China CDE has cleared the Investigational New Drug (IND) application for LF0376, a CCR2/5 antagonist developed by Lingfang Biotech, for use in patients with DLBCL.
Lingfang Biotech initiated a phase 1a trial of LF0376 in 2022, targeting patients with solid tumors (colorectal cancer, pancreatic cancer, liver cancer) and lymphomas. The administered doses are 50 mg or 100 mg once daily (QD), and as of now, no clinical data has been reported.
In 2019, Lingfang Biotech filed a patent claiming CCR2/5 antagonists with compounds named WX*** (following Wuxi Apptech naming rules).
| Structures |
Anti-tumor activity of WX001 in combination with anti-PD-1 antibody was investigated in vivo using a colon cancer MC38 tumor model in mice as above. "the WX001+PD-1 combination group had a significant enhanced efficacy compared to the PD-1 single-use group." The curves of the PD-1 group and CVC+PD-1 group appear to closely overlap, with the CVC+PD-1 group exhibiting numerically higher values.
Additionally, compounds were investigated the inhibition of human liver microsomal cytochrome P450 isoenzymes. "WX001 has no inhibitory effect on CYP3A4, the main metabolic enzyme of drug metabolism, thereby avoiding occurrence of such risks". The inhibition for CYP2C19 isoenzyme was measured at 1.42 μM, with the explanation that "The drugs that CYP2C19 involves in their metabolism account for only 2% of marketed drugs"
*Clinical trials of Cenicriviroc (CVC) targeting patients with NASH and HIV-1 infection yielded disappointing results.
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