Our Science

We are a neuroscience-focused company with a unique approach to modulating well-validated targets for the treatment of life-threatening, rare CNS (Central Nervous System) disorders.

The human brain is capable of astonishingly complex sets of activities.

The precise and intricate instructions needed to accomplish these actions are created in a web of communication between large networks of brain cells, or neurons. Many thousands of neurons must communicate in a precise sequence to allow someone to dance a waltz, perform math calculations or remember where to find a parked car. Because many of these different activities need to happen at the same time, the brain uses a combination of excitatory connections, or synapses, to relay information between neurons and inhibitory connections to restrict the flow of information. A constant, delicate balance between excitatory and inhibitory neurotransmission allows the brain to multi-task without getting the various messages confused.

This complex balancing act between excitatory and inhibitory connections can become disturbed in a variety of brain disorders, perhaps most prominently in seizure disorders like epilepsy and status epilepticus.

Our science is focused on using allosteric modulation of specific excitatory and inhibitory neurotransmitter systems to reshape this disturbed balance during seizure or other CNS disorders, thus restoring normal brain function. The allosteric modulator therapies being developed by SAGE modify the activity of critical neurotransmitter receptor systems, which we believe leads to a restoration of a normal balance between excitatory and inhibitory signals within the brain.

GABA and NMDA Receptors

Our discovery and development efforts are centered on two critical nervous system receptor families: GABAA receptors, one of the key families of inhibitory neurotransmitter receptors, and NMDA receptors, one of the key families of excitatory neurotransmitter receptors.

Imbalances in GABAA and NMDA receptor activity have been implicated in a broad spectrum of disorders, including disorders of mood, seizure, cognition, anxiety, sleep, pain, epilepsy and movement. These receptor systems 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. However, many drugs approved to modulate these receptor systems have safety and efficacy limitations related to poor pharmaceutical properties and adverse side effect profiles.

We believe our approach to correcting imbalances of GABAA and NMDA receptor function through allosteric modulation offers significant opportunity to treat a variety of diseases.

By influencing a natural regulatory pathway within the brain, our therapies have the potential to have a profound effect while maintaining a strong safety profile, and may deliver new options to patients suffering from a number of diseases.

Our Platform

We have developed a powerful chemistry engine to fuel our drug discovery process. Beginning with naturally occurring, or endogenous, molecules as the starting point, the SAGE drug discovery platform enables the design and identification of highly selective and potent allosteric modulators of GABAA or NMDA receptors.

We believe our strategy focused on developing drugs based on allosteric modulation of GABAA or NMDA receptors offers therapeutic and safety advantages over drugs that directly activate or inhibit these receptors. Allosteric modulation of neurotransmitter receptor activity results in varying degrees of desired activity rather than complete activation or inhibition of the receptor, making it a highly attractive therapeutic approach. Additionally, in the case of GABAA receptor modulators, SAGE compounds differentiate from approved therapies in their ability to impact neurotransmitter receptors at both synaptic and extra-synaptic sites.

Our novel platform also enables a broad range of pharmacologic customization. As a result, we can efficiently design and optimize molecules by controlling important properties such as half-life (how long the drug is effective), brain penetration (the ability to get into the central nervous system) and the types of receptors with which our drugs interact. This leads to the rapid discovery of product candidates with the potential to bind with targets in the brain with more precision, increased safety and tolerability, and fewer off-target side effects than current CNS therapies and previous therapies, which have often failed in development.

Our team has leveraged this platform to assemble a portfolio of more than 1,500 novel, proprietary compounds that have the potential to evolve into clinical candidates and ultimately, life-changing therapies for patients in need.