Gene drugs have capacity issues. The engineered viruses used to deliver them have limited space for their genetic cargo, which in turn limits how diseases can be treated—if they can be treated. A new biotech company called Replay has assembled a suite of technologies that could enable it to deliver “big genes” or even multiple genes, and has secured $55 million to advance its research.
This seed round The announcement on Monday was led by KKR & Co. and OMX Ventures.
The delivery vehicle of choice for many experimental genetic drugs is adeno-associated virus (AAV), which can be engineered to deliver DNA to target cells. AAVs have a capacity of less than 5 kilobases (kb). San Diego-based Replay claims it can achieve up to 30 times the payload capacity. It aims to achieve this through its synHSV technology, which uses an engineered herpes simplex virus (HSV). In addition, Replay’s toolkit includes technologies that allow it to efficiently write its large genes and DNA, as well as technologies that can produce “off-the-shelf” therapies.
The capacity limitation of AAV is evident in a genetic drug study in Duchenne muscular dystrophy. Sarepta therapySolid State Bioscience and Pfizer Already clinically tested with their respective gene therapies, each has been engineered to deliver the functional version of the gene needed to treat hereditary muscular dystrophy. But the genes that make key proteins in Dulbecco’s roots are large, so the treatment consists of “miniature” versions of the genes that are small enough to fit in an AAV vector.
Duchenne is one of Replay’s disease targets. According to the company’s website, the therapy being developed for this muscle-debilitating disease is 14 kb. But Replay won’t go head-to-head with Duchenne’s potential gene therapy field. Under Replay’s business model, the various technologies it has are developed in a disease-agnostic way. When Replay identifies an area that it can specifically address through one or more of its technologies, it forms a product company to pursue that area. Duchenne Research is housed in such a 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 generated a model to accommodate these differences. Our ability to write and deliver large DNA has the potential to disrupt many areas of genomic medicine.”
Replay said it has formed five product companies so far. On the eye side, one company focused on retinitis pigmentosa, a group of rare retinal diseases that cause photoreceptor degeneration. The Replay website lists two gene therapy constructs for retinitis pigmentosa: one is 7 kb and the other is 9 kb. A Replay skin products company is developing a treatment for dystrophic epidermolysis bullosa, a genetic disorder that causes the skin to be extremely fragile and prone to large blisters. That company’s experimental therapy is 19.2 kb. Replay’s Brain Products company has the largest genetic medicine in development, a 40 kb Parkinson’s disease treatment. A fifth product company focuses on enzyme writing.
There are other startups, like Replay, that are turning to AAV alternatives for better genetic medicines.Last month, startups in the Philadelphia area Code Bio Closes $75M Series A to Support Development of DNA-Based Synthetic Therapeutics For two main indications, Duchenne and type 1 diabetes.
Replay’s new funding round includes participation from Artis Ventures, Lansdowne Partners, SALT, DeciBio Ventures and Axial.
photo: iLexxGetty Images
