Praxis Precision Medicines, Inc.

Sage Therapeutics, Inc.

Andrew Mark Griffin

Gabriel Martinez Botella

Brian Edward Marron

Kiran Reddy

Francesco Gerald Salituro

Albert Jean Robichaud

Boyd Lynn Harrison

Paul S Charifson

Daniel La

Maria Jesus Blanco-Pillado

Sapna Makhija Garad

Carlos Loya

Marion Wittmann

Walter J Lunsmann

David Reed

Michael Kristopher Mathieu Kahlig

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

Ion channel modulators

Provided, in part, are compounds of Formula I. pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of conditions associated with the activity of sodium channels. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

Substituted pyridines as ion channel modulators

Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R, R, n, R, R, R, and Rare as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

C7 substituted oxysterols and methods of use thereof

The present invention is directed to, in part, a compound having the structure: or a pharmaceutically acceptable salt thereof, useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

3-(ethoxydifluoromethyl)-6-(5-fluoro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-[1,2,4]triazolo[4,3-α]pyrazine as an ion channel modulator

Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R, R, R, R, R, R, and Rare as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

Oxysterols and methods of use thereof

The present invention is directed to, in part, fused heteroaryl compounds of Formula (III-II):

Substituted [1,2,4]triazolo[4,3-a]pyrazines as ion channel modulators

Provided, in part, are compounds of Formula I: pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of conditions associated with the activity of sodium channels. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

Described herein are neuroactive steroids of Formula (I), Formula (V), or Formula (IX) or a pharmaceutically acceptable salt thereof; wherein each instance of R, R, R, R, R, R, R, R, R, R, R, R, andare as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such as for inducing sedation and/or anesthesia.

C7, C12, and C16 substituted neuroactive steroids and their methods of use

Compounds and their methods of use

Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R, R, R, R, and Rare as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. The fused heteroaryl compounds of the disclosure are represented by Formula (I): wherein X, Y, Z, A, Rand Rare as defined in the specification. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.

The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.

KCNT1 inhibitors and methods of use

The present invention is directed to, in part, fused heteroaryl compounds of Formula (II-II): and compositions thereof, useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

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L'ile Bizard, Canada

Andrew Mark Griffin