Sana, Mayo Clinic Advance A New Model For Cell Therapy Delivery In T1D
By Erin Harris, Editor-In-Chief, Cell & Gene
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Aiming to move beyond lifelong disease management toward a one-time, potentially curative intervention, Sana Biotechnology is building its approach to engineered cell therapies around both scientific innovation and clinical execution. In collaboration with Mayo Clinic, the company is working to standardize how its investigational therapy SC451 is delivered, monitored, and scaled across care settings worldwide. I caught up with Sana’s President and CEO, Steve Harr, M.D., who describes a strategy that combines hypoimmune cell engineering with rigorous protocol development to reduce variability, expand patient access, and ultimately redefine treatment expectations for people living with type 1 diabetes (T1D).
Tell us a little bit about Sana Biotechnology and its mission.
SC451 is designed as a one-time, hypoimmune cell therapy. How does that therapeutic profile shape your approach to clinical delivery, site readiness, and long-term patient management?
Insulin therapy has meaningfully improved patient outcomes, but even with state-of-the-art medical care and technology and glucose control, a person with T1D will live approximately a decade less than somebody without the disease and have a significant treatment burden for life. In contrast, our goal is to develop a one-time treatment that leads to normal blood glucose with no insulin injections and no immunosuppression in an effort to restore the patient to a life similar to that from before the T1D diagnosis.
A one-time, potentially curative cell therapy fundamentally changes the clinical paradigm from episodic treatment to a tightly orchestrated, managed intervention. For site-readiness for the Phase 1 trial, we are partnering with clinical sites experienced in T1D care and transplant medicine. For site-readiness beyond the Phase 1 trial, we are working to create standardized protocols to ensure that cell transplantation therapies are reproducible, safe, and consistently effective regardless of where they are delivered, and we recently announced we are collaborating with the Mayo Clinic on this effort. Clinical delivery involves specialized handling of the cell product and a standardized implantation procedure performed in a controlled clinical setting, ensuring consistent and reliable delivery across patients. SC451 aims for durable insulin independence, and our goal is to minimize the long-term burden for these patients, but as part of drug development we will monitor safety, function, immune response, and durability of effect.
This collaboration emphasizes standardizing protocols across Mayo Clinic and global sites. What are the biggest operational challenges in making a complex cell therapy reproducible across different clinical settings?
Standardizing protocols across sites is essential to ensuring that cell transplantation therapies are reproducible, safe, and consistently effective regardless of where they are delivered. By developing and validating standardized processes, the collaboration helps ensure that SC451 is administered in a consistent way across diverse clinical environments. Important workstreams include optimizing handling the product inside the clinic, preparing the product for delivery, clinical and operational workflows, refining and harmonizing surgical techniques, and establishing uniform approaches to post-treatment management.
Together, these standards aim to reduce variability in how the therapy is delivered and how patients are followed over time.
The hypoimmune platform aims to eliminate immunosuppression. How does that change the clinical development strategy, particularly around patient selection, monitoring, and endpoints?
Scientists have shown that transplanted pancreatic islets, either from a deceased donor or manufactured from stem cells, can allow patients to come off insulin and maintain normal blood glucose. However, the impact of these therapies has been limited, as patients must remain on life-long systemic immunosuppression to prevent the patient’s immune system from rejecting these transplanted cells. The potential complications of immunosuppression, which include increased susceptibility to infection, heightened cancer risk, cardiovascular disease, metabolic syndrome, chronic kidney disease, and osteoporosis, outweigh the potential benefits of these treatments in most patients.
These considerable factors ultimately dictate that only a very select patient population should be considered. The two populations of patients with T1D that often receive such islet transplants are those with severe, life-threatening hypoglycemia, where the risks of insulin outweigh the risks of immunosuppression, and those who are already on immunosuppression for another organ transplant, typically a kidney transplant in T1D.
As SC451 avoids the need for immunosuppression, all patients with T1D may be considered. With islet cell transplants, blood type of the donor and recipient also needs to match. With SC451 being derived from a female O-negative donor, the universal donor blood type, a patient with any blood type could be eligible to receive SC451.
As this will be a first-in-human study for SC451, clinical monitoring will largely follow typical post-transplant glucose monitoring consistent with deceased donor islet transplant. The glycemic monitoring post-transplant is related to the lysis of beta cells (of at least 25% or more cells) administered into the portal vein via a process called immediate blood mediated inflammatory reaction (IBMIR). This often requires patients to remain in the hospital for up to a week for glycemic monitoring. As SC451 will be administered intramuscularly, the large % of beta cell lysis post-transplant is anticipated to be less, based on available preclinical and clinical data. If the data bear out, this may eventually allow us to consider administering SC451 as an outpatient therapy in the future, further facilitating the scaling of the administration of SC451 to the millions of patients worldwide with T1D.
Furthermore, because SC451 is given without immunosuppression (IS), there is no monitoring of IS drug levels or titration of IS doses as part of the islet cell transplant. In addition, SC451 should avoid the safety and tolerability risks associated with IS, potentially allowing an even broader population of patients with T1D to receive SC451.
With SC451, our goal is to provide a one-time therapy to cure T1D and as such, monitoring of glycemic control, endogenous insulin production, and exogenous insulin delivery will be routinely assessed over time. In addition to the above efficacy parameters, ongoing, routine safety monitoring will also be performed.
With Mayo Clinic making both an operational and equity commitment, what does this partnership model enable that a traditional biotech/clinical site relationship would not?
This collaboration represents a reimagining of how breakthrough therapies move from concept to clinical reality, and it is also a recognition of the potential SC451 holds for redefining patient care in T1D. Unlike a traditional clinical site arrangement between a clinic and a biotech sponsor, this collaboration reflects a strategic commitment to advancing care, with Mayo Clinic making significant investments to delve with us into the biggest challenges in making this medicine broadly accessible. Mayo Clinic will also expand its capabilities in delivering investigational islet cell therapies. Rather than serving primarily as a site for patient enrollment and data collection, Mayo Clinic is an active, strategic collaborator helping to shape how SC451 should be integrated into clinical practice based on its extensive expertise. This level of involvement reflects a shared commitment to innovation and long-term impact, distinguishing it from the more transactional nature of a traditional clinical site arrangement.