Th128 - Safety and Pharmacodynamic Effects of Novel Fully Human Anti-thymocyte Polyclonal Igg Antibodies in an IND Enabling GLP Toxicology Study

Thomas Luke; Hua Wu; Diane Maher; Eddie Sullivan; Christoph Bausch; Alexandra Kropotova; Mohamed Ezzelarab; Kurt Griffin; Jared Wollman; Alexei Savinov

Abstract Text: SAB-142 is a first-in-class fully human polyclonal anti-thymocyte immunoglobulin (ATG) produced in SAB Biotherapeutic’s proprietary DiversitAb platform. As a fully human antibody treatment, SAB-142 is expected to be non-immunogenic and well tolerated when used in humans, as previously demonstrated by several clinical phase investigational products produced in the DiversitAb platform. In contrast, other anti-thymocyte agents currently on the market, such rabbit-ATG, are known to cause serum sickness and severe hypersensitivity reactions in humans. Transchromosomic bovines that produce fully human polyclonal antibodies underwent a series of immunizations with human thymocytes. Post immunization plasma was collected and purified into an anti-thymocyte fully human IgG immunotherapeutic (SAB-142). In vitro characterization of SAB-142 demonstrated binding to multiple human PBMC populations. In an IND-enabling GLP NHP Toxicology study, a single infusion of SAB-142 was administered at 1, 5, and 10 mg/kg (N=6 per dose) and an FDA approved rabbit-ATG was administered at 5 mg/kg (N=6). All 24 animals were assessed for safety and pharmacodynamic effects with clinical assessments, clinical labs, and PBMCs collected at various timepoints. Analysis of peripheral blood lymphocyte populations post-treatment showed dose-dependent depletion of CD45+ CD3+ pan-T lymphocytes, CD45+ CD3+ CD4+ T helpers, and CD45+ CD3+ CD8+ cytotoxic T lymphocytes through day 28. Our data suggest that SAB-142 demonstrates safety and dose-dependent pharmacodynamic effects in NHPs. These results support IND applications for human clinical trials to prevent and/or treat various diseases and conditions, including type 1 diabetes, other autoimmune diseases, and transplant indications.