GS-5745

Drug Overview

GS-5745 (Gilead) is a humanized monoclonal antibody designed to selectively target the matrix metalloproteinase-9 (MMP9) enzyme. MMP9 plays a key role in the regulation of processes that contribute to chronic inflammation, tumorigenesis, and metastasis by degrading structural components of the extracellular matrix. In vivo and in vitro models have suggested that MMP9 may also enable pro-oncogenic signaling through its ability to release epidermal growth factors and vascular endothelial growth factors. Upon administration, GS-5745 binds to MMP9 and blocks its enzymatic activity, resulting in inhibition of tumor growth, invasion, angiogenesis, and metastasis.

Analyst Outlook

GS-5745 (Gilead) is a matrix metalloproteinase-9 (MMP9)-targeted monoclonal antibody (MAb) currently under development for the first-line treatment of advanced gastric cancer. Early-phase studies of GS-5745 suggest that the drug may have clinical activity in advanced gastric cancer patients when combined with chemotherapy without significant additional toxicities. However, there have been no observed responses in patients treated with single-agent GS-5745, and Phase I trials of drug have lacked chemotherapy treatment arms for comparison. This makes it difficult to analyze whether GS-5745 provides additional benefits when combined with chemotherapy over chemotherapy treatment alone. GS-5745 is currently undergoing Phase III clinical trials to test its potential efficacy in first-line gastric cancer patients, a treatment area with few approved targeted therapies. Keytruda (pembrolizumab; Merck & Co) and Cyramza (ramucirumab; Eli Lilly/Shire) are also both looking to gain first-line approval, which could negatively impact GS-5745’s commercial uptake.