BIOTECH: Replay launches first two companies under unique business model

BIOTECH: Eudora, Telaria Utilize Next-Gen HSV Delivery

After coming out of stealth this summer with a $55 million seed round for its “huband-spoke” business model, Replay's hub is already producing spoke companies.

On Halloween, Replay announced the launch of its first platform company to utilize Replay's high payload capacity herpes simplex virus (HSV) delivery vector, synHSV. Eudora is a gene therapy company targeting genetic retinal diseases. On Nov. 21, the company followed up that announcement with the launch of its second company, Telaria – a gene therapy company targeting rare skin diseases. Both companies utilize Replay's high payload capacity herpes simplex virus (HSV) delivery vector, synHSV.

Replay's distinctive hub-and-spoke corporate structure separates technology development from therapeutic product development within disease area-specific product companies. Eudora and Telaria are the first of Replay's four synHSV gene therapy product companies, with the other two yet to launch companies applying gene therapy to monogenic diseases of the brain and muscle.

“Eudora is the first of a series of Replay product companies, each of which showcases unique aspects of our suite of proprietary genomic medicine platform technologies,” said Replay CEO and co-founder Lachlan MacKinnon. “We believe that our distinctive paradigm of separating platform development from product development represents the most optimal structure for efficiently leveraging the potential of our genomic medicine technology platforms and for bringing forward a new generation of genomic medicines to patients with high unmet medical needs.”

Retinal Disease Pipeline

Eudora launched with a pipeline targeting retinitis pigmentosa, Stargardt disease and Usher syndrome type 1B. The company's HSV-1 technology was licensed from the University of Pittsburgh, where it was developed by leading HSV specialist and entrepreneur Professor Joe Glorioso, who now also serves as synHSV senior advisor at Replay.

Glorioso and Eudora co-founders Mark Blumenkranz, HJ Smead Professor Emeritus in the Department of Ophthalmology at the Stanford School of Medicine; and David Schaffer, Hubbard Howe Professor of Chemical and Biomolecular Engineering, Bioengineering, and Molecular and Cell Biology at the University of California, Berkeley, previously founded publicly traded biotech companies Oncorus, Adverum and 4D Molecular Therapeutics, respectively. Vinit Mahajan, professor of ophthalmology at the Stanford School of Medicine, is also on the co-founding team.

“I believe that our next-generation HSV delivery platform has several distinct advantages, and the potential to be disruptive to existing viral delivery platforms,” Glorioso said. “It will enable the delivery of large genes, as well as genomic genes that cannot readily be accommodated by AAV vectors. I am delighted to be able to further advance this technology with this distinguished team, who have a compelling track record of developing eye gene therapies and progressing them into the clinic.”

Replay's synHSV technology is capable of delivering up to eight times the payload of adeno-associated virus (AAV) vectors. This facilitates the delivery of genes that are too big to fit into AAV and enables polygenic gene therapy.

The technology “offers the possibility of addressing genetic eye diseases caused by large genes and genomic genes,” Mahajan said. “This will result in an increased variety of gene therapy options for patients with genetic eye diseases.”

Hope For Rare Skin Disease

Glorioso is also a co-founder of Telaria, Replay's second company to use the synHSV tech he developed. In addition to Glorioso, Telaria's co-founders include John McGrath, a leading expert in genetic skin diseases, and Alexander Silver, co-founder and Chairman Emeritus of the Epidermolysis Bullosa Research Partnership. Jakub Tolar, distinguished McKnight Professor in the Department of Pediatrics, Blood and Bone Marrow Transplantation & Cellular Therapy at the University of Minnesota Medical School, is the senior advisor to the company.

The lead indication in Telaria's pipeline is recessive

dystrophic epidermolysis bullosa (RDEB), a genetic skin disease with no cure that causes the skin to be fragile and blister easily. RDEB affects approximately 50,000 people worldwide and is generally more severe than its dominant counterpart and involves widespread blistering that may lead to scarring, severe pain, and disfigurement. It can also affect multiple internal organs and cause serious medical issues including chronic inflammation and squamous cell carcinoma. A disease-modifying gene therapy with the ability to heal wounds more rapidly or prevent their formation would represent a significant benefit to patients.

“The skin is an attractive target for gene therapies and is the largest and most accessible organ,” said Adrian Woolfson, chairman, president and co-founder of Replay, adding that Telaria “represents another significant step towards building an enduring company with the potential to shape the future of genomic medicine through addressing some of the most substantive challenges that currently limit the progress of clinical medicine.”

Technology Development

In Replay's “hub” portion of its business model, technology development, the company is currently building on its synHSV platform and developing an HSV vector capable of delivering up to 30 times the AAV payload.

Other technologies in the works include a genomically rewritten stem cell source for regenerative medicines and therapies that is universal and renewable; a genome writing platform for creating low-cost libraries of synthetic genes and DNA; and an inference algorithm platform for rewriting proteins to optimize their functionality.