Arrowhead Pharmaceuticals recently announced a significant achievement, securing a $100 million milestone payment from Sarepta Therapeutics upon reaching the initial enrollment target and securing authorization for dose escalation in its Phase 1/2 clinical study of ARO-DM1. This investigational RNA interference (RNAi) therapeutic is specifically designed to treat type 1 myotonic dystrophy (DM1), the most prevalent adult-onset muscular dystrophy, by aiming to reduce the expression of the problematic dystrophia myotonica protein kinase (DMPK) gene in skeletal muscle, thereby addressing the underlying genetic cause of the disease. This payment stems from a substantial global licensing and collaboration agreement signed in November 2024 and finalized in February 2025, which strategically leverages Arrowhead’s proprietary Targeted RNAi Molecule (TRiM™) platform. This innovative platform enables precise and targeted delivery of RNAi triggers, effectively silencing disease-causing genes in specific tissues like muscles, the central nervous system, and lungs, a significant advancement beyond traditional liver-targeted RNAi therapies.

The financial terms of this extensive partnership provided Arrowhead with an initial $500 million upfront payment, an additional $325 million from Sarepta's purchase of Arrowhead common stock, and a guaranteed $250 million in annual installments over five years. The newly earned $100 million milestone is part of a potential $300 million in near-term payments tied directly to the continued progress of ARO-DM1's clinical study, with Arrowhead anticipating an additional $200 million by the end of 2025, alongside significant future development and sales milestones, plus tiered royalties. Beyond ARO-DM1, the collaboration is robust, encompassing a diverse pipeline of RNAi-based therapeutics, including other clinical-stage programs like ARO-DUX4 for facioscapulohumeral muscular dystrophy type 1, ARO-MMP7 for idiopathic pulmonary fibrosis, and ARO-ATXN2 for spinocerebellar ataxia 2. The agreement also includes several preclinical programs targeting conditions such as Huntington’s disease and other spinocerebellar ataxias, with Sarepta retaining the option to propose up to six new CNS or muscle targets for Arrowhead to develop. Crucially, Arrowhead will continue to handle the manufacturing of clinical drug supply for all programs, and commercial drug product for the four currently clinical programs, underscoring its pivotal role in the partnership's long-term success.