Heptares Initiates Clinical Study With First Selective Muscarinic M1 Receptor Agonist for Improving Cognition in Patients With Alzheimer's Disease

LONDON and BOSTON, December 9, 2013 /PRNewswire/ --

First Human Trial of Novel Small Molecule Drug Derived From Heptares GPCR-Focused Structure-Based Drug Design Platform

Heptares Therapeutics, the leading GPCR structure-guided drug discovery and development company, announces that it has initiated a Phase 1 clinical study of HTL9936, the first fully selective muscarinic M₁ receptor agonist to enter clinical development. HTL9936 is an orally available, small molecule drug candidate discovered using the Heptares GPCR structure-based drug design (SBDD) platform. Heptares plans to develop HTL9936 as a novel treatment for improving cognitive function (memory and thinking abilities) in patients with Alzheimer's disease and other diseases associated with dementia and cognitive impairment.

"We are excited to initiate clinical development of HTL9936, a first-in-class agent with the potential to become an important new medicine for improving cognitive function in patients with Alzheimer's disease and other potential indications including schizophrenia and Lewy body dementia," said Malcolm Weir, CEO of Heptares. "In addition, the initiation of this clinical trial with HTL9936 marks an important milestone for Heptares, as we evolve into a clinical-stage business with a rich portfolio of novel GPCR-targeted agents advancing through Phase 1 and 2a clinical trials in the near-term."

M₁ receptor agonism is a well-validated mechanism of action for treating cognitive impairment and a valuable pharmacological profile that the pharmaceutical industry has endeavored to create for decades. The principal challenge has been to engineer selective compounds that activate the M₁ receptor subtype without also activating the M₂ or M₃ receptors, which are associated with undesirable side effects. All previous compounds have been discontinued due to inadequate selectivity. Using a new structure-guided approach, Heptares scientists determined the x-ray crystal structure of the M₁ receptor for the first time and leveraged unique insights into the receptor to identify new chemistries with fully selective M₁ agonist profiles.

The Phase 1 study will evaluate the safety, tolerability and pharmacokinetics of HTL9936. In addition, the clinical pharmacodynamics of the drug will be investigated in a series of studies over the next year. This study aims to recruit more than 100 healthy volunteers including elderly people at a single clinical centre in the UK. Initial results are expected in mid-2014

About Alzheimer's Disease and Other Disorders of Cognitive Impairment

Today there is significant unmet medical need and heavy economic burden across multiple diseases characterised by cognitive impairment and dementia. In Alzheimer's disease, currently available drugs provide limited and transient effects on cognition. Healthcare costs associated with the epidemic of AD, including nursing home care, continue to grow dramatically and new therapies with better and more durable efficacy are urgently needed. In addition, an estimated 80% of schizophrenics suffer from cognitive impairment and 1.3 million patients in the US suffer from Lewy body dementia. Currently there are no approved therapies for treating cognitive impairment in schizophrenia or for treating Lewy body dementia.

About Heptares Therapeutics

Heptares creates new medicines targeting clinically important, yet historically challenging, GPCRs (G protein-coupled receptors), a superfamily of drug receptors linked to a wide range of human diseases. Leveraging our proprietary structure-based drug design technology platform, we have built an exciting pipeline of novel drug candidates with the potential to transform the treatment of serious diseases, including Alzheimer's disease, ADHD, diabetes, schizophrenia, and migraine. Our pharmaceutical partners include Cubist, MorphoSys, Takeda, AstraZeneca and MedImmune, and we are backed by Clarus Ventures, MVM Life Science Partners, Novartis Venture Fund, the Stanley Family Foundation and Takeda Ventures. To learn more about Heptares, please visit http://www.heptares.com

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