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Acetylon Pharmaceuticals Presents Data On The Potent Activity Of Ricolinostat (ACY-1215) In Preclinical Models Of Lymphoma At The American Society of Hematology Annual Meeting
12/10/2013 12:04:01 PM
Boston – December 9, 2013 – Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, announced that positive preclinical data of selective HDAC6 inhibitor, ricolinostat (ACY-1215), in models of lymphoma were presented today in an oral presentation by Dr. Jennifer Amengual, Assistant Professor of Medicine & Experimental Therapeutics, Columbia University Medical Center, and in a poster session on December 8 at the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans, LA. The data highlight the potent activity of ricolinostat in preclinical models of lymphoma, both alone and in combination with proteasome inhibitor, bortezomib (Velcade®), PI3K inhibitors, GS-101 and GDC-0941, and Bruton’s tyrosine kinase inhibitor, ibrutinib (Imbruvica™), recently granted accelerated approval for the treatment of patients with mantle cell lymphoma following prior therapy.
“In the data presented at ASH, we demonstrated that ricolinostat and bortezomib (Velcade®) synergistically inhibit dual pathways of protein degradation that ultimately enhance lymphoma cell apoptosis in vitro and in vivo,” said Owen O’Connor, M.D., Ph.D., Professor of Medicine and Experimental Therapeutics, Director of the Center for Lymphoid Malignancies, and Co-Program Director of the Lymphoid Development and Malignancy Program in the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and Principal Investigator in one of the studies presented. “This represents a novel potential approach to the treatment of lymphoma for patients who do not adequately respond to current standard of care.”
“The data presented at ASH further our preclinical evidence of ricolinostat’s activity in non-Hodgkin’s lymphomas both as a single agent and in combination with next-generation targeted therapies in B-cell lymphomas,” commented Simon S. Jones, Ph.D., Vice President, Biology and Preclinical Development of Acetylon. “We plan to initiate a single agent study with ricolinostat in patients with non-Hodgkin’s lymphoma and Hodgkin’s lymphoma in 2014, while we continue to explore optimal combination regimens for ricolinostat in these diseases.”
Highlights of the Presentations at ASH
Dual Targeting With the Selective Histone Deacetylase (HDAC) 6 Inhibitor, ACY-1215, and Bortezomib (BOR) Leads to Marked Disruption of Protein Degradation Pathways and Apoptosis in Preclinical Models of Lymphoma (oral presentation, Abstract # 648)
• In six lymphoma cell lines, ricolinostat in combination with bortezomib (Velcade®) led to a synergistic increase in apoptosis
• In an in vivo model of diffuse large B-cell lymphoma (DLBCL), a single treatment of the combination of ricolinostat and bortezomib (Velcade®) demonstrated statistically significant delay in tumor growth and extended overall survival
Inhibition of HDAC6 in Combination with Targeted Agents Results in Broad Synergistic Decreases in Viability in Non-Hodgkin’s Lymphoma (NHL) Cells (poster presentation, Abstract # 3071)
• Ricolinostat in combination with Bruton’s tyrosine kinase inhibitor, ibrutinib (Imbruvica™), or PI3K inhibitors, GS-1101 and GDC-0941, resulted in synergistic decreases in non-Hodgkin’s lymphoma (NHL) cell viability
• Ricolinostat also demonstrated significant decrease in NHL cell viability as a single agent
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) selectively inhibits 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 affect the expression of numerous 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.
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 1b 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 the Harvard University, the Dana-Farber Cancer Institute, the Massachusetts General Hospital, and Harvard Medical School. www.acetylon.com
Imbruvica™ is a trademark owned by Pharmacyclics, Inc. Velcade® is a registered trademark of Millennium Pharmaceuticals, Inc.
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