SAGE Therapeutics Presents New Preclinical Data on SAGE-217 at Eilat Conference on New Anti-Epileptic Drugs

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Data Highlight Potential of SAGE-217 to Address Acute and Chronic Forms of Epilepsy and Seizure Disorders

September 2, 2014

SAGE Therapeutics today presented preclinical data on its second-generation neuroactive steroid, SAGE-217, at the Twelfth Eilat Conference on New Anti-Epileptic Drugs in Madrid, Spain. The data suggest improved activity for this compound versus other first-generation neuroactive steroids in development, as well as favorable selectivity and pharmacokinetic profile of the drug.

“SAGE has developed a proprietary chemistry platform that we believe allows us to efficiently identify and design selective neuroactive molecules that impact two important, validated nervous system targets – GABAA and NMDA receptors,” said Albert Robichaud, Ph.D., chief scientific officer of SAGE Therapeutics. “The data presented suggest the potential for high potency and selectivity of SAGE-217 and its potential efficacy in well-validated, preclinical seizure models. This promising compound is the second of several we plan to develop in our seizure franchise targeting a range of disorders from status epilepticus to orphan genetic epilepsies, such as Dravet syndrome.”

SAGE-217 is a GABA-potentiating, second-generation neuroactive steroid that has demonstrated favorable CNS exposure (rodent brain to plasma ratio >1.3-3.2), an attractive pharmacokinetic profile and the potential for IV, IM and oral administration. Preclinical data generated through in vitro electrophysiology studies utilizing mammalian cell lines showed that SAGE-217 was more efficacious in in vitro assays of GABAA modulation than either allopregnanolone or ganaxolone at both synaptic α1β2γ2-containing GABAA receptors and extra-synaptic α4β3δ-containing GABAA receptors. SAGE-217 also exhibited reduced off-target activities compared to the known first-generation analogs. In addition, in comparison to first-generation neurosteroids, SAGE-217 demonstrated efficacy at reduced levels of plasma and brain exposure in models of benzodiazepine-resistant seizure.

The company also presented data previously reported on SAGE-547, an allosteric modulator of GABAA receptors currently in clinical development for super-refractory status epilepticus (SRSE).

“We continue to make good progress on our portfolio of seizure product candidates,” said Steve Kanes, M.D., chief medical officer of SAGE. “SAGE-547 is advancing on track as an acute therapy in our Phase 1/2 clinical trial in patients with SRSE. We look forward to initiating development of SAGE-217 as a potential maintenance or chronic treatment for status epilepticus, as well as for other orphan genetic seizure disorders.”

About SAGE-217

SAGE-217 is a novel neuroactive steroid that acts as a positive allosteric modulator of synaptic and extra-synaptic GABAA receptor subtypes. Unlike many of the naturally occurring neuroactive steroids, SAGE-217 has a pharmacokinetic profile to potentially support once-daily oral dosing and a selectivity profile that minimizes potential off-target side effects. SAGE-217 is currently in preclinical development for a range of seizure conditions, including orphan genetic epilepsy disorders, such as Rett syndrome and Dravet syndrome.

About SAGE-547

SAGE-547 is an allosteric modulator of both synaptic and extra-synaptic GABAA receptors. GABAA receptors are widely regarded as validated drug targets for a variety of CNS disorders, with decades of research and multiple approved drugs targeting these receptor systems. SAGE-547 is an intravenous agent in Phase 1/2 clinical development as an adjunctive therapy, a therapy combined with current therapeutic approaches, for the treatment of SRSE.

About SAGE Therapeutics

SAGE Therapeutics is a clinical-stage biopharmaceutical company committed to developing and commercializing novel medicines to treat life-threatening, rare central nervous system, or CNS disorders. SAGE’s lead program, SAGE-547, is in clinical development for super-refractory status epilepticus, or SRSE, and is the first of several compounds the company is developing in its portfolio of potential seizure medicines. SAGE’s proprietary chemistry platform has generated multiple new compounds that target GABAA and NMDA receptors, which are broadly accepted as impacting many psychiatric and neurological disorders. For more information, please visit

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