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Acetylon Pharmaceuticals Announces Ricolinostat Continues to Demonstrate Clinically Meaningful and Durable Disease Response Rates in Phase 1b Combination Studies in Multiple Myeloma

FOR IMMEDIATE RELEASE

-- Data Presented at the 56th ASH Annual Meeting in San Francisco --

Boston – December 9, 2014 – Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, today announced positive data from two ongoing Phase 1b combination clinical trials of ricolinostat, a selective HDAC6 inhibitor, for the treatment of relapsed or refractory multiple myeloma. In both studies, ricolinostat continues to demonstrate a favorable safety profile and substantial disease response rates. For ricolinostat in combination with lenalidomide (Revlimid®) and dexamethasone, the most common treatment emergent adverse events (AEs) were fatigue, upper respiratory infection, anemia, neutropenia, diarrhea, nausea, thrombocytopenia, muscle spasms, dizziness and rash as well as asymptomatic laboratory abnormalities. In combination with lenalidomide and dexamethasone, ricolinostat demonstrated an overall response rate of 64%, with of 80% of patients achieving minimal response or better, per modified International Myeloma Working Group (IMWG) criteria. The response rate in 21 relapsed, lenalidomide refractory patients was 50%, whereas the response rate in 13 non-refractory patients was 85%. These responses were durable, with patients remaining on therapy up to 23+ cycles of therapy.

The most common AEs for ricolinostat in combination with bortezomib (Velcade®) and dexamethasone were diarrhea, increased creatinine, fatigue, anemia, nausea and thrombocytopenia that were predominantly grade 1-2. Diarrhea was the only AE that increased with higher ricolinostat exposure. Grade 3-4 thrombocytopenia was seen in 42% of patients. In combination with bortezomib and dexamethasone, ricolinostat demonstrated an overall response rate of 45% in disease evaluable patients and 30% in all patients, with 31% of all patients enrolled achieving minimal response or better (per modified IMWG criteria). The data were presented at the 56th American Society of Hematology (ASH) Annual Meeting in San Francisco, California.

“It is becoming increasingly clear that selective HDAC6 inhibition has great potential to afford durable and clinically meaningful responses without treatment-limiting safety concerns that are associated with  non-selective HDAC inhibitors,” said Noopur Raje, MD, Associate Professor, Department of Medicine, Harvard Medical School, Director, Multiple Myeloma Program, Medical Oncology, Massachusetts General Hospital and investigator in both clinical studies of ricolinostat. “In addition, we have observed that patients who have become resistant to standard-of-care multiple myeloma therapies are again responding to those therapies with the addition of ricolinostat.”

“The highly encouraging disease response rates and tolerability seen in these studies continue to support the advancement of ricolinostat in multiple combination regimens in multiple myeloma, and we are pleased to have our new Phase 2 study of ricolinostat in combination with pomalidomide (Pomalyst®) and dexamethasone now underway,” commented Catherine A. Wheeler, MD, Senior Vice President, Clinical Development and Chief Medical Officer of Acetylon. “In 2015, we will continue to build the clinical profile of ricolinostat. We believe that selective HDAC6 inhibition therapies could be an important component of the treatment landscape for patients with multiple myeloma who are in need of new options.”

Highlights of the data presentations are below.

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 (poster presentation, Abstract #4772):

  • Of 25 patients, 2 patients achieved stringent complete response (sCR), 6 achieved very good partial response (VGPR), 8 achieved partial response (PR), 4 achieved minimal response (MR) and 5 achieved stable disease (SD) per modified IMWG criteria (Rajkumar SV et al, Blood 2011; 117(18):4691-5).
  • 12 of 25 patients were refractory to lenalidomide, and within these patients, a 50% overall response rate was achieved.
  • 13 of 25 patients were not refractory to lenalidomide; within these patients, a 85% overall response rate was achieved.
  • Responses were durable and patients remained on therapy for 23+ cycles of therapy. 24 of 25 patients remained on study for at least two cycles of therapy.
  • The most common treatment emergent events (>15%) were fatigue, upper respiratory infection, anemia, neutropenia, diarrhea, nausea, thrombocytopenia, muscle spasms, dizziness and rash as well as asymptomatic laboratory abnormalities. Most were grade 1 and 2 with no clear relationship to ricolinostat dose.
  • Ten grade 3 and 4 events in 10 patients were attributed to ricolinostat: neutropenia, thrombocytopenia, anemia, fatigue, supraventricular tachycardia, migraine, muscle cramps and syncope. Syncope and muscles cramps, at 160 mg BID, were the only dose-limiting toxicity (DLT); the patient with syncope continued on study with a dose reduction and there were no other DLTs in the expanded cohort.

Phase 1B Results of Ricolinostat (ACY-1215) Combination Therapy with Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma (MM) (poster presentation, Abstract #4764):

  • Of 43 patients, 3 achieved VGPR, 10 achieved PR, 2 achieved MR, 10 achieved SD and 4 had progressive disease, per modified IMWG criteria (Rajkumar, Blood 2011).
  • 27 of 43 patients were refractory to bortezomib; within these patients, a 29 % overall response rate was achieved in response evaluable patients (4 of 14), and in 15% of all refractory patients entered on study.
  • Treatment emergent adverse events (AEs) were predominantly grade 1-2. The most common AEs were diarrhea, thrombocytopenia, increased creatinine, fatigue, nausea, throat irritation, electrolyte abnormalities, cough, anemia, decreased appetite, peripheral neuropathy, peripheral edema, upper respiratory tract infection, dizziness, fever and vomiting. Thrombocytopenia and anemia were the most common grade 3 and 4 adverse events.
  • Although there was no difference in the grade or frequency of overall AEs when ricolinostat dosing was increased to twice daily, diarrhea occurred earlier in the course of treatment and there was an increase in the frequency of serious adverse events.
  • A dose limiting toxicity (DLT) of asymptomatic increase in amylase was observed in the first treatment cohort. No other DLTs have been observed in the cohort dose escalations.

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 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

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

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