Farletuzumab Ecteribulin

Strategic collaboration with Bristol Myers Squibb ended TOKYO, Japan I July 01, 2024 I Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has agreed to end its global strategic collaboration with Bristol Myers Squibb for the co-development and co-commercialization of farletuzumab ecteribulin (FZEC), formerly known as MORAb-202, a folate receptor alpha (FRα)-targeting antibody drug conjugate (ADC) due to ongoing portfolio prioritization efforts within Bristol Myers Squibb. Based on the agreement, Eisai now owns all rights to FZEC and will solely conduct the global development and commercialization of the agent. Eisai will accelerate the development of the agent as a high priority with the hope to deliver it to patients as early as possible. Eisai plans to refund a part of the unused portion of the $200 million payment it received towards research and development expenses from Bristol Myers Squibb under the collaboration agreement and record the remaining as other income. FZEC is Eisai’s first ADC and is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the FRα, and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. Currently, three clinical studies are ongoing: Eisai’s Phase 1/2 study for solid tumors (NCT04300556), and Bristol Myers Squibb’s Phase 2 studies for ovarian, peritoneal and fallopian tube cancers (NCT05613088) and non-small cell lung cancer (NCT05577715). Eisai positions oncology as a key franchise area and aims to contribute toward the cure of cancers by exploring the depths of human biology. FZEC development for refractory cancers is a testament of our dedication to addressing the unmet medical needs of patients with cancer. Eisai will make continuous efforts to increase the benefits provided to patients with cancer and their families. [Notes to editors] 1. Farletuzumab ecteribulin (FZEC, formerly known as MORAb-202) FZEC is Eisai’s first antibody drug conjugate (ADC) and that is composed of Eisai’s in-house developed farletuzumab, a humanized IgG1 monoclonal antibody that binds to the folate receptor alpha (FRα), and Eisai’s in-house developed anticancer agent eribulin, using an enzymatically cleavable linker. After FZEC enters the target FRα-positive cancer cells, it is thought that the linker is enzymatically cleaved, releasing eribulin from the antibody leading to its antitumor activity. When the anticancer agent and antibody components of an ADC are separated inside a targeted antigen-positive cancer cell, it is theorized that the released anticancer agent also has a bystander effect on neighboring antigen-negative cancer cells and the component cells of the tumor microenvironment. In pre-clinical studies, FZEC demonstrated a bystander effect*, with antitumor activity on the FRα-negative cancer cells surrounding the FRα-positive cancer cells. The payload eribulin was the first in the halichondrin class of microtubule dynamics inhibitor. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai, and functions by inhibiting the growth phase of microtubule dynamics which prevents cell division. Eribulin has been approved in countries including Japan, the United States, China, in Europe and in Asia for use in the treatment of advanced breast cancer and liposarcoma (soft tissue sarcoma in Japan). *Bystander effect: When the anticancer agent and antibody parts of an ADC are separated inside a targeted antigen-positive cancer cell, the released anticancer agent also affects neighboring antigen-negative cancer cells and the component cells of the cancer microenvironment. SOURCE: Eisai

Eisai will “accelerate the development of the agent as a high priority.” Bristol Myers Squibb is walking away from its $650 million bet on an Eisai antibody-drug conjugate (ADC). The Japanese drugmaker said BMS decided to end the co-development agreement as part of an ongoing portfolio prioritization push. BMS partnered with Eisai in 2021, paying $450 million upfront for rights to MORAb-202. Eisai, which had phase 1 data from 22 patients at the time of the deal, conjugated an anti-folate receptor alpha (FRα) antibody and anticancer agent to create the candidate. BMS paid the upfront, plus $200 million in R&D support, and dangled $2.5 billion in milestones to land the deal.   Three years later, BMS has decided the candidate is no longer part of its plans. The Big Pharma had joint rights to MORAb-202 in markets including the U.S. and Europe, plus exclusive rights in other parts of the world. Eisai has regained full rights to the ADC, which is now called farletuzumab ecteribulin (FZEC), and plans to refund “a part of the unused portion of the $200 million” BMS paid to support R&D costs.  The Japanese drugmaker said it will “accelerate the development of the agent as a high priority.” BMS began two phase 2 trials, one in ovarian, peritoneal and fallopian tube cancers and another in non-small cell lung cancer, in 2022. Both studies have passed their estimated primary completion dates but are still listed as recruiting on ClinicalTrials.gov. BMS cut its enrollment targets and dropped a dose in both trials. The indications targeted in the phase 2 trial reflect evidence that FRα is highly expressed in patients with certain types of solid tumors. Using an antibody to direct a cytotoxic payload to those targets could drive the destruction of the tumors and spare healthy tissues. Eisai is also still running a phase 1/2 study in solid tumors that began in 2020. Since striking the deal, BMS has seen ImmunoGen win approval for the rival FRα-directed ADC Elahere and sell up to AbbVie for $10.1 billion. Other companies are lining up to challenge Elahere. Genmab joined the chasing pack earlier this year when it agreed to buy ProfoundBio for $1.8 billion. In April, BMS unveiled plans for a significant “pipeline rationalization” that would see the Big Pharma lay off over 2,000 staff this year and end work on about a dozen programs, including CTLA4- , SIRPα- and BET-targeting meds. “Throughout the year we'll continue to look at these same principles and see what else we need to take out from our pipeline and either externalize it or not be able to develop it further,” Chief Medical Officer Samit Hirawat, M.D., said at the time.