Sana Biotechnology Announces Promising Follow-Up Publication in The New England Journal of Medicine on Gene-Edited Islets for Type 1 Diabetes

A groundbreaking new publication in The New England Journal of Medicine details the continued success of the first individual with type 1 diabetes (T1D) to receive gene-edited islets, a revolutionary cell therapy developed by Sana Biotechnology. This landmark trial participant is now over 14 months post-transplant and continues to produce insulin endogenously, remarkably, without the need for immunosuppressant medications. This development marks a significant stride forward in the pursuit of a functional cure for T1D, a chronic autoimmune disease affecting millions worldwide.

The Science Behind Sana’s Hypoimmune Islets

Sana Biotechnology’s innovative approach centers on the creation of "hypoimmune" islet cells. This novel cell therapy strategy is engineered to protect transplanted islet cells from the body’s immune system, thereby preventing the immune attack that typically leads to the destruction of these vital insulin-producing cells. Type 1 diabetes is characterized by the immune system mistakenly targeting and destroying the beta cells within the islets of Langerhans in the pancreas, which are responsible for insulin production. Without insulin, the body cannot regulate blood glucose levels, leading to severe health complications if left unmanaged.

The hypoimmune strategy employs advanced gene-editing techniques to modify the islet cells. These modifications aim to render the cells virtually invisible to the immune system, specifically by downregulating or masking molecules that trigger immune responses, such as Major Histocompatibility Complex (MHC) Class I and Class II molecules, and by introducing immune-suppressing proteins. Crucially, these genetic alterations are designed to preserve, and not interfere with, the natural insulin-producing function of the islet cells. This approach aligns with the next-generation cell therapy strategies being aggressively prioritized by organizations like Breakthrough T1D, which identifies overcoming immune rejection as a paramount barrier to successful cell replacement therapies for T1D.

The initial phase 1 clinical trial, a first-in-human study, utilized islets sourced from deceased donors. These islets underwent the proprietary gene-editing process to become immune-evasive before being transplanted into the forearm of the participant. As is standard for phase 1 trials, the primary objective of this study was to meticulously assess the safety of the treatment. Alongside safety monitoring, researchers are closely observing the functional capacity of the transplanted islets by measuring C-peptide levels. C-peptide is a byproduct of insulin production and serves as a reliable indicator of the body’s endogenous insulin synthesis.

It is important to note the exploratory nature of this initial trial. The transplant procedure involved only approximately 5% of the number of islet cells typically required to fully restore insulin independence in individuals with T1D. This deliberate low-cell-dose approach allows for a more cautious evaluation of safety and initial efficacy.

A Timeline of Encouraging Results

The journey of the first participant in Sana’s trial has yielded increasingly positive outcomes since the initial transplant. The publication in The New England Journal of Medicine provides a detailed chronological account of the participant’s progress over the 60-week period following transplantation.

• Initial Transplant and Early Recovery: Following the transplantation of the gene-edited islets, the participant began to show signs of restored insulin production.
• Month 14 Post-Transplant: The most significant finding reported is the continued detectable C-peptide levels at 14 months after the transplant. This indicates that the transplanted islet cells have survived and are actively functioning, producing insulin.
• Imaging Confirmation: Further bolstering the evidence of cell viability, PET and MRI imaging confirmed the presence and location of the transplanted islet cells within the participant’s forearm.
• Beta Cell Dynamics and Recovery: Researchers observed a temporary decline in C-peptide levels around the one-year mark. This phenomenon is hypothesized to be due to beta cell exhaustion, a common occurrence in transplanted cells under stress. However, the subsequent recovery of C-peptide levels offers a highly encouraging signal, suggesting that the transplanted beta cells possess a remarkable capacity to regain their functional capacity.
• Immune Tolerance Achieved: Critically, the study reported no detectable immune response directed against the transplanted islet cells. While T1D autoantibodies, markers of the underlying autoimmune attack, remained at their pre-transplant levels, they did not negatively impact the survival or function of the gene-edited islets. This demonstrates the effectiveness of Sana’s hypoimmune technology in shielding the transplanted cells from immune surveillance and attack, even in the presence of ongoing autoimmunity.
• Safety Endpoint Met: The trial met its primary safety endpoint, with no severe adverse events reported throughout the 60-week observation period. This is a crucial finding for any novel cell therapy, especially one involving gene editing and transplantation.

Implications for the Future of T1D Treatment

The results from this first-in-human study offer a compelling proof of concept for the potential of gene-edited, immune-evasive islet cells as a viable therapeutic option for T1D. If these findings are replicated and validated in larger, more diverse patient populations, this approach could represent a paradigm shift in T1D management, moving towards a functional cure that eliminates the need for lifelong insulin injections and the constant burden of blood glucose monitoring.

A particularly significant implication of Sana’s work is the potential to circumvent the requirement for broad and potentially toxic immunosuppressant drugs. Current cell replacement therapies, such as whole-pancreas or islet transplants from deceased donors, necessitate lifelong immunosuppression to prevent the recipient’s immune system from rejecting the transplanted organs or cells. This immunosuppression comes with its own set of risks, including increased susceptibility to infections and a higher risk of certain cancers. Sana’s hypoimmune cell technology promises to overcome this hurdle, offering a pathway to immune-independent cell therapy.

The Road Ahead: Scalability and Accessibility

Looking beyond this initial success, Sana Biotechnology is poised to advance its technology by translating its hypoimmune gene-editing strategy to manufactured islets. This transition is a critical step towards developing a scalable and widely accessible cell therapy. The company plans to initiate a new clinical trial focused on these manufactured, immune-evasive islets. This initiative directly aligns with Breakthrough T1D’s "Project ACT" (Accelerate Cell Therapies), a comprehensive program dedicated to dramatically expediting the development, regulatory approval, and widespread adoption of islet cell therapies for all individuals with T1D who could benefit.

Project ACT aims to tackle the multifaceted challenges of bringing advanced cell therapies to patients by simultaneously driving progress in research, development, regulatory pathways, and ensuring equitable access and adoption. The development of a scalable, manufactured cell therapy, combined with immune evasion, is seen as the most promising route to making these life-changing treatments available to the millions living with T1D globally.

Driving Innovation Through Strategic Investment

Sana Biotechnology is a portfolio company of the T1D Fund, a venture philanthropy initiative established by Breakthrough T1D. Through strategic equity investments, the T1D Fund has played a pivotal role in supporting the growth and advancement of Sana’s T1D pipeline, culminating in the human clinical trials of their gene-edited islet cell therapy. The T1D Fund’s commitment to fostering innovation extends to other promising companies, such as Century Therapeutics, which is also developing manufactured islet cell therapies with immune-evasive capabilities. The T1D Fund remains dedicated to collaborating closely with Sana and other forward-thinking companies, providing crucial support for their product development efforts and accelerating the realization of scalable islet cell therapy approaches that do not necessitate immunosuppression.

The journey from initial discovery to a widely available therapy is complex and requires sustained investment, collaborative efforts, and unwavering scientific rigor. The progress demonstrated by Sana Biotechnology, supported by organizations like the T1D Fund, underscores the transformative potential of cutting-edge research in the fight against type 1 diabetes. The successful translation of these early-stage findings into a safe, effective, and accessible therapy could fundamentally alter the landscape of T1D treatment, offering renewed hope for a future free from the daily challenges of managing this chronic condition.

This article was written by Sandy Vogt, Ph.D., and Brian Herrick.