New Type of Stem Cell Transplant Shows Promise in Type 1 Diabetes

A first-in-human study of Sana Biotechnology’s transplanted islet cells has shown potential as a possible treatment for type 1 diabetes, enabling an enrolled patients to avoid immune rejection and produce insulin.

“The clinical data are highly promising for patients and provide the first evidence in humans for overcoming allogeneic and autoimmune rejection with pancreatic islet cell transplantation in type 1 diabetes with no immunosuppression,” Per-Ola Carlsson, M.D., study principal pnvestigator, senior physician and professor at the Clinic for Endocrinology and Diabetology at Uppsala University Hospital, said in a news release.

The therapy, UP421, is an allogeneic primary islet cell therapy engineered with Sana’s hypoimmune (HIP) technology.

“Cell therapy has offered significant promise, but its impact has been limited, in part, because of immune rejection of allogenic cells,” Steve Harr, M.D., Sana’s president and CEO, said in an investor call earlier this month.

The company’s platform enables it to make a series of genetic modifications to cells, which it calls hypoimmune platform. This, Harr said, renders the cells invisible to a patient’s immune system. “The data are consistent that modification with HIP to evade immune detection,” Harr said. “The area where we think we can have the most impact is in type 1 diabetes.

In this investigator-sponsored study of UP421, researchers wanted to test the hypothesis whether HIP-engineered insulin-producing pancreatic cells can be transplanted safely and help to regain insulin production in people with type 1 diabetes without need of simultaneous treatment with immunosuppressive medicines.

Investigators at Oslo University Hospital administered UP421 through an intramuscular surgical transplantation of deceased donor-derived HIP-engineered islet cells into the forearm of patients with type 1 diabetes. The primary objective of the study is to investigate the safety of UP421 transplantation in patients with type 1 diabetes, with secondary endpoints including cell survival, immune evasion, and C-peptide production. Circulating C-peptide is a measure of endogenous insulin production.

A low dose of HIP-modified primary islets is being used initially to establish the safety and function of HIP-modified islets without immunosuppression and, as a result, is not intended to show improvement in glycemia and/or reduction in exogenous insulin administration.

Researchers found that four weeks after cell transplantation, UP421 demonstrated the survival and function of pancreatic beta cells as measured circulating C-peptide, a biomarker indicating that transplanted beta cells are producing insulin. Additionally, insulin secretion was seen in response to a meal. MRI scanning also demonstrated a sustained signal at the site of transplanted cells over time, which is consistent with graft survival.

The study identified no safety issues, and the HIP-modified islet cells evaded immune responses.

Sana is also conducting preclinical development of SC451 (HIP-modified stem cell-derived pancreatic islet cells), also for patients with type 1 diabetes.