Exploring the Potential of YBL-006: A Comprehensive Preclinical Evaluation of a Novel Human Anti-PD-1 Antibody

YBL-006 is a novel human monoclonal IgG4 antibody targeting PD-1, a protein that plays a key role in immune evasion by cancer cells. This new antibody has been evaluated in both in vitro and in vivo studies to assess its therapeutic potential. It has demonstrated a high affinity for human PD-1, with a dissociation constant (KD) of 0.372 nM, which is superior to that of existing drugs nivolumab and pembrolizumab. YBL-006 also shows a strong binding to cynomolgus monkey PD-1 and, to a lesser extent, to mouse PD-1, unlike the other two antibodies which do not bind to mouse PD-1.

In functional assays, YBL-006 effectively blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, leading to an increase in interferon-gamma (IFN-γ) production, a cytokine indicative of T-cell activation. In a mouse model of colon cancer, YBL-006 treatment resulted in a 25% reduction in tumor weight compared to controls. In a humanized mouse model of non-small cell lung cancer, YBL-006 reduced tumor volume by 35%, which is more significant than the reductions achieved with nivolumab.

Pharmacokinetic studies in monkeys revealed that YBL-006 concentrations increased in a dose-dependent and proportional manner, with a mean estimated half-life of 70.8 to 110 hours. The drug's clearance and distribution suggest it is primarily found in the blood. In a one-month toxicity study, YBL-006 showed no adverse effects at doses up to 100 mg/kg/day, although the presence of anti-drug antibodies was noted in some monkeys. Tissue cross reactivity studies did not indicate any potential toxicity.

YBL-006 is characterized by its high affinity for PD-1, its promising anti-tumor effects in animal models, and a favorable safety profile. A phase I clinical trial to assess the safety and efficacy of YBL-006 in patients with advanced solid cancers is planned for 2020. The findings were presented at the Annual Meeting of the American Association for Cancer Research in 2020.