HFB10-1E1, a novel OX-40 agonistic antibody with a unique pharmacological profile and biomarker strategy
1HiFiBiO Therapeutics, Cambridge, MA, United States
2Nankai University, China
Agonistic antibodies against the co-stimulatory receptor OX-40 have shown promising activity in preclinical models, but clinical activity has only been observed in isolated cases. While co-stimulation of T cells is described as the primary pharmacological mechanism of these antibodies, high expression of OX-40 on tumor-infiltrating regulatory T cells has also been observed and discussed as a potentially confounding factor in a clinical setting.
We present HFB10-1E1, a novel OX-40 agonistic antibody with an optimized pharmacological profile. HFB10-1E1 binds specifically to a unique epitope on human OX-40 and cross-reacts with cynomolgus monkey OX-40. Upon cross-linking, HFB10-1E1 induces NFκB signaling in a reporter cell line and leads to co-stimulation of T cells in vitro
. The agonistic activity of HFB10-1E1 is further enhanced in the presence of the endogenous ligand OX-40L. In contrast to other anti-OX-40 antibodies, treatment with HFB10-1E1 does not result in reduced expression of OX-40 on T cells, which will ease the prediction of clinical dose-schedule and potentially lead to better activity. HFB10-1E1 demonstrates more potent in vivo
anti-tumor activity in human OX-40 knock-in mice bearing MC-38 syngeneic tumors as compared to a previously published anti-OX-40 antibody. HFB10-1E1 has a favorable developability profile, and stable cell lines with high production yield have been obtained.
Further, we present a novel concept for identifying potential responding patients to HFB10-1E1 using HiFiBiOs proprietary Drug Intelligent Science (DIS) platform. The DIS approach for discovery of predictive response biomarkers combines high-throughput single-cell profiling of a patients T cell repertoire with functional read-outs to characterize tumor-specific T cell clones responsive to HFB10-1E1. Our results provide the foundation for the implementation of the DIS platform to guide the clinical development of HFB10-1E1 for selected patients that are most likely to benefit from the treatment.
HFB10-1E1 is being developed as a potential novel treatment option for cancer coupled with a patient stratification biomarker.
Session: Therapeutic Antibodies 1
(Virtual Poster Session)
Category: IMMUNOLOGY: Preclinical and Clinical