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Convergence collaborates with Dr Stephen Waxman of Yale University to evaluate pharmacology of Nav1.7 mutations in chronic pain disorders

Cambridge, EnglandTuesday, October 7, 2014, 10:00 Hrs  [IST]

Convergence Pharmaceuticals, a company focussed on the development of novel and high value analgesic medicines for the treatment of chronic pain via a pharmacologically and genetically defined approach, announces a collaboration with Dr Stephen Waxman, the Bridget Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University.

The collaboration aims to identify patient groups likely to respond to Nav1.7 blockers and ultimately initiate clinical studies. Today's broader and more closely linked strategic collaboration follows an earlier one between Convergence and Dr Waxman, findings from which will be presented at The International Association for the Study of Pain via a poster in Buenos Aires, Argentina, October 6-11, 2014.

A pharmacological evaluation of Nav1.7 gain of function mutations identified in patients suffering from chronic paroxysmal pain disorders such as erythromelalgia, small fibre neuropathy and paroxysmal extreme pain disorders, will be performed to discover selective drug therapy matched to a pain genotype. The ground breaking research conducted by Dr Waxman's laboratory has pioneered the field by showing that many Nav1.7 gain of function mutations lead to cellular hyper excitability which is an underlying cause of pain in patients with paroxysmal pain disorders. The collaboration will study existing mutations and identify novel pathogenic mutations in ion channels associated with chronic pain phenotypes.

By screening a range of novel proprietary molecules from the Convergence pipeline, and also existing sodium channel blockers currently used in clinical practice to treat neuropathic pain, this collaborative venture will build a rationale for future clinical studies, through pharmacological validation of genetically defined patient groups.

The first sodium channel blocker to be evaluated will be CNV1014802 which has shown outstanding efficacy and safety in a recent phase II trigeminal neuralgia study run by Convergence. This work will lay the ground for future proof-of-concept studies with CNV1014802 in paroxysmal pain disorders.

In the preceding collaboration between Dr Waxman and Convergence, findings showed that Convergence's compounds demonstrate preferential activity against patient-derived Nav1.7 gain of function mutations that have previously been linked by Dr. Waxman and his co-workers to human pain disorders.

Valerie Morisset, VP and Head of Biology for Convergence, commented: "Dr Steve Waxman is a world-renowned leader in the field of sodium channel mutations and we are incredibly excited to be working with him.  Paroxysmal pain disorders are notoriously difficult to treat in the clinic because current therapies show sub-optimal efficacy and have a poor tolerability profile.  We hope, therefore, that by using genetics to stratify these patients, we can discover novel and more effective methods of treatment with minimal side effects.  Data so far has been exciting and so now we will embark upon a broader and more closely linked strategic collaboration with Dr Waxman."

Dr Stephen Waxman, the Bridget Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University, said: "I have been impressed with the rigor and novelty of the work Convergence has done in this area, particularly by the recent phase II results of its novel sodium channel blocker CNV1014802 for trigeminal neuralgia.  I strongly believe that genotyping will provide the answers to finding optimal treatments for patients with paroxysmal pain disorders and I am looking forward to continuing and building on our existing strong and exciting collaboration."

Dr Waxman served as Chairman of Neurology at Yale from 1986 until 2009. He founded and is Director of the Neuroscience & Regeneration Research Center at Yale. Prior to moving to Yale, Dr. Waxman worked at Harvard, MIT, and Stanford.  Dr. Waxman's research has defined the ion channel architecture of nerve fibers, and demonstrated its importance for axonal conduction (Science, 1985). He demonstrated increased expression of sodium channels in demyelinated axons (Science, 1982), identified the channel isoforms responsible for this remarkable neuronal plasticity which supports remission in multiple sclerosis (PNAS, 2004), and delineated the roles of sodium channels in axonal degeneration (PNAS, 1993). He has made pivotal discoveries on pain after nerve injury. In translational leaps from laboratory to humans, he carried out molecule-to-man studies combining molecular genetics, molecular biology, and biophysics to demonstrate the contribution of ion channels to human pain (Trends in Molec.Med, 2005; PNAS, 2006), led an international coalition that identified sodium channel mutations as causes of peripheral neuropathy (PNAS, 2012) and has used atomic-level modelling to advance pharmacogenomics (Nature Comm., 2012).

Dr. Waxman has published more than 600 scientific papers and has edited nine books.  He has trained more than 200 academic neurologists and neuroscientists who lead research teams around the world.

 
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