The CREB-binding protein (CBP)/β-catenin inhibitor E7386, co-created by Eisai and PRISM BioLab, achieved the clinical POC (Proof of Concept)

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and PRISM BioLab Co., Ltd. (Headquarters: Kanagawa, President and CEO: Dai Takehara, “PRISM”) announced today that the ?CREB-binding protein (CBP) / β-catenin inhibitor E7386, a medium-molecular weight compound created through collaboration research between Eisai and?PRISM, has achieved the clinical POC (Proof of Concept).

Eisai is conducting a Phase I clinical study of E7386 monotherapy for?solid tumors, and a Phase Ib clinical trial of E7386 plus lenvatinib mesylate (product name: LENVIMA?, “lenvatinib”), the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, for solid tumors including hepatocellular carcinoma. The achievement of the POC, which is defined in a collaborative research agreement between Eisai and PRISM, was confirmed based on data such as antitumor activity and changes of biomarkers in these clinical trials.

The E7386 targets, β-catenin, is considered to be one of the undruggable targets that are particularly difficult to develop into drug discovery. β-catenin, along with CBP, which is also the target of E7386, is located at the downstream of the Wnt signaling and regulates the Wnt signaling-dependent transcription activity. E7386 is a CBP / β-catenin inhibitor that inhibits CBP and β-catenin protein-protein interactions and regulates the Wnt signal-dependent gene expression. It is expected to suppress tumor growth dependent on the Wnt signaling. 1 E7386 is also expected to release the suppression of tumor-infiltrating T cells by the Wnt signaling activation, and to enhance the effect of immune checkpoint inhibitors1. The antitumor effect of E7386 alone and the combination of E7386 and anti-PD-1 antibody has been confirmed in a cancer-bearing mouse model.

Based on the POC achievement, Eisai has initiated a phase Ib/II clinical trial (Study 201) of E7386 in combination with anti-PD-1 therapy pembrolizumab for solid tumors in Japan.*

Dr. Takashi Owa, Senior Vice President, President of Oncology Business Group, at Eisai said, “With achieving the POC, we are confident with the prospect of offering E7386 to patients as a cancer treatment. E7386 may overcome lenvatinib and pembrolizumab treatment resistances through its combination therapy with lenvatinib or pembrolizumab. Eisai will accelerate clinical trials of E7386 in combination with lenvatinib or pembrolizumab, and do its utmost aiming to create new treatments for cancers with high unmet medical needs.”

Dai Takehara, President and CEO of PRISM commented, “The approval of the clinical POC for the E7386 demonstrates that PRISM’s drug discovery platform is an effective option for novel drug targets which have been considered difficult. We are grateful to Eisai for advancing this development. We will continue to take on the challenge of targeting more novel targets, with the aim of providing new treatment to as many patients as possible.”

* Study 201 is being conducted under a clinical trial collaboration and supply agreement between Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A.