The Leukaemia & Lymphoma Society (LLS) and Acetylon Pharmaceuticals announced a newly formed business alliance whereby Acetylon and LLS will jointly support a phase I/II clinical trial of Acetylon’s oral selective HDAC6 inhibitor drug candidate, ACY-1215, in multiple myeloma. LLS has committed to provide up to $4.85 million in milestone-tranched funding to Acetylon, and a joint clinical oversight committee will be formed. Acetylon is focused on the discovery and development of potential drug candidates based on next-generation Class II-selective HDAC inhibitors.

“We are very excited about the rapid bench-to-bedside translation of HDAC6-selective inhibitors in multiple myeloma, both alone and in combination with proteasome inhibitors,” said Ken Anderson, MD, the Kraft Family Professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School and co-founder of Acetylon. “Based on our preclinical studies, we expect ACY-1215 to demonstrate very potent anti-tumour activity and a very favourable side effect profile. We are highly honoured and most grateful to partner with The Leukaemia & Lymphoma Society in bringing this first-in-class selective HDAC6 inhibitor to patients.”

“Selective inhibition of HDAC proteins has the potential to dramatically improve the efficacy and tolerability of this promising class of targeted therapies. The successful development of ACY-1215, the first pharmaceutical HDAC6 selective inhibitor, represents a major advance. Acetylon’s partnership with The Leukaemia & Lymphoma Society reflects a shared interest in realizing an improved standard of care for patients with blood cancers, and in particular multiple myeloma,” said James (Jay) E Bradner, MD, assistant professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School, who is also a co-founder of Acetylon.

“Multiple myeloma is one of the most common and therapeutically challenging haematologic malignancies, and development of a therapeutic agent that reduces side effects while providing greater efficacy is a key goal for LLS,” said Richard Winneker, senior vice president, Research at LLS. “Our work with Acetylon represents LLS’ commitment to finding cures in multiple myeloma and all other blood cancers and explores the clinical potential for HDAC6-selective inhibition, which has demonstrated exciting results in preclinical studies at the Dana-Farber Cancer Institute and Massachusetts General Hospital.”

“The Leukaemia & Lymphoma Society has been a driving force behind many breakthroughs in the treatment of multiple myeloma, as well as other blood cancers,” said Walter C Ogier, president and chief executive officer and co-founder of Acetylon Pharmaceuticals, Inc. “We are excited to partner with them and grateful that they have agreed to provide major support for the clinical development of Acetylon’s lead drug candidate, ACY-1215.”

Under the agreement, Acetylon will conduct a three-part phase I/II clinical trial of ACY-1215 in adults with relapsed and relapsed/refractory multiple myeloma to achieve human proof-of-concept for selective HDAC6 inhibition. LLS will provide $4.85 million in non-dilutive, milestone-based, conditionally repayable funding, representing half of the projected costs of the clinical trial. The phase I a portion of the trial involving patients with relapsed and relapsed/ refractory multiple myeloma is expected to begin in the next several months.

Blood cancers such as multiple myeloma are characterized by successive genetic mutations resulting in rapid cell proliferation and excess production of intracellular proteins. ACY-1215 selectively inhibits the intracellular enzyme HDAC6, leading to inactivation of the “aggresome” pathway for degradation of damaged proteins. The resultant accumulation of excess waste protein in malignant cells triggers programmed cell death, called “apoptosis,” in stressed cancer cells, with little or no effect on normal cells. Currently available HDAC drugs non-selectively target multiple HDAC enzymes including those of Class I, resulting in dysregulated expression of numerous genes in normal cells as well as cancer cells.

Side effects commonly associated with non-selective HDAC drugs include gastrointestinal dysfunction, lowered blood platelet levels and risk of haemorrhage, and profound fatigue as well as potential for severe cardiac complications. 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.

The Leukaemia & Lymphoma Society (LLS) is the world's largest voluntary health agency dedicated to blood cancer. Its mission is to cure leukaemia, lymphoma, Hodgkin's disease and multiple myeloma, and improve the quality of life of patients and their families. LLS funds lifesaving blood cancer research around the world and provides free information and support services.

Acetylon Pharmaceuticals, Inc. is applying its unique capabilities to discover and develop next-generation, highly selective small molecule drugs to realize the therapeutic potential of HDAC inhibition to treat cancer, autoimmune and other diseases, while reducing the side effects common to this class of drugs.