Sernova Testing AgeX’s UniverCyte Technology to Deliver FVIII to Hemophilia A Patients

Sernova will use AgeX Therapeutics’ UniverCyte gene technology to create a cell-based therapy that delivers therapeutic levels of factor VIII (FVIII) — the blood clotting protein deficient in people with hemophilia A — specifically designed to avoid immune detection, eliminating the need for tissue matching or immunosuppressive medications. 

Sernova plans to use these so-called off-the-shelf, universal therapeutic cells with its Cell Pouch System, a delivery device inserted under the skin that acts as a natural environment in the body to house and support long-term cell survival and function. 

With a similar intent, the company is evaluating UniverCyte technology to create immune-protected pancreatic cells to produce insulin for treating people with type 1 diabetes. 

“We are thrilled with our collaboration with Sernova, which is at the forefront of cellular therapies for diabetes and hemophilia and is already in the clinic for the former,” said Nafees Malik, MD, chief operating officer of AgeX, in a press release. “The combination of AgeX’s UniverCyte to cloak cells from a patient’s immune system and Sernova’s Cell Pouch technologies to permit cells to function long-term upon transplantation would be a landmark for regenerative medicine.”

Under the terms of the agreement, AgeX licensed UniverCyte gene technology to Sernova for a specific period, which, depending on the outcome of studies, may be negotiated further.

“This deal marks another important step in AgeX’s collaboration and licensing strategy to work with the very best people, companies and institutions in the world of regenerative medicine,” Malik said.

The hemophilia A treatment strategy will be first to isolate endothelial cells that line blood vessels, shown to produce FVIII, then insert an altered human form of the F8 gene using a harmless lentivirus, which has a long incubation period. 

These cells will be modified by UniverCyte technology, which uses an altered form of a cell-surface protein called HLA-G, a potent immunomodulatory molecule. Normally, HLA-G protects an unborn child from its mother’s immune system. After birth, its production is silenced in almost all human cells. 

Adding HLA-G to cells has been shown to resist this silencing, evading immune detection, potentially eliminating the need for tissue matching (to prevent rejection) or immunosuppressive medications. 

Sernova’s implanted Cell Pouch, which merges with tissue and forms highly vascularized chambers, then will house these immune-protected cells for the sustained production of FVIII. 

In a preclinical study, 80% of F8-corrected endothelial cells produced high levels of FVIII. When delivered on tiny carrier beads into the abdominal (peritoneal) cavity of mice engineered to mimic symptoms of hemophilia A, the corrected cells survived and secreted FVIII at therapeutic levels (12%) for up to 18 weeks, and eased bleeding. 

The Cell Pouch implanted under the skin showed successful grafting for up to 12 weeks.

In adults with diabetes, the Cell Pouch System has demonstrated initial safety and efficacy in an ongoing Phase 1/2 clinical trial (NCT03513939). 

“We look forward to working with AgeX and its outstanding team as we continue to identify and evaluate technologies complementary to Sernova’s therapeutic platform and expand our immune protection offerings,” said Philip Toleikis, PhD, president and CEO of Canada’s Sernova. 

“AgeX’s UniverCyte technology is a significant advancement in the field of cell therapy and a perfect fit with Sernova’s Cell Pouch technologies and therapeutic pipeline with its potential benefit over current immunosuppressive strategies for regenerative medicine therapeutics,” he added.