Mozart Therapeutics reported interim Phase Ib results for MTX-101 in adults with Stage 3 type 1 diabetes, with data from five patients presented at the 21st Immunology of Diabetes Society Congress in Brisbane showing selective CD8 regulatory T cell activation, reductions in pathogenic T cell populations, and — at the higher dose level — maintained or increased C-peptide values relative to baseline through approximately 20 weeks.
Across all five participants, the company said interim data from the ongoing NCT06324604 trial demonstrated selective activation and proliferation of CD8 Treg, reduced prevalence of pathogenic CD4 and CD8 T cells in peripheral blood, and diminished responses to autoantigen restimulation, which Mozart characterized as proof-of-mechanism. The three patients who received a single dose at 0.15 mg/kg maintained or increased C-peptide values compared to baseline through end-of-study; the two patients at 0.05 mg/kg were not separately quantified in the press release. As a historical reference, the company cited a meta-analysis of 21 clinical studies in newly diagnosed type 1 diabetes patients in which 246 placebo recipients experienced C-peptide declines of approximately 17% at 12 weeks and approximately 37% at 26 weeks. Treatment-emergent adverse events were described as mostly transient and generally mild or moderate in severity, consistent with other immunomodulatory therapies; no specific event types, grades, or frequencies were disclosed.
The Phase Ib study randomized participants to receive MTX-101 at 0.05 mg/kg or 0.15 mg/kg as a single dose, with blinding status not explicitly stated in the company's disclosure. The five patients in this interim analysis were aged 30 to 39 years, were diagnosed between 6 and 252 months prior to enrollment (median 36 months), all presented with at least one T1D autoantibody, and three had at least one comorbid autoimmune diagnosis; all had screening C-peptide of at least 0.2 nmol/L. No placebo arm for the Phase Ib cohort was described in the press release, and the data remain interim, drawn from a subset of enrolled patients. Mozart said it plans to complete the Phase Ib study and initiate enrollment in a global Phase II study in early 2027.
MTX-101 is a bispecific antibody targeting inhibitory KIR and CD8 on regulatory CD8 T cells, designed to restore CD8 Treg function and suppress pathogenic T cell activity. Teplizumab (Tzield), an anti-CD3 monoclonal antibody approved in the US to delay onset of Stage 3 type 1 diabetes in at-risk individuals, produced a median delay of approximately 25 months in progression from Stage 2 to Stage 3 disease in its pivotal trial, though that effect was demonstrated in a prevention setting rather than established Stage 3 disease. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.
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