Biotech startup Dyno Therapeutics formally unveiled itself Monday, announcing plans to design better gene therapies in partnership with Novartis and Sarepta Therapeutics, both leading companies in the field.
Dyno grew out of Harvard University's gene therapy laboratories, which have studied techniques for using artificial intelligence to design more efficient delivery vehicles for genetic treatments.
Many current gene therapies use adeno-associated viruses, or AAVs, which don't cause disease in humans and only stimulate a mild immune response. Roche's Luxturna and Novartis' Zolgensma, for example, both use AAV vectors to deliver functional genes into cells impaired by DNA mutations.
AAVs, however, have limitations ranging from how well they target cells that need to receive gene replacements, to how much genetic material they can carry, to how efficiently they can be manufactured. Dyno hopes to address some of those issues by designing capsids — the viral shell that enables a virus to enter a human cell — that will optimize gene therapy delivery.
"The natural capsids don't do it," Dyno CEO Eric Kelsic said in an interview with BioPharma Dive. "They were never evolved for therapeutic use, so they have some beneficial features, but they're certainly far from optimal."
Dyno joins Affinia Therapeutics and Taysha Gene Therapies in a new burst of university-based gene therapy spinouts this year built around improved AAV technologies. The activity is much needed: gene therapy pioneer James Wilson recently expressed disappointment at lack of progress in delivery tools.
Dyno's platform, which it calls CapsidMap, uses high-speed engineering and sequencing of DNA libraries to measure how a capsid would perform if used in humans. The data can then be used to develop a synthetic AAV capsid that will have properties sought after by biotech partners.
"Engineering them has been a challenge because what often happens is that you try to improve the capsids for one property, but the other properties get broken or get worse," Kelsic said of efforts that pre-date CapsidMap.
The Harvard Wyss Institute for Biologically Inspired Engineering built the technology before spinning out Dyno a year and a half ago. George Church, head of the laboratory, is co-founder and chairs its scientific advisory board.
The collaborations announced Monday will have Dyno apply its capsid-engineering tools to help Novartis develop gene therapies for eye diseases and Sarepta develop them for muscle diseases. In total, the partnerships could eventually yield $2 billion worth of revenue in the form of fees, research support and milestones, with the Sarepta collaboration delivering $40 million in near-term payments.
Under the terms of the collaboration, once Dyno identifies a capsid with the set of properties specified by its partners, those partners will then take over for gene insertion, pre-clinical and clinical work.
The collaboration revenue, plus money from a $9 million funding round in 2018, means Dyno has no need for an immediate fundraising, according to the company.
For Sarepta, the AAV capsid it had already selected for its leading Duchenne muscular dystrophy treatment has been satisfactory in targeting muscle cells while avoiding immune response. But there is room for improvement, Louise Rodino-Klapac, the company's gene therapy head, said in an interview.
"The body consists of 40% muscle. It's a lot of targets," she said. "Any way you can improve the efficiency of dosing, it's an advantage."
For now, Dyno will apply its technology to collaborations with pharma and biotech companies, in part because it is trying to make the capsid engineering platform more powerful. For now, the company will not be involved directly in drug development.
"A lot of young companies, as they move into developing a drug, lose their focus from their platform," said Alan Crane, Dyno's executive chairman and a partner at venture capital company Polaris Partners. "So in the early stage of the company we really want to stay focused on the leading platform, but we really reserved the opportunity in the future to develop our own product.'