Tzield (teplizumab-mzwv) / MacroGenics, Sanofi, Ligand - LARVOL DELTA

The future of type 1 diabetes therapy. (PubMed, Lancet) - "Teplizumab, the first immunotherapy treatment to delay the onset of clinical type 1 diabetes, has been approved by the US Food and Drug Administration...New-generation insulins (those that are ultrarapid, ultralong, and glucose-responsive) improve outcomes by minimising blood sugar fluctuations. Together, these breakthroughs offer renewed hope for improving long-term management and quality of life for people living with type 1 diabetes."

Journal • Review • Diabetes • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus

TN-10 extension study: teplizumab following stage 3 type 1 diabetes diagnosis in participants from the TN-10 trial (EASD 2025) - P2 | "Teplizumab was safe and well tolerated in participants with stage 3 T1D. No new safety signals emerged in participants who received 1 course of teplizumab in stage 2 T1D and then 1 in stage 3 T1D."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Progression from stage 2 to stage 3 type 1 diabetes in children identified by general population screening (EASD 2025) - "In this population-based screening program, family history of T1D, race/ethnicity or sex of the child did not influence the rate of progression from stage 2 to stage 3. Children positive for multiple IAbs and those younger than 8 y experienced faster progression."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Press Release: Tzield approved in China as first disease-modifying therapy for adult and pediatric patients with stage 2 type 1 diabetes (The Manila Times) - "Approval based on the TN-10 study, demonstrating Tzield’s ability to delay the onset of stage 3 T1D in adult and pediatric patients aged eight years and older, with stage 2 T1D compared to placebo."

China approval • Type 1 Diabetes Mellitus

Plea for an early diagnosis of people at risk of developing symptomatic type 1 diabetes (PubMed, Rev Med Liege) - "Teplizumab, an anti-CD3 monoclonal antibody, slows down the decline of insulin secretion by beta cells, both in people at stage 2 and early stage 3. This medication, which may be considered as a disease-modifying agent of T1D, was approved in November 2022 by the U.S. Food and Drug Administration (FDA) and is currently evaluated by the European Medicines Agency (EMA)."

Biomarker • Journal • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Immunotherapies and their potential to preserve beta cells in type 1 diabetes: a review of current immunotherapy. (PubMed, Bol Med Hosp Infant Mex) - "Following decades of research and advances in therapeutic technologies, approaches have been developed based on diverse mechanisms in the disease's pathogenesis. This review focuses on new immunotherapy approaches for type 1 diabetes, including cell-targeted therapies, cytokines, and cell transplants to preserve beta-cell function."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus

Identifying therapeutic targets for erectile dysfunction in the European population using genome-wide Mendelian randomization. (PubMed, Sex Med) - "Our study highlighted three potential drugs targeting three of these hub genes: benztropine for CD27, teplizumab for CD3E, and natalizumab for ITGB1. Tissue-specific expression quantitative trait loci confounders and lack of experimental validation for prioritized drugs require caution. This work advances ED research by mapping druggable genes (PRKCA, IFNG, ITGB1) and pathways via MR, offering precision medicine opportunities and actionable drug repurposing candidates."

IO biomarker • Journal • Erectile Dysfunction • BCL2L1 • CD27 • CD3D • CD3E • IFNG • ITGB1 • LAMA5 • PPARG • PRKCA

Historically Based Perspective on the Immunotherapy of Type 1 Diabetes: Where We Have Been, Where We Are, and Where We May Go. (PubMed, J Clin Med) - " Initial therapies such as corticosteroids and cyclosporine offered proof-of-concept for immune modulation, yet suffered from relapse and toxicity. The introduction of monoclonal antibodies (e.g., teplizumab) marked a shift toward immune-specific intervention, particularly in stage 2 preclinical T1DM...Cellular therapies such as Treg adoptive transfer, chimeric antigen receptor Tregs (CAR-Tregs), and stem cell-derived islet replacements (e.g., VX-880) have shown promise in preserving β-cell function and modulating autoimmunity...The convergence of targeted biologics, regenerative cell therapies, and β-cell replacement approaches, supported by AI-enabled patient stratification, offers a realistic path toward durable immune tolerance and functional β-cell preservation. Continued integration of these modalities, coupled with rigorous long-term evaluation, will be essential to transform these scientific advances into sustained clinical benefit."

Journal • Diabetes • Immune Modulation • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

The Medicines and Healthcare products Regulatory Agency (MHRA) has…approved teplizumab (Tzield) to delay the onset of Stage 3 type 1 diabetes (T1D) by an average of three years in adults and children aged 8 years and older with Stage 2 T1D. (GOV.UK) - "This medicine has been approved through the International Recognition Procedure...Teplizumab is administered via intravenous infusion once daily for 14 days."

MHRA approval • Type 1 Diabetes Mellitus

βETA PRESERVE: A Study to Investigate Efficacy and Safety of Teplizumab Compared With Placebo in Participants 1 to 25 Years of Age With Stage 3 Type 1 Diabetes (clinicaltrials.gov) - P3 | N=723 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

βETA PRESERVE: A Study to Investigate Efficacy and Safety of Teplizumab Compared With Placebo in Participants 1 to 25 Years of Age With Stage 3 Type 1 Diabetes (clinicaltrials.gov) - P3 | N=723 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Structure based design of acylhydrazone compounds for the treatment of Type 1 Diabetes (ACS-Fall 2025) - "More recently, a monoclonal antibody (Tzield) has been shown to be used in Stage 2 to delay the onset of Stage 3 Type 1 diabetes by providing some protection for β-cells.We have identified a commercially available small molecule, an acylhydrazone (EPB-1), that has been shown to increase insulin secretion in β-cells and lower the cytokine-induced cell death...In addition, we will describe a preliminary SAR for this class of compounds. Additional studies to demonstrate their potential utility for treating Type 1 diabetes will also be reported."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Perspectives on prevention of type 1 diabetes and heterogeneities. (PubMed, Diabetologia) - "Using simulations, I illustrate uncertainties in efficacy estimates in prevention trials with time-to-event endpoints, using the TN10 teplizumab trial as an example. I emphasise that risk heterogeneity does not equate to treatment effect heterogeneity...A prevention trial targeting infants in the general population with a multivalent antiviral vaccine will likely need over 50,000 participants, depending on circumstances and assumptions. While such a trial is conceivable, it would demand robust safety data before initiation."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

TEPLI-REAL: Description of Patients With Type 1 Diabetes Treated With Teplizumab (clinicaltrials.gov) - P=N/A | N=110 | Completed | Sponsor: Sanofi | Recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Historical and Epistemological Review of Type 1 Diabetes Mellitus. (PubMed, J Clin Med) - "Notably, the approval of immunotherapies like teplizumab underscores the translational impact of these scientific insights. The historical trajectory of T1DM exemplifies the dynamic nature of medical knowledge and the interplay between clinical observations and scientific research. Recognizing these developments enhances our comprehension of disease mechanisms and informs current approaches to diagnosis and treatment."

Journal • Review • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

NonCME Breakfast Symposium: Let's Talk Type 1 Diabetes (NMA 2025) - "Following participation in this session, attendees should be able to: 1) navigate the T1D Journey – Screen – Monitor – TZIELD Considerations for Primary Care; 2) Recognize key clinical characteristics of type 1 diabetes; and 3) Identify best practices for screening and monitoring type 1 diabetes."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

What type 1 diabetes endotype is most suitable for anti-CD3 antibodies prevention trials? (PubMed, J Diabetes Complications) - "This paper underscores the need for expanded endotype-specific prevention trials and optimised screening protocols to identify high-risk individuals at the earliest stage. Future research should explore teplizumab's efficacy in younger populations and refine predictive biomarkers to enhance personalised intervention strategies in T1D management."

Journal • Review • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

SI03-11. Navigating the T1D Journey Screen – Monitor – TZIELD Considerations for Specialty Care (ENDO 2025) - "The Endocrine Society thanks the following supporters: Funded Sanofi Expanded information on T1D patient journey with emphasis on disease management, monitoring pre-symptomatic T1D, and care coordination."

Challenges and Opportunities for Understanding the Pathogenesis of Type 1 Diabetes: An Endocrine Society Scientific Statement. (PubMed, J Clin Endocrinol Metab) - "Notably, the first disease-modifying therapy (teplizumab, a monoclonal antibody targeting CD3+ on T lymphocytes) was approved by the US Food and Drug Administration in November 2022 to delay the clinical onset of T1D, thus opening new avenues to treat T1D as an immunologic disease rather than simply as a metabolic disease with lifelong insulin administration. In this Scientific Statement, we will integrate and summarize information about the pathogenesis of T1D, highlight gaps in current knowledge, and propose future activities that may lead to additional approaches to treat the underlying autoimmunity and β-cell defects in diabetes. Hopefully, these efforts, when combined with other rapidly improving T1D therapeutics including automated insulin delivery and cell replacement therapy, will lead to better long-term outcomes for those living with T1D."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Shed light on molecular immunogenetic pathophysiology of type 1 diabetes to improve advanced treatment strategies. (PubMed, Diabetes Res Clin Pract) - "It also discusses emerging treatments, such as Teplizumab-mediated immune modulation, CRISPR-based gene editing, and stem cell-derived β-cell replacement, as well as their efficacy in preserving β-cell function to delay disease progression. By integrating recent therapeutic advancements with a deeper understanding of the molecular aspects of the disease, this article highlights next-generation treatments' potential to significantly improve the management of T1D. Future investigations should focus on precision medicine approaches to achieve greater success in long-term treatments."

IO biomarker • Journal • Review • Diabetes • Immune Modulation • Immunology • Infectious Disease • Metabolic Disorders • Oncology • Type 1 Diabetes Mellitus • PTPN22 • TYK2

A systematic review and network meta-analysis of interventions to preserve insulin-secreting beta cell function in people newly diagnosed with type 1 diabetes: results from randomised controlled trials of immunomodulatory therapies. (PubMed, BMC Med) - "Eleven of 42 interventions demonstrated statistically significantly higher C-peptide levels than placebo at 12 months in the network meta-analysis. These results have identified the 11 most promising therapies trialled and help to direct future head-to-head clinical trials to support approvals for interventions to treat those newly diagnosed with type 1 diabetes. However, data for some interventions originated from small studies (mesenchymal stem cell therapies, azathioprine, autologous dendritic cells) and findings should be considered as hypothesis generating and interpreted with caution due to evidence heterogeneity."

Clinical • Journal • Retrospective data • Review • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Pharmacy-directed coordination of gene and high-cost therapies. (PubMed, Am J Health Syst Pharm) - "The creation of a pharmacy-directed program for coordination of gene and high-cost therapies has been crucial to the hospital's success in offering these innovative and potentially life-altering therapies."

Journal • Gene Therapies • Pediatrics

Engineering Islet Tolerance in Nonobese Diabetic (NOD) Mice via Costimulation Blockade Nanotherapy (ADA 2025) - "Introduction and Objective: Teplizumab (anti-CD3 antibody) is the first FDA-approved therapy to delay the onset of type 1 diabetes (T1D) and prolong insulin independence...We have previously demonstrated that rapamycin-loaded polymersome nanoparticles (rPS) induce antigen-specific tolerance towards transplanted fully-MHC mismatched islets via a costimulation blockade in mice1... rPS is a promising early-intervention therapy to delay the onset of T1D. rPS leverages antigen presenting cells to reprogram T cells for antigen-specific islet tolerance and can mitigate adverse events of chronic, nonspecific immunosuppression.1. Burke JA, et al."

Late-breaking abstract • Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus

The Use of Continuous Glucose Monitoring to Diagnose Stage 2 Type 1 Diabetes (ADA 2025) - "If these individuals are identified, then useful treatments, such as teplizumab, may help delay the onset of stage 3 (symptomatic) T1D. We used a group consensus process consisting of an in-person meeting of authors and panelists on October 15, 2024, and a virtual meeting with additional panelists... CGM offers promise as a tool to identify people with stage 2 T1D. These individuals could then undergo traditional venous blood glucose testing to screen for stage 2 T1D, to confirm the diagnosis so that an immune protective drug may be prescribed. Eventually, instead of serving as an adjunctive tool, CGM testing may be designated to replace plasma glucose testing and HbA1c testing to identify individuals with stage 2 T1D who may benefit from immunotherapy."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Two-Pronged Approach for Preventing and Treating Type 1 Diabetes (ADA 2025) - "Introduction and Objective: The approval of Tzield represents the first disease modifying therapy of T1D, yet it only delays T1D onset by ~ 2.5 years among people at risk... Our preclinical data in NOD mice supports the feasibility and efficacy of a two-pronged approach by simultaneously modulating the immune system and targeting the beta-cell to enhance its resilience."

Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus