It’s an exciting time for type 1 diabetes (T1D) research. Nearly every day, we’re seeing incredible progress across each area of Breakthrough T1D’s research portfolio to cure, prevent, and treat T1D and its complications.

One area in particular is making headlines: Cell therapies. 

In T1D, the immune system destroys the beta cells in the pancreas, which produce insulin. Cell therapies aim to replace those destroyed cells—and keep them safe from the immune system—so they can thrive inside the body and restore insulin production. 

Vertex Pharmaceuticals is one of the companies pursuing cell therapies for T1D. They are currently researching a cell therapy treatment in an ongoing Phase 1/2/3 clinical trial—an investigational manufactured islet therapy that requires the use of immunosuppression. JoyL Silva, Senior Vice President, Disease Area Executive, Type 1 Diabetes, is leading the T1D portfolio at Vertex and answered a few questions about herself, Vertex, and their work.

Watch the videos below to learn more about Vertex’s cell therapy work, their commitment to the T1D community (spoiler alert: they’re all in on T1D), how they’re applying what they learned in cystic fibrosis to T1D, and much more.

History with Breakthrough T1D

Breakthrough T1D has a long-term collaborative partnership with Vertex and its leading researchers that goes back decades. Our key collaborations include:

• In 2004, Breakthrough T1D funded researcher Doug Melton started to work to turn stem cells into insulin-producing cells in the lab. He accomplished this in 2014.

• In 2015, Melton founded Semma Therapeutics with hopes that these cells would have a transformative impact for T1D. In 2017, the T1D Fund made a catalytic investment in Semma. 

• The T1D Fund also invested in ViaCyte, which was acquired by Vertex in 2022. 

Thanks to JoyL and Vertex for taking the time to answer our questions. We look forward to more updates on your cell therapy program and other manufactured islet therapies in the future! 

Here’s what you need to know about deceased donor islet cell transplants—and our plan to expand availability to them safely and responsibly. 

What Is Deceased Donor Islet Cell Transplantation? 

Deceased donor islet cell transplantation is a procedure in which insulin-producing islet cells are isolated from the pancreases of deceased donors and transplanted into a person living with type 1 diabetes (T1D). These islets are infused into the liver, where they can begin producing insulin in response to blood glucose levels.  

Deceased donor islet cell transplants are intended for, and only FDA-approved for, adults with T1D who experience: 

• Severe hypoglycemia (dangerous low blood sugar) 
• Hypoglycemia unawareness (the inability to sense when blood sugar is dropping)

These individuals often cannot safely manage their blood glucose levels with the standard therapies used to manage T1D, including continuous glucose monitors (CGMs) and automated insulin delivery (AID) systems. 

Do They Work?

Yes. For adults with T1D who experience severe hypoglycemia and hypoglycemia unawareness, deceased donor islet cell transplantation has been shown to significantly reduce—or even eliminate—the need to take external insulin.  

Do Deceased Donor Islet Cell Transplants Require Immunosuppression? 

Yes. Recipients of deceased donor islet cell transplants must take immunosuppressives to prevent the body from rejecting the transplanted cells. Due to the side effects of immunosuppressives, these transplants are only approved for adults whose risk from severe hypoglycemia outweighs the risks associated with immunosuppression. 

Breakthrough T1D is working on alternatives to traditional immunosuppression so more people can benefit. This includes our funding of the University of Chicago’s clinical trial with Eledon’s drug, tegoprubart.

Why Aren’t They Widely Available?

Deceased donor islet cells come from organ donors. A single transplant often requires multiple pancreases as isolating islet cells is a complicated process. In addition to those challenges, the availability in the U.S. is more limited than it is in other countries due to regulatory classification.  

The U.S. currently regulates deceased donor islet cells as biological drugs requiring a Biologics License Application (BLA). This is different from how whole organ transplants are regulated in the U.S. and how deceased donor islet cells are regulated in many other countries, including Canada, the United Kingdom and countries in the European Union.   

How Is Breakthrough T1D Advocating for Expanded Deceased Donor Islet Cell Transplant Availability?

Breakthrough T1D has strongly urged HHS to reclassify and expand availability of deceased donor islet cells. 

Our proposal outlines a framework to ensure safety and accessibility for the T1D community. You can read the letter here. 

We are putting 100% of our energy behind this approach, and we are doing it with the full support of leading transplant surgeons and organizations.  

Why Is Breakthrough T1D Pursuing This Route (HHS) as Opposed to Legislation (ISLET Act)?

This is our best chance of success. Passing legislation is extremely difficult at best, and HHS has existing authority over the regulatory framework governing cell therapies and organ transplantation. They can make this change. 

Additionally, the ISLET Act does not require the development of safety standards for reclassified deceased donor islet cell transplants, nor does it address insurance coverage, which could limit access to these costly treatments. 

What Are the Details of Breakthrough T1D’s Recommendations in the Letter to HHS?

Our proposal outlines a clear strategy to ensure the safety and quality of deceased donor islet cells under this reclassification. They include: 

• Designating Centers of Excellence staffed with experts in deceased donor islet cell transplants 
• Strict quality control to ensure islets are functional—and they work 
• A way to get cells from the deceased donors’ pancreases and into people with T1D
• A strategic roadmap for adding additional centers

Why Not Work with HHS and Support the ISLET Act? 

Our Breakthrough T1D legislative agenda includes several critical priorities essential to advancing our mission. This includes the ongoing renewal of the Special Diabetes Program (SDP) to fund T1D research and efforts to improve insulin affordability. These issues require legislative action, which is why we continue to focus our legislative advocacy on them. 

Not every priority is best achieved through Congress. Reclassifying deceased donor islet cells as organs, for example, can be accomplished under current law through the Department of Health and Human Services (HHS), without new legislation. This is one of the key reasons we believe the path through HHS is the best path for this issue. 

Simply put, we are pursuing each of our priorities through the channel where it has the greatest likelihood of success. And given how difficult it is to pass legislation, putting 100% of our effort toward working with HHS has the best chance of success.  

Why Doesn’t Breakthrough T1D Recommend an Amendment to the ISLET Act?

Given how difficult it is to pass legislation, we believe our effort to reclassify deceased donor islet cells as organs is much more likely to succeed focusing on HHS. 

What effect would this have on stem cell-derived islets?

Breakthrough T1D believes that stem cell-derived islets are appropriately regulated by FDA as biologic products. There is no need to change the regulatory status for manufactured islets. If adopted, our proposal would not affect them.  
 
Through Project ACT, Breakthrough T1D is working with all parties to clear the way for future, manufactured islet therapies and to ensure they are accessible. 

One of our most promising avenues toward cures for type 1 diabetes (T1D) is cell therapies. Cell therapies replace destroyed beta cells with functional, insulin-producing cells to restore insulin therapy independence. Right now, there are nearly a dozen cell therapies in clinical testing—and OPF-310 is one of them.

OPF-310 cells are derived from porcine (pig) islets. This approach is different from other cell therapies in the pipeline, which are either harvested from human deceased donor pancreases or manufactured in the lab.

Xenotransplantation

Xenotransplantation involves transplanting organs, tissues, or cells from a non-human animal into a human. This approach holds promise to address the shortage of organs from deceased donors and is being investigated in clinical trials for kidney transplantation—and now islet transplantation, too. Yet, this isn’t the first time porcine-derived islets have been tested in T1D. In fact, before human insulin was widely available, insulin derived from pigs was commonly used to manage diabetes.

Porcine islets, like other cell therapies that come from a source other than the recipient, have the potential to activate an immune response after transplantation. To overcome this, OPF-310 uses an encapsulation device that protects the islets from destructive immune cells. This means that no immunosuppression is needed.

Read on to learn more about the trial, who may be eligible for OPF-310, and the team in the Windy City performing these transplants. 

Essential information about the trial

The goal of this first-in-human, phase 1/2a study is to assess the safety, tolerability, and efficacy of OPF-310 transplantation and to define the recommended phase 2 dose. Right now, the trial is only enrolling at a single location: the University of Illinois Hospital & Health Sciences System (UI Health) in Chicago, IL. For eligible participants that live out of state or more than 100 miles from UI Health, reimbursement for travel expenses (such as flights, hotels, and food) is available.

People who enroll in the trial will need to meet with the team at UI Health before and after the transplant as a part of their participation in the study.

These visits include:

• Four onsite visits prior to surgery
• Follow-up visits with the endocrine team within the first four weeks post-transplant
• 18 follow-up visits within the first year after the transplant
• Long-term follow-up visits that continue throughout each participant’s lifetime

These visits include bloodwork and other tests that can let researchers know how well the cells are functioning and making insulin and ensure participants’ continued safety. Also, for a year after the transplant, participants are required to use a second continuous glucose monitor (CGM) so researchers can track changes in blood sugar levels.

As with all new therapies and treatments, there are some risks involved. For xenotransplantation in particular, there is the risk of developing zoonotic infections (those that can be transferred from animals to humans), or passing these infections to close contacts. Safety is the top priority for the study team at UI Health. To help mitigate these risks, the porcine islets undergo testing to ensure that they are sterile before transplantation, and participants are routinely tested for possible infections.

The risks associated with surgical transplantation, such as infections at the transplant site, are managed by detailed pre-operative care and assessments, a top-notch and highly experienced surgical team, and close monitoring post-transplant.

“The OPF-310 trial is an important first step toward new treatments for type 1 diabetes. It uses pig islet cells to help people who have trouble controlling blood sugar or experience severe lows,” explains Benito Valdepeñas, a Co-Investigator on the trial. “If you join, you will be closely monitored by a team of specialists who will guide and support you every step of the way.”

Get involved!

Right now, there are three people enrolled in this study—and ten more are needed. The team needs your help! If you or someone you know may be interested in the OPF-310 trial, learn more about the study or email bvalde2@uic.edu to connect with Dr. Valdepeñas and the study team to see if you are eligible to enroll.

Clinical trials are the key to cures

The team at UI Health agrees: the future is looking bright for T1D. “Every one of these innovations began as an idea and relied on volunteers willing to help bring it to life,” says Miranda Kipp, a Clinical Research Nurse. From the perspective of Memunat Ogunmefun, a Clinical Research Coordinator, “…the work we do now could lead to new and improved treatment options for patients in the years to come.” It’s true: the only way to bring therapies like OPF-310 to life is through clinical trial participation, which can transform the lives of the T1D community now and in the future.

“I’m inspired by the possibility that emerging trials, like OPF-310, could give patients a level of stability and freedom they’ve never had before. Being part of research that could potentially ease their daily burden, prevent complications, and offer a more hopeful future is what drives me. Ultimately, my inspiration comes from the patients themselves.” – Benito Valdepeñas III, Pharm.D., Co-Investigator

“…participation in this trial goes beyond contributing to data, it is about being a part of an effort to explore therapies that could potentially change how we treat type 1 diabetes. Every participant plays a vital role in helping us evaluate both the safety and effectiveness of OPF-310, and their involvement directly shapes the future of care. We recognize that joining a clinical trial is a big commitment, so we prioritize patient safety, transparency, and support at every stage.” – Memunat Ogunmefun, MPH, BDS, Clinical Research Coordinator

“…your safety and support are our top priorities throughout this study. After your transplant, you will receive very close follow-up from the UI Health team to make sure you’re healing well and have everything you need. Once this early period is complete, your care will smoothly transition back to your regular healthcare provider, with our teams staying closely coordinated. Our goal is to make you feel supported at every step while ensuring you continue to receive care from the providers who know you best.” – Miranda Kipp, MSN, RN, Clinical Research Nurse

We’ve come a long way: cell therapies with curative potential, like OPF-310, are in clinical trials. The only way to get these therapies through the testing process and into the hands of people with T1D is through clinical trial participation. We need volunteers from the T1D community to help us get there. Consult our clinical trials web page to learn more about how you can get involved. Use our Clinical Trials Matching Tool to find a trial near you that you or a loved one may be eligible for. Connect with a Clinical Trial Education Volunteer in your area to have all your questions answered. We need your help!

Breakthrough T1D extends a heartfelt thank-you to Dr. Valdepeñas, Ogunmefun, and Kipp for taking the time to speak with us about the OPF-310 trial and what inspires them to do T1D clinical research. Breakthrough T1D also thanks Otsuka Pharmaceutical Factory for making this connection and driving research into cures for T1D.

Q: Patti, can you tell us about your diabetes journey?

A: I was diagnosed with T1D in October 1986. I’ve lived with it for nearly 39 years. As anyone who knows this disease can tell you, it’s very hard. I’ve used every possible management system—pumps, continuous glucose monitors (CGMs), inhaled insulin, and I even have a diabetic alert dog named Otto. Despite these tools, I always struggled with low blood sugars, and I struggled with the mental burden of this disease. I was the kid at diabetes camp who had to get a glucagon injection in the middle of the night.

Q: What did you use to manage your T1D?

A: I’ve done everything—pumps, injections, CGMs, everything. But now I use multiple daily injections. I also rely on my diabetic alert dog—Otto! Otto, my service dog would often jump in my bed 20 minutes before a CGM would go off. And he consistently does that!

How did you hear about the clinical trial?

A: Having been around T1D for so long, I knew about the concept of islet transplants. I also knew that the end goal is making these cells. It was exciting but not something I thought was a reality today.

About two years ago, I heard about a clinical trial being done by Vertex. I found out about it on Instagram, actually. I then reached out to them and began the screening process.

Q: What was the screening process like?

A: The screening was extremely thorough. I answered a ton of questions about my insulin usage, diet, blood type, history of hypoglycemia, and more. I even had to prove I had had T1D for all these years. They tested me for autoantibodies. They tested me for seemingly everything!

Q: How did it feel to make it into the trial?

A: Clinical trials like this are important. Clinical trials have to happen. We can’t get a cure without them, so somebody has to step up. I am lucky enough that I can step up—and I’m so glad to. 

Why this matters

Breakthrough T1D extends a heartfelt thank you to Patti for courageously sharing her story with us so we can truly understand why the work we’re doing is critically important. If you choose to participate in a clinical trial, like Patti, you have the potential to provide transformative benefits to the entire T1D community by accelerating the pace of clinical research. Learn more about clinical trials and how you can get involved. If you’re interested in the zimislecel clinical trial, check out the trial sites and eligibility criteria.

To accelerate T1D cures faster than ever, Breakthrough T1D’s Project ACT (Accelerate Cell Therapies) is simultaneously advancing research, development, regulatory policies, access, and adoption of manufactured islet therapies that do not require broad immunosuppression. We will not stop until these therapies are available to everyone with T1D who wants them—and clinical trial participants like Patti are getting us there faster.

We are well on our way to seeing manufactured cell therapies like zimislecel come to life. We owe a huge thank you to our supporters and the broader T1D community for inspiring us every day to keep pushing forward until functional cures for T1D are a reality.

A new study funded by Breakthrough T1D and published in the journal Diabetes Therapy shows that people with type 1 diabetes (T1D) and caregivers are largely willing to try next-generation therapies, drawn by the promise of reduced insulin reliance, greater normalcy, and freedom from constant disease management.

The findings highlight the importance of ensuring patient and caregiver perspectives guide regulatory decisions around the balance of a therapy’s risks and benefits.

The promise of next-gen therapies

Advances in T1D management, such as automated insulin delivery (AID) systems, mark major progress over the past decade. Despite these gains, insulin therapy remains physically, mentally, and emotionally demanding, and substantial unmet needs persist.

Next-generation therapies aim to move beyond insulin replacement through two approaches:

1. Disease-modifying therapies (DMTs): Preserve insulin production by slowing or halting autoimmune destruction of beta cells.
2. Cell Therapies: Restore insulin production by delivering new functional cells, with the potential for partial or complete insulin independence.

For the study, researchers interviewed people with T1D and caregivers to better understand their perspectives on the risks and benefits of these therapies.

What participants said

Participants expressed willingness to try new therapies, with 92% of adults, 70% of caregivers, and 100% of adolescents saying they would try a DMT at the time of T1D diagnosis. Every participant said they would try cell therapies.

Participants also shared their thoughts on top benefits of both DMTs and cell therapies.

• Top benefits: DMTs: Reduced insulin reliance and an extended period when a
  person with T1D produces their own insulin; cell therapies: insulin independence,
  more normalcy, and freedom from constant demands on diabetes.

Why this matters

To approve a product, regulators must judge whether the therapy’s benefits outweigh its
risks. This study shows that , people living with T1D and their caregivers have strong view
about which benefits matter and how much they matter. Because DMTs and cell therapies
bring significant benefits compared to insulin therapy, regulators should incorporate these
patient perspectives into regulatory decision-making.

About the study

The Breakthrough T1D Patient Preference Study is being conducted in two phases. In the first phase, researchers interviewed 26 individuals—12 adults, 4 adolescents, and 10 caregivers—about their views on DMTs and cell therapies. These insights are now shaping a large-scale survey that will measure how the T1D community prioritizes different risks and benefits. Results from that survey are expected later this year.

Hy-Vee’s dedication to Breakthrough T1D’s mission is personal.

Type 1 diabetes (T1D) first struck the Hy-Vee family in 1921, when company co-founder Charles Hyde’s oldest son, Paul, died from the disease when he was 8 years old.

Since 1998, Hy-Vee has been a trusted partner of Breakthrough T1D, raising nearly $20 million through a variety of corporate and store events, including Walks in the Midwestern and Southern U.S. Hy-Vee also participates in Rides across the country; in 2025, they were recognized as a top fundraising team, bringing in over $230,000 for T1D research.

Hy-Vee’s 2025 in-store fundraising campaign for Breakthrough T1D runs from September 1 through 30. Find your local Hy-Vee here.

Working together for cures

Sam and Lauren Raiche are loyal Hy-Vee customers. They’re also dedicated fundraisers, advocates, and volunteers for Breakthrough T1D. Their 8-year-old son, Alexander, was diagnosed with T1D at age 3.

They appreciate Hy-Vee’s commitment to Breakthrough T1D’s mission. “It means so much to know that a company we already trust and shop with is also supporting a mission so close to our hearts,” Lauren said. “Living with type 1 diabetes is a daily challenge for our family, and seeing Hy-Vee stand behind research and programs that directly impact families like ours makes us feel grateful and supported every time we walk through their doors.”

Alexander represented Kansas at the 2025 Breakthrough T1D Children’s Congress. As a Delegate, he met with representatives to advocate for renewal of the Special Diabetes Program, which funds critical type 1 diabetes research. “Advocacy has become a cornerstone of our journey,” Lauren said. “We firmly believe that raising awareness and engaging with the community are essential steps toward making meaningful progress and, ultimately, achieving cures.”

Accelerating cell therapy breakthroughs

Support from partners like Hy-Vee helps fuel that progress toward cures for type 1 diabetes. Breakthrough T1D’s cures portfolio includes cell therapies, which replace destroyed beta cells with protected functional cells to restore insulin therapy independence and glucose control, ideally without immunosuppression.

Over the past decade, Breakthrough T1D has funded more than $156 million in cell therapies research, including partnerships with organizations like Vertex Pharmaceuticals and Sana Biotechnology.

In 2024, Vertex launched a pivotal clinical trial for zimislecel (formerly VX-880), which uses manufactured islets to restore the body’s ability to produce insulin. The therapy, however, requires the use of immunosuppression to protect the transplanted cells from rejection. The islets used in zimislecel are derived from the Breakthrough T1D-funded work of Doug Melton, Ph.D., who first turned precursor cells into insulin-producing cells in 2014.

A 2025 study from Sana Biotechnology showed that hypoimmune (HIP) donor-derived islets are making insulin and avoiding immune detection in the first person treated. The T1D Fund: A Breakthrough T1D Venture invested in Sana to help advance their HIP technology platform.

Breakthrough T1D continues to drive innovation to develop cell replacement therapies and eliminate the need for immunosuppression. With the generosity and support of partners like Hy-Vee and families like the Raiches, we will change the lives of everyone facing type 1 diabetes.

The short version

Breakthrough T1D’s newest publication outlines what the future of beta cell replacement therapies looks like—and how we can make these therapies a reality for everyone with type 1 diabetes (T1D) who wants them through innovative clinical trial design and expanding the pool of eligible trial participants.

Breakthrough T1D, in collaboration with other leading experts in the field, recently published an article titled “Future Directions and Clinical Trial Considerations for Novel Islet β-Cell Replacement Therapies for Type 1 Diabetes” in the journal Diabetes. Breakthrough T1D Research and Advocacy staff who contributed to the publication include Sanjoy Dutta, Ph.D., Chief Scientific Officer, Esther Latres, Ph.D., Vice President of Research, and Marjana Marinac, Pharm.D., Associate Vice President of Regulatory Affairs.

Beta cell replacement therapies have the potential to cure type 1 diabetes (T1D) by removing the need for external insulin. While donor islet transplantation can result in insulin independence and results from early trials with manufactured islets are encouraging, people with T1D need better tools and therapies. This publication serves as a roadmap for the entire field—including researchers, product developers, industry, regulators, clinicians, and people with T1D—to address these needs and ensure that beta cell replacement therapies can get to people with T1D as quickly and safely as possible.

Read on to learn more about what the future of beta cell replacement therapies looks like.

Where we are now

People living with T1D depend on external insulin to manage their condition throughout their lives. Despite advancements in diabetes technology, such as continuous glucose monitors (CGMs) and automated insulin delivery (AID) systems, most people with T1D are unable to achieve blood sugar targets, rendering them at a higher risk for complications, reduced quality of life, and lower life expectancy.

 It’s simple: we need to do more for the T1D community.

One promising avenue to meet these needs is through cell replacement therapy. Lantidra®, the first FDA-approved donor-derived islet replacement therapy for T1D, has proven to be safe and effective in eliminating severe hypoglycemia, providing insulin independence, and improving quality of life. However, this therapy is limited to people with severe hypoglycemia and requires immunosuppression to prevent rejection of the transplanted cells, which can have side effects. Even more, these donor-derived islets are in limited supply.

Alternative beta cell replacement therapies are emerging—and we can no longer limit their development to people experiencing severe hypoglycemia.

Developing cell therapy strategies to meet unmet needs of the T1D population

Breakthrough T1D’s vision for the T1D community includes beta cell replacement therapies with no immunosuppression that are available to everyone who wants them. We are committed to making this a reality through our Project ACT (Accelerate Cell Therapies) initiative, which will accelerate the development of these therapies to achieve our vision as quickly as possible.

We are entering an exciting era of beta cell replacement. Emerging therapies are addressing challenges such as cell source and scalability, resulting in the development of islets derived from sources other than donors, including manufactured islets and porcine islets. Up-and-coming therapies are also testing different transplantation sites, methods of delivery, and cell protection strategies to prevent immune rejection with the fewest side effects possible (and ideally no immunosuppression). Learn more about what scientists are doing to optimize beta cell replacement therapies.

Breakthrough T1D’s continuous support of many of these therapies, such as Vertex’s manufactured islet therapy zimislecel, has been critical to accelerating them through the clinical pipeline. Explore emerging beta cell replacement therapies in clinical trials now—and see how Breakthrough T1D’s commitment to these therapies helped make this possible.

When successful, the advent of new, safe, scalable, and effective beta cell replacement therapies will provide the T1D community with options. As these therapies are moving their way through the pipeline, we need to ensure they are being studied in a broader T1D population who stand to benefit.

So, how do we make this happen?

The roadmap for emerging beta cell replacement therapies

Expanding the T1D population eligible for beta cell transplantation

Current trials testing beta cell therapies necessitating immunosuppression require participants to have elevated HbA1c levels and recurrent severe hypoglycemic events. This limits the pool of participants to people who meet the requirements and are most likely to benefit, given the side effects associated with chronic, broad immunosuppressants.

Clinical trials for emerging beta cell replacement therapies should broaden eligibility criteria so more people with T1D can participate—and experience the potential benefits. When designing new clinical trials, sponsors and regulators should consider including a broader range of HbA1c levels, clinically important or serious hypoglycemic events, and other complications.

Studies have found that the T1D community is generally open to beta cell replacement therapies as a potential solution to T1D, and people are willing to accept the associated risk versus benefit considerations for the possibility of becoming insulin independent. A Breakthrough T1D assessment also found that physicians are interested in recommending beta cell replacement therapies to people with T1D—especially if they don’t require immunosuppression.

“Clinical trials to support the development of islet cell replacement therapies need to evolve to include a broader representation of people living with T1D who could benefit from these novel therapies. This includes expanding the outcomes used to assess the benefits of cell replacement that reflect how people with T1D feel and function.”

Marjana Marinac, Pharm.D., Associate Vice President of Regulatory Affairs

Placing people with T1D at the center of clinical trial design

The outcomes used to assess the effectiveness of cell therapies currently in clinical trials, including those involving deceased donor islets, are acceptable for emerging beta cell replacement therapies. These include on-target HbA1c levels, absence of severe hypoglycemia, significant reduction or elimination of external insulin, and restoration of the body’s insulin production as measured by C-peptide.

Other endpoints that should be considered include CGM metric targets like time-in-range in addition to person-reported outcomes. Understanding how a beta cell therapy may affect a person’s health-related quality of life—such as diabetes distress, fear of hypoglycemia, or social and family dynamics—will be critically important for calculating the risk to benefit ratio of these therapies.

Read more about why person-reported outcomes are important for cell therapies.

“There are still significant unmet needs in the T1D community. Breakthrough T1D’s roadmap is supported by the assessment of clinically meaningful outcomes and driving research toward solutions that address key factors such as cell sources and protections strategies that will broaden the people with T1D who could benefit from emerging cell replacement therapies.”

Esther Latres, Ph.D., Vice President of Research

Innovative trial designs to accelerate development of cell therapies

Clinical trials for beta cell replacement therapies are generally based on a single-arm, open-label design—meaning there is no placebo group and both participants and researchers know which therapy is being administered. While this design can work for emerging beta cell therapies, single trials with multiple arms testing alternative transplant sites, immune protection strategies, or other methods have the potential to speed up the pace of development.

Similarly, adaptive trial designs use mid-trial interim analyses of study data to inform the remainder of the trial. This helps researchers learn what’s working (or not working) and adjust the design accordingly, with guidance from regulatory agencies, so the rest of the trial is a focused and efficient use of time and resources. Potential interim changes to trial design include reducing the number of participants required, eliminating doses, recruiting people who are most likely to benefit, or stopping the trial outright due to clear success or failure.

By applying guidance in therapeutic development and innovative trial designs to emerging beta cell replacement therapies, we can move early-stage trials along faster, thereby allowing regulators to make decisions sooner. To support quicker trials and reduce the possibility for delays, researchers, developers, and regulators around the world need to work together to achieve convergence on trial populations, endpoints, and innovative designs that will meet regional requirements.

Learning from past successes

People with T1D continue to live with unmet needs with still significant risk for long-term complications, and they need more therapeutic options. Right now, most clinical trials for beta cell replacement therapies requiring immunosuppression are limited to a small portion of the T1D population. This needs to change—especially given the potential for insulin independence. The T1D community must be put first when making decisions about beta cell replacement therapies, and Breakthrough T1D is making sure that this happens.

Adjusting how we approach clinical trials for emerging beta cell replacement therapies will be critical for ensuring we accelerate the research, development, regulatory approval, access and adoption of these novel therapies. Breakthrough T1D successfully accomplished this for AID systems—and we are confident that following a similar roadmap for cell therapies will get us to the finish line, faster.

Curative therapies for T1D are in reach. This roadmap, in conjunction with our Project ACT initiative, is key to bringing beta cell replacement therapies to every person with T1D who wants them.

To make this a reality, everyone needs to work together. As stated in the publication, “This requires a comprehensive strategy and a coordinated collaboration across stakeholders in every field relevant to islet cell replacement.” This roadmap is a guide for moving toward our common goal of a cure for T1D as soon as possible.

Breakthrough T1D will continue to lead the way until the T1D community can choose the beta cell replacement therapy that works best for them, regardless of blood glucose management or hypoglycemia status. Everyone deserves the chance to benefit.

Sana Biotechnology’s hypoimmune (HIP) donor-derived islets are genetically engineered to avoid immune destruction without the need for immunosuppressants.

Earlier this year, we reported on an update from the first person with type 1 diabetes (T1D) to receive a transplant of these cells, which showed that they were making insulin—without immunosuppression—after four weeks. Then, at the American Diabetes Association (ADA) 85^th Scientific Sessions, we heard firsthand from Per-Ola Carlsson, M.D., Ph.D., the Principal Investigator at Uppsala University conducting the study, who provided more exciting data to a packed audience.

Now, these data have just been published in the prestigious New England Journal of Medicine in an article titled “Survival of Transplanted Allogenic Beta Cells with No Immunosuppression.”  This study was supported by the Helmsley Charitable Trust, a long-time partner of Breakthrough T1D.

Read on to learn more.

Surviving and thriving

In this first-in-human study, the recipient of Sana’s HIP islets had no detectable insulin production at the time of the transplant (as measured by C-peptide). They received a small dose of islet cells—less than the eventual therapeutic dose—implanted into the forearm to evaluate safety.

C-peptide

C-peptide is an easily measurable biomarker of insulin production and islet function.

After 12 weeks, researchers found that the transplanted islets were successfully avoiding destruction by the immune system—meaning they are surviving AND making insulin!

The recipient had decreased HbA1c levels and stable insulin production between seven days and 12 weeks post-transplant, although, as expected with the small dose of cells used in this pilot study, they still required external insulin therapy. They experienced some non-serious side effects possibly related to the surgical transplant procedure, but not the islet cells themselves. Overall, the recipient is doing well and in good health—an exciting step for the T1D community.

Why this matters

To put it plainly: this is a huge step toward cures for T1D.

Immunosuppression is a major barrier to cell therapies because of the side effects associated with them. This is the first proof-of-concept evidence that we can genetically engineer islets to avoid immune destruction—eliminating the need for chronic, broad immunosuppressants. This means that more people may have the opportunity to benefit.

Importantly, the person in this study received only a fraction of the islet cells that would eventually be used therapeutically. Researchers are just beginning to understand the full potential of engineered HIP islets. Because more islet cells means more insulin production, there’s the possibility of insulin therapy independence if higher doses of HIP islets are implanted—something that will be addressed in future studies.

Thanks to this study, we’ve gained more evidence that forearm muscles may be a possible minimally invasive site for islet transplantation. This transplant site also provides researchers with the advantage of visualizing the islets—and making sure they’re alive—using magnetic resonance imaging (MRI), which isn’t possible with the current transplant site in the hepatic portal vein.

Excitingly, Sana is working to apply this technology to manufactured islets, opening the doors to producing HIP islets at large scale. They expect to begin phase 1 clinical trials for this next-generation HIP islet therapy as early as 2026.

Cell therapies without immunosuppression are a Breakthrough T1D priority

Cell replacement therapies—especially those that do not require immunosuppression—are a priority of Breakthrough T1D’s Cell Therapies Program and the goal of our Project ACT (Accelerate Cell Therapies) initiative.

To accelerate the development of cell therapies that do not require immunosuppression, The T1D Fund: A Breakthrough T1D Venture invested in Sana to help advance their HIP technology platform. Breakthrough T1D continues to support creative and promising approaches that may eliminate the need for immunosuppression with cell replacement therapies, and we are hopeful and excited about what the future may hold.

This wouldn’t have been possible without supporters like you. Thank you for all that you do to drive Breakthrough T1D’s mission, and together we celebrate each step towards a world without T1D.

ADA Recap Series

This article is the second of our three-part ADA Recap Series. Breakthrough T1D was on site in Chicago, IL from June 20-23 for the American Diabetes Association’s (ADA) 85th Scientific Sessions. We’re here to report on the latest-and-greatest type 1 diabetes (T1D) advancements—including many driven by Breakthrough T1D funding. Look out for tomorrow’s article for updates on Medical Affairs.

Cell therapies were front-and-center at ADA 2025. We have some exciting clinical trial updates and new ideas for optimizing islet transplantation.

Cell therapies

Autologous cell transplantation

Autologous cells are those removed from an individual and implanted back into the same individual. These cells can be modified in a laboratory before implantation. Autologous cells are still susceptible to autoimmunity in T1D, so cell protection strategies (gene-editing, encapsulation, immune modulation, etc.) are expected to be required.

Allogenic cell transplantation

Allogenic cells are those that are derived from a source other than the recipient, such as deceased donors or precursor-derived manufactured cells. Allogenic cell transplants require immunosuppression because they stimulate an immune response. Breakthrough T1D’s Cell Therapies program is focused on allogenic cells—specifically manufactured cells—because they can be generated at large scale.

One-year updates on Vertex’s manufactured cell therapy, zimislecel

• Presenter: Michael Rickels, M.D. (University of Pennsylvania)
• Zimislecel (VX-880) is a manufactured islet therapy that requires immunosuppression, infused into a vein in the liver in people with T1D who have impaired hypoglycemic awareness and severe hypoglycemic events.
• The phase 1/2 clinical trial, which is part of the pivotal phase 1/2/3 FORWARD-101 trial, is complete. Twelve participants received a single infusion of a full dose of cells and were followed for at least one year.
• All 12 participants achieved the primary endpoint, which was elimination of severe hypoglycemic events and HbA1c levels less than 7%. 10/12 (83%) participants are insulin independent.
• All 12 participants demonstrated sustained insulin production as measured by C-peptide, reduced external insulin therapy use, and achieved greater than 70% time in range.
• There were no serious adverse events. Mild to moderate adverse events were consistent with the immunosuppression regimen, infusion procedure, and complications from T1D.
• These data were published in the New England Journal of Medicine and represent further evidence of the curative potential of manufactured islet transplantation for T1D.
• Breakthrough T1D’s support for Doug Melton, Ph.D.—whose proprietary lab-created beta cells are now being advanced by Vertex—goes back decades, both via research grants and an investment from the T1D Fund: A Breakthrough T1D Venture.

6-month update on Sana Biotechnology’s immune-evasive islets

• Presenter: Per-Ola Carlsson, M.D., Ph.D. (Uppsala University)
• Sana’s donor-derived islet therapy engineered with Hypoimmune (HIP) technology can evade the immune system without immunosuppression.
• These cells were implanted intramuscularly in a first-in-human study into a person with T1D with no measurable insulin production.
• Six months post-transplant, this person is consistently making their own insulin, as measured by C-peptide levels. Yet, they still require external insulin therapy because they received a smaller dose of cells than the dose that would be required to achieve insulin independence. They did not experience any serious side effects, so the cells and procedure are safe and well-tolerated.
• A Mixed Meal Tolerance Test (MMTT) confirmed that these cells are not only surviving but also responding to changes in blood glucose levels.
• This is a promising first step toward a functional cure for T1D that does not require immunosuppression. Sana Biotechnology is planning on applying this technology to manufactured islets.
• Sana has received support from the T1D Fund to advance their HIP technology in islets, and Breakthrough T1D continues to work closely with them.

A new transplantation site for autologous manufactured islets

• Presenter: Hongkui Deng, M.D. (Peking University)
• Cells derived from adipose tissue (fat) can be removed from a person and chemically induced in the laboratory to become islet cells.
• Implantation of autologous manufactured islets into the sub-anterior rectus sheath in preclinical models of T1D improves glycemic control.
• In humans, this implantation site is easily accessible by an ultrasound-guided needle.
• In a first-in-human study, autologous manufactured islets were implanted into this site in a person with T1D. This person no longer needs external insulin therapy and has greatly improved blood glucose control. This person had also received a liver transplant and was taking immunosuppressants.

A new encapsulation device for immune protection of transplanted islets

• Presenter: Nicolas Laurent, Ph.D. (Adocia)
• Adoshell® is a novel islet cell encapsulation device that can shield islets from the immune system, meaning that immunosuppressants are not needed.
• The hydrogel-based device is non-degradable, easily retrievable, and allows the exchange of glucose and insulin from the vasculature surrounding the device while excluding immune cells from encapsulated islets based on pore size.
• This device showed promise in animal models, and human clinical testing is next.

Disease-modifying therapies

A major focus at ADA 2025 was addressing the underlying immune mechanisms of T1D—including alterations in immune cells that facilitate beta cell destruction and other factors that contribute to autoimmunity onset. Read on for some highlights.

The role of B cells in T1D autoimmunity

• Presenter: Mia Smith, Ph.D., DVM (University of Colorado)
• B cells are a type of immune cell that can activate destructive immune cells that facilitate autoimmunity in T1D.
• B cells can become wrongly activated against insulin-producing beta cells due to converging dysregulation of factors that regulate immunity.
• These cells represent another potential target for disease-modifying therapies in T1D.

Early detection

A key focus at ADA 2025 was the growing recognition of the heterogeneity of T1D, including autoantibody-negative disease onset, genetic variation, and the frequent misdiagnosis of T1D in adults, underscoring the need for greater diversity and inclusion in research and care. The expanded role of continuous glucose monitoring (CGM) and continuous ketone monitoring (CKM) was also highlighted, not only for daily management but as essential tools for understanding disease progression.

Using genetics to predict T1D risk

• Presenters: Richard Oram, M.D., Ph.D. (University of Exeter), Leslie Lange, Ph.D. (University of Colorado), Aaron Deutsch, M.D. (Massachusetts General Hospital), Josep Mercader, Ph.D.(Massachusetts General Hospital) and Eimear Kenny, Ph.D. (Icahn School of Medicine at Mount Sinai)
• Polygenic risk scores (PRS) estimate the risk a person has for developing a disease like T1D based on variations in different genes.
• Ancestry is a major influence on PRS, particularly based on differences in genes that regulate whether the immune system can distinguish between “self” and “non-self.”
• Most PRS models have been developed using data from European populations and have a limited ability to accurately determine risk in other ethnic groups, such as individuals of African and East Asian descent.  
• Potential applications of PRS include incorporation into screening to better understand T1D risk, ensure accuracy in diagnostic tests, and develop precision medicine-based therapeutic approaches.

Understanding how genetic diversity contributes to T1D

• Presenters: Suna Onengut-Gumuscu, Ph.D. (University of Virginia), Dominika A. Michalek, MS (University of Virginia), Aaron Deutsch, M.D. (Massachusetts General Hospital), and Stephen I Stone, M.D. (Washington University School of Medicine), among others.
• These talks highlighted several studies conducted in diverse populations to better understand the pathophysiology of T1D.
• Work presented from Consortia, such as RADIANT, focused on rare and atypical forms of diabetes.

Controversies in CGM and benefits for early detection

• Presenters: Peter Calhoun, Ph.D. (Jaeb Center for Health Research), Michael Kohn, M.D., MPP (University of California San Francisco), Nicole Ehrhardt, M.D. (University of Washington) and Tadej Battelino, M.D., Ph.D. (University of Ljubljana)
• CGM use holds value in identifying progression in early stages of T1D prior to symptomatic onset.
• There was a call to update the clinical guidelines so that the benefits of CGM can be maximized within the T1D community—including at early and later stages of T1D.
• Integrating newer measures of blood glucose, like the glucose management indicator (GMI) and time in tight range (TITR), will be essential.

Contributions of CKM to early detection

• Presenters: Ketan Dhatariya, MBBS, M.D., Ph.D. (Norfolk and Norwich University Hospitals), Lori Laffel, M.D., MPH (Harvard University), Jennifer Sherr, M.D., Ph.D. (Yale University), and Richard Bergenstal, M.D. (HealthPartners Institute).
• It will be critical to explore whether ketone monitoring could help reduce the incidence of diabetic ketoacidosis (DKA) at stage 3 clinical T1D onset.
• Early detection of rising ketones will be important for people with T1D to take action before DKA occurs.

Look out for tomorrow’s article for an update on Medical Affairs presented at ADA 2025!

We’ve made major progress in the development of cell replacement therapies for type 1 diabetes (T1D) over the past few decades. We know that manufactured islets can be safely implanted into people and produce insulin. Yet, there is more work to do to advance cell therapy research and bring these therapies to the larger T1D community. Breakthrough T1D’s Project ACT (Accelerate Cell Therapies) will make manufactured cell replacement therapies that do not require broad immunosuppression a reality, faster.

The Breakthrough T1D x Stem Cell Network Partnership

To drive innovation in manufactured islet therapies, Breakthrough T1D, Breakthrough T1D Canada, and the Stem Cell Network (SCN) have partnered to support four new projects led by Canadian researchers. The organizations issued a joint Request for Applications and together will maximize resources to drive high-impact research into manufactured cells. This partnership is a novel and meaningful part of Breakthrough T1D’s global Project ACT effort to power high-impact cell therapies research.

“Accelerating cell therapies is a central focus of Breakthrough T1D’s research strategy to drive toward cures for type 1 diabetes,” said Breakthrough T1D Vice President of Research Esther Latres, Ph.D. “We’re excited to join Stem Cell Network and Breakthrough T1D Canada in funding these outstanding cell therapy researchers and projects that can build on the current momentum to overcome barriers and advance cell therapies that can benefit all those who live with type 1 diabetes.”

These projects will receive support from May 2025 to April 2027. They are a part of a broader SCN investment totaling more than $33 million to support 36 regenerative medicine research projects and clinical trials.

Read on to learn more about the exciting, newly funded projects.

 A closer look at the projects

Current cell therapies for T1D, while often effective, are hampered by reliance upon donor-derived cells and poor cell survival after transplant, necessitating large doses of cells and repeat procedures.  This ambitious new project will address both the source of islet cells and the low cell survival rates associated with islet transplantation by accelerating Lunar Therapeutics’ preclinical development of a manufactured islet replacement product. Takebe’s lab describes it as “complex miniature organs” for T1D.  

This product will consist not only of insulin-producing cells, but also endothelial cells, which line blood vessels. Endothelial cells will support islet cell survival and engraftment upon transplantation.  

Organoid

An organoid is a three-dimensional tissue grown in the lab that resembles an organ.

To accomplish this objective, Lunar Therapeutics will bring together Canadian expertise in manufactured islets and clinical islet transplantation led by Drs. Timothy Kieffer and James Shapiro. The team will also include U.S.-based Dr. Takanori Takebe, who specializes in designing complex organoids composed of various cell types. Using technologies developed across each laboratory, this multidisciplinary team will work to address challenges in islet cell transplantation.  

The implantation of manufactured islets into people with T1D can restore insulin production, eliminating the for external insulin and improving quality of life. However, after islet cells are derived from donors or manufactured in the lab, they must be stored before being used to treat a person with T1D. Currently, the storage and transportation of islet cells is difficult, and the only storage method is freezing at low temperatures in the presence of chemical solutions that help with the freezing process. However, these solutions cause cell death during thawing and may also cause allergic reactions in people after transplantation.   

This project will address this gap in the field by aiming to develop non-toxic, naturally derived gels to optimize islet freezing and storage. The gel-based products will be evaluated for large-scale commercial production. The success of this project will provide new intellectual property that will be of interest to researchers and companies in regenerative medicine in Canada and across the globe. 

Manufactured islets offer a potentially unlimited source of islets for transplantation. Since manufactured islets carry unique risks compared to donor-derived islets, containment within a device could allow retrieval if off-target growth ever occurs. However, encapsulation devices that have been tested in clinical trials so far and have shown minimal success, mainly because blood supply to the cells is limited by the device barrier. In this project, the team proposes to develop a device where the manufactured islets are placed around pre-established vessels that can improve islet cell survival and speed of insulin responses via improved blood supply. In this project, they will optimize their device design and conduct advanced preclinical studies. 
 
This project could lead to better survival and function of manufactured islets, so they can keep producing insulin. The project may also pave the way for other engineered human-scale encapsulation devices, also sometimes called bioartificial organs.

There are many new treatments on the horizon for T1D, including those that block autoimmunity or replace insulin-producing cells. However, a major barrier to these therapies is the lack of an easy-to-use model in which their effects on human cells can be tested before advancing to human trials. The standard preclinical model is to test therapies in small animal models of T1D, but this has significant limitations since it is nearly impossible to replicate the human immune system. In fact, diabetes has been “cured” hundreds of times in a mouse model, which has not translated to humans. 
 
To overcome this barrier, Dr. Levings and her team will establish a new a model that recreates human T1D autoimmunity in the lab. The model will use manufactured cells to create the three types of cells that are involved in the disease: insulin-producing cells and two different types of immune cells. Using the model, cells can then be combined in different ways to recreate what usually happens during autoimmunity. 
 
A model of human T1D that can be generated in the lab will help test potential treatments and prompt new questions about why T1D develops, and how to prevent it. Thus, this research has the potential to support the further development of innovative therapies that may offer new approaches to prevent or treat people with T1D. 

Putting it all together

Curing T1D is the north star of Breakthrough T1D. These partnerships will help us work together toward our shared goal of a world without T1D—through innovation, forward-thinking cell therapy research, and the best and brightest scientists.