favorable gene expression pattern similar to that driven by retinoic acid in neuroblastoma cells. Retinoids are chemicals related to vitamin A that can lead to cancer cell differentiation, thereby slowing neuroblastoma cell growth and promoting neuroblastoma cell death (apoptosis). As a result, retinoic acid has become a common component of aggressive neuroblastoma treatment. The findings reported today showed that preclinical compounds from Acetylon’s HDAC1/2 inhibitor program exhibited a similar ability to induce cell death at therapeutically relevant concentrations, and that anti-cancer activity was synergistic with retinoic acid compared with application of either agent alone.

In a separate poster session to be presented on Wednesday, Acetylon has demonstrated in multiple AML cancer cell lines that HDAC1/2 inhibition reduces cell viability, induces cell differentiation, arrests cell cycle progression and initiates apoptosis. Acetylon also explored the impact of selectively inhibiting other HDAC enzymes and found that inhibition of HDAC3 induced differentiation, but had no effect on cell cycle progression or apoptosis, while inhibition of HDAC6 had no effect on differentiation, cell cycle arrest or apoptosis in this type of cancer. Furthermore, HDAC1/2 inhibition significantly enhanced apoptosis when combined with azacitidine (Vidaza®, Celgene) that inhibits a complementary epigenetic mechanism of action to HDAC1/2. Azacitidine is a DNA methyltransferase inhibitor FDA-approved for the treatment of myelodysplastic syndrome, a hematologic condition that frequently leads to development of AML, and it is currently being studied as a component of several combination therapies for AML where there is a significant unmet medical need.

“Our selective HDAC inhibition drug development platform gives us the unique ability to determine which HDACs are critical therapeutic targets in specific cancers, as well as which may contribute to dose-limiting toxicity if inhibited non-selectively. As a result, we are able to design targeted inhibitors with the potential to provide strong anti-cancer activity in combination with other anti-cancer drugs while minimizing treatment-limiting side effects,” commented Simon S. Jones, Ph.D., Senior Vice President, Preclinical Development at Acetylon. “We have recently expanded our HDAC1/2 inhibitor program into oncology, where we believe it has great therapeutic opportunity. We now have a substantial body of preclinical evidence supporting the pharmacologic importance of either selective Class I or selective Class II HDAC inhibition in various cancers, as well as evidence supporting the pairing of particular selective HDAC inhibitors in synergistic combination regimens to achieve maximal activity.”

The Company is already developing this hypothesis in the clinic with its lead candidate, ricolinostat (ACY-1215), a selective HDAC6 inhibitor, that has been well-tolerated in over 150 patients treated to date and has shown early signs of clinical activity in multiple myeloma.

Details of the presentations from Acetylon’s HDAC1/2 inhibitor program are as follows:

Date: Monday, April 20, 2015

Time: 1:00-5:00pm EDT

Location: Section 12

Session: Transcriptional Deregulation

Poster Board Number: 7

Abstract Number: 2196

Title: Novel and selective histone deacetylase (HDAC) 1 & 2 inhibitors enhance differentiation of neuroblastoma cells in combination with retinoic acid


Date: Wednesday, April 22, 2015

Time: 8:00am-12:00pm EDT

Location: Section 29

Session: Histone Deacetylase Inhibitors, Methytransferase Inhibitors, and Other Targets

Poster Board Number: 2

Abstract Number: 5372

Title: Novel and selective inhibitors of histone deacetylases (HDAC) 1 and 2 significantly enhance the activity of the DNA methyltransferase inhibitor azacitidine in acute myeloid leukemia (AML)

A copy of the posters will be available on the Company’s website at the start of each poster session.

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 stable and 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 also can lead to cancer and other diseases.

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
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Kari Watson

Michelle Avery