From platform to clinic

Partnership between Heptares Therapeutics and Cubist Pharmaceuticals targets GCPRs for unmet needs in acute care

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WELWYN GARDEN CITY, U.K.—Heptares Therapeutics is a pioneerin the discovery and development of G protein-coupled receptors (GPCRs). CubistPharmaceuticals Inc. has expertise in the development and commercialization ofproducts that address significant unmet medical needs in the acute care andhospital environment. Together, the two companies will collaborate on theresearch and discovery of new medicines targeting GPCRs, membrane proteinsinvolved in a broad range of biological processes and diseases.
The agreement gives Cubist exclusive worldwide rights toresearch, develop and commercialize products generated from the collaboration.The collaborative research agreement will focus on up to two GPCR drug targetsselected by Cubist. For the first target, Heptares will receive $5.5 millionupfront and up to approximately $4 million in research funding, plus milestonesand royalties. Cubist also has the option to nominate a second GPCR target at alater point in the collaboration, which Heptares will work on according topredetermined financials.
According to Malcolm Weir, Heptares' CEO, GPCRs play acentral role in many biological processes and are linked to a wide range ofdisease areas. GPCRs involved in CNS and metabolic diseases are perhaps thebest characterized, and there are a number of very attractive commercialproduct opportunities, "so it made sense for Heptares to focus its initialefforts in this area to build its internal pipeline," says Weir.
The GPCR superfamily is the largest and single mostimportant family of drug targets in the human body. GPCRs are expressed inevery type of cell in the body, where their function is to transmit signalsfrom outside the cell across the membrane to signaling pathways within the cell,between cells and between organ systems. More than 375 GPCRs are encoded in thehuman genome, of which 225 have known ligands and 150 are orphan targets. GPCRsare the site of action of 25 to 30 percent of current drugs. Six of the top-10and 60 of the top-200 best-selling drugs in the United States in 2010 targetedGPCRs. Seven of 37 drugs approved in 2012 by the U.S. Food & DrugAdministration target GPCRs.
Heptares is constantly talking to companies about targets inmany indications. 
"Cubist was one such company, a partner-of-choice and clearbusiness leader in a space in which certain GPCRs could be medically veryimportant," Weir says. "Discussions moved forward very rapidly with a focus onGPCRs with significant medical promise in the acute care space."
Steve Gilman, Cubist's executive vice president of researchand development and chief scientific officer, says, "Heptares is a recognizedleader in the GPCR field, and we are pleased to collaborate in the pursuit ofpotential new GPCR drug candidates. This partnership underscores our commitmentto develop a robust pipeline of novel products that address high unmet medicalneeds in patients with acute diseases. We bring expertise in the discovery,development and commercialization of therapies used in settings in and aroundthe hospital where acutely ill patients are treated for days or weeks—versusthe months or years of treatment with a chronic care therapy."
He adds, "Cubist's acute-care channel strategy embracesmultiple therapeutic areas in the development and commercial areas of itsbusiness, while our discovery and preclinical research remains focused onantibiotics as well as non-opioid pain and inflammation."
An industry pioneer in GPCR structure-based drug design(SBDD), Heptares has built a special capability for discovering novel moleculesthat target historically "undrugable" or challenging GPCRs, according to Weir.Heptares' integrated discovery platform includes proprietary technologies forengineering stabilized GPCRs (known as StaRs) in their natural pharmacologicalconformations, identifying previously unknown chemistries for GPCR protein-druginteractions and deploying advanced fragment-based approaches to GPCR targetspace for the first time. 
The company has generated structural and functionalinformation to drive SBDD for a range of important clinically validated GPCRs,including Adenosine A2A, Muscarinic M1, Orexin 1/2, MGluR5 and GLP-1. Heptares'broad pipeline of novel product candidates against challenging GPCRs is designedto transform the treatment of serious diseases, including Alzheimer's disease,Parkinson's disease, schizophrenia, depression, chronic insomnia, addiction,migraine and diabetes, with the first two candidates expected to enter clinicaltrials in 2013.
In the partnership, Heptares will focus on creating leadsusing its SBDD platform (structure, chemistry and pharmacology) for Cubist totake into development. Cubist will be responsible for preclinical and clinicaldevelopment, as well as regulatory and commercial activities on a global basis.The goal is to discover and develop new medicines that target the first (andpotentially a second) GPCR selected. 
"The initial target is one that both companies believe iswell suited to addressing with Heptares' SBDD platform and also that a newmedicine hitting this target will make a very important difference in the livesof patients," Weir concludes.

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