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EP-4739303-A2 - MDMA ENANTIOMER COMPOSITIONS AND METHODS FOR MODULATING AGGRESSION RESPONSE

EP4739303A2EP 4739303 A2EP4739303 A2EP 4739303A2EP-4739303-A2

Abstract

Disclosed are pharmaceutical compositions and formulations of enantiomerically enriched or pure 3,4-methylenedioxymethamphetamine (MDMA) and methods for modulating aggression response behaviors that may be associated with a disorder and/or disease.

Inventors

  • SHORT, GLENN
  • BOWEN, Carrie

Assignees

  • EmpathBio, Inc.

Dates

Publication Date
20260513
Application Date
20240703

Claims (20)

  1. 1. A method of treating aggression in a subject who has a disease or disorder associated with aggression, comprising administering to the subject a therapeutically effective amount of a composition comprising an enantiomerically enriched or pure 3,4- methylenedioxymethamphetamine (MDMA) or a pharmaceutically acceptable salt thereof.
  2. 2. A method of reducing aggression in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising an enantiomerically enriched or pure MDMA or a pharmaceutically acceptable salt thereof.
  3. 3. A method of treating aggression in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising an enantiomerically enriched or pure MDMA or a pharmaceutically acceptable salt thereof.
  4. 4. The method of any one of claims 1-3, wherein the aggression in the subject comprises irritability, impulsivity, hypervigilance and/or hyperarousal.
  5. 5. The method of claim 1, wherein the disease or disorder is a social anxiety disorder (SAD).
  6. 6. The method of claim 1, wherein the disease or disorder is an autism spectrum disorder (ASD).
  7. 7. The method of any one of claims 1-6, wherein the enantiomerically enriched or pure MDMA comprises R(-)-MDMA in excess relative to S(+)-MDMA.
  8. 8. The method of any one of claims 1-6, wherein the enantiomerically enriched or pure MDMA comprises S(+)-MDMA in excess compared to R(-)-MDMA.
  9. 9. The method of any one of claims 1-8, wherein the therapeutically effective amount comprises a range from about 0.1 mg/kg to about 40 mg/kg. Atty Ref. ATAI-092/01 WO 338067-2474 (EMP-008)
  10. 10. The method of any one of claims 1-8, wherein the therapeutically effective amount comprises a range from about 1 mg/kg to about 20 mg/kg.
  11. 11. The method of any one of claims 1-8, wherein the therapeutically effective amount comprises a range from about 25 mg to about 350 mg.
  12. 12. The method of any one of claims 1-11, wherein administering the composition comprises injection, oral delivery, transdermal delivery, or transmucosal delivery.
  13. 13. The method of any one of claims 1-12, comprising administering the enantiomerically enriched or pure MDMA comprising R(-)-MDMA in excess relative to S(+)-MDMA as a single dose.
  14. 14. The method of any one of claims 1-12, comprising administering the enantiomerically enriched or pure MDMA comprising R(-)-MDMA in excess relative to S(+)-in repeated doses.
  15. 15. The method of any one of claims 1-12, comprising administering the enantiomerically enriched or pure MDMA comprising S(+)-MDMA in excess relative to R(-)-MDMA as a single dose.
  16. 16. The method of any one of claims 1-12, comprising administering enantiomerically enriched or pure MDMA comprising S(+)-MDMA in excess relative to R(-)-MDMA in repeated doses.
  17. 17. The method of any one of claims 1-16, further comprising administering a second therapy.
  18. 18. The method of claim 17, wherein the second therapy comprises a selective serotonin reuptake inhibitor (SSRI) or a form of psychotherapy. Atty Ref. ATAI-092/01 WO 338067-2474 (EMP-008)
  19. 19. The method of claim 18, wherein the SSRI comprises fluoxetine, paroxetine, sertraline, escitalopram or citalopram.
  20. 20. The method of claim 18, wherein the psychotherapy comprises cognitive processing therapy (CPT), cognitive behavioral therapy (CBT), prolonged exposure therapy (PET), brief eclectic psychotherapy (BEP), narrative exposure therapy (NAT), or eye-movement desensitization or reprocessing (EMDR).

Description

Atty Ref. ATAI-092/01 WO 338067-2474 (EMP-008) MDMA ENANTIOMER COMPOSITIONS AND METHODS FOR MODULATING AGGRESSION RESPONSE Cross-Reference To Related Applications [0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63/524,735, filed July 3, 2023, which is hereby incorporated by reference in its entirety for all purposes. BACKGROUND [0002] 3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine analog targeting neurotransmitter systems within the brain. MDMA is a ring-substituted derivative of phenethylamine with a chiral center. There are two stereoisomers of MDMA: S(+)-MDMA and R(-)-MDMA. Phenethylamines including MDMA are known to have psychoactive and stimulant effects, and MDMA has been evaluated clinically for a number of potential therapeutic indications. Depending on the indication, the activity and acute effects of the different MDMA compositions (R(-) enriched, S(+) enriched, and racemic mixture) is unpredictable and can vary widely. In some cases, a specific form or forms of MDMA can be associated with specific adverse effects. [0003] The term aggression response behavior refers to a number actions and/or personality traits that can result in physical and psychological harm to oneself as well as others. As such, effective compositions that can manage, modulate, or otherwise reduce aggression response are of great importance. [0004] The present disclosure provides compositions and methods that are effective in modulating aggression response by providing enantiomerically enriched compositions of MDMA, i.e., compositions comprising specific ratios of the R(-) and S(+) enantiomers (up to enantiomerically pure R(-)-MDMA or S(+)-MDMA). SUMMARY [0005] The present disclosure provides compositions comprising enantiomerically enriched or pure R(-)-MDMA (or S(+)-MDMA) or a pharmaceutically acceptable salt thereof and the use of such compositions in methods for treating aggression response behaviors. [0006] In aspects, the disclosure provides methods of treating aggression in a subject who has a disease or disorder associated with aggression, comprising administering to the subject a Atty Ref. ATAI-092/01 WO 338067-2474 (EMP-008) composition comprising administering a therapeutically effective amount of an enantiomerically enriched or pure 3, 4-methylenedi oxymethamphetamine (MDMA) or a pharmaceutically acceptable salt thereof . [0007] In aspects, the disclosure provides methods of reducing aggression in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising an enantiomerically enriched or pure MDMA or a pharmaceutically acceptable salt thereof. [0008] In aspects, the disclosure provides methods of treating aggression in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising an enantiomerically enriched or pure MDMA or a pharmaceutically acceptable salt thereof. [0009] In aspects, the method is effective for the treatment of aggression in a subject who has a social anxiety disorder (SAD). In embodiments, the method is effective for the treatment of aggression in a subject who has autism spectrum disorder (ASD). [0010] In embodiments, the methods comprise administering a composition comprising an enantiomerically enriched or pure MDMA comprising R(-)-MDMA in excess relative to S(+)- MDMA. In embodiments, the amount of R(-)-MDMA in the enantiomerically enriched or pure MDMA comprises at least 50.1% of the total amount of MDMA and up to about 99.99% or 100% of the total amount of MDMA. [0011] In embodiments, the methods comprise administering a composition comprising an enantiomerically enriched or pure MDMA comprising S(+)-MDMA in excess relative to R(- )-MDMA. In embodiments, the amount of S(+)-MDMA in the enantiomerically enriched or pure MDMA comprises at least 50.1% of the total amount of MDMA and up to about 99.99% or 100% of the total amount of MDMA. [0012] In embodiments, the methods comprise administering an effective amount of the enantiomerically enriched or pure MDMA in a range from about 0.1 mg/kg to about 350 mg/kg. [0013] Other aspects and embodiments will be apparent to one skilled in the art in light of the detailed description and Examples that follow. BRIEF DESCRIPTION OF THE DRAWINGS [0014] FIG. 1 shows aggressive behavior (latency to first attack, number of attacks, and duration of attacks) in socially isolated male NMRI mice administered racemic MDMA HC1 Atty Ref. ATAI-092/01 WO 338067-2474 (EMP-008) at 3, 5.6, or 7.8 mg/kg free base by intraperitoneal (i.p.) administration, compared to vehicle and risperidone (“RISP”) positive control. [0015] FIG. 2 shows aggressive behavior (latency to first attack, number of attacks, and duration of attacks) in mice administered R-MDMA HC1 at 10, 17, or 30 mg/kg (i.p.), compared to vehical and risperidone (“RISP”) positive control. [0016] FIG. 3 shows aggressive behavior (la