Collaboration centers on gene silencing therapy targeting Parkinson’s-linked protein alpha-synuclein, with $200m up front.
Gene silencing biotech Arrowhead Pharmaceuticals has entered into a global license and collaboration agreement with Novartis for ARO-SNCA, an experimental RNA interference therapy designed to target alpha-synuclein in the treatment of synucleinopathies such as Parkinson’s disease. The preclinical program makes use of Arrowhead’s Targeted RNAi Molecule, or TRiM, platform, which enables subcutaneous administration and delivery to the central nervous system.
ARO-SNCA aims to reduce expression of the gene that encodes alpha-synuclein, a protein closely associated with the pathology of Parkinson’s and other related neurodegenerative conditions. By applying RNA interference, the approach is intended to silence the gene, limiting protein production and potentially altering disease progression. Arrowhead’s TRiM technology is designed to enable targeted delivery of these RNAi therapies with the goal of achieving durable knockdown of disease-driving proteins, including in deep brain regions that have historically been difficult to reach with genetic medicines.
For Novartis, the deal adds to its neuroscience pipeline and reflects an ongoing interest in RNA-based medicines that address neurodegeneration.
“Our TRiM platform has generated impressive preclinical results demonstrating delivery to CNS, including distribution to deep brain regions, after subcutaneous administration,” said Arrowhead CEO Dr Christopher Anzalone. “The potential translation of these results in upcoming clinical trials would represent an important leap forward for neurodegenerative diseases and gene targets in the CNS that have been historically difficult to address.”
For Arrowhead, it represents a significant financial infusion and an opportunity to expand the reach of its RNAi platform into indications beyond its existing portfolio.
“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 Novartis’ head of biomedical research Dr Fiona Marshall. “We see Arrowhead’s TRiM technology as having great potential to achieve the type of widespread and effective delivery in key brain structures that will be necessary to see the full benefit of RNA medicines in neurodegeneration.”
Under the terms of the agreement, Arrowhead will receive $200 million upfront once the deal closes, expected in the second half of 2025 pending regulatory clearance under the Hart-Scott-Rodino Act and other customary conditions. Beyond the initial payment, Arrowhead said it could earn up to $2 billion in development, regulatory, and commercial milestones, along with tiered royalties that could reach into the low double digits on eventual sales.
Novartis will hold an exclusive worldwide license to research, develop, manufacture, and commercialize ARO-SNCA, as well as to select additional collaboration targets outside of Arrowhead’s current pipeline for development using the TRiM platform. Arrowhead will be responsible for completing preclinical work necessary to enable a clinical trial application, after which Novartis will take over all aspects of development, manufacturing, medical affairs, and commercialization.
