IP Library › Granted Patent US 12,582,652
Granted Patent B2
US 12,582,652 · App. 18/927,377 · Granted Mar 24, 2026

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

Inventors: Michael Kristopher Mathieu Kahlig (Redwood City, CA); Marion Wittmann (Medford, MA); Zoe A. Hughes (Newton, MA); Bernard Ravina (Newton, MA)
Assignee: Praxis Precision Medicines, Inc.
A61K31/4985A61P25/08
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Quick Facts
Patent No.
US 12,582,652
App. No.
18/927,377
Granted
Mar 24, 2026
Kind
B2
Abstract

The present disclosure is generally directed to methods of treating a disease, disorder, or condition, e.g., a neurological disorder, a disorder associated with excessive neuronal excitability, or a disorder associated with de novo gain-of-function or loss-of-function mutations in major central nervous system sodium channel genes, such as for example, SCN1A, SCN2A, and SCN8A, using a Compound 1, or a pharmaceutically acceptable salt thereof, of the following formula:

Claims (96)

1 . A method for treating a genetic epilepsy or a genetic epilepsy syndrome in a human in need thereof, wherein the method comprises administering to the human a therapeutically effective amount of Compound 1 of the following formula:

or a pharmaceutically acceptable salt thereof;

wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in need thereof in a therapeutically effective dosage amount in the range of 0.1 mg/kg/day to 10 mg/kg/day; and

wherein the administration of the therapeutically effective dosage amount of Compound 1, or a pharmaceutically acceptable salt thereof, to the human in need thereof results in any one of (a), (b), (c), (d), (e), (f), or (g);

(a) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(b) a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(c) a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(d) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(e) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(f) a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(g) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof;

a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein the genetic epilepsy or the genetic epilepsy syndrome is selected from the group consisting of KCNQ2 epileptic encephalopathy, KCNT1 epileptic encephalopathy, SCN1A epileptic encephalopathy, SCN2A epileptic encephalopathy, cryptogenic pediatric partial epilepsy with SCN3A mutation, focal epilepsy with SCN3A mutation, and SCN8A epileptic encephalopathy.

3 . The method of claim 2 , wherein the SCN1A epileptic encephalopathy is Dravet syndrome with SCN1A mutation.

4 . The method of claim 2 , wherein the genetic epilepsy or the genetic epilepsy syndrome is SCN2A epileptic encephalopathy or SCN8A epileptic encephalopathy.

5 . The method of claim 1 , wherein the genetic epilepsy or the genetic epilepsy syndrome is a pediatric epilepsy or a pediatric epilepsy syndrome.

6 . The method of claim 1 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in a therapeutically effective dosage amount in the range of 0.25 mg/kg/day to 1 mg/kg/day.

7 . The method of claim 1 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in a therapeutically effective dosage amount selected from the group consisting of (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), (m), (n), (o), and (p):

(a) 0.25 mg/kg/day;

(b) 0.30 mg/kg/day;

(c) 0.35 mg/kg/day;

(d) 0.40 mg/kg/day;

(e) 0.45 mg/kg/day;

(f) 0.50 mg/kg/day;

(g) 0.55 mg/kg/day;

(h) 0.60 mg/kg/day;

(i) 0.65 mg/kg/day;

(j) 0.70 mg/kg/day;

(k) 0.75 mg/kg/day;

(l) 0.80 mg/kg/day;

(m) 0.85 mg/kg/day;

(n) 0.90 mg/kg/day;

(o) 0.95 mg/kg/day; and

(p) 1.0 mg/kg/day.

8 . The method of claim 7 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in a therapeutically effective dosage amount selected from the group consisting of (a), (f), and (p):

(a) 0.25 mg/kg/day;

(f) 0.50 mg/kg/day; and

(p) 1.0 mg/kg/day.

9 . The method of claim 1 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered orally or via a gastrostomy/jejunostomy tube (G/J-tube) to the human.

10 . The method of claim 1 , wherein the seizure is selected from the group consisting of an absence seizure, a clonic seizure, a focal seizure, a myoclonic seizure, an obtundation status seizure, and a tonic seizure, or a combination thereof.

11 . The method of claim 10 , wherein the clonic seizure is a generalized clonic seizure.

12 . The method of claim 10 , wherein the tonic seizure is a generalized tonic seizure.

13 . The method of claim 1 , wherein the seizure is a motor seizure.

14 . The method of claim 1 , wherein the human is a pediatric human.

15 . A method for effecting any one of (a), (b), (c), (d), (e), (f), or (g) in a human having a genetic epilepsy or a genetic epilepsy syndrome, wherein the method comprises administering to the human in need thereof a therapeutically effective amount of Compound 1 of the following formula:

or a pharmaceutically acceptable salt thereof;

wherein (a), (b), (c), (d), (e), (f), or (g) is:

(a) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(b) a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(c) a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(d) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(e) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(f) a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; or

(g) a reduction in the severity of seizures experienced by the human as compared to the severity of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof;

a reduction in the number of seizures experienced by the human as compared to the number of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

a reduction in the frequency of seizures experienced by the human as compared to the frequency of seizures experienced by the human prior to administration of Compound 1, or a pharmaceutically acceptable salt thereof; and

wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in need thereof in a therapeutically effective dosage amount in the range of 0.1 mg/kg/day to 10 mg/kg/day.

16 . The method of claim 15 , wherein the genetic epilepsy or the genetic epilepsy syndrome is selected from the group consisting of KCNQ2 epileptic encephalopathy, KCNT1 epileptic encephalopathy, SCN1A epileptic encephalopathy, SCN2A epileptic encephalopathy, cryptogenic pediatric partial epilepsy with SCN3A mutation, focal epilepsy with SCN3A mutation, and SCN8A epileptic encephalopathy.

17 . The method of claim 16 , wherein the SCN1A epileptic encephalopathy is Dravet syndrome with SCN1A mutation.

18 . The method of claim 16 , wherein the genetic epilepsy or the genetic epilepsy syndrome is SCN2A epileptic encephalopathy or SCN8A epileptic encephalopathy.

19 . The method of claim 15 , wherein the genetic epilepsy or the genetic epilepsy syndrome is a pediatric epilepsy or a pediatric epilepsy syndrome.

20 . The method of claim 15 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in need thereof in a therapeutically effective dosage amount in the range of 0.25 mg/kg/day to 1 mg/kg/day.

21 . The method of claim 20 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in need thereof in a therapeutically effective dosage amount selected from the group consisting of (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), (m), (n), (o), and (p):

(a) 0.25 mg/kg/day;

(b) 0.30 mg/kg/day;

(c) 0.35 mg/kg/day;

(d) 0.40 mg/kg/day;

(e) 0.45 mg/kg/day;

(f) 0.50 mg/kg/day;

(g) 0.55 mg/kg/day;

(h) 0.60 mg/kg/day;

(i) 0.65 mg/kg/day;

(j) 0.70 mg/kg/day;

(k) 0.75 mg/kg/day;

(l) 0.80 mg/kg/day;

(m) 0.85 mg/kg/day;

(n) 0.90 mg/kg/day;

(o) 0.95 mg/kg/day; and

(p) 1.0 mg/kg/day.

22 . The method of claim 21 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered to the human in need thereof in a therapeutically effective dosage amount selected from the group consisting of (a), (f), and (p):

(a) 0.25 mg/kg/day;

(f) 0.50 mg/kg/day; and

(p) 1.0 mg/kg/day.

23 . The method of claim 15 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered orally or via a gastrostomy/jejunostomy tube (G/J-tube) to the human in need thereof.

24 . The method of claim 15 , wherein the seizure is selected from the group consisting of an absence seizure, a clonic seizure, a focal seizure, a myoclonic seizure, an obtundation status seizure, and a tonic seizure, or a combination thereof.

25 . The method of claim 24 , wherein the clonic seizure is a generalized clonic seizure.

26 . The method of claim 24 , wherein the tonic seizure is a generalized tonic seizure.

27 . The method of claim 15 , wherein the seizure is a motor seizure.

28 . The method of claim 15 , wherein the human is a pediatric human.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 26, 2026
From: KAHLIG, MICHAEL KRISTOPHER MATHIEU; WITTMANN, MARION; HUGHES, ZOE A.; RAVINA, BERNARD
To: PRAXIS PRECISION MEDICINES, INC.
Reel/Frame 073580/0716 →
Continuity (5)
Continuation PCTUS2023019652 · Apr 24, 2023
Provisional Application 63357944 · Jul 1, 2022
Provisional Application 63349402 · Jun 6, 2022
Provisional Application 63335204 · Apr 26, 2022
Related Publication 20250049790A1 · Feb 13, 2025
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