Sana reports 14-month survival of hypoimmune islet cells without immunosuppression in Type 1 diabetic patient

Seattle-based Sana Biotechnology announced 14-month follow-up data from a first-in-human study of UP421, an allogeneic islet cell therapy engineered with the company’s hypoimmune (HIP) platform, in a patient with Type 1 diabetes. The data support proof of concept for immunosuppression-free islet transplantation but remain early and not yet generalizable.

Trial specifics

The investigator-sponsored study, conducted at Uppsala University Hospital in Sweden, involved intramuscular transplantation of a single low dose of HIP-modified primary islet cells into the forearm of one patient with Type 1 diabetes. UP421 was derived from the islet cells of a deceased donor and engineered using Sana’s hypoimmune platform at Oslo University Hospital. The study was supported by a grant from The Leona M. and Harry B. Helmsley Charitable Trust.

The primary objective was safety, with secondary endpoints including cell survival, immune evasion, and C-peptide production — a circulating biomarker of endogenous insulin secretion. At baseline, the patient had undetectable C-peptide both fasting and during a mixed meal tolerance test (MMTT). At 14 months, fasting and MMTT-stimulated C-peptide levels were detectable and, according to the company, comparable to levels observed during the first six months of the study. C-peptide levels exceeded those measured at months 9 and 12, a difference the company attributed to tighter glycemic control achieved between months 12 and 14. A 52-week PET-MRI scan confirmed the presence of islet cells at the transplant site. No safety issues were identified through 14 months, the company said. The study was designed to establish safety and proof-of-concept at a low dose and was not intended to demonstrate glycemic improvement or reduction in exogenous insulin use.

Sana said it plans to file an investigational new drug (IND) application for SC451, a HIP-modified stem cell-derived islet cell therapy designed as a more scalable product, and to initiate a Phase I trial as early as this year. Full 14-month data were presented at the Advanced Technologies & Treatments for Diabetes (ATTD) conference.

Research context

Type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic beta cells. Islet cell transplantation from deceased donors is an established procedure that can restore endogenous insulin production, but it has historically required lifelong immunosuppression to prevent both allogeneic rejection and recurrence of the autoimmune attack. Sana’s HIP technology modifies cells to evade detection by the recipient’s immune system, potentially eliminating the need for immunosuppressive drugs.

The UP421 data, from a single patient, provide early evidence that HIP-modified cells can evade both allogeneic and autoimmune rejection, though the single-patient design limits generalizability. The treatment landscape for Type 1 diabetes centers on exogenous insulin delivery via injections or pumps, continuous glucose monitoring, and automated insulin delivery systems. Teplizumab (Tzield), developed by Provention Bio/Sanofi, received US FDA approval in 2022 to delay the onset of stage 3 Type 1 diabetes in at-risk individuals, but it does not restore beta cell function in patients with established disease. No stem cell-derived or genetically engineered islet cell therapy has received regulatory approval for established Type 1 diabetes.

Another notable competitor in the same field is Vertex Pharmaceuticals’ VX-880, an allogeneic stem cell-derived islet cell therapy requiring immunosuppression, evaluated in a Phase I/II trial in Type 1 diabetes and now the subject of Phase III study.