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

项目摘要 酒精使用和酒精使用障碍（AUD）在现代美国社会仍然很高。估计在 到2020年，超过一半的成年人（18岁或以上的54.9%）使用酒精，导致2760万人 成年美国人（11%）被诊断患有AUD。美国疾病控制中心估计， 过量饮酒导致的死亡人数超过14万人，经济成本为249澳元 亿目前AUD的治疗包括认知行为疗法、药物治疗和其他治疗的组合。 辅导目前有四种FDA批准的治疗AUD的药物;双硫仑，纳洛酮， 缓释纳洛酮和阿坎酸。尽管似乎有大约25%的澳元持有者 在不接受治疗的情况下实现康复（即无症状的低风险饮酒或戒酒）， 治疗方式往往有更好的结果。不幸的是，只有110万人（占2760万人的4%） 有362，000人（1.3%）接受了任何形式的治疗， 强调需要改善获得护理的机会， 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ALDH 2抑制作为治疗的潜力。 治疗AUD的有效靶点。杏仁核神经科学公司正在开发ANS-858，一种专有的， 有效、选择性和可逆的ALDH 2抑制剂，用于安全治疗AUD。 我们的目的是：1）进行一项研究，以确认ANS-858在AUD动物模型中的疗效， 2）完成ANS-858的必要IND使能研究， 能够提交IND以安全治疗AUD患者。 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