SpliceBio has raised 50 million euros ($57 million) from a starry syndicate to tackle one of the biggest barriers in gene therapy. Armed with the series A funds, the Barcelona-based biotech will advance gene therapies based on a platform that could bypass the cargo capacity of adeno-associated vectors (AAVs).
AAVs are the go-to delivery gene therapy vehicle but their packaging capacity limits the diseases that can be tackled. With a packaging capacity of around 4.7 kb, AAVs are simply too small to deliver some genes, preventing progress in the treatment of many diseases with known genetic causes. SpliceBio's answer is to split genes and use inteins to create a functioning, full-length protein out of the resulting fragments.
The idea of splitting up the cargo to sidestep the AAV capacity limit has been knocking around for years, with researchers exploring homologous recombination and trans-splicing without finding a definitive solution to the problem. SpliceBio thinks it can improve on those approaches with a platform based on technology developed in the Muir Lab at Princeton University.
“They were not very efficient, so they failed to produce significant levels of the protein that you want to reconstitute. What we have seen with our data is that we can actually reconstitute levels of protein that are very close to the wild type levels, so significantly higher than what you can achieve with these other platforms out there,” SpliceBio CEO Miquel Vila-Perelló said.
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SpliceBio has persuaded some big-name investors that it is on the right track. UCB Ventures co-led the series A round with Ysios Capital, the cornerstone of the blossoming Spanish biotech scene. SpliceBio also received money from New Enterprise Associates, Gilde Healthcare and Novartis Venture Fund, as well as existing investor Asabys Partners.
The mix of corporate and institutional investors, and European and U.S. backers, means SpliceBio has an unusually diverse syndicate by the standards of series A round as it sets out to show its platform can live up to its promise. SpliceBio’s first goal is to use its platform to tackle Stargardt disease, a form of juvenile macular dystrophy that affects more than 80,000 people in the U.S. and the EU.
“It's a gene that is an ideal target for our approach because it's too large for AAVs, so we can address an unmet need,” Vila-Perelló said. “Also, something that makes it attractive as a first indication is that it's a retinal disease, so we can do a very localized administration and don’t need to get into doing systemic administration of the gene therapy product.”
The total AAV dose will be split evenly between the two payloads but Vila-Perelló said SpliceBio can keep in the dose ranges that are known to be safe in the clinic. SpliceBio will face other challenges as it moves beyond the eye but, having validated the technology in other organs, it has ongoing research programs outside of ophthalmology.