1060-OR: Clinical Safety, Pharmacokinetics, Immunogenicity, and Pharmacodynamics following Repeat Dosing of SAB-142, a Fully Human Multispecific Antithymocyte Globulin for New-Onset Type 1 Diabetes

Introduction and Objective: There is no approved therapy to halt new-onset Type 1 diabetes (NOT1D). Although rabbit anti-thymocyte globulin has shown promise in preserving C-peptide and HbA1C, it is limited by safety concerns, including serum sickness and immunogenicity that prevents re-dosing. SAB-142, a fully human, multi-specific anti-thymocyte globulin, is designed to delay NOT1D onset and progression with low to no immunogenicity, enabling re-dosing and maintenance without serum sickness. Methods: SAB-142-101 is a randomized, double-blind, placebo-controlled Phase I trial designed to evaluate safety, tolerability, PK, and PD of SAB-142 in healthy volunteers and T1D patients. SAB-142 was administered intravenously as an ascending dose up to 4.5 mg/kg. A re-dosing cohort was included to support the anticipated every 6-month dosing regimen. Results: In the SAB-142-101 study, no deaths or drug-related SAEs occurred, and no TEAEs led to withdrawal. Hematologic parameters show no sustained lymphodepletion, neutropenia, thrombocytopenia, anemia, or coagulation abnormalities. The PK profile of SAB-142 in the re-dosing cohort showed that systemic exposure after re-dosing was comparable to that observed in the single-dose cohort at the same dose, demonstrating consistent exposure following re-dosing. No ADA were detected in subjects from the re-dosing cohort. Re-dosing caused a transient increase in cytokines similar to the initial dose. There were no significant changes from baseline for CD4 and CD8 T-cell subsets and Tregs were preserved and activated by expression of TIGIT following re-dosing. Conclusion: Clinical data from SAB-142-101 demonstrated a favorable safety and immunogenicity profile, consistent PK, transient cytokine increase, and a PD profile indicative of the desired mechanism of action suggesting safe re-dosing every 6 months as a maintenance dose and supporting advancement to the Phase 2B SAFEGUARD study in pediatric and adult NOT1D patients.