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Acetylon Presents Data on the use of HDAC 6 Inhibitors Ricolinostat (ACY-1215) and ACY-241 in Combination with Pomalidomide for the Treatment of Multiple Myeloma

--Interim Results from Phase 1b/2 ACE-MM-102 and Phase 1a/1b ACE-MM-200 Studies to be Presented at the 57th Annual Meeting of the American Society of Hematology –


BOSTON – December 7, 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 clinical data demonstrating promising tolerability and overall response rates from a Phase 1b/2 study of a selective HDAC6 inhibitor, ricolinostat (ACY-1215), in combination with pomalidomide (Pomalyst®, Celgene) and dexamethasone for the treatment of relapsed-and-refractory multiple myeloma (ACE-MM-102 study). These data will be presented in a poster presentation this evening from 6:00pm to 8:00pm EST at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida. In addition, preliminary results from the Phase 1a/1b ACE-MM-200 study investigating the safety of ACY-241, a structurally related analog of ricolinostat, in combination with pomalidomide and dexamethasone in patients with relapsed or relapsed-and-refractory multiple myeloma were presented in a poster session on Sunday, December 6 at the ASH Annual Meeting.

“The data from both the 102 study with ricolinostat and the 200 study with ACY-241 demonstrate that selective HDAC6 inhibition combines favorably with pomalidomide and dexamethasone, and we believe this approach has the potential to become a powerful treatment option for patients with relapsed or refractory multiple myeloma while having minimal side effects that are commonly seen with pan-HDAC inhibition,” said Catherine Wheeler, SVP Clinical Development & Chief Medical Officer of Acetylon. “The promising activity profile of ricolinostat reported for the earlier portions of the 102 trial has been maintained in the Phase 2 portion. At a planned interim analysis of patients refractory to their most recent therapy and followed for at least six months, the overall response rate (ORR) was greater than 50%. Furthermore, the ORR rate was similar for those patients who were previously refractory to lenalidomide (Revlimid®, Celgene) or bortezomib (Velcade®, Millennium), or who have high risk disease cytogenetics (17p deletion and/or 4:14 translocation). Minimal toxicity was associated with once daily administration of ricolinostat or ACY-241, and no dose-limiting toxicities­­ have been observed in either study to-date.”

The Phase 1b/2 ACE-MM-102 clinical trial is a multicenter, open-label, dose escalation study designed to determine the maximum tolerated dose, safety, and efficacy of ricolinostat in combination with pomalidomide and dexamethasone in patients with relapsed-and-refractory multiple myeloma. Preliminary data from this study indicate that selective HDAC6 inhibition in combination with pomalidomide and dexamethasone is well tolerated, with no dose-limiting toxicities observed to-date. The most common adverse events were fatigue, diarrhea and hematologic toxicity, and most were low grade and not associated with ricolinostat.  Diarrhea initially observed with twice-daily dosing of ricolinostat was less frequent after a recommended oral dose of 160 mg once daily for 21 days of a 28 day cycle was identified. A planned interim analysis demonstrates promising clinical activity for 30 evaluable patients having at least 6 months of follow up, including a confirmed overall response rate (defined as a partial response or better) of 53%, a clinical benefit rate (defined as minimal response or better) of 63%, and a disease control rate (defined as stable disease or better) of 90%.

ACY-241 is a structurally related, orally available selective HDAC6 inhibitor administered in tablet form. A Phase 1a/1b clinical trial, ACE-MM-200, was initiated to determine the maximum tolerated dose, safety, and preliminary anti-tumor activity of ACY-241 alone and in combination with pomalidomide and dexamethasone in patients with relapsed or relapsed-and-refractory multiple myeloma. A sequential monotherapy/combination trial design allows patients access to combination therapy based on an established regimen starting in the second cycle of treatment, while establishing the safety, pharmacokinetics, and pharmacodynamics of ACY-241 as both a monotherapy and in combination. Preliminary results indicate that ACY-241 is well tolerated as a monotherapy and in combination with pomalidomide and dexamethasone, and no dose-limiting toxicities have been observed in either case. The most common adverse events for ACY-241 monotherapy were low grade nausea and hematologic toxicity, while the most common adverse events for the combination regimen were low grade fatigue and hematologic toxicity. As a monotherapy, ACY-241 has demonstrated a dose-proportional increase in exposure from 180 mg (Cohort 1) to 360 mg (Cohort 2), and exposure at the 180 mg dose level surpassed exposure for ricolinostat at the clinical dose of 160 mg. Preliminary evidence of anti-tumor activity was observed, although most evaluable patients had received only 1-3 cycles of treatment at the time of analysis.

“These promising interim results from our ricolinostat and ACY-241 trials in multiple myeloma are building a strong rationale for advancement of our HDAC6 selective inhibitors program to the pivotal phase of clinical development over the coming year,” said Walter C. Ogier, President and Chief Executive Officer of Acetylon. “We also look forward to publishing the completed results of these studies and to the near term initiation of several new company- and investigator-sponsored clinical trials exploring combinations of our HDAC6 inhibitor drug candidates with additional, established drug regimens for patients with hematologic and solid tumor cancers.”



Details of the presentations are as follows:

Date: Sunday, December 6, 2015

Time: 6:00 PM-8:00 PM

Location: Hall A, Level 2 (Orange County Convention Center)

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

Abstract Number: 3040

Title: ACY-241, a Novel, HDAC6 Selective Inhibitor: Synergy with Immunomodulatory (IMiD®) Drugs in Multiple Myeloma (MM) Cells and Early Clinical Results (ACE-MM-200 Study)


Date: Monday, December 7, 2015

Time: 6:00 PM-8:00 PM

Location: Hall A, Level 2 (Orange County Convention Center)

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

Abstract Number: 4228

Title: Ricolinostat (ACY-1215), the First Selective HDAC6 Inhibitor, Combines Safely with Pomalidomide and Dexamethasone and Shows Promising Early Results in Relapsed-and-Refractory Myeloma (ACE-MM-102 Study)


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. In 2013, the Company 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