TIXiMED Initiates Phase 1b MAD Study of Oral TXNIP Inhibitor TIX100 for Type 1 Diabetes
Key Insights
TIXiMED has launched a Phase 1b Multiple Ascending Dose study of TIX100, an investigational oral TXNIP (search) inhibitor, in 18 healthy subjects across three dose cohorts.
The Phase 1a single-dose trial demonstrated safety, tolerability, and the first metabolic signal of TIX100 in humans, with no hypoglycemia observed even during extended fasting.
TIX100 targets the underlying mechanism of pancreatic beta-cell loss driven by TXNIP (search), a protein elevated in diabetes, potentially offering the first oral disease-modifying therapy for type 1 diabetes (search).
BIRMINGHAM, Ala. — TIXiMED, Inc. (search), a clinical-stage pharmaceutical company, announced on July 7 the initiation of a Phase 1b Multiple Ascending Dose (MAD) study of TIX100, an investigational oral inhibitor of thioredoxin-interacting protein (TXNIP (search)) being developed as a disease-modifying therapy for type 1 diabetes (search) (T1D). The announcement marks a significant step toward what could become the first oral treatment targeting the underlying biology of beta-cell loss in T1D.
The double-blind, randomized, placebo-controlled trial (NCT07675590) will enroll 18 healthy subjects across three ascending dose cohorts at a single U.S. center. Participants will receive either TIX100 or placebo twice daily for 28 days, followed by a seven-day follow-up period. Six participants in the first cohort have already been successfully enrolled.
Building on Phase 1a Results
The MAD study follows the successful completion of a Phase 1a Single Ascending Dose trial, in which TIX100 was found to be safe and well tolerated across all four dose cohorts. Notably, the drug produced no hypoglycemia even during extended fasting and lowered postprandial glucose excursion in a healthy, normoglycemic population — representing the first metabolic signal of TIX100 in humans.
The current trial is further supported by favorable results from expanded pharmacokinetics and safety pharmacology studies conducted as part of the Investigational New Drug package approved by the U.S. Food and Drug Administration.
Two Decades of TXNIP (search) Research
TIX100 is grounded in more than two decades of research led by Anath Shalev, M.D., professor in the UAB Division of Endocrinology, Diabetes and Metabolism and director of the UAB Comprehensive Diabetes Center. Shalev's work identified TXNIP (search) as a key driver of pancreatic islet beta-cell loss and diabetes progression. TXNIP is elevated in diabetes and leads to beta-cell loss, whereas inhibiting it protects the body's own insulin-producing beta cells and promotes overall islet cell health — findings demonstrated in multiple mouse models of diabetes as well as in humans with T1D.
"Over two decades, our research has established TXNIP (search) as a key driver of pancreatic islet beta cell loss and diabetes progression. TIX100 now provides a clinical translation of these biological findings," said Shalev, who serves as Chief Scientific Officer and Co-Founder of TIXiMED. "The single-dose study gave us a first, encouraging metabolic signal in humans, and the MAD study will generate the longer-term safety data we need before advancing into a Phase 2a study including people with recent-onset type 1 diabetes (search)."
Addressing an Unmet Need
An estimated 9.5 million people worldwide live with type 1 diabetes (search), a chronic disease in which insulin-producing beta cells are damaged or destroyed. While existing therapies, including daily insulin injections, help manage blood sugar, no oral treatment currently targets the underlying loss of beta-cell function.
"Each milestone we reach brings a differentiated oral approach for type 1 diabetes (search) closer to the patients who need it. People at different stages of type 1 diabetes, from those at risk to those living with long-standing disease, still have no oral options or therapy designed to address the underlying damage to islet biology, and that is the gap we are working to close," said Stephen Daly, Chief Executive Officer of TIXiMED.
Broader Therapeutic Potential
Beyond type 1 diabetes (search), TIX100 may have applications in type 2 diabetes (search) and obesity (search). A recent preclinical study found that the drug prevented weight regain and preserved lean muscle mass after discontinuation of GLP-1 therapies in animal models.
The development program has received support through a Program Related Investment in the form of a loan from The Leona M. and Harry B. Helmsley Charitable Trust. "The progress TIXiMED has made into multiple-dose clinical evaluation reflects the kind of disciplined, science-driven development we are pleased to support," said Ben Williams, Ph.D., Program Officer, Type 1 Diabetes (search) Program at the Helmsley Charitable Trust.
Shalev co-founded TIXiMED in 2021 through UAB's Bill L. Harbert Institute for Innovation and Entrepreneurship. She holds the Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Juvenile Diabetes Research.