Investigational New Drug (IND)-enabling and Early-Stage Development of Selective, Reversible, Orally Bioavailable ALDH2 inhibitor ANS-00858 to Treat Alcohol Use Disorder.

SUMMARY项目 酒精使用和酒精使用障碍(AUD)在现代美国社会中仍然很高。据估计，在 2020年，超过一半的成年人(18岁及以上人口中的54.9%)饮酒，导致2760万人饮酒 美国成年人(11%)被诊断为AUD。美国疾病控制中心估计，每年平均 过量饮酒导致的死亡人数超过140,000人，澳元的经济成本为249美元 十亿美元。目前对AUD的治疗包括认知行为疗法、药物和其他疗法的组合。 心理咨询。目前FDA批准的治疗AUD的药物有四种：双硫仑、纳曲酮、 缓释纳曲酮和氨基己酸酯。尽管看起来大约25%的澳元患者 获得康复(即，无症状的低风险饮酒或戒酒)，无需治疗，接受任何 治疗形式往往有更好的结果。不幸的是，只有110万人(或2760万人中的4%) 符合条件)接受了任何形式的治疗，其中362,000人(1.3%)接受了批准的治疗 强调需要更好地获得护理和更有效、更好的药物治疗 可耐受的药物治疗。 临床前和现有的临床数据强调了选择性、可逆的ALDH2抑制作为一种 AUD治疗的有效靶点前景看好。杏仁核神经科学公司正在开发ANS-858，一种专利， 有效、选择性和可逆的ALDH2抑制剂，用于安全治疗AUD。 我们的目标是1)进行一项研究，以肯定ANS-858在AUD动物模型中的疗效 2)使用ANS-858完成必要的IND使能研究，以 允许提交用于AUD患者安全治疗的IND。 1

PROJECT 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