molecules of the month

6. The Lilly beta-site APP cleaving enzyme (BACE) inhibitor LY3202626 is an oral, low-dose, CNS-penetrant molecule which entered a Phase II of clinical trial against AlzheimerÕs disease in 2016. In a Ph. I study, only 9.2 mg of LY3202626 were needed to achieve 90% CSF A_ reduction. Similar to other BACE inhibitors, development was halted due to a lack of an efficacy signal. The article shares a lot of preclinical and clinical data (with remarkable alignment between human projections and actual human data) and summarizes many challenges that were overcome including retinal toxicity of earlier molecules due to CatD inhibition as well as a high (>300 mg) dose projection for another candidate. These Òpost-humousÓ program reports are always educational because…