Non-Clinical Evaluation of the Anti-PD-1 Antibody UDIZ-007

Background/Objectives: Programmed cell death protein 1 (PD-1) is a key immune checkpoint that suppresses anti-tumor T cell responses and is an established target for cancer immunotherapy. UDIZ-007 is a fully human anti-PD-1 antibody that blocks PD-1/PD-L1 and PD-1/PD-L2 interactions and eradicates MC38-hPD-L1 colon tumors in B-hPD-1 transgenic mice. This study further characterized the pharmacokinetics (PK), immunogenicity, and safety of UDIZ-007 to support its clinical development. Methods: UDIZ-007 was produced in a stable Chinese hamster ovary (CHO) cell line, and its biophysical and in vitro functional profiles were assessed. PK, immunogenicity, and safety were evaluated in mice and cynomolgus macaques. Results: UDIZ-007 showed biophysical and in vitro functional properties consistent with therapeutic antibodies and demonstrated potent, dose-dependent anti-tumor activity against MC38-hPD-L1 colon tumors engrafted in B-hPD-1 transgenic mice. Single-dose PK studies in mice at 10 and 100 mg/kg and in cynomolgus macaques at 10, 50, and 101.2 mg/kg showed dose-proportional exposure. In cynomolgus macaques, UDIZ-007 had a prolonged half-life of approximately 12 days. Repeated intravenous administration at 10, 50, or 101.2 mg/kg in cynomolgus macaques was generally well tolerated, with no major treatment-related toxicities. Accordingly, the no-observed-adverse-effect level (NOAEL) was established at the highest tested dose, 101.2 mg/kg. Anti-drug antibodies (ADAs) were detected in some animals and were associated with expected PK variability but not with adverse effects. Tissue cross-reactivity studies across 32 human and cynomolgus macaque tissues showed binding primarily restricted to lymphoid tissues known to express PD-1. Conclusions: UDIZ-007 demonstrated robust anti-tumor activity, favorable PK and safety profiles, as well as selective binding to PD-1-expressing tissues, supporting its clinical development as a potential cancer immunotherapy.