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Acetylon's Oral Selective HDAC6 Inhibitor ACY-241 Enhances Anti-tumor Activity of Paclitaxel in Preclinical Solid Tumor Models

--Studies to be Presented Today at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics--


BOSTON – November 6, 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 synergistic activity for the orally available, selective HDAC6 inhibitor ACY-241 in combination with paclitaxel for the treatment of solid tumors. The study explored the potential activity of ACY-241 plus paclitaxel in several preclinical models, including solid tumor cell lines and in vivo disease models of pancreatic and ovarian cancers. The mechanism of action appears to involve the synergistic inhibition of tumor cell proliferation through enhanced inhibition of cell division and increased frequency of multipolar spindle formation, leading to aberrant cell division (mitosis) and cell death. These data will be presented in a poster presentation this afternoon from 12:15pm to 3:15pm EST at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA.

“The synergistic combination drug activity observed in preclinical models presented today, in addition to the favorable tolerability profile that we have seen in clinical studies to-date with our selective HDAC6 inhibitors ricolinostat and ACY-241, provide a solid rationale for their clinical investigation in combination treatment regimens in patients with advanced solid tumors,” said Simon S. Jones, Ph.D., Senior Vice President, Preclinical Development of Acetylon. “We are currently evaluating the safety and preliminary antitumor activity of ACY-241 alone and in combination with pomalidomide and low-dose dexamethasone in a Phase 1a/b dose-escalation study in patients with multiple myeloma. These new preclinical data in solid tumors highlight the potential for broad versatility with our selective HDAC6 inhibitors in drug combinations across multiple oncology indications.”

“Our partnership with Celgene has supported the advancement of a robust portfolio of selective HDAC inhibitors in oncology and hematology, including clinical-stage HDAC6 inhibitors ricolinostat and ACY-241 as well as our HDAC1/2 inhibitor program,” commented Walter C. Ogier, President and Chief Executive Officer of Acetylon. “With the planned initiation in the coming weeks of a new Phase 1b/2 clinical trial with ACY-241 in solid tumors in combination with paclitaxel, we continue to advance toward the goal of providing patients improved treatment options in a wide range of oncology applications.”

Highlights of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics poster presentation include:

  • Treatment of solid tumor cell lines with ACY-241 in combination with paclitaxel synergistically enhanced inhibition of cell proliferation and increased cell death.
  • Treatment with either ACY-241 or paclitaxel led to increased acetylation of α-tubulin, which was further increased by combination treatment, resulting in enhanced anti-cancer cell death across multiple cancer cell lines.
  • Treatment with the combination of ACY-241 (or ricolinostat) and paclitaxel was well-tolerated in vivo and demonstrated enhanced efficacy in preclinical disease models of pancreatic and ovarian cancer relative to either agent alone.

Details of the presentation are as follows:

Date: Friday, November 6, 2015
Time: 12:15pm-3:15pm EST
Location: Hall C-D
Session: Tubulin-Interacting Agents
Poster Board Number: A187
Abstract Number: A187
Title: Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models

Acetylon will also present data from preclinical studies for its HDAC1/2 inhibitor program in acute myeloid leukemia (AML) and neuroblastoma at the conference. Details of these presentations are as follows:

Date: Friday, November 6, 2015
Time: 12:15pm-3:15pm EST
Location: Hall C-D
Session: Pediatric-Early Drug Development
Poster Board Number: A136
Abstract Number: A136
Title: A novel, orally bioavailable and selective histone deacetylase (HDAC) 1 & 2 inhibitor enhances retinoic acid mediated differentiation of neuroblastoma

Date: Saturday, November 7, 2015
Time: 12:30pm-3:30pm EST
Location: Hall C-D
Session: Epigenetic Targets
Poster Board Number: B84
Abstract Number: B84
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)


About HDAC6 Inhibition

Ricolinostat (ACY-1215) and ACY-241 selectively inhibit the intracellular enzyme HDAC6, which leads to an accumulation of excess protein and in addition may disrupt critical proliferative signals in malignant cells. Disruption of these molecular processes in cancer cells triggers programmed cell death, called "apoptosis," with little or no effect on normal cells. Currently available HDAC drugs also affect the expression of numerous other genes in normal cells as well as cancer cells, which can result in side effects such as gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage and profound fatigue as well as potential for significant cardiac toxicity. Selective inhibition of HDAC6 is expected to reduce or eliminate these often-severe side effects associated with non-selective HDAC inhibition and may enable the development of optimized treatment regimens, including maximally effective combination drug therapies.

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