Sana Biotechnology, in partnership with Uppsala University Hospital, has announced positive initial results from a first-in-human study evaluating UP421, an allogeneic primary islet cell therapy, in a patient with type 1 diabetes. The groundbreaking aspect of this study is the use of Sana's hypoimmune (HIP) technology, which allowed for islet cell transplantation without the need for immunosuppression.
The data, announced January 7, 2025, demonstrated the survival and function of pancreatic beta cells four weeks post-transplantation, as evidenced by the presence of circulating C-peptide, a key biomarker indicating insulin production. The patient also showed increased C-peptide levels during a mixed meal tolerance test (MMTT), suggesting that the transplanted cells were responsive to glucose stimulation. Furthermore, MRI scans confirmed graft survival at the transplantation site.
Hypoimmune Platform Efficacy
Steve Harr, Sana's President and CEO, emphasized the significance of these findings, stating, "As far as we are aware, this is the first study showing survival of an allogeneic transplant with no immunosuppression or immune-protective device in a fully immune competent individual." This outcome suggests that Sana's HIP technology effectively shields the transplanted cells from both allogeneic and autoimmune rejection, a major hurdle in cell-based therapies for type 1 diabetes.
Clinical Implications and Future Directions
Per-Ola Carlsson, MD, Study Principal Investigator and Professor at Uppsala University Hospital, highlighted the potential for a scalable, curative treatment. "Today's data, when combined with progress elsewhere in the field, provide real hope that a scalable, curative treatment for patients with type 1 diabetes, meaning normal blood glucose with no insulin injections or immunosuppression, is possible," said Carlsson.
Aaron J. Kowalski, Ph.D., CEO of Breakthrough T1D, echoed this sentiment, noting, "These initial clinical results show that cell therapies that replace insulin-producing cells without immunosuppression are approaching reality as a meaningful and potentially life-changing cure for type 1 diabetes."
UP421: Details of the Clinical Trial
The investigator-sponsored study of UP421 is supported by a grant from The Leona M. and Harry B. Helmsley Charitable Trust. In the study, UP421 cells, engineered using Sana's HIP platform at Oslo University Hospital, were transplanted intramuscularly into the forearm of a patient with type 1 diabetes. The primary objective was to assess the safety of UP421 transplantation, with secondary endpoints including cell survival, immune evasion, and C-peptide production.
Addressing the Unmet Need in Type 1 Diabetes
Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing beta cells in the pancreas. Current treatments, including insulin injections and islet cell transplantation with immunosuppression, have limitations. Insulin injections require careful management to avoid hypo- and hyperglycemia, while conventional islet cell transplantation necessitates chronic immunosuppression to prevent rejection, which can lead to serious side effects.
Sana's HIP technology offers a potential solution to these challenges by enabling islet cell transplantation without the need for immunosuppression. This approach could significantly improve the safety and efficacy of cell-based therapies for type 1 diabetes, offering a more durable and convenient treatment option for patients.
Advancing SC451
Sana Biotechnology plans to leverage the insights gained from the UP421 study to advance its SC451 program, a stem cell-derived pancreatic islet cell therapy also engineered with HIP technology. By combining stem cell technology with immune evasion strategies, Sana aims to develop a scalable and potentially curative treatment for type 1 diabetes that can benefit a broader population of patients.
