Logo
Contact    |    Site Map    |    Careers

News & Publications

Acetylon Presents Data on Synergistic Activity of Selective HDAC6 Inhibition in Preclinical Models of Multiple Myeloma and Mantle Cell Lymphoma at the American Association for Cancer Research Annual Meeting

--Company Initiates Phase 1a/b Study of ACY-241 in Combination with Pomalyst® in Relapsed or Relapsed-and-Refractory Multiple Myeloma--

BOSTON – April 22, 2015 – Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, today announced that it presented comparative preclinical data for the selective HDAC6 inhibitors, ricolinostat and ACY-241, in combination with the immunomodulatory (IMiD®) class of drugs for the treatment of multiple myeloma (MM) and mantle cell lymphoma (MCL). The data demonstrated profound synergies of selective HDAC6 inhibitors, which retain a low level of Class 1 HDAC inhibition, and IMiD drugs, Pomalyst® (pomalidomide) and Revlimid® (lenalidomide), in killing MM and MCL cells. Similar results have been seen clinically in the Phase 1/2 study of ricolinostat in combination with Revlimid in MM. The mechanism of action is suggested to involve the synergistic reduction of the oncogenic transcription factors, MYC and IRF4, both known to be major drivers of B-cell malignancies, as well as other cancers. These data were presented in a poster presentation at the American Association for Cancer Research Annual Meeting in Philadelphia, PA.

Acetylon also announced today that it is initiating a Phase 1a/b multicenter, single-arm, open-label, dose escalation study of ACY-241. The trial is designed to determine the maximum tolerated dose and evaluate the safety and preliminary antitumor activity of ACY-241 as monotherapy and in combination with pomalidomide and low-dose dexamethasone in eligible patients with relapsed or relapsed-and-refractory MM.

“The preclinical findings presented at AACR today lead us to believe that the HDAC6 inhibitor, ACY-241, will perform in the clinic similarly to ricolinostat and provide our partner, Celgene, with a potential second HDAC6 drug candidate,” said Catherine A. Wheeler, MD, Senior Vice President, Clinical Development and Chief Medical Officer of Acetylon. “The data suggest that continued and expanded clinical evaluation of these compounds in B-cell malignancies is warranted, and we are exploring additional clinical opportunities for ricolinostat and ACY-241 in other cancers as well. We expect to review results of the Phase 1a/b study of ACY-241 in combination with pomalidomide later this year.”

“Our partnership with Celgene has provided the resources necessary to develop a robust portfolio of selective HDAC inhibitors in oncology, including the HDAC6 inhibitor candidates ricolinostat and ACY-241, as well as HDAC1/2 inhibitors,” commented Walter C. Ogier, President and Chief Executive Officer of Acetylon. “We believe that the development of ricolinostat and ACY-241 in B-cell malignancies and other cancers positions us well to make the strongest positive impact for patients within the evolving clinical landscape.”

 

Highlights of the AACR poster presentation include:

  • Treatment of MM and MCL cell lines with ricolinostat or ACY-241 in combination with either lenalidomide or pomalidomide synergistically increases cell death.
  • Both HDAC inhibitors and IMiDs® as single agents reduce expression of the oncogenic transcription factors, MYC and IRF4, and this effect was further enhanced by combination treatment in MM and MCL cells.
  • Prolonged treatment with the combination of ACY-241 and pomalidomide was well-tolerated in vivo, and significantly delayed tumor growth in a MM xenograft model.

Details of the presentation are as follows:

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: 10

Abstract Number: 5380

Title: Selective HDAC inhibition by ricolinostat (ACY-1215) or ACY-241 synergizes with IMiD® immunomodulatory drugs in Multiple Myeloma (MM) and Mantle Cell Lymphoma (MCL) cells

 

A copy of the poster is available on the Company’s website.

 

About HDAC6 Inhibition

Blood cancers such as multiple myeloma and lymphoma are characterized by successive genetic mutations resulting in uncontrolled cell proliferation and dysfunctional production of intracellular proteins. 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

 

Revlimid® and Pomalyst® are registered trademarks of Celgene Corporation.

 


CONTACT:
Acetylon

Walter C. Ogier
President and Chief Executive Officer
(617) 435-1300
wogier@acetylon.com

 

MEDIA:
MacDougall Biomedical Communications
(781) 235-3060

Kari Watson
kwatson@macbiocom.com

Michelle Avery
mavery@macbiocom.com

Back