Skip to content
type1.science
Phase 1Not yet recruitingNCT06239636

Sana SC451: hypoimmune stem-cell-derived islets without immunosuppression

A stem-cell-derived islet therapy gene-edited to hide from the immune system, aiming to cure type 1 diabetes with a single off-the-shelf treatment and no immunosuppression. SC451 has no trial registered yet (IND/Phase 1 expected 2026), but is built on a landmark first-in-human study in which gene-edited donor islets survived and made insulin for over a year in a patient taking no immunosuppressive drugs.

Primary endpoints

  • SC451: endpoints not yet defined (trial not registered); expected to be safety/tolerability and evidence of engraftment and insulin production in a first-in-human Phase 1
  • Foundational UP421 study primary endpoint: safety, measured by number of treatment-related adverse events (CTCAE v5.0) over 12 months

Results so far

No SC451 clinical results yet (trial not started). In the foundational UP421 first-in-human study, gene-edited donor islets transplanted into a forearm muscle without any immunosuppression produced stable, glucose-responsive insulin with no immune response at 12 weeks; the sponsor reported continued cell survival, insulin production, and immune evasion through 14 months, with no serious treatment-related adverse events.

The full picture

What is being tested and why it matters

SC451 is an experimental cell therapy that aims to cure type 1 diabetes rather than manage it. The idea is to replace the insulin-making islet cells the immune system destroyed — but to do it without the lifelong anti-rejection drugs that have kept islet transplants from being practical for most people.1 Today, transplanting donor islets works, but it requires both a scarce supply of donor pancreases and heavy immunosuppression, whose side effects often outweigh the benefit for all but the most severe cases.2

SC451 attacks both problems at once. The cells are grown from induced pluripotent stem cells (iPSCs), so supply is effectively unlimited, and they are "O-negative" to act as a universal, off-the-shelf product.3 Crucially, they are gene-edited with Sana's "hypoimmune" (HIP) technology so the body's immune system does not see them as foreign — the goal being a single treatment, with no immunosuppression, that restores normal blood sugar without insulin injections.3

Who it's for

SC451 is being developed for people with established type 1 diabetes. As of 2026 it has no trial registered yet — Sana has said it expects to file an IND (the FDA application to begin human testing) and start a Phase 1 trial as early as 2026.3 Exact eligibility will be set when that trial opens.

The landmark study it is built on

SC451's credibility rests on a first-in-human study (NCT06239636) run at Uppsala University Hospital in Sweden and published in the New England Journal of Medicine in 2025.4 In that study, an earlier product, UP421 — HIP-edited islets from a donor, edited using CRISPR-Cas12b and lentiviral methods — was transplanted into a forearm muscle of a man with long-standing type 1 diabetes who received no immunosuppressive drugs.4 At 12 weeks he showed no immune response against the cells, and C-peptide (the marker of the body's own insulin production) was stable and rose appropriately after meals.4 Four adverse events occurred, none serious or related to the cells.4 The sponsor later reported the cells were still surviving, making insulin, and evading the immune system at 14 months, with imaging confirming live islet cells at the transplant site.5

Design

This was a tiny first-in-human safety study — about 2 participants, "Early Phase 1," with safety over 12 months as the main endpoint.6 It was a proof of concept, not a randomized efficacy trial. The same hypoimmune approach previously achieved insulin independence in a diabetic monkey without immunosuppression.7

What it means and what's next

The takeaway: gene-edited islets can hide from the immune system and keep working for over a year in a person, drug-free — the central bet of a universal cure.45 The open question is moving from scarce donor cells (UP421) to scalable stem-cell-derived cells (SC451), and from one patient to many. Watch for SC451's IND filing and first Phase 1 results.3

References

  1. Ziegler A-G, Cengiz E, Kay TWH. The future of type 1 diabetes therapy. Lancet (2025). https://doi.org/10.1016/S0140-6736%2825%2901438-2 ↩

  2. Perrier Q, Lablanche S, Benhamou P-Y. Cell therapy for type 1 diabetes: Tracing historical progress and exploring emerging technologies. Cell Transplantation (2025). https://doi.org/10.1177/09636897251394787 ↩

  3. Sana Biotechnology. Reports Fourth Quarter and Full Year 2025 Financial Results and Business Updates. GlobeNewswire (2026). https://www.globenewswire.com/news-release/2026/03/03/3248908/0/en/Sana-Biotechnology-Reports-Fourth-Quarter-and-Full-Year-2025-Financial-Results-and-Business-Updates.html ↩ ↩2 ↩3 ↩4

  4. Carlsson P-O, Hu X, Scholz H, et al. Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression. N Engl J Med (2025);393:887-894. https://doi.org/10.1056/NEJMoa2503822 ↩ ↩2 ↩3 ↩4 ↩5

  5. Sana Biotechnology. Announces Continued Positive Clinical Results Through 14 Months from Type 1 Diabetes Study of Islet Cell Transplantation Without Immunosuppression. GlobeNewswire (2026). https://www.globenewswire.com/news-release/2026/03/13/3255502/0/en/Sana-Biotechnology-Announces-Continued-Positive-Clinical-Results-Through-14-Months-from-Type-1-Diabetes-Study-of-Islet-Cell-Transplantation-Without-Immunosuppression.html ↩ ↩2

  6. ClinicalTrials.gov. First-in-human Safety Study of Hypoimmune Pancreatic Islet Transplantation in Adult Subjects With Type 1 Diabetes (NCT06239636). https://clinicaltrials.gov/study/NCT06239636 ↩

  7. Hu X, White K, Young C, et al. Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate. Cell Stem Cell (2024);31:334-340. https://doi.org/10.1016/j.stem.2024.02.001 ↩