Sana Biotechnology (SANA) Study Result summary

Study background and objectives

• Type 1 diabetes results from autoimmune destruction of pancreatic beta cells, leading to lifelong insulin dependence and complications.

• The study investigated the use of HIP-edited allogeneic islet cells to evade immune rejection in type 1 diabetes without immunosuppression.

• First-in-human, single-arm, open-label phase 1 trial (UP421) was conducted at Uppsala University Hospital, targeting safety, immune evasion, and cell survival.

• Patient received a low dose (2%-7% of curative dose) of HIP-modified islet cells intramuscularly, with no immunosuppressive drugs.

• Manufacturing of UP421 took seven days and met all release criteria.

Preclinical and clinical evidence

• HIP-modified islet cells controlled glucose in diabetic non-human primates for six months without immunosuppression.

• Preclinical data show HIP PSC-derived islet cells persist and control glucose in mice for over 64 weeks.

• Transplanted HIP islet cells survived, functioned, and normalized glucose in NHPs, with a safety switch demonstrated via anti-CD47 antibody.

• Patient had undetectable C-peptide at baseline, confirming new insulin production was from transplanted cells.

• The product (UP421) consisted of 25-80 million HIP islet cells injected intramuscularly.

Key results and findings

• All interim primary and secondary endpoints were met, with no adverse or serious adverse events related to the drug product.

• Stable and detectable C-peptide levels observed post-transplant, with increases after mixed meal tolerance testing, indicating new insulin production.

• MRI at day 28 confirmed graft survival at the injection site with no inflammation or pathological findings.

• HIP islet cells survived and functioned without immunosuppression, while non-HIP or partially edited cells were rejected.

• C-peptide levels increased during mixed meal tolerance tests, indicating insulin secretion in response to meals.