Startup aiming to push boundaries of gene therapy nets $55M in seed cash

2022-07-25

基因疗法

Genetic medicines have a capacity problem. The engineered viruses used to deliver them have limited room for their genetic cargo, which in turn limits the way diseases can be treated—if they can be treated at all. A new biotech company named Replay has assembled a suite of technologies that could enable it to deliver “big genes” or even multiple genes, and it has emerged with $55 million to advance its research. The seed round announced Monday was led by KKR & Co. and OMX Ventures. The delivery vehicle of choice for many experimental genetic medicines is the adeno-associated virus (AAV), which can be engineered to ferry DNA to target cells. The capacity of AAV is just under 5 kilobases (kb). San Diego-based Replay claims it can achieve a payload capacity up to 30 times greater. It aims to do so with its synHSV technology, which employs an engineered herpes simplex virus (HSV). In addition, Replay’s toolkit includes technologies that enable it to efficiently write its big genes and big DNA, and a technology that can produce “off-the-shelf” therapies. The capacity limitation of AAV is apparent in the research of genetic medicines for Duchenne muscular dystrophy. Sarepta Therapeutics, Solid Biosciences and Pfizer have reached clinical testing with their respective gene therapies, each one engineered to deliver a functioning version of the gene needed to treat the inherited muscle-wasting disorder. But the genes that produce the key protein at the root of Duchenne are big, so the therapies are comprised of “micro” versions of the gene small enough to fit on an AAV vector. Duchenne is one of the disease targets of Replay. The therapy in development for that muscle-weakening disorder is 14 kb, according to the company’s website. But Replay won’t be going directly head to head against the field of potential gene therapies for Duchenne. Under Replay’s business model, the various technologies it owns are developed in a disease-agnostic way. When Replay identifies an area that can specifically be addressed by one or more of its technologies, it forms a product company to pursue that area. The Duchenne research is housed in one such product company. “Technology and product development have different talent requirements, timelines, costs and cultures,” Replay CEO and co-founder Lachlan MacKinnon said in a prepared statement. “By separating technology development from product development, we have generated a model to accommodate these differences. Our ability to write and deliver big DNA has the potential to disrupt many areas of genomic medicine.” Replay says it has formed five product companies to date. In the eye, one company is focused on retinitis pigmentosa, a group of rare retinal disorders that leads to degeneration of photoreceptors. The Replay website lists two gene therapy constructs for retinitis pigmentosa: one is 7 kb and the other is 9 kb. A Replay skin product company is developing a treatment for dystrophic epidermolysis bullosa, an inherited disorder that leads to extremely fragile skin that is prone to widespread blistering. The experimental therapy of that company is 19.2 kb. Replay’s brain product company has the biggest of its genetic medicines in development, a 40 kb therapy for Parkinson’s disease. A fifth product company is focused on enzyme writing. There are other startups that, like Replay, are turning to AAV alternatives in the quest for better genetic medicines. Last month, Philadelphia-area startup Code Bio closed a $75 million Series A round of funding to support the development of synthetic DNA-based therapies for two lead indications, Duchenne and type 1 diabetes. The new round of financing for Replay included participation from Artis Ventures, Lansdowne Partners, SALT, DeciBio Ventures and Axial.

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