Novartis has signed a global licensing agreement with Arrowhead Pharmaceuticals for the preclinical RNA interference (RNAi) therapy ARO-SNCA, targeting alpha-synuclein in Parkinson’s disease and related disorders. The deal, announced Tuesday and reported by Reuters, includes a $200 million upfront payment to Arrowhead, with up to $2 billion in potential milestones, plus tiered royalties (capped in the low double digits) on future sales.
Under the agreement, Novartis gains exclusive worldwide rights to develop, manufacture and commercialize ARO-SNCA, which uses Arrowhead’s proprietary Targeted RNAi Molecule (TRiM) platform to silence the SNCA gene encoding alpha-synuclein. Arrowhead says the therapy is administered subcutaneously and is designed to deliver small interfering RNA (siRNA) to the central nervous system, including deep brain regions.
“Our TRiM platform has generated impressive preclinical results demonstrating delivery to CNS, including distribution to deep brain regions, after subcutaneous administration,” said Christopher Anzalone, Ph.D., President and CEO at Arrowhead, in a company statement. “The potential translation of these results in upcoming clinical trials would represent an important leap forward for neurodegenerative diseases.”
The partnership comes as Novartis renews its push into alpha-synuclein targeting after previous setbacks. The company’s UCB-partnered oral small-molecule minzasolmin failed a phase 2 Parkinson’s trial last year, joining other attempts—such as Roche/Prothena’s antibody prasinezumab—that missed primary endpoints while reporting exploratory signals.
The RNA interference (RNAi) approach differs fundamentally from previous strategies by attacking the pathway upstream, reducing alpha-synuclein production rather than attempting to clear existing protein aggregates. This mechanism has attracted significant industry interest, with Arrowhead previously securing partnerships with GSK, Amgen, Takeda and Sarepta Therapeutics for various applications of its RNAi technology.
“We believe that one way to effectively target core drivers in Parkinson’s and other neurodegenerative diseases requires completely novel approaches to deliver RNA medicines to the brain,” said Fiona Marshall, Ph.D., President of Biomedical Research at Novartis, according to the press release.
Under the collaboration structure, Arrowhead will complete preclinical research activities necessary to file a clinical trial application (CTA), after which Novartis will assume full control of development, manufacturing, and commercialization. The companies indicated human studies are planned following completion of IND-enabling activities, though specific timelines were not disclosed.
The agreement also grants Novartis options to select additional collaboration targets outside Arrowhead’s current pipeline for development using the TRiM platform, potentially expanding the partnership beyond Parkinson’s disease to other synucleinopathies.
Arrowhead’s shares rose after the announcement. The transaction is expected to close in the second half of 2025, subject to regulatory clearances under the Hart-Scott-Rodino Act.
The deal underscores continued pharmaceutical industry investment in genetic medicine approaches for neurodegenerative diseases, despite the field’s history of clinical setbacks. With no disease-modifying treatments currently available for Parkinson’s disease, successful development of ARO-SNCA would address a significant unmet medical need.
Filed Under: Biotech, Brain Breakthroughs, Cell & gene therapy, M&A trends, Neurological Disease
