Sixfold Bioscience snares U.K. grant to test cancer-fighting siRNA delivery system

Gene silencing therapies have made small gains in diseases affecting the liver, but pitting those RNA-based treatments against cancer has proven a more formidable task. A targeted delivery system could be just the ticket, one British biotech thinks, and it recently won its third government grant to prove its platform has what it takes.

Sixfold Bioscience snared an Innovate UK Smart Grant to run early tests on its targeted cancer drug delivery system, the company said. Set to run for 18 months, the project will yield a preclinical data pack to help Sixfold hustle its platform into the clinic, potentially by early 2022.

The young biotech, based at the Innovation and Translation Hub in White City, London, is developing a Programmable Oligonucleotide Delivery System, or PODS, that aims to deliver short interfering RNA (siRNA) gene silencing cargo to specific cancer cells while leaving healthy cells unharmed.

Sixfold is partnering with the U.K.’s Medicines Discovery Catapult on the project, with plans to leverage the drug discovery program’s imaging facilities for preclinical assessment and delivery system validation. That information will go toward a clinical plan-of-attack, with Sixfold shooting for “rapid commercialization” and clinical advancement of the drug delivery platform once the project wraps.

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Gene silencing RNA treatments have yet to muster an approval in cancer patients, but Sixfold’s delivery system could change that, co-founder and managing director Anna Perdrix Rosell, Ph.D., figures.

RNA therapeutics have the strongest foothold in the liver, and Alnylam Pharmaceuticals has the only two siRNA drugs currently on the market: Onpattro, which boasts a green light in adults with peripheral nerve disease, or polyneuropathy, caused by hereditary transthyretin-mediated amyloidosis—and Givlaari (givosiran), approved to treat adults with the ultra-rare genetic disease acute hepatic poryphyria (AHP).

The most common delivery routes for siRNA drugs—GalNAc conjugates, self-delivery and lipid nanoparticles—can only be used to deliver the gene silencers to a few key organs, namely the liver and the eye.

Despite drugmakers' efforts to mount siRNA treatments against cancer, none has advanced beyond the clinic, and several have fallen short because of weaknesses in their delivery systems, Sixfold posited in a white paper earlier this summer.

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The defunct Arrowhead subsidiary Calando Pharmaceutical, for instance, axed its polymer-based siRNA hopeful for solid tumors because of an unstable delivery system, which prevented sufficient buildup of the drug in tumors, Sixfold said.  

Meanwhile, Sixfold’s delivery platform has been gaining heat over the past year. The company in late 2019 won a separate set of Innovate UK grants to run cell tests on its delivery platform with the U.K.’s National Metrology Institute, The National Physical Laboratory (NPL) and the National Measurement Laboratory (NML).

At the time, Sixfold said it would use NML’s mass spectrometry and NPL’s high-resolution imaging services to establish in vivo quantification methods for PODS, optimizing the system for targeted cancer treatment.

That project kicked off in October of last year and is scheduled to wrap this month.