8-K: Sana Biotechnology Reports Groundbreaking Six-Month Clinical Success in Type 1 Diabetes Trial Without Immunosuppression

Sana Biotechnology, Inc. announced positive six-month clinical results from a first-in-human study of its UP421 allogeneic primary islet cell therapy, demonstrating safety, survival, and insulin production in a type 1 diabetes patient without the need for immunosuppression.

Summary

• Sana Biotechnology, Inc. announced positive six-month clinical results from an investigator-sponsored, first-in-human study of UP421, an allogeneic primary islet cell therapy engineered with its hypoimmune (HIP) technology.
• The study involved transplanting UP421 into a patient with type 1 diabetes without any immunosuppression, conducted in partnership with Uppsala University Hospital.
• Results at six months demonstrate the survival and function of pancreatic beta cells, as measured by consistent circulating C-peptide levels and increased C-peptide with a Mixed Meal Tolerance Test (MMTT), indicating insulin production.
• MRI scans at 12 weeks showed signals consistent with graft survival at the transplant site (a forearm muscle).
• The study identified no safety issues, and the HIP-modified islet cells successfully evaded immune responses.
• The data was shared at an invited presentation at the 85th Annual American Diabetes Association (ADA) Scientific Sessions.
• Sana is incorporating the immune evasion technology from the UP421 trial to develop SC451, a HIP-modified, stem cell-derived islet cell therapy, with an Investigational New Drug (IND) application intended for filing as soon as next year.
• The current study used a low dose of HIP-modified primary islets to establish safety and function, and was not intended to show improvement in glycemia or reduction in exogenous insulin administration.

Sentiment

Score: 9

Explanation: The clinical results are highly positive and represent a significant breakthrough in the treatment of type 1 diabetes, potentially enabling a functional cure without the need for lifelong immunosuppression. This is a major de-risking event for the company's core technology platform and future programs.

Positives

• Positive six-month clinical results from a first-in-human study of UP421 in type 1 diabetes.
• Demonstrated the potential to treat type 1 diabetes by transplanting insulin-secreting cells without the need for immunosuppression, a groundbreaking achievement.
• Sana's transplanted pancreatic islet cells (UP421) modified with its Hypoimmune (HIP) technology were safe and well-tolerated.
• The transplanted cells survived, evaded detection by the immune system, and continued to produce insulin in the patient.
• Function and persistence of pancreatic islets were detectable by consistent levels of circulating C-peptide, a marker of insulin production.
• C-peptide levels increased with a Mixed Meal Tolerance Test (MMTT), consistent with insulin secretion in response to a meal.
• MRI showed signals consistent with graft survival six months after transplantation.
• The HIP platform has achieved proof-of-concept in humans, showing evasion of immune recognition with broad potential application for allogeneic transplantation without immunosuppression.
• Sana is developing SC451, a HIP-modified, stem cell-derived therapy, with a goal of achieving normal blood glucose, no insulin, and no immunosuppression for type 1 diabetes patients.

Risks

• Risks inherent in drug development, such as those associated with the initiation, cost, timing, progress, and results of current and future research and development programs, preclinical and clinical trials.
• Economic, market, and social disruptions could affect the company's actual results.

Future Outlook

The study continues to evaluate the safety, survival, and function of the transplanted cells. Sana is incorporating the immune evasion learnings and technology from the UP421 trial to develop SC451, a HIP-modified, stem cell-derived islet cell therapy, for which it intends to file an Investigational New Drug (IND) application as soon as next year. The company's vision is to treat diabetes with a broadly available therapy leading to normal blood glucose control without either insulin or immunosuppression, bringing this closer to reality. Study results are expected to be submitted for publication in a peer-reviewed journal.

Management Comments

• Per-Ola Carlsson, MD, Study Principal Investigator, Uppsala University Hospital: "Consistent with the previously reported four-week and 12-week data, we believe todays six-month update continues to suggest that a functional cure for type 1 diabetes without immunosuppression is possible... These groundbreaking results build upon the extensive preclinical and translational studies of Dr. Sonja Schrepfer and the team at Sana and provide hope for a cure. We look forward to continued follow-up, with study results submitted for publication in a peer-reviewed journal."
• Steve Harr, MD, Sana's President and CEO: "Durable survival, function, and immune evasion of transplanted allogeneic pancreatic islet cells with no immunosuppressive medicines, particularly in the context of a pre-existing autoimmune response to these cells, represents a transformative and necessary step to making cellular and transplant medicine more accessible... The data presented today bring our visiontreating diabetes with a broadly available therapy leading to normal blood glucose control without either insulin or immunosuppressioncloser to reality. We are incorporating the immune evasion learnings and technology from the current UP421 trial to develop SC451, a HIP-modified, stem cell-derived islet cell therapy, for which we intend to file an investigational new drug application (IND) as soon as next year."
• Aaron J. Kowalski, Ph.D., CEO of Breakthrough T1D: "A paradigm shift in the treatment of diabetes is long overdue... The prospect of administering insulin-producing cells into people with this diseaseenabling stable glycemic control without lifelong injections, drugs that suppress their immune system, or constant daily managementrepresents a transformative and potentially life-changing breakthrough. We are extremely grateful for the collaborative efforts of the research teams at Sana, Uppsala University Hospital, and all those involved, for their dedication to this work. The entire team at Breakthrough T1D looks forward to working with Sana and others to ensure all members of the T1D community can benefit from these life-changing breakthroughs."

Industry Context

Type 1 diabetes impacts over nine million people globally, with relatively few transformational advances since the discovery of insulin over 100 years ago. Current treatments, including exogenous insulin administration and automated insulin delivery systems, often fail to achieve ideal glucose levels, leading to complications. While primary islet cell transplantation with immunosuppression is an established procedure, Sana's HIP technology aims to overcome the historical requirement for lifelong immune suppression, representing a potential paradigm shift in diabetes treatment and making cellular and transplant medicine more accessible.

Comparison to Industry Standards

• Primary islet cell transplantation is an established procedure for type 1 diabetes, but it historically requires lifelong immunosuppression to prevent immune rejection of allogeneic cells and resurgence of autoimmune attack.
• Sana's UP421 study demonstrated durable survival, function, and immune evasion of transplanted allogeneic pancreatic islet cells *without any immunosuppressive medicines*, which is a significant advancement over the current standard of care.
• The results provide evidence that Sana's HIP technology can evade both allogeneic and autoimmune detection, addressing a major limitation of existing transplant procedures.

Stakeholder Impact

• **Patients with Type 1 Diabetes:** Potential for a transformative treatment that could lead to normal blood glucose control without lifelong insulin injections or immunosuppressive drugs, significantly improving quality of life and reducing complications.
• **Shareholders:** Highly positive clinical results are likely to increase investor confidence and potentially lead to a significant positive impact on the company's share price.
• **Medical Community:** The groundbreaking success in achieving immune evasion without immunosuppression could revolutionize cellular and transplant medicine, setting new standards for allogeneic therapies.
• **Employees:** Positive clinical progress can boost morale and reinforce the company's mission and vision.
• **Research Partners (Uppsala University Hospital, Breakthrough T1D):** Validation of their collaborative efforts and enhanced reputation in diabetes research and advocacy.

Next Steps

• Continued follow-up of the UP421 study to evaluate safety, survival, and function of transplanted cells.
• Submission of UP421 study results for publication in a peer-reviewed journal.
• Sana intends to file an Investigational New Drug (IND) application for SC451, a HIP-modified, stem cell-derived islet cell therapy, as soon as next year.

Key Dates

Recommendation

Keywords

Sana Biotechnology, Type 1 Diabetes, Islet Cell Transplantation, Hypoimmune Technology, HIP, UP421, SC451, Immunosuppression, C-peptide, Pancreatic Islet Cells, Cell Therapy, Allogeneic, Clinical Trial, Biotechnology, Diabetes Treatment, Regenerative Medicine