Eisai to Present E7386 at ESMO Annual Meeting

PRISM BioLab, a prominent biotechnology firm specializing in the development of small molecule inhibitors targeting protein-protein interactions (PPIs), has announced significant interim findings from a study involving the drug E7386. The study was conducted in collaboration with Eisai Co., Ltd. and focused on combining E7386 with Lenvatinib mesylate. These findings will be shared at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona.

E7386, an orally administered small molecule that inhibits interactions between the transcription factor CBP and β-catenin, is a key part of this study. It aims to regulate the Wnt signaling pathway. The drug achieved proof of concept in October 2021 and is currently undergoing several clinical trials. These include Phase I studies for solid tumors as a standalone treatment, Phase Ib trials in combination with Lenvatinib, and Phase Ib/II trials in combination with pembrolizumab, an anti-PD-1 antibody.

The Phase Ib open-label study (NCT0400879) was designed to determine the recommended dose of E7386 when used with Lenvatinib. The study targeted patients with advanced endometrial cancer who had not responded to platinum-based chemotherapy and anti-PD-(L)1 immunotherapy. By the data cutoff date of March 7, 2024, the study had enrolled 16 patients. Of these, 31% (five patients) exhibited a partial response with a tumor size reduction of more than 30%, while another 31% (five patients) had stable disease, with tumor size changes ranging from -30% to +20%.

These results demonstrate that the combination of E7386 and Lenvatinib has promising antitumor activity and a manageable safety profile. The study is ongoing, with additional patient enrollment continuing for the expansion part.

Lenvatinib, a multi-kinase inhibitor developed by Eisai, is co-commercialized with Merck & Co., Inc. It targets various receptors, including vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs). Lenvatinib is approved for treating multiple cancers, including thyroid cancer, hepatocellular carcinoma, thymic cancer, and renal cell carcinoma, often in combination with other drugs such as pembrolizumab.

The NCT04008797 study is another open-label Phase Ib trial for E7386 combined with Lenvatinib. Conducted in multiple countries, including Japan, Korea, Taiwan, the US, and France, this study aims to determine the safety and recommended Phase 2 dose of the drug combination. It also seeks to understand the pharmacokinetics and efficacy of this treatment in patients with various solid tumors, such as hepatic, colon, and endometrial cancers.

PRISM BioLab, the biotechnology company behind E7386, uses its proprietary PepMetics® technology to develop orally available small molecule inhibitors of PPIs. This innovative approach mimics the three-dimensional structures of alpha-helix and beta-turn peptide structures, commonly found in intracellular PPI interfaces and receptor-ligand interactions. By leveraging AI-supported design and proprietary chemistry, PepMetics® technology aims to transform previously undruggable PPIs into viable drug targets. This technology holds significant promise for expanding drug discovery and providing oral small molecule alternatives to injectable biologics.

PRISM BioLab is actively collaborating with global and Japanese pharmaceutical companies to target new PPIs. Notably, PepMetics® targeting CBP/β-catenin PPIs, licensed to Eisai and Ohara Pharmaceuticals, are currently in clinical development for cancer and liver disease, respectively.