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Concert Pharmaceuticals Presents Preclinical Data on Novel Deuterium-Containing Drug Compound at Antiepileptic Drug Trials XI Conference

Sigma-1 Agonist, C-10068, Shown to Have Anti-Convulsant and Neuroprotective Effects

LEXINGTON, Mass.--(BUSINESS WIRE)--May 2, 2011 - Concert Pharmaceuticals, Inc. today announced that C-10068, a novel deuterium-containing sigma-1 agonist, was found to have activity in preclinical models of epilepsy, neuroprotection and neuropathic pain. C-10068 is based on a molecule that was reported to have preclinical anti-convulsant efficacy, but was limited by poor metabolic stability resulting in low oral bioavailability. Applying its DCE Platform™ (deuterated chemical entity platform), Concert improved the compound's metabolic stability by selective incorporation of deuterium. As a result, in a preclinical model, bioavailability was increased approximately three-fold following oral dosing of C-10068 compared to the non-deuterated molecule. These results were presented by Philip Graham, Ph.D., Vice President, Program Development of Concert Pharmaceuticals, during the Pipeline Day at the Antiepileptic Drug Trials XI Conference in Miami, Florida.

“C-10068 has demonstrated anti-epileptic and neuroprotective activity in a number of in vivo and ex vivo experiments to warrant further investigation as a potential first-in-class agent for management of seizures,” said Roger Tung, Ph.D., President and Chief Executive Officer of Concert Pharmaceuticals. “There are few drugs with new mechanisms of action currently in development for epilepsy. Concert is moving forward with further evaluation of C-10068, in collaboration with our government research partners, which could potentially offer a novel mechanism to address this unmet need.”

C-10068 was studied in preclinical and anti-convulsant models that are considered to be indicative of clinical efficacy. The results of these studies showed the anti-convulsant and neuroprotective effects of C-10068 at a dose that did not induce adverse effects. Importantly, C-10068 demonstrated anti-convulsant activity in models of both grand mal and partial seizures. In vitro neuroprotection tests showed that C-10068 inhibited hippocampal neurotoxicity induced by the model. Like many currently approved anti-epileptic drugs, C-10068 is also active in models of neuropathic pain.

The preclinical studies with C-10068 were conducted in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS) Anti-Convulsant Screening Program. This government-sponsored effort is focused on preclinical testing of drug compounds, through a series of preclinical models, to define their potential as antiepileptic and neuroprotective agents. Further preclinical evaluation of C-10068 is also ongoing at Concert, in addition to an ongoing collaboration with Walter Reed Army Institute of Research to investigate its potential as a treatment for non-convulsive seizures following traumatic brain injury.

About C-10068

C-10068 was created using Concert's DCE PlatformTM (deuterated chemical entity platform). It is a novel deuterium-containing sigma-1 agonist devoid of opioid activity based on the morphinan scaffold, which encompasses numerous biologically active agents. C-10068 was identified as the lead compound from a series of Concert compounds following evaluation by NINDS. The anti-convulsant properties of C-10068 are believed to result from its activity at the sigma-1 receptor, which is reported to have unique modulatory actions on pathways that are important in the control of epilepsy. The sigma-1 receptor may also play an important role in synapse formation in hippocampal neurons consistent with Concert's data showing that C-10068 may have neuroprotective effects. C-10068 is based on a molecule which showed evidence of preclinical anti-convulsant efficacy, but was limited by poor metabolic stability. Concert has stabilized metabolism with C-10068 through selective incorporation of deuterium.

About Deuterium

Deuterium is a safe, non-radioactive relative of hydrogen that can be isolated from sea water and has been used extensively in human metabolic and clinical studies. Since deuterium is an isotope of hydrogen, deuterium-containing compounds are expected to have similar pharmacological activity as their hydrogen analogs. However, because deuterium is heavier than hydrogen, it forms a stronger chemical bond to carbon. The stronger chemical bond obtained by selective deuterium modification may in certain cases substantially improve the drug's metabolic properties, potentially resulting in better safety, tolerability and/or efficacy.

About Concert

Concert Pharmaceuticals is a clinical stage biotechnology company focused on applying the company's DCE Platform™ (deuterated chemical entity platform) to create novel and differentiated small molecule drugs. Concert's approach leverages decades of pharmaceutical and clinical experience to reduce the time, risk and expense needed to create important new medicines. The Company has a broad research pipeline encompassing many therapeutic areas including infectious disease, renal disease and CNS disorders, among others. Founded in 2006, Concert has raised more than $110 million of venture and institutional capital. For more information on Concert Pharmaceuticals, please visit

Concert Pharmaceuticals, the CoNCERT logo and the DCE Platform are trademarks of Concert Pharmaceuticals, Inc.


Contact: (Investors)
Concert Pharmaceuticals, Inc.
Justine E. Koenigsberg, 781-674-5284
The Yates Network
Kathryn Morris, 845-635-9828



Posted: May 2011