Harnessing FS102: Overcoming HER2 Resistance with a Novel Fcab Approach

HER2 is a well-established target in oncology, commonly overexpressed in various cancer types. Despite the availability of HER2-targeted biologics that have improved outcomes for HER2-positive cancers, resistance remains a significant challenge. A new HER2-specific Fcab, FS102, has been developed with high affinity for HER2 and a unique epitope recognition not shared with existing drugs like trastuzumab or pertuzumab.

FS102 has been engineered with a half-life of approximately 60 hours in mice and has been characterized for its potential as a therapeutic agent. It has been evaluated both in vitro and in vivo for its pharmacological activity, compared to trastuzumab alone or in combination with pertuzumab. Using the SKBr3 breast cancer cell line, FS102 was found to efficiently internalize and induce a significant reduction in HER2 protein levels, unlike trastuzumab. While both agents reduced cell proliferation, they did so through different mechanisms; FS102 notably induced apoptosis, an effect not observed with trastuzumab.

In vivo, FS102 has shown potent anti-tumor effects in patient-derived xenograft (PDX) models overexpressing HER2, with significant tumor inhibition observed across gastric, colorectal, and breast cancer models. Remarkably, FS102 achieved complete tumor regression in some models and was more effective than trastuzumab in biomarker-positive PDX tumors. In a model resistant to trastuzumab-pertuzumab combination therapy, FS102 treatment led to tumor reversal and complete regression.

These findings suggest that FS102 has the potential to address resistance to standard HER2 therapies and offers a novel mechanism of action. The Fcab platform, which FS102 is based on, is a promising approach for developing new biologics with unique antigen recognition. Further research is being conducted to understand the ErbB receptor degradation pathway induced by FS102.