Type 1 Diabetes (T1D) arises from the autoimmune destruction of insulin-producing islet cells in the pancreas. This destruction results in a complete loss of insulin production, leading to significant impairment in blood glucose control. Without insulin, the body cannot properly process nutrients, causing persistently high blood glucose levels.

High blood glucose can precipitate diabetic ketoacidosis and, over time, lead to severe complications such as kidney disease/failure, eye disease (including vision loss), heart disease, stroke, nerve damage, and even death. Managing T1D is further complicated by the limitations and complexities of current insulin delivery systems. Achieving and maintaining balanced glucose control remains a challenging task for individuals with T1D.

Despite advancements, current standards of care do not address the underlying causes of T1D. Treatment options beyond insulin are limited, and there is no cure for diabetes. This highlights the urgent need for innovative therapies and improved management strategies to alleviate the burden of T1D and enhance the quality of life for those affected.

In light of this, here are a few key updates in T1D research and treatment presented at the American Diabetes Association (ADA) scientific sessions.

1. Vertex’s VX-880 Shows Promise in Transforming T1D Treatment

Vertex Pharmaceuticals presented promising data from its ongoing Phase I/II clinical trial of VX-880, an investigational stem cell-derived islet cell therapy for T1D, at the American Diabetes Association’s 84th Scientific Sessions. All 12 patients who received a full dose of VX-880 via a single infusion demonstrated significant islet cell engraftment and glucose-responsive insulin production by Day 90. They achieved ADA-recommended HbA1c levels below 7.0% and maintained over 70% time-in-range, with 11 out of 12 reducing or eliminating exogenous insulin use. Three patients with at least 12 months of follow-up met the primary endpoint of eliminating severe hypoglycemic events (SHEs) and achieving insulin independence. The therapy was well-tolerated, with mostly mild or moderate adverse events and no serious events related to VX-880.

In September 2019, Vertex acquired VX-880 through a USD 950 million buyout of Semma Therapeutics, recognizing its potential as a multibillion-dollar opportunity. VX-880 aims to restore glucose regulation by re-establishing pancreatic islet cell function, offering a potentially transformative therapy for T1D patients. Granted RMAT, Fast Track, and PRIME designations, Vertex plans to expand the VX-880 trial to 37 participants, enrolling across additional sites in the US, Canada, and Europe, and progressing toward pivotal development.

2. SAB Biotherapeutics’s Drug: A Potential Game-Changer in Type 1 Diabetes Treatment

SAB-142, a novel human antibody, is poised to revolutionize the treatment of T1D by offering a safer and more effective alternative to the traditional rabbit anti-thymocyte globulin (ATG). Rabbit ATG, which has been clinically validated in multiple trials, has shown the ability to slow disease progression in patients with Stage 3 T1D by modulating the immune response and preserving insulin-producing beta cells. However, its animal origin often leads to serum sickness and the development of anti-drug antibodies, limiting its long-term use.

SAB-142 mimics the mechanism of action of rabbit ATG by targeting the immune cells responsible for the destruction of pancreatic beta cells. This action helps preserve these crucial cells and maintain insulin production, essential for blood sugar regulation. Unlike rabbit ATG, SAB-142’s human origin allows for consistent redosing without the risk of severe immune reactions, making it suitable for the lifelong management of T1D.

Following FDA Investigational New Drug (IND) clearance in May, SAB-142 has advanced into a Phase I clinical trial to evaluate its safety in humans. Preclinical studies in Cynomolgus macaques and various in vitro assays demonstrated that SAB-142 has a favorable safety profile. The antibody showed minimal binding to human serum proteins and GBM antigens, indicating a lower likelihood of adverse reactions. In vivo studies confirmed that SAB-142 was well tolerated, with no significant adverse effects observed, even at higher dosages.

The promising preclinical and early clinical data suggest that SAB-142 could be a transformative therapy for T1D, offering a safer and more effective option compared to existing treatments. As the clinical program for SAB-142 expands, it holds significant potential to improve the quality of life for individuals managing this chronic disease.

3. MTX-101 from Mozart Therapeutics: Pioneering Autoimmune Therapy by Targeting CD8 T Regulatory Cells

Mozart Therapeutics is pioneering a novel approach to treating autoimmune diseases with its innovative therapies targeting the CD8 T regulatory network. At the 2024 American Diabetes Association’s 84th Scientific Sessions, the company unveiled promising new preclinical data for its lead program, MTX-101.

MTX-101 is a bispecific antibody designed to target inhibitory KIR and CD8 expressed on regulatory CD8 T cells. This unique autoimmune checkpoint inhibitor aims to reinstate the intrinsic functions of regulatory CD8 T cells, intervening early in the autoimmune disease process. The goal is to suppress and eliminate pathogenic cells, halt downstream inflammation, and prevent tissue destruction.

Currently, MTX-101 is undergoing a randomized, blinded, placebo-controlled Phase I clinical study. The study comprises two parts: Part A involves healthy adults, while Part B focuses on patients with celiac disease or type 1 diabetes mellitus. The newly presented data highlight the potential of MTX-101 in modulating the regulatory CD8 T cell network in autoimmune diseases, particularly T1D.

Preclinical findings revealed that treatment with MTX-101 increases the prevalence of CD8 Treg cells. Moreover, the functionality of these cells, in terms of activation and cytolytic capacity, can be restored in the autoimmune setting of T1D. This suggests that MTX-101 may effectively reinstate the immune-regulatory functions needed to combat autoimmune conditions.

The results underscore the promise of MTX-101 in potentially transforming the treatment landscape for autoimmune diseases by restoring the function of regulatory CD8 T cells. Mozart Therapeutics continues to advance its clinical evaluations, with ongoing efforts to assess the efficacy and safety of MTX-101 in patients with type 1 diabetes mellitus during the latter part of their Phase I study.

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