Heptares Therapeutics Ltd., the U.K. biotech focused on G-protein coupled receptor (GPCR) research, has announced the latest in what is becoming a series of licensing agreements with major pharmaceutical companies, this time with Shire Pharmaceuticals, a subsidiary of Shire Plc.

Shire is to take an exclusive option on a novel adenosine A2A antagonist currently in preclinical development at Heptares for the treatment of the symptoms of Parkinson's disease, and which also has potential in the treatment of other central nervous system diseases. Upon completion of certain preclinical studies, Shire will receive an exclusive option to license worldwide development and commercial rights to Heptares' adenosine A2A program.

Shire already has significant business in the CNS area, with the ADHD therapy, Vyvanse (lisdexamfetamine), being its top-selling product, and its Hunter Syndrome therapy, Elaprase (idursulfase), the largest selling product in its human genetic therapies unit [A#110211]).

The adenosine antagonist project is exciting because it uses the company's fragment structure-based approach to produce a small molecule with a novel chemical structure, Heptares' CEO Malcolm Weir said in an interview. Laboratory studies indicate the compound is expected to have good pharmacokinetics and oral bioavailability in man, and should be associated with fewer side effects than other compounds that interact with the adenosine A2A receptor, Weir commented.

The financial terms of the option agreement with Shire were not disclosed, but include an upfront payment and downstream terms that would be quite significant for Heptares, Weir said. If the option is exercised, Heptares would receive an option to exercise payment, milestone payments and royalties on sales.

According to Weir, Heptares is now well set financially, with excellent venture capital backers and some non-dilutive financing coming from the deals it has concluded. The Shire deal is the second to be announced by the company in the past few weeks - in April, it entered into a $100 million collaboration with Japan's Takeda Pharmaceutical Company, to characterize a GPCR believed to play a role in CNS disorders Also see "Takeda To Hunt For New CNS Therapeutics With Heptares' Technology" - Pink Sheet, 11 April, 2011.).

And Shire is the second pharmaceutical company to sign an option agreement with Heptares. In 2009, the Novartis Option Fund entered into an option agreement worth up to $200 million to Heptares in undisclosed upfront, milestone and royalty payments Also see "Deals Of The Week: Onyx Proteolix, Novartis/Heptares, Wyeth/Progenics ..." - Pink Sheet, 19 October, 2009.).

Weir pointed out that there are only a few adenosine antagonists in development, with Merck & Co's preladenant- in Phase III for Parkinson's disease- possibly the most advanced. Another adenosine antagonist - Kyowa Hakko Kirin's istradefylline - received a non-approvable letter from the U.S. FDA in 2008 Also see "Kyowa Hakko’s Parkinson’s Drug Is Not Approvable – U.S. FDA" - Scrip, 28 February, 2008.).

The adenosine A2A receptor is one of more than 200 GPCRs found in the human body; such receptors are the site of action of around 25%-30% of all marketed drugs. However, GPCRs are unstable when extracted from cell membranes, making it difficult to conduct structure-activity studies to enable agonists or antagonists to be designed. Heptares has developed a method of stabilizing GPCRs so that fragment-binding studies can be conducted and new compounds designed that interact with the receptors.

- John Davis (j.davis@elsevier.com )

Shire To Strengthen CNS Focus With Option On Heptares' Novel Parkinson's Therapy

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