From The Editor | July 6, 2022

AAV Gene Therapy Takes On Kidney Disease

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By Matthew Pillar, Editor, BioProcess Online

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Some 37 million U.S. adults are living with chronic kidney disease. Global prevalence is more than 840 million. Yet over the past several decades, little therapeutic progress has been made, leaving patients with high burden and invasive treatment options including dialysis and transplant.

UK-based Purespring therapeutics set out to change that paradigm when it launched in 2020, but the scientific foundation on which the company was formed has been taking shape for more than two decades. Prof. Moin Saleem began studying podocytes—epithelial cells that cover the outer surfaces of the glomerular capillaries critical to the kidney’s filtration function—more than two decades ago in his academic work at the University of Bristol. At the time, his work was considered a bit on the fringe. “Everyone thought he was mad,” says Richard Francis, CEO at Purespring and a recent guest on episode 95 of the Business of Biotech podcast. “And today, there are conferences dedicated to the study of podocytes and the understanding of their role in cellular-level kidney function.”

Translating Cell-Level Kidney Research Into The Therapeutic Arena

Richard Francis, CEO, Purespring Therapeutics
Beyond his academic research chops, Prof. Saleem is a clinician, a pediatric nephrologist, to be specific, and Francis says Saleem’s enthusiastic drive to translate his research into viable treatments for patients was central to his decision to join the company in 2021. “He’s desperate to create products that help patients, and that's the type of partner that I wanted to have,” says Francis.

Prof. Saleem’s work has shown preclinical promise. His in vitro work and animal models replicating kidney disease in humans is well-recognized. He developed the first human podocyte cell lines, now used in research laboratories around the world. Ultimately, he cured monogenic kidney disease in mice, where gene therapy hadn’t previously been done.

Francis, who previously served as Division Head & CEO at Sandoz and President and SVP at Biogen during his nearly 20 years in big bio, had been looking for an early-stage opportunity when he met Prof. Saleem. He had three criteria for the company he’d lead: great science, a platform that would accommodate the development of multiple assets, and financiers willing to take a company to the commercial finish line. “I spent a bout a year talking to many biopharma leaders and venture capitalists, and I frequently found one of those things, often two of them, but never all three until I learned of Purespring,” he says.

Populating A Platform Around The Podocyte

The science is well-stated. The funding came to the tune of a $62 million series A led by Syncona last summer. The platform revolves around the podocyte, the function of which, says Francis, is central to more than 60 percent of kidney diseases. “The platform gives us an opportunity to address multiple kidney disease indications by targeting one cell. That’s exciting in AAV gene therapy, because all the important capsid and promoter development work will be reproducible from one program to the next. The one thing we’re hoping to change from one indication to the next is the gene of interest we insert,” he says.

The platform model creates the potential to shrink timelines, reduce regulatory risk, and minimize cost—three key challenges in the AAV gene therapy arena. The company is also pursuing a differentiator in a unique route of administration—direct to the kidney—which Francis says promises to require lower (thereby less costly) doses and address some of the toxicity issues that have beleaguered the clinical trials in the space.

Tune in to the Business of Biotech episode 95 for Francis’ take on the CMC and manufacturing strategies Purespring is building with the intent to take its candidates all the way to the commercial finish line.