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.
Cures
Breakthrough T1D’s Cures program focuses on early detection, disease-modifying therapies, and cell therapies with the goal of working toward effective cures for T1D.
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.
Cell therapies highlight: Breakthrough T1D-funded research
Tom Bollenbach, Ph.D. (Advanced Regenerative Manufacturing Institute; ARMI) presented on challenges and solutions for large-scale manufacturing of islet cells. The goal is to generate scalable, automated manufactured islets that can be used by labs around the world to accelerate research progress using a unique, validated, and reliable cell source. Some challenges include ensuring the manufactured cells can survive shipment from the facility to research labs and maintain their insulin-producing capacity when they are used in different labs. ARMI is working with the Beta Cell Replacement Consortium to address these challenges.
Antonio Citro, Ph.D. (San Raffaele Hospital) presented his work on ensuring that transplanted islets have enough oxygen and nutrients (“vascularization”) to survive and function. Dr. Citro described an approach tested in animal models referred to as “natural scaffolds” in which all cells are removed from a donor organ, such as a lung, leaving behind blood vessel structures and other structural components. Islet cells can be injected and grafted onto this scaffold to create a mini organ of islet cells, which can then be tested for functionality before and after implantation.
Andrew Pepper, Ph.D. (University of Alberta) also presented vascularization strategies to increase the survival and functionality of transplanted islets. The implantation of a biomaterial under the skin will trigger the immune system and initiate a foreign body reaction, which results in the formation of blood vessels and structural components around the foreign object. Removal of the object leaves a hollow pre-vascularized core suitable for islet transplantation. This process can be optimized by using a biodegradable material, so no removal is required, and by the addition of “accessory cells” that help maintain a vascularized environment for islets.
Key takeaways
Cell therapies are making significant headway in clinical trials, and people receiving manufactured cells are becoming insulin independent. Researchers are tackling the biggest challenges for optimizing islet transplantation, including large-scale manufacturing, ensuring cell survival, and preventing detection by the immune system.
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.
Disease-modifying therapies highlight: Breakthrough T1D-funded research
Emrah Altindis, Ph.D. (Boston College) presented on the role of the gut microbiome in T1D. His studies found that people with T1D tend to have more inflammatory bacteria in their gut microbiome. Dr. Altindis and his team identified a particular bacterial population that can enhance T1D onset in animal models due to changes in immune cells that contribute to T1D autoimmunity. These studies provide insight into additional factors that can drive immune changes in T1D.
Laura Sanz Villanueva, MSc (St. Vincent’s Institute of Medical Research), who works in the lab of Breakthrough T1D-funded researcher Professor Thomas Kay, MBBS, Ph.D., presented on a mechanistic follow-up study to the BANDIT clinical trial. The Breakthrough T1D-funded phase 2 BANDIT study showed that baricitinib, a JAK1/2 inhibitor that prevents immune cell communication, can increase insulin production as measured by C-peptide in people with recently diagnosed T1D. The present study found that baricitinib can reduce the number of natural killer (NK) cells in the pancreas, which are involved in the autoimmune destruction of beta cells. These data provide valuable insight into the mechanism of baricitinib-mediated protection of beta cells.
Key takeaways
T1D is driven by dysregulation of the immune system, which results in an attack on insulin-producing beta cells. Researchers at ADA 2025 spoked about novel factors—including B cells, NK cells, and T1D autoimmunity triggers—that may contribute to immune cell dysfunction 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.
Early detection highlight: Breakthrough T1D-funded research and awardees
Brigitte Frohnert, M.D., Ph.D. (Barbara Davis Center for Diabetes), co-investigator with Breakthrough T1D-funded researcher Andrea Steck, M.D., presented on the evolution of CGM patterns prior to stage 3 T1D. Their longitudinal approach, with CGM data collected at three-month intervals, successfully distinguished individuals who progressed to stage 3 T1D clinical onset from those who did not. This research suggests that CGM may be beneficial for predicting clinical progression of T1D.
Anette-Gabriele Ziegler, M.D. (Helmholtz Munich) was awarded the Harold Hamm Prize for Biomedical Research in Diabetes 2025, highlighting her important contributions on T1D screening in the pediatric population.
Barbara B Kahn, M.D. (Beth Israel Deaconess Medical Center and Harvard Medical School) received the 2025 Albert Renold Award, and her role model for women in science was highlighted at the Women’s Interprofessional Network of the ADA (WIN ADA).
Key takeaways
T1D arises in diverse ways across age groups and ancestries, complicating diagnosis and treatment. At ADA 2025, experts highlighted how genetic and clinical heterogeneity demands more inclusive strategies. Tools like CGM and CKM were highlighted for their potential to enhance clinical management in the early stages of T1D.
Breakthrough T1D’s Cures team making an impact
Sanjoy Dutta, Ph.D., Chief Scientific Officer, participated in a panel discussion titled “Encapsulation vs. Naked Cell Therapy—Immune Challenges and Beta-Cell Perspectives in Diabetes Treatment.” The panelists covered different approaches to preventing immune attack of transplanted islets, including gene-editing, in addition to pros and cons of different transplantation sites.
Esther Latres, Ph.D., Vice President of Research, and Jay Tinklepaugh, Ph.D., Senior Scientist, hosted a workshop immediately after ADA titled “Islet Cells in T1D.” Breakthrough T1D-funded researchers gathered from around the world to discuss cell therapy clinical trial updates, mechanistic insights into islet function, targeted delivery of therapeutics to beta cells, and optimization strategies for islet transplantation.
Look out for tomorrow’s article for an update on Medical Affairs presented at ADA 2025!
