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Acetylon's Selective HDAC Inhibitors to be Featured in Multiple Presentations of Positive Clinical and Preclinical Data at the 56th ASH Annual Meeting and Exposition


Boston – December 1, 2014 – Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, today announced that ricolinostat, the Company’s lead selective HDAC6 inhibitor, and selective HDAC1/2 inhibitors will be featured in one oral presentation and five posters at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 6-9, 2014, in San Francisco, CA.

“Along with our collaborators, Acetylon is continuing to demonstrate the importance of selective HDAC inhibition in the potential  treatment of hematologic diseases with clinical data in multiple myeloma and preclinically with lymphomas, leukemia and sickle cell disease/beta-thalassemia,” said Walter C. Ogier, President and Chief Executive Officer and co-founder of Acetylon. An investigator sponsored Phase 1b/2 clinical study of ricolinostat as monotherapy in lymphoma was recently initiated at Columbia University Medical Center, New York, NY, with Jennifer Amengual, MD, and Owen O’Connor, MD, PhD, as principal investigators, based on preclinical data presented at the last two ASH Annual Meetings.

“In the data presented at ASH this year, our collaborators are setting the stage for expanding clinical evaluation of ricolinostat in lymphoma and leukemia by further describing its mechanism of action and potential synergistic combinations, enabling us to rationally select combination regimens to study in patients,” said Simon Jones, PhD, Senior Vice President, Preclinical Development.

“Together with the early clinical results of ricolinostat with lenalidomide (Revlimid®, Celgene) or bortezomib (Velcade®, Takeda Millennium) in multiple myeloma, also being reported at ASH this year, these data lead us to believe that ricolinostat could prove to be an important treatment option for patients with hematologic malignancies,” said Catherine Wheeler, MD, Senior Vice President, Clinical Development and Chief Medical Officer.

The details of the presentations are as follows:

Multiple Myeloma

Date: Monday, December 8, 2014

Time: 6:00-8:00pm PT

Location: West Building, Level 1 (Moscone Center)

Session: 653. Myeloma: Therapy, excluding Transplantation: Poster III

Abstract #: 4772

Title: Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma

Authors Affiliated with the Following Institutions: Harvard Medical School, University of North Carolina at Chapel Hill, Fred Hutchinson Cancer Research Center, Sarah Cannon Research Institute, Massachusetts General Hospital, Dana-Farber Cancer Institute, Acetylon Pharmaceuticals

Description: Ricolinostat, in combination with lenalidomide and dexamethasone, provided durable and significant responses, including responses in patients previously refractory to lenalidomide. The overall response rate (ORR) was 63%: 15 patients have greater than or equal to partial responses (PR), including 1 stringent complete response (sCR), 5 very good partial responses (VGPR), and 9 PR. Four patients had minimal response (MR) and 5 had stable disease (SD) as the best response. Responses are durable up to 23+ cycles of therapy.


Date: Monday, December 8, 2014

Time: 6:00-8:00pm PT

Location: West Building, Level 1 (Moscone Center)

Session: 653. Myeloma: Therapy, excluding Transplantation: Poster III

Abstract #: 4764

Title: Phase 1B Results of Ricolinostat (ACY-1215) Combination Therapy with Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma (MM)

Authors Affiliated with the Following Institutions: University of Pennsylvania Perelman School of Medicine, Massachusetts General Hospital, Medical College of Wisconsin, Acetylon Pharmaceuticals, The University of Texas MD Anderson Cancer Center, Dana-Farber Cancer Institute, Emory University School of Medicine, Mount Sinai Medical Center

Description: Ricolinostat, in combination with bortezomib and dexamethasone, was well tolerated at doses up to 240 mg QD and 160 mg BID and responses were observed even in bortezomib-refractory patients. Overall response rate (ORR) was 44%: 2 patients had a VGPR, 9 had a PR, and 2 had an MR, with 9 patients achieving SD and 3 with progressive disease (PD). Responding patients remained on study for a median of 4 cycles (range 2 to 18).



Date: Saturday, December 6, 2014

Time: 5:30-7:30pm PT

Location: West Building, Level 1 (Moscone Center)

Session: 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Poster I

Abstract #: 1777

Title: Development and Characterization of Two Lymphoma Cell Lines Resistant to the Selective HDAC6 Inhibitor Ricolinostat (ACY-1215) As a Tool to Better Understand the Biology of HDACs on Lymphoma

Authors Affiliated with the Following Institutions: Columbia University Medical Center, Stanford University

Description: Lymphoma cell lines were cultured in increasing concentrations of ricolinostat over time to induce resistance. Two such cell lines were created. The development of these ricolinostat resistant cell lines has proven to be a powerful tool to better understand the mechanistic role of HDAC6 in lymphoma and may potentially lead to the identification of biomarkers of response or resistance to help guide clinical development. These lines are also useful in guiding rational drug partners that target complimentary pathways.


Date: Sunday, December 7, 2014

Time: 6:00-8:00pm PT

Location: West Building, Level 1 (Moscone Center)

Session: 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Poster II

Abstract #: 3124

Title: Preclinical Screening of the HDAC6 Inhibitor Rocilinostat (ACY-1215) Combined with Bendamustine in Lymphoma Cell Lines

Authors Affiliated with the Following Institutions: University of Modena and Reggio Emilia

Description: Ricolinostat and alkylating agent bendamustine demonstrated a synergistic killing of multiple lymphoma cell lines, including follicular, mantle cell and t-cell lines using low concentrations of both drugs below IC50 values. Importantly, the combination did not trigger relevant decreases in the viability of normal peripheral blood mononuclear cells. In addition, ricolinostat alone demonstrated increases in apoptosis of the lymphoma cell lines. These preclinical results indicate that rocilinostat can have marked activity in lymphoma cell lines in combination with bendamustine. Further investigation is required to continue to study the activity of rocilinostat in lymphoma both as a single agent and in combinations.


Date: Sunday, December 7, 2014

Time: 6:00-8:00pm PT

Location: West Building, Level 1 (Moscone Center)

Session: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster II

Abstract #: 3311

Title: Histone Deacetylase 6 (HDAC6) As a Regulator of Immune Check-Point Molecules in Chronic Lymphocytic Leukemia (CLL)

Authors Affiliated with the Following Institutions: H. Lee Moffitt Cancer Center & Research Institute, Tianjin Medical University, Acetylon Pharmaceuticals

Description: HDAC6 plays a role in the regulation of immunogenicity in chronic lymphocytic leukemia (CLL). HDAC6 is overexpressed in human CLL cells, and ricolinostat can modulate the expression of co-inhibitory molecules in CLL. In addition, ricolinostat significantly lowered levels of PD-L1 expression and restores the T-cell CD4:CD8 ratio in vivo. Selective inhibition of HDAC6 in both B- and T-cell compartments of CLL results in the reduction of co-inhibitory molecules, which in combination with a subsequent therapeutic regimen could provide a successful immunotherapeutic strategy for this disease.


Sickle Cell Disease/Beta-thalassemia

Date: Monday, December 8, 2014

Time: 11:30am PT (oral)

Location: Yerba Buena Ballroom Salon 9 (San Francisco Marriott Marquis)

Session: 112. Thalassemia and Globin Gene Regulation: Targeting the epigenome to treat Thalassemia

Abstract #: 335

Title: Pharmacological Inhibition of Histone Deacetylases 1 and 2 (HDAC1/2) Induces Fetal Hemoglobin (HbF) through Activation of Gata2

Authors Affiliated with the Following Institutions: Acetylon Pharmaceuticals

Description: ACY-957, a selective HDAC1/2 inhibitors downregulate repressors of the fetal beta-like globin gene (HbG), Bcl11a and Sox6, and the upregulate Gata2, which is thought to activate HbG. Through this work, a role for Gata2 in HbG induction was elucidated and ACY-957’s mechanism of action is reported to be through the dual upregulation of Gata2 by acetylation-induced activation of a positive autoregulatory loop and downregulation of Bcl11a and Sox6.


About Ricolinostat

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.

About HDAC1/2 Inhibition

The induction of fetal hemoglobin (HbF) is an established therapeutic strategy for sickle cell disease and could potentially also be effective for beta-thalassemia. HDAC inhibition has been shown to induce HbF, however, clinical development of non-selective HDAC inhibitors has been limited due to the number of off-target side effects. Selective HDAC1/2 inhibition represents a novel treatment approach that could represent a safer and more effective treatment option for patients with sickle cell disease and beta-thalassemia.

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

Velcade® is a registered trademark of Millennium Pharmaceuticals, Inc. Revlimid® is a registered trademark of Celgene Corporation.


Walter C. Ogier
President and Chief Executive Officer
(617) 435-2664

MacDougall Biomedical Communications

Kari Watson
(781) 235-3060

Michelle Avery
(781) 235-3060