The Alzheimer's Drug Discovery Foundation (ADDF) and The Association for Frontotemporal Degeneration (AFTD) announced that they have partnered to support Wave Life Sciences' FOCUS-C9 Phase 1b/2a clinical trial investigating WVE-004 as a potential treatment for C9orf72-associated frontotemporal degeneration (C9-FTD), as well as amyotrophic lateral sclerosis (C9-ALS). The partnership provides an investment from ADDF and AFTD that will support the evaluation of fluid biomarkers, functional assessments, and digital biomarkers in FOCUS-C9, potentially leading to clinically meaningful endpoints to inform development of treatments for FTD. ADDF and AFTD made the decision to support the FOCUS-C9 trial following a review of Wave's clinical research application for the Treat FTD Fund, which supports the development of new medicines to treat FTD.

Specifically, members of the Treat FTD Fund Joint Steering Committee, a panel of experts convened by ADDF in collaboration with AFTD, and ADDF's Scientific Review Board reviewed and commented on the Phase 1b/2a study plan, preclinical data supporting the program, and credentials of the study team. The FOCUS-C9 trial is novel in that it is a "basket" type study designed to assess the effects of a genetically targeted treatment in patients with different disease phenotypes (FTD, FTD with ALS, or ALS) who share a common molecular etiology, as has been used in oncology trials but has yet to be applied in neurology and to the C9orf72 population specifically. Wave's focus on C9-FTD makes this a unique program in the C9orf72 clinical research landscape.

It is also unique in the use of novel oligonucleotide chemistry which has shown improved cellular and nuclear uptake. WVE-004 is a stereopure antisense oligonucleotide designed to selectively target transcriptional variants containing a hexanucleotide repeat expansion (G4C2) associated with the C9orf72 gene, thereby sparing C9orf72 protein. G4C2 expansions in C9orf72 are one of the most common genetic causes of the sporadic and inherited forms of ALS and FTD.