Spot Biosystems announced its launch from stealth with $40 million in venture financing, along with preclinical research published in Nature Biomedical Engineering and an ongoing first-in-human clinical trial for Duchenne muscular dystrophy.
The company is developing a non-viral extracellular vesicle delivery platform for genetic medicines. Its lead program is focused on Duchenne muscular dystrophy, a severe and progressive neuromuscular disease caused by mutations in the DMD gene.
The peer-reviewed study in Nature Biomedical Engineering demonstrated that full-length dystrophin, whose absence causes Duchenne muscular dystrophy, could be delivered non-virally to skeletal muscle. In DMD knockout mice, extracellular vesicle-delivered dystrophin mRNA produced sustained protein expression and significantly improved muscle strength, endurance, and motor function. In non-human primates, repeated intravenous dosing resulted in sustained dystrophin expression without liver, kidney, or cardiac toxicity.
The research involved collaborators from Spot Biosystems, Peking University Shenzhen Graduate School, MD Anderson Cancer Center, Stanford School of Medicine, and the SMART Greater Bay Area International Clinical Trials Center.
Based on the preclinical data, Spot Biosystems has launched an investigator-initiated trial at Shanghai Children’s Medical Center. The first two pediatric DMD patients dosed in the study demonstrated safe delivery of full-length dystrophin to skeletal muscle tissue, which the company described as the world’s first reported case in humans.
The company said the two patients exhibited respective increases of more than 1,000% and more than 2,000% in dystrophin after one month of dosing, with functional muscle improvement observed for up to six months after dosing cessation. These findings are preliminary and based on a first-in-human cohort of two patients. Study investigators will continue assessing drug response and safety in larger patient populations and over longer treatment durations.
Spot Biosystems’ technology is designed to encapsulate large nucleic acid cargo encoding full-length dystrophin inside engineered extracellular vesicles and deliver them intravenously to skeletal muscle. The company said this approach offers potential advantages over viral vector technologies, including non-viral delivery, repeat dosing, the ability to carry larger therapeutic cargo, and applicability to chronic genetic diseases requiring long-term protein supplementation.
The company plans to continue generating and reporting first-in-human data through the investigator-initiated trial in China, with the goal of using those results to inform and accelerate a future U.S. regulatory pathway.
Spot Biosystems is backed by investors including LDV Partners, IDG Capital, Advantech Capital, Tiger Jade Capital, Shanda Ventures, the Stanford StartX fund, and Saltagen Ventures.
KEY QUOTES:
“We’re proud to achieve a fundamental breakthrough enabling non-viral gene therapy solutions for neuromuscular conditions like Duchenne muscular dystrophy, which potentially overcome the core challenges with riskier approaches. By using the body’s own delivery machinery to carry medicines that viral vectors cannot, we are able to successfully deliver the complete dystrophin gene to skeletal muscle and generate a positive response in animals, primates, and now in early trials with human patients. Our approach is a clinical proof of concept for a new modality of non-viral gene therapy that is not limited by nucleic acid cargo size and bears promise for hundreds of thousands of individuals suffering from rare disease in need of new treatment solutions.”
Andrew Lee, MD, PhD, Co-Founder of Spot Biosystems
“Although modern neuromuscular medicine has made strides in treating Duchenne muscular dystrophy, challenges with organ toxicity have unfortunately emerged with adeno-associated virus mediated gene therapy. While additional research on longer treatment regimens is needed, early sustained and improved muscle function without liver, kidney, or cardiac toxicity is a promising outcome for the future of EV-based gene therapy.”
Paul Heidenreich, MD, Professor and Vice-Chair for Quality, Department of Medicine at the Stanford University School of Medicine
“The extracellular vesicle delivery approach is a novel technology for DMD treatment that sidesteps the problems that have limited the viral gene therapy field for years. The combination of strong animal model findings and preliminary clinical signals in DMD patients augurs well for translation to the clinical sphere — and underscores that this platform is worth watching closely for broader indications.”
David Naylor, MD, DPhil, former President and Dean of Medicine at the University of Toronto
“Safe, repeatable delivery of a dystrophin-targeting therapy is a meaningful step towards bringing powerful new solutions to patients and families in the DMD community. This early progress driven by Spot Biosystems and their collaborators is incredibly encouraging.”
Pat Furlong, Founding President and former CEO of Parent Project Muscular Dystrophy and advisor to Spot Biosystems
