Sarepta Therapeutics Announces Global Licensing and Collaboration Agreement with Arrowhead Pharmaceuticals for Multiple Clinical and Preclinical siRNA Programs

On Nov 27, 2024

Sarepta Therapeutics, Inc. announced an exclusive global licensing and collaboration agreement with Arrowhead Pharmaceuticals, Inc. Sarepta will obtain exclusive global rights to multiple clinical, preclinical, and discovery-stage programs for rare, genetic diseases of the muscle, central nervous system (CNS), and the lungs.

The agreement will add meaningfully to Sarepta’s mid- and early-stage pipeline, complementing the Company’s existing leadership in Duchenne muscular dystrophy and limb-girdle muscular dystrophies and gene therapy, while adding new indications and expanding into adjacent therapeutic areas. In addition, Doug Ingram, president and chief executive officer, Sarepta, will be appointed to Arrowhead’s Board of Directors.

The clinical-stage programs covered under the agreement include:

ARO-DUX4: designed to reduce the production of human double homeobox 4 (DUX4) protein in skeletal muscle; currently in a Phase 1/2 clinical study for the treatment of facioscapulohumeral muscular dystrophy (FSHD)
ARO-DM1: designed to target and suppress myotonic dystrophy protein kinase (DMPK) in skeletal muscle; Phase 1/2 clinical study for myotonic dystrophy type 1 (DM1)
ARO-MMP7: designed to reduce expression of matrix metalloproteinase 7 (MMP7) in pulmonary epithelial cells; Phase 1/2 clinical study for idiopathic pulmonary fibrosis (IPF)
ARO-ATXN2: designed to target the ataxin-2 protein (ATXN2) in the CNS; expected to begin Phase 1/2 clinical study for spinocerebellar ataxia 2 (SCA2) by the end of 2024

The clinical programs use Arrowhead’s proprietary Targeted RNAi Molecule (TRiM^TM) platform, which is designed to deliver siRNA to multiple tissue and cell types throughout the body to initiate the RNA interference mechanism and induce rapid and durable knockdown of target genes.

The preclinical programs covered under the agreement will leverage Arrowhead’s TRiM CNS delivery platform designed for subcutaneous administration and include:

ARO-ATXN1: designed to target the ataxin-1 protein (ATXN1) for SCA1
ARO-ATXN3: designed to target the ataxin-3 protein (ATXN3) for SCA3
ARO-HTT: designed to target huntingtin (HTT), a gene linked to Huntington’s disease

Additionally, Sarepta and Arrowhead have entered into a discovery collaboration for up to six additional muscle, cardiac, and/or CNS targets, using Arrowhead’s novel delivery technologies. As part of the collaboration, Sarepta has an exclusive license to Arrowhead’s technology to develop therapeutics against a broad range of skeletal muscle gene targets.

“With the launch of Elevidys going exceedingly well, this broad siRNA collaboration with Arrowhead provides a synergistic platform to complement Sarepta’s gene therapy and gene editing engine. Through a strategic deployment of capital, we are able to access Arrowhead’s leading RNAi platform and will work to rapidly advance new treatments for devastating genetic diseases where there is significant unmet need. The agreement affords multiple potential blockbuster opportunities, serves our strategic priorities for the remainder of the decade and beyond, and diversifies our business model across one-time therapies and chronic treatments allowing for long-term growth and success. Given the strength of our performance and ability to generate substantial cash to invest in our business over the next several years, Sarepta’s Board of Directors has approved a $500 million share repurchase program as part of our overall capital allocation strategy,” said Mr. Ingram. “We look forward to embarking on this partnership with Arrowhead, having been impressed with their scientific capabilities in developing a potentially best-in-class approach to siRNA and the quality of the team they have built. Over the course of the next 12-18 months, we expect to share multiple data readouts from across our pipeline.”

“We welcome the Sarepta team as new Arrowhead collaboration partners who bring a wealth of clinical, regulatory, and commercial expertise in key areas outside of our cardiometabolic focus. We see our TRiMplatform as a broad and elegant solution for delivery of siRNA to multiple cell types throughout the body. We also have a very efficient drug discovery engine that continues to generate many promising programs, and we have great confidence in Sarepta’s ability to take the next steps to advance and commercialize multiple Arrowhead-discovered drug candidates, which we believe have the potential to be best-in-class,” said Chris Anzalone, Ph.D., president and CEO at Arrowhead. “At the close of this agreement, Doug Ingram will be appointed to the Arrowhead board of directors. He has led Sarepta as they advanced multiple investigational medicines through the clinical and regulatory process, built a commercial organization from the ground up, launched multiple drugs, and moved the company toward profitability. His experience and guidance will be valuable as Arrowhead seeks the same transition.”

“Robust and compelling early data from Arrowhead’s differentiated siRNA approach platform suggests potentially best-in-class treatments that will profoundly improve the lives of those with rare, genetic diseases,” said Louise Rodino-Klapac, Ph.D., chief scientific officer and head of research and development, Sarepta. “The targeted ligand approach, combined with Arrowhead’s clinically validated siRNA chemistry, suggests the potential for deep and durable knockdown of proteins that are over-expressed in these conditions. Arrowhead’s innovative approach to cross the blood brain barrier with subcutaneous dosing represents a potential paradigm shift for the CNS preclinical and discovery programs as part of this collaboration.”