Novartis Inks $2.2B Deal for Arrowhead's Preclinical siRNA Therapy ARO-SNCA Targeting Parkinson’s Disease

On September 2, Arrowhead Pharmaceuticals (hereinafter referred to as "Arrowhead") announced a global exclusive licensing and strategic collaboration agreement with Novartis. Under the agreement, Novartis will obtain the global exclusive rights for the development, manufacturing, and commercialization of Arrowhead's preclinical siRNA drug ARO-SNCA. According to the agreement, Novartis will pay Arrowhead an upfront payment of $200 million; Arrowhead is also eligible to receive up to $2 billion in milestone payments (covering R&D, regulatory, and sales milestones) as well as tiered sales royalties. The transaction is expected to be completed in the second half of 2025.

ARO-SNCA is an siRNA therapy developed based on the RNA interference (RNAi) mechanism, which aims to reduce the expression of α-synuclein in the central nervous system by targeting the gene encoding α-synuclein. The pathological accumulation of α-synuclein is considered a core pathogenic mechanism of Parkinson's disease and other synucleinopathies. This drug is currently in the preclinical development stage.

In addition to ARO-SNCA, the two parties will also collaborate on the development of other nucleic acid drugs based on Arrowhead's proprietary TRiM™ technology platform. Novartis has the right to select additional projects outside of Arrowhead’s existing pipeline and utilize the TRiM™ technology platform to advance the development of candidate drugs. Arrowhead will be responsible for completing all preclinical studies required for the collaboration projects and submitting clinical trial applications; thereafter, Novartis will lead subsequent clinical development, manufacturing, and product commercialization activities.

Arrowhead Pharmaceuticals, founded in 1989 and listed on NASDAQ in 2004, is a global leader in the siRNA field. The company focuses on developing novel therapies for metabolic and neurological diseases using RNA interference technology.

In 2007, CEO Chris Anzalone decided to focus strategically on the RNAi field, divesting non-core assets. After more than a decade of development, Arrowhead has gradually built up industry-leading RNA drug development capabilities. Its therapies achieve efficient and long-lasting silencing of specific genes through a combination of highly effective delivery systems and RNA chemistry, thereby intervening in the expression of disease-related proteins.

Arrowhead's core technological advantage lies in its TRiM™ Targeted RNAi Molecule Platform. This platform achieves highly efficient and precise targeting of specific tissues through a ligand-mediated delivery strategy. The TRiM™ system consists of four key components: a high-affinity targeting ligand, an adjustable linker, structural elements that improve pharmacokinetics, and chemically modified RNAi trigger molecules with high stability and high activity. The research team can flexibly adjust each component based on the characteristics of different drug candidates to achieve efficient delivery.

Notably, the TRiM™ platform also incorporates computational biology-assisted design, which can optimize siRNA sequences, reduce off-target risks, enhance stability and activity, and significantly improve the development efficiency of candidate drugs.

Arrowhead has set ambitious R&D goals, planning to advance 20 drugs into clinical stages by 2025. To expand its global market presence, in 2022 Arrowhead co-founded Visirna Therapeutics in China with Vivo Capital, granting it the rights to develop and commercialize four RNAi drug candidates for cardiometabolic disease treatment in the Chinese market.

This collaboration with Novartis not only demonstrates Arrowhead's technical capabilities but also represents recognition of its TRiM™ platform, particularly in the area of drug delivery for central nervous system disorders.

Arrowhead CEO Dr. Christopher Anzalone stated that the TRiM™ technology platform has achieved breakthrough preclinical results, enabling efficient siRNA delivery to the CNS via subcutaneous injection, with drug distribution reaching deep brain regions. If these results successfully translate into subsequent clinical trials, it will provide a new therapeutic breakthrough for difficult-to-target CNS gene targets, such as alpha-synuclein, potentially transforming the clinical treatment landscape of neurodegenerative diseases. Moving forward, the collaborating parties will accelerate the clinical development of ARO-SNCA, bringing new hope to Parkinson's disease patients while exploring further collaboration opportunities for additional CNS targets.

This collaboration with Arrowhead is not Novartis' first move in the nucleic acid drug field. In recent years, facing the challenge of the patent cliff, Novartis has been actively expanding its innovative drug pipeline through acquisitions and collaborations, particularly with frequent activities in the nucleic acid drug sector.

In June 2025, Novartis acquired Regulus Therapeutics for up to $1.7 billion, obtaining its investigational therapy farabursen for the treatment of autosomal dominant polycystic kidney disease (ADPKD). Farabursen is an oligonucleotide drug targeting miR-17, which has completed a Phase 1b multiple-dose escalation clinical trial.

One of Novartis' strategic focuses in the layout of nucleic acid drugs is to break through the bottleneck of extrahepatic delivery technology. Currently, most of the small nucleic acid drugs on the market mainly rely on liver-targeted delivery technologies (such as GalNAc conjugation technology or lipid nanoparticles LNP), but about 90% of disease-causing genes are expressed in extrahepatic tissues such as the central nervous system, muscles, and lungs. Overcoming extrahepatic delivery is considered key to expanding the indications for small nucleic acid therapies.

In addition to asset acquisitions, Novartis has also been actively investing in related technology platforms. In 2023, Novartis acquired DTx Pharma for up to $1 billion, gaining access to its FALCON platform, which aims to address the delivery challenges of oligonucleotide therapies to extrahepatic tissues such as the central nervous system and muscles.

In April 2025, Novartis announced a $23 billion investment in the United States over the next five years to expand its production facilities and R&D infrastructure. For the first time, the company will fully introduce its siRNA technology platform to the U.S. to achieve localized supply of key drugs.

Through this collaboration, Novartis has gained the rights to utilize the TRiM™ platform for developing drugs targeting other indications, demonstrating confidence in the platform's ability to address challenges in central nervous system delivery. Dr. Fiona Marshall, Head of Biomedical Research at Novartis, stated that neurodegenerative diseases affect millions of patients worldwide, and Novartis aims to efficiently slow disease progression through innovative medicines. RNA therapies open new avenues for targeting the core pathogenic factors of these diseases. Arrowhead's TRiM™ technology holds the potential for broad and effective delivery, meeting the drug delivery needs of key brain structures in the central nervous system, thereby laying the foundation for RNA therapeutics to achieve maximum efficacy.