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From platform to clinic
February 2013
by Ilene Schneider  |  Email the author


WELWYN GARDEN CITY, U.K.— Heptares Therapeutics is a pioneer in the discovery and development of G protein-coupled receptors (GPCRs). Cubist Pharmaceuticals Inc. has expertise in the development and commercialization of products that address significant unmet medical needs in the acute care and hospital environment. Together, the two companies will collaborate on the research and discovery of new medicines targeting GPCRs, membrane proteins involved in a broad range of biological processes and diseases.  
The agreement gives Cubist exclusive worldwide rights to research, develop and commercialize products generated from the collaboration. The collaborative research agreement will focus on up to two GPCR drug targets selected by Cubist. For the first target, Heptares will receive $5.5 million upfront and up to approximately $4 million in research funding, plus milestones and royalties. Cubist also has the option to nominate a second GPCR target at a later point in the collaboration, which Heptares will work on according to predetermined financials.  
According to Malcolm Weir, Heptares' CEO, GPCRs play a central role in many biological processes and are linked to a wide range of disease areas. GPCRs involved in CNS and metabolic diseases are perhaps the best characterized, and there are a number of very attractive commercial product opportunities, "so it made sense for Heptares to focus its initial efforts in this area to build its internal pipeline," says Weir.  
The GPCR superfamily is the largest and single most important family of drug targets in the human body. GPCRs are expressed in every type of cell in the body, where their function is to transmit signals from 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 the human genome, of which 225 have known ligands and 150 are orphan targets. GPCRs are the site of action of 25 to 30 percent of current drugs. Six of the top-10 and 60 of the top-200 best-selling drugs in the United States in 2010 targeted GPCRs. Seven of 37 drugs approved in 2012 by the U.S. Food & Drug Administration target GPCRs.   Heptares is constantly talking to companies about targets in many indications. 
"Cubist was one such company, a partner-of-choice and clear business leader in a space in which certain GPCRs could be medically very important," Weir says. "Discussions moved forward very rapidly with a focus on GPCRs with significant medical promise in the acute care space."  
Steve Gilman, Cubist's executive vice president of research and development and chief scientific officer, says, "Heptares is a recognized leader in the GPCR field, and we are pleased to collaborate in the pursuit of potential new GPCR drug candidates. This partnership underscores our commitment to develop a robust pipeline of novel products that address high unmet medical needs in patients with acute diseases. We bring expertise in the discovery, development and commercialization of therapies used in settings in and around the hospital where acutely ill patients are treated for days or weeks—versus the months or years of treatment with a chronic care therapy."  
He adds, "Cubist's acute-care channel strategy embraces multiple therapeutic areas in the development and commercial areas of its business, while our discovery and preclinical research remains focused on antibiotics 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 molecules that target historically "undrugable" or challenging GPCRs, according to Weir. Heptares' integrated discovery platform includes proprietary technologies for engineering stabilized GPCRs (known as StaRs) in their natural pharmacological conformations, identifying previously unknown chemistries for GPCR protein-drug interactions and deploying advanced fragment-based approaches to GPCR target space for the first time.   
The company has generated structural and functional information 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 designed to 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 clinical trials in 2013.  
In the partnership, Heptares will focus on creating leads using its SBDD platform (structure, chemistry and pharmacology) for Cubist to take into development. Cubist will be responsible for preclinical and clinical development, as well as regulatory and commercial activities on a global basis. The goal is to discover and develop new medicines that target the first (and potentially a second) GPCR selected.    "The initial target is one that both companies believe is well suited to addressing with Heptares' SBDD platform and also that a new medicine hitting this target will make a very important difference in the lives of patients," Weir concludes.  
Code: E021318



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