679. From Bench to Clinic: Zatolmilast and the Translation of Neurobiology Research into a Targeted Therapy for Fragile X Syndrome

Abstract

Abstract Background Drug development in Fragile X syndrome (FXS) has been challenging with multiple development programs failing to achieve positive pivotal study results over decades of continued effort. Meanwhile translational research has continued to lead to the identification of clinically relevant biological pathways within FXS and subsequently the discovery of new investigational therapies. Aims & Objectives This presentation will describe the scientific trajectory that led to the development of zatolmilast, a negative allosteric PDE4D inhibitor, as an investigational treatment for FXS Method Review of preclinical and clinical research. Results Through collaboration among patient advocacy, FXS researchers, and the pharmaceutical industry, preclinical studies have informed early clinical testing and a positive proof of concept study ultimately led to the initiation of a registrational clinical development program aimed at delivering the first targeted FXS treatment to the community. Phase 2/3 study results are forthcoming. Discussion & Conclusions This session will provide a comprehensive overview of the translational, preclinical, and early clinical research, including key methodological considerations, that has helped to propel zatolmilast into a registrational, Phase 2/3 clinical development program in FXS. By sharing both the experience and learnings from this foundational work, we aspire to inform future interventional clinical trials in FXS.