A Look at Sage Therapeutics’ NMDA Receptor Portfolio



NMDA products

As discussed earlier, Sage Therapeutics (SAGE) is focused on the development of products for the treatment of life-threatening central nervous system (or CNS) disorders. The products under development include SAGE-718 and SAGE-904.

The above chart shows details about products under development in the NMDA receptor program.

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NMDA receptor

There are three types of ionotropic glutamate receptors:

  • NMDA (or N-methyl-D-aspartate) receptor
  • Kainic acid receptor
  • AMPA (Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor

Sage Therapeutics has developed products such as SAGE-718 and SAGE-904 that target the NMDA receptor.


SAGE-718, the first compound outside the GABA receptor program from Sage, is an oxysterol-based positive allosteric modulator of the NMDA receptor.

SAGE-718 is under phase one clinical study for the treatment of cerebrosterol deficit disorders and also for anti-NMDA receptor encephalitis and other indications that involve NMDA receptor hypofunction.

SAGE-718 was developed as a once-daily dosage compound. The phase one single ascending dose (or SAD) trial is a double-blind, placebo-controlled study to evaluate the safety, tolerance, and pharmacokinetics as well as pharmacodynamics effects of the drug when administered orally once a day to adults. Sage plans to begin the phase one multiple ascending dose trial for the evaluation of SAGE-718 in 2018.


SAGE-904 is the second compound developed by Sage using its NMDA receptor program. SAGE-904 is a positive allosteric modulator, but the drug has a differentiated pharmacologic and pharmacokinetic profile as compared to SAGE-718. Sage has initiated the IND-enabling studies for SAGE-904.

The iShares NASDAQ Biotechnology ETF (IBB) holds 0.9% of its total portfolio in Sage Therapeutics (SAGE), 0.9% in Bluebird Bio (BLUE), 1.5% in Seattle Genetics (SGEN), and 1.7% in Incyte (INCY).


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