Stat3 degraders and uses thereof

Patent metadata

Field	Value
Publication number	US-2025019388-A1
Application number	US-202418894810-A
Country	US
Kind code	A1
Filing date	Sep 24, 2024
Priority date	Dec 11, 2021
Publication date	Jan 16, 2025
Grant date	—

Abstract

The present invention relates to STAT3 degraders, their liquid formulations, and methods of use thereof for treating cancer.

First claim

1 . A liquid formulation comprising Compound A, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient and/or carrier:
wherein Compound A is (2-(((5S,8S,10aR)-3-acetyl-8-(((S)-5-amino-1-(2-chloro-3-(4-(((S)-1-((2S, 4R)-4-hydroxy-2-(((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl) amino)-4-oxobutyl)phenoxy)-5-oxopentan-2-yl)carbamoyl)-6-oxodecahydropyrrolo [1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indole-5-carbonyl)phosphonic acid.

2 . The liquid formulation of claim 1 , comprising Compound A at a concentration of about 0.995% w/w of the total weight of the formulation.

3 . The liquid formulation of claim 1 , comprising Compound A ammonium hydrogen salt at a concentration of about 1.00% w/w of the total weight of the formulation.

4 . The liquid formulation of claim 1 , comprising Compound A at a concentration of about 10 mg/mL.

5 . The liquid formulation of claim 1 , comprising Compound A ammonium hydrogen salt at a concentration of about 10.14 mg/mL.

6 . The liquid formulation of any one of claims 1-5 , comprising a sodium phosphate buffer at a concentration of about 50 mM.

7 . The liquid formulation of any one of claims 1-5 , comprising a sodium phosphate buffer at a concentration of about 0.64% w/w of the total weight of the formulation.

8 . The liquid formulation of any one of claims 1-5 , comprising a sodium phosphate buffer at a concentration of about 6.4 mg/mL.

9 . The liquid formulation of any one of claims 1-8 , which is at about pH 6.5.

10 . The liquid formulation of any one of claims 1-9 , which is a formulation selected from the following:
1) a liquid formulation at about pH 6.5, comprising Compound A at a concentration of about 0.995% w/w of the total weight of the formulation, and a sodium phosphate buffer at a concentration of about 50 mM; 2) a liquid formulation at about pH 6.5, comprising Compound A at a concentration of about 10 mg/mL, and a sodium phosphate buffer at a concentration of about 50 mM; 3) a liquid formulation at about pH 6.5, comprising Compound A at a concentration of about 0.995% w/w of the total weight of the formulation, and a sodium phosphate buffer at a concentration of about 0.64% w/w of the total weight of the formulation; 4) a liquid formulation at about pH 6.5, comprising Compound A at a concentration of about 10 mg/mL, and a sodium phosphate buffer at a concentration of about 0.64% w/w of the total weight of the formulation; 5) a liquid formulation at about pH 6.5, comprising Compound A at a concentration of about 0.995% w/w of the total weight of the formulation, and a sodium phosphate buffer at a concentration of about 6.4 mg/mL; 6) a liquid formulation at about pH 6.5, comprising Compound A at a concentration of about 10 mg/mL, and a sodium phosphate buffer at a concentration of about 6.4 mg/mL; 7) a liquid formulation at about pH 6.5, comprising Compound A ammonium hydrogen salt at a concentration of about 1.00% w/w of the total weight of the formulation, and a sodium phosphate buffer at a concentration of about 50 mM; 8) a liquid formulation at about pH 6.5, comprising Compound A ammonium hydrogen salt at a concentration of about 10.14 mg/mL, and a sodium phosphate buffer at a concentration of about 50 mM; 9) a liquid formulation at about pH 6.5, comprising Compound A ammonium hydrogen salt at a concentration of about 1.00% w/w of the total weight of the formulation, and a sodium phosphate buffer at a concentration of about 0.64% w/w of the total weight of the formulation; 10) a liquid formulation at about pH 6.5, comprising Compound A ammonium hydrogen salt at a concentration of about 10.14 mg/mL, and a sodium phosphate buffer at a concentration of about 0.64% w/w of the total weight of the formulation; 11) a liquid formulation at about pH 6.5, comprising Compound A ammonium hydrogen salt at a concentration of about 1.00% w/w of the total weight of the formulation, and a sodium phosphate buffer at a concentration of about 6.4 mg/mL; and 12) a liquid formulation at about pH 6.5, comprising Compound A ammonium hydrogen salt at a concentration of about 10.14 mg/mL, and a sodium phosphate buffer at a concentration of about 6.4 mg/mL.

11 . The liquid formulation of any one of claims 1-10 , which is a unit dosage form, with a volume of about 10 mL.

12 . A method for treating a hematological malignancy or solid tumor in a patient, comprising administering to the patient a therapeutically effect amount of the liquid formulation of any one of claims 1-11 .

13 . The method of claim 12 , wherein the hematological malignancy or solid tumor is a relapsed or refractory lymphoma.

14 . The method of claim 12 , wherein the hematological malignancy or solid tumor is selected from large granular lymphocytic leukemia (LGL-L), peripheral T-cell lymphoma (PTCL), and cutaneous T-cell lymphoma (CTCL).

15 . The method of any one of claim 12-14 , wherein the method comprises administering up to about 3.0 mg/kg of Compound A to the patient per day.

16 . The method of any one of claim 12-14 , wherein the method comprises administering up to about 500 mg of Compound A to the patient per day.

17 . The method of any one of claims 12-16 , wherein the method comprises administering Compound A to the patient intravenously.

18 . The method of any one of claims 12-17 , wherein the method comprises administering Compound A to the patient once per week (QW).

19 . The method of any one of claims 12-18 , wherein the method comprises administering Compound A to the patient on days 1, 8, 15, and 22 of a 28-day cycle.

Assignees

• Kymera Therapeutics Inc

Inventors

• Agarwal Sagar
• De Savi Christopher
• Dey Joyoti
• Dixit Vaishali
• Enerson Bradley
• Gollerkeri Ashwin
• Gollob Jared
• Ho Chris
• Mayo Michele
• Rong Haojing
• Yang Bin

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/551 Primary

  having two nitrogen atoms, e.g. dilazep · CPC title