Arrowhead Presents Preclinical Data on ARO-DUX4 at FSHD Society International Research Congress

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today presented preclinical data on the development of ARO-DUX4, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with facioscapulohumeral muscular dystrophy (FSHD), at the 28^th Annual FSHD Society International Research Congress. Arrowhead intends to file for regulatory clearance in the third quarter of 2021 to begin clinical studies of ARO-DUX4.

James Hamilton, M.D., MBA, senior vice president of discovery and translational medicine at Arrowhead, said: “Preclinical development of ARO-DUX4 has produced very promising results that we believe strongly support advancement into clinical testing. In our preclinical studies in relevant models, ARO-DUX4 achieved deep knockdown of DUX4 and its target genes. Importantly, in a transgenic mouse model of FSHD, treatment with ARO-DUX4 prevented and reversed tamoxifen-induced increases in DUX4 and DUX4 target gene expression. In addition, ARO-DUX4 prevented and reversed DUX4-induced body weight loss, muscle fibrosis, and rotarod performance loss. Collectively, these preclinical results suggest that ARO-DUX4 achieved good target engagement, which led to a downstream beneficial physiological change. We look forward to initiating our clinical program and translating these results into humans. A significant unmet need exists in FSHD, an indication with no currently available treatments.”

Preclinical data demonstrated that Arrowhead’s Targeted RNAi Molecule (TRiM) muscle delivery platform can achieve functional delivery to various types of skeletal muscle. Using RNAscope to detect RNAi, after a single 3 mg/kg intravenous (IV) dose in a mouse, 76-99% of myofibers in gastrocnemius contained TRiM RNAi. In addition, nonhuman primates receiving three doses of 10 mg/kg (day 1, 7, and 28) of a TRiM RNAi targeting myostatin achieved 79% serum myostatin knockdown with a greater than 70% reduction still being observed at week 12.

ARO-DUX4 also achieved dose-dependent knockdown of DUX4 and a deep reduction of DUX4 target gene expression in differentiated FSHD patient-derived myotubes. Additionally, ARO-DUX4 was evaluated in a transgenic FSHD-like mouse model, which has muscle-specific expression of human DUX4 and increased expression of DUX4 target genes. These animals develop a FSHD-like muscle phenotype which includes functional loss. In this model, ARO-DUX4 treatment: