Elixir Pharmaceuticals, Inc. announced that its partner, Siena Biotech S.p.A., has commenced Phase 1 clinical testing of Elixir's potent, first-in-class SIRT1 (sirtuin-1) inhibitor for the treatment of Huntington's Disease. EX-527, also known as SEN0014196, is currently in a Phase 1a combined single and multiple ascending dose study in the European Union to assess safety, tolerability and pharmacokinetics in healthy volunteers.

In addition to initiation of the Phase 1 study, Elixir announced EX-527/SEN0014196 was granted orphan designation by the European Medicines Agency (EMEA) on October 28, 2009, and by the Office of Orphan Products Development of the U.S. FDA on December 7, 2009. Orphan designation allows for various terms of market exclusivity, as well as possible regulatory fee exemptions or reductions.

"This is a major accomplishment for Elixir and its partner, Siena Biotech," said Peter DiStefano, CSO of Elixir. "This represents the first sirtuin inhibitor to enter clinical trials and validates the work of our drug discovery and design program focused on the sirtuin family of enzymes, specifically, our selective SIRT1 inhibitor program. Based on in vivo preclinical and mechanistic studies, EX-527/SEN0014196 offers the potential for novel and effective therapy for Huntington's Disease, a debilitating and ultimately fatal neurodegenerative disease."

In preclinical studies, EX-527/SEN0014196 reduced neuronal death caused by mutant huntingtin protein in cell-based assays. In addition, the molecule was efficacious in a widely employed transgenic model of Huntington's Disease while demonstrating highly favorable safety profiles and pharmaceutical properties.

Elixir entered into a research collaboration agreement with Siena in 2007, and Elixir licensed EX-527 to Siena in 2009. Under the terms of the license Siena has exclusive worldwide rights to EX-527/SEN0014196 in certain diseases.

About EX-527

EX-527 was discovered by Elixir scientists as part of the Company's pathways-of-aging platform. Human SIRT1, a member of the family of human histone deacetylase enzymes, was screened using a library of 300,000 drug-like compounds. EX-527 stands as one of the most potent SIRT1 inhibitors reported to date and also shows high selectivity for SIRT1 compared to other sirtuin deacetylases and over 50 other receptors, enzymes, transporters and ion channels.

Siena and Elixir have shown that EX-527/SEN0014196 is orally bioavailable, penetrates the blood-brain barrier, and shows excellent drug-like properties. It is highly safe in toxicology studies and is efficacious in an in vivo preclinical model of Huntington's Disease.

About Huntington's Disease

Huntington's Disease is a devastating inherited neurological disorder characterized as the prototype of poly-glutamine repeat diseases. Patients expressing >37 repeats of the amino acid glutamine in the huntingtin protein begin to manifest the disease between the fourth and fifth decade of life. The disease is characterized by progressive degeneration of neurons in the striatum of the brain that control movement. Patients with the disease exhibit chorea or uncontrolled movements of the limbs, anti-social behaviors, psychosis and dementia. Currently, there is little in the way of effective treatment for this fatal disease.

Source
Elixir Pharmaceuticals