Arrowhead Pharmaceuticals has achieved a significant milestone in its collaboration with Sarepta Therapeutics, earning a $100 million payment for advancing ARO-DM1, an investigational RNA interference therapeutic for type 1 myotonic dystrophy (DM1). The milestone was triggered when Arrowhead reached the first of two prespecified enrollment targets and received subsequent authorization to dose escalate in a Phase 1/2 clinical study.
Type 1 myotonic dystrophy represents the most common adult-onset muscular dystrophy, highlighting the clinical significance of this therapeutic development. Arrowhead expects to receive the milestone payment within 60 days in accordance with the license and collaboration agreement.
Clinical Progress and Future Milestones
The company currently expects to achieve the second enrollment target by the end of 2025, which would trigger an additional $200 million milestone payment from Sarepta. ARO-DM1 is designed to reduce expression of the dystrophia myotonica protein kinase (DMPK) gene in skeletal muscle as a potential treatment for patients with type 1 myotonic dystrophy.
The therapeutic leverages Arrowhead's Targeted RNAi Molecule (TRiM) platform, which triggers the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. This approach represents a novel strategy for treating intractable diseases by silencing the genes that cause them.
Comprehensive Partnership Agreement
The milestone payment stems from a global licensing and collaboration agreement signed in November 2024 and closed in February 2025. Under this agreement, Sarepta received rights to multiple investigational treatments across rare, genetic diseases of the muscle, central nervous system, and lungs.
The financial terms of the collaboration are substantial. Upon closing, Arrowhead received a $500 million upfront payment and $325 million through Sarepta's purchase of Arrowhead common stock at $27.25 per share, representing a 35% premium to the 30-day volume weighted average price when the agreement was signed. Additionally, Arrowhead will receive $250 million paid in annual installments of $50 million over five years.
Extensive Pipeline Coverage
The collaboration encompasses multiple programs at various development stages. In the clinical stage, four programs are currently active:
ARO-DUX4 targets the gene encoding the DUX4 protein as a potential treatment for facioscapulohumeral muscular dystrophy type 1, currently dosing patients in a Phase 1/2 clinical study. ARO-MMP7 is designed to reduce expression of matrix metalloproteinase 7 (MMP7) in the lung for idiopathic pulmonary fibrosis treatment, also in Phase 1/2 trials. ARO-ATXN2 silences expression of the toxic ATXN2 protein in the central nervous system for spinocerebellar ataxia 2 (SCA2) treatment, with a Phase 1/2 study open for enrollment.
The preclinical pipeline includes ARO-HTT for Huntington's disease, expected to be CTA-ready in 2025, and ARO-ATXN1 and ARO-ATXN3 for spinocerebellar ataxia types 1 and 3, respectively, both expected to be CTA-ready in 2026.
Future Development Opportunities
The agreement allows Sarepta to select up to six new targets during the five-year term for Arrowhead to conduct discovery and preclinical development activities. These targets would focus on CNS or muscle areas complementary to Sarepta's leadership in precision genetic medicine for rare diseases.
Arrowhead remains eligible for substantial additional payments, including development milestone payments of between $110 million and $180 million per program, sales milestone payments of between $500 million and $700 million per program, and tiered royalties on commercial sales up to the low double digits.
Manufacturing Responsibilities
Under the collaboration terms, Arrowhead will manufacture clinical drug supply for all programs arising from the license and collaboration, as well as commercial drug product for the four programs currently in clinical trials. This arrangement ensures continuity of supply and leverages Arrowhead's manufacturing expertise in RNAi therapeutics.
