Phase I Amount
$1,000,000
SUMMMARY Use of alcohol and alcohol use disorder (AUD) remains high in modern American society. It is estimated that in 2020 over half of the adult population (54.9% of those 18 years or older) used alcohol resulting in 27.6 million adult Americans (11%) diagnosed with AUD. The US Centers for Disease Control estimated the annual average deaths attributable to excessive alcohol use to be more than 140,000 and the economic cost of AUD to be $249 billion. Current treatments for AUD include a combination of cognitive behavioral therapy, medication, and other counseling. Currently there are four FDA approved medications for treatment of AUD; disulfiram, naltrexone, extended-release naltrexone, and acamprosate. Although it appears that approximately 25% of those with AUD achieve recovery (that is, asymptomatic low risk drinking or abstinent) without treatment, those receiving any form of treatment tended to have better outcomes. Unfortunately, only 1.1 million (or 4% of the 27.6 million eligible) received any form of treatment, with 362,000 (1.3%) receiving treatment with an approved pharmacological therapeutic highlighting the need for improved access to care and more effective and better tolerated pharmacological treatments. Preclinical and available clinical data highlight the potential of selective, reversible ALDH2 inhibition as a promising validated target for treatment of AUD. Amygdala Neurosciences is developing ANS-858, a proprietary, potent, selective, and reversible inhibitor of ALDH2, for the safe treatment of AUD. Our objective is to 1) conduct a study to affirm the efficacy of ANS-858 in an animal model of AUD occurs at doses predicted to be efficacious and 2) complete the requisite IND-enabling studies with ANS-858, to enable submission of an IND for the safe treatment of patients with AUD. 1
Public Health Relevance Statement: PROJECT NARRATIVE Preclinical and available clinical data highlight the potential of selective, reversible ALDH2 inhibition as a promising validated target for safe treatment of alcohol use disorder (AUD). We have discovered ANS-858 that merits the completion of studies, enabled by this research grant, required for the application of an investigational new drug (IND) to the FDA.
Project Terms: 21+ years old; Adult Human; adulthood; Adult; Alcohol Drinking; EtOH drinking; EtOH use; alcohol ingestion; alcohol intake; alcohol product use; alcohol use; alcoholic beverage consumption; alcoholic drink intake; ethanol consumption; ethanol drinking; ethanol ingestion; ethanol intake; ethanol product use; ethanol use; Alcohol consumption; ethanol use disorder; alcohol use disorder; Alcohol Chemical Class; Alcohols; Amygdala; Amygdaloid Body; Amygdaloid Nucleus; amygdaloid nuclear complex; Amygdaloid structure; inhibitor; Anxiety; Behavior Therapy; Behavior Conditioning Therapy; Behavior Modification; Behavior Treatment; Behavioral Conditioning Therapy; Behavioral Modification; Behavioral Therapy; Behavioral Treatment; Conditioning Therapy; behavior intervention; behavioral intervention; Biological Availability; Bioavailability; Physiologic Availability; Centers for Disease Control and Prevention (U.S.); Centers for Disease Control; Centers for Disease Control and Prevention; United States Centers for Disease Control; United States Centers for Disease Control and Prevention; Cognitive Therapy; Cognition Therapy; Cognitive Psychotherapy; cognitive behavior intervention; cognitive behavior modification; cognitive behavior therapy; cognitive behavioral intervention; cognitive behavioral modification; cognitive behavioral therapy; cognitive behavioral treatment; Counseling; Diagnosis; Disulfiram; Antabuse; Tetraethylthiuram Disulfide; Drug Combinations; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Investigational Drugs; Investigational New Drugs; Eligibility Determination; Eligibility; Protocol Screening; Enzymes; Enzyme Gene; Grant; Health Services Accessibility; Access to Care; access to health services; access to services; access to treatment; accessibility to health services; availability of services; care access; health service access; health services availability; service availability; treatment access; Human; Modern Man; Liver; hepatic body system; hepatic organ system; Modernization; Naltrexone; Nalorex; Nemexin; ReVia; Vivitrol; Neurosciences; Pamphlets; Booklets; Brochures; Patients; Drug Kinetics; Pharmacokinetics; Prodrugs; Drug Precursors; Pro-Drugs; Program Development; Research Personnel; Investigators; Researchers; Research Support; Risk; Societies; Work; Investigational New Drug Application; Penetration; Phase; Failure; Hepatotoxic effect; Liver Toxicity; Toxic effect on liver cells; hepatic toxicity; hepatoxicity; Hepatotoxicity; Recovery; European; R-Series Research Projects; R01 Mechanism; R01 Program; Research Grants; Research Projects; Research Project Grants; N-acetylhomotaurine; acamprostate; acamprosate; Therapeutic; Oral; Protocols documentation; Protocol; American; experience; success; Animal Model; Animal Models and Related Studies; model of animal; member; economic cost; drinking; Pharmacodynamics; craving; drug development; Documentation; alcohol abuse therapy; alcohol abuse treatment; alcohol treatment; drug discovery; Dose; Improve Access; Clinical Data; research clinical testing; Clinical Evaluation; Clinical Testing; clinical test; Pharmacological Treatment; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Development; developmental; pre-clinical; preclinical; attributable death; attributable mortality; Outcome; scale up; Population; FDA approved; risk mitigation; clinical candidate; pharmacologic
