CAMBRIDGE, MA, USA I April 27, 2017 I Sage Therapeutics (NASDAQ:SAGE), a clinical-stage biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, today announced it has initiated a Phase 1 single ascending dose (SAD) trial of SAGE-718 in healthy volunteers. Top-line results from the SAD study are expected in the second half of 2017.
“Advancing SAGE-718 into Phase 1 clinical development represents a significant achievement in broadening our clinical pipeline beyond GABA, with a new product development platform focused on a novel mechanism to modulate the NMDA receptor system,” said Jeff Jonas, M.D., Chief Executive Officer of Sage. “Loss of NMDA function may have significant impact in many neuropsych disorders, and SAGE-718 and our novel follow-on compounds have the potential to further extend our pipeline into a broad array of CNS indications.”
SAGE-718 is a novel, oral, first-in-class oxysterol-based positive allosteric modulator (PAM) of the N-methyl-D-aspartate (NMDA) receptor, acting in a similar manner as 24(S)-hydroxycholesterol (cerebrosterol), an endogenous modulator of NMDA receptor function. Positive modulation of NMDA receptors may have potential in the treatment of a range of neurological disorders associated with a variety of cognitive, neurological and behavioral symptoms.
SAGE-718 may also have potential in the treatment of CNS disorders associated with a high prevalence of anti-NMDA antibodies or reduced levels of plasma cerebrosterol. In preclinical studies, SAGE-718 improved social behavior in an animal model of NMDA hypofunction, and ameliorated both behavioral and electrophysiological deficits in a model of compromised cholesterol regulation. The effects of NMDA PAMs on cerebrosterol deficit preclinical models were presented at the 2016 annual meetings of the Society of Biological Psychiatry and the Society for Neuroscience.
“SAGE-718 is our lead NMDA PAM candidate, and was selected from over 800 novel compounds in our NMDA modulator library. SAGE-718 is designed for once-daily dosing, good oral bioavailability, and high selectivity for the NMDA receptors,” said Albert Robichaud, Ph.D., Chief Scientific Officer of Sage. “The NMDA receptor system plays a critical role in brain network balance and plasticity. Sage has discovered a novel platform and approach to modulating NMDA receptors by enhancing receptor response without the direct activation which may contribute to the limitations of prior NMDA-targeted compounds.”
The Phase 1 single ascending dose study of SAGE-718 is a double-blind, placebo-controlled trial to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of SAGE-718 administered orally in healthy adult volunteers.
About SAGE-718 and NMDA Receptors
SAGE-718 is a novel, oral, first-in-class, oxysterol-based positive allosteric modulator (PAM) of N-methyl-D-aspartate (NMDA) receptors. SAGE-718 is the lead compound from Sage’s NMDA modulator platform.
NMDA receptors are glutamate-gated cation channels that play a critical role in the health and regulation of neurons, and are involved in learning, memory and neuroplasticity. Positive modulation of NMDA receptors may have potential in the treatment of conditions associated with NMDA hypofunction and disorders associated with a high prevalence of anti-NMDA antibodies, such as anti-NMDA receptor encephalitis, as well as in disorders associated with reductions in plasma cerebrosterol, such as Huntington’s disease and Alzheimer’s disease.
About Sage Therapeutics
Sage Therapeutics is a clinical-stage biopharmaceutical company committed to developing novel medicines to transform the lives of patients with life-altering central nervous system (CNS) disorders. Sage has a portfolio of novel product candidates targeting critical CNS receptor systems, GABA and NMDA. Sage’s lead program, brexanolone (SAGE-547), is in Phase 3 clinical development for super-refractory status epilepticus, a rare and severe seizure disorder, and for postpartum depression. Sage is developing its next generation modulators, including SAGE-217 and SAGE-718, in various CNS disorders. For more information, please visit www.sagerx.com.
SOURCE: Sage Therapeutics
