POSITIVE RESULTS

Sana's hypoimmune islet cells still working without immune drugs at 14 months

A NEJM letter details 14-month follow-up on the first human dosed with UP421, showing the HIP-modified islets survived, evaded rejection and kept producing insulin without immunosuppression.

By AppliedXLJuly 13, 2026Trial NCT06239636

Executive Summary

A hypoimmune-modified islet cell transplant kept producing insulin and evading immune rejection more than a year after dosing, without any immunosuppressive drugs.
The finding builds on data already featured in a 2025 NEJM article, adding longer follow-up that shows the effect persisting and even improving rather than fading.
The durability signal underwrites the sponsor's push to move a stem cell-derived, scalable version of the same platform into a larger clinical trial.
The evidence still rests on a single treated patient, so the readout demonstrates biological proof of concept rather than a population-level result.

The finding

The letter describes results in NCT06239636, a first-in-human, Early Phase 1 safety study of UP421 in adults with type 1 diabetes run at Uppsala University Hospital in Sweden. At 14 months after transplantation, the treated patient's islet cells remained detectable on imaging and continued secreting C-peptide, a marker that beta cells are producing insulin, both at rest and in response to a mixed meal tolerance test (MMTT). The patient had undetectable C-peptide at baseline. Fasting and MMTT-stimulated C-peptide levels at month 14 matched those seen in the first six months of the study and exceeded the levels measured at months 9 and 12, and the patient achieved tighter glycemic control between months 12 and 14. NCT06239636+1

Probability of Success

Endpoint Met11%

Completes42%

Clinical Significance20%

Regulatory73%

The design

The trial is registered to enroll 2 adults aged 30 to 45 with long-standing type 1 diabetes, C-peptide negative at baseline, and it is testing safety as its registered primary endpoint, measured by treatment-related adverse events under CTCAE v5.0. Ten secondary endpoints cover C-peptide response, HbA1c change, glucose variability, insulin requirement, immune evasion markers, and cell survival by MRI. Per-Ola Carlsson, the study's principal investigator and a professor at Uppsala University Hospital's Clinic for Endocrinology and Diabetology, said the follow-up data support that 'a functional cure for type 1 diabetes without immunosuppression is possible'. The cells were engineered with Sana Biotechnology's hypoimmune (HIP) gene-editing platform to evade allogeneic and autoimmune rejection without drug-based immune suppression. NCT06239636+1

What comes next

Sana Biotechnology, which supplied the HIP editing technology, said it expects to file an investigational new drug application and start a Phase 1/2 trial as early as this year for SC451, a stem cell-derived successor therapy built on the same hypoimmune platform. Gary Meininger, Sana's Chief Medical Officer, said the company is 'inspired by the opportunity to move beyond lifelong disease management' with SC451. The single-patient UP421 program remains Recruiting toward its anticipated 2-subject enrollment target, with a primary completion date registered as May 1, 2025. Sana+1

The competitive frame

Islet and stem-cell-derived transplant approaches are an established modality in type 1 diabetes, with 47 trials using cell therapy identified in the indication. Peer programs in early clinical testing include Treg-cell and other regulatory-immune approaches from PolTREG, islet or stem-derived candidates from Seraxis, Encellin, GentiBio and Celregen, and an islet transplant program from Hangzhou Reprogenix that shares the same modality but not the hypoimmune target. None of these identified peers share UP421's specific gene-edited immune-evasion mechanism, so the durability signal in this single patient stands without a direct mechanistic precedent to benchmark against in the current field. NCT06239636

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