UP421 by Sana Biotechnology: status and timeline

UP421

Demonstrate that engineered donor islet cells can restore insulin production in type 1 diabetes patients without immunosuppression, enabling allogeneic cell transplants to replace failed beta cells.

PilotStage 3 of 5

14-month follow-up published; donor islet cells survived without immunosuppression.

Updated Jul 2026Checked 11 Oct0 updates this week

Milestones

No announced next step

Trial initiated at Uppsala University Hospital2023Complete.
Patient receives UP421 transplantJun 2023Complete.
Four-week data shows insulin productionJul 2023Complete.
12-week results published in NEJMAug 2025Complete.
14-month follow-up shows insulin productionJul 2026Complete.

Most important updates

Current obstacles

Donor cell availabilityPrimary pancreatic islet cells come from organ donors and have limited supply, constraining the number of patients who can be treated.
Transplant procedure complexityIslet transplantation is technically demanding and requires specialized centres with experience; it can be performed into the liver or other sites.

Physics limits

Islet cell fragilityPancreatic islet cells are sensitive to isolation and culture stress; maintaining viability and function during harvest, modification, and transplant remains a challenge.
Immune tolerance durabilityWhile HIP modifications prevent immune attack, long-term tolerance and the possibility of the immune system adapting to modified cells must be monitored over years.

How it works

3 parts

Cell harvest

Donor pancreatic islets

Primary pancreatic islet cells (containing insulin-producing beta cells) are isolated from organ donor pancreases.

HIP modification

Immune evasion engineering

Cells are genetically modified with Sana's hypoimmune platform to suppress immune recognition markers and avoid both allogeneic and autoimmune rejection.

Transplantation

Direct implant

Modified islet cells are transplanted, where they re-establish insulin production and glucose regulation without need for immunosuppressive drugs.

Spec sheet

Spec	UP421
Cell source	Human organ donor pancreatic islets^R (reported)
Genetic modification	HIP (hypoimmune platform) gene edits^R (reported)
Clinical follow-up duration	14 months^R (reported)
C-peptide (4-week post-transplant)	Detected and elevated post-meal^R (reported)
Graft survival at 14 months	Confirmed by MRI imaging^R (reported)

^R reported by the company

Papers & demos

2 items

Jul 2026paper
Long-Term Survival of Hypoimmune Allogeneic Islets without Immunosuppression (opens doi.org)14-month follow-up in NEJM showing durability and continued insulin production.
Aug 2025paper
Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression (opens doi.org)First human proof that HIP-modified islet cells survive and produce insulin without immunosuppression.

Update log

2 updates

Jul 2026

Major: UP421 maintains graft survival and insulin production at 14 months without immunosuppressionPaperResearch

Aug 2025

Major: UP421 demonstrates first human proof of insulin-producing islet cells surviving without immunosuppressionPaperResearch

About Sana Biotechnology

The team behind UP421

Sana Biotechnology

UP421, SC451, hypoimmune islet cells, type 1 diabetes

Sana Biotechnology develops engineered pancreatic islet cell therapies using its hypoimmune (HIP) platform to enable transplants without immunosuppression. Founded 2018, Seattle; NASDAQ public (SANA) since February 2021.

UP421 (primary islet cells) achieved insulin production without immunosuppression in trial; published NEJM 14-month follow-up data.
SC451 (iPSC-derived islets) planned IND filing 2026; uses same hypoimmune technology; Mayo partnership for development.
HIP platform genetically modifies cells to hide from immune system, enabling transplants without lifelong immunosuppressive drugs.

sana.com (opens sana.com)Company profile →

Founded: 20188 yrs
Headquarters: United States
Status: Public
Listed: SANA (opens google.com)NASDAQ
Valuation: public
Last round: IPO4 Feb 2021
Works in: BiotechCell & organ therapies
Coverage: 2 programs · 3 updateslatest 1 Jul 2026checked 11 Oct
Partners: Mayo Clinic (opens mayoclinic.org)Uppsala University Hospital (opens akademiska.se)
People: Steve Harr (opens investors.sana.com)CEO

Spec

UP421

Cell source

Human organ donor pancreatic islets^R (reported)

Genetic modification

HIP (hypoimmune platform) gene edits^R (reported)

Clinical follow-up duration

14 months^R (reported)

C-peptide (4-week post-transplant)

Detected and elevated post-meal^R (reported)

Graft survival at 14 months

Confirmed by MRI imaging^R (reported)