3D Rendering of Antibody Drug Conjugate Molecules
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Eisai and Bristol Myers Squibb are ending their $650M collaboration for the co-development and co-commercialization of antibody-drug conjugate (ADC) farletuzumab ecteribulin (FZEC), due to “ongoing portfolio prioritization efforts within Bristol Myers Squibb (BMS).” Formerly known as MORAb-202, FZEC is a folate receptor alpha (FRα)-targeting antibody drug conjugate (ADC). Eisai and BMS inked the co-development deal in 2021.

Eisai now owns all rights to FZEC and will develop and commercialize it. The company says the agent’s development is a high priority and will be accelerated. Eisai plans to refund a part of the unused portion of the $200 million payment it already received towards research and development expenses from BMS under their agreement.

ADCs have three critical components: a monoclonal antibody, a cytotoxic drug (the payload), and a chemical linker moiety. The mAb is designed to specifically release the cytotoxic payload at a tumor site. When the cytotoxic and antibody components of an ADC are separated inside a targeted antigen-positive cancer cell, the released anticancer agent may also have a bystander effect on neighboring antigen-negative cancer cells and the cells of the tumor microenvironment. In preclinical studies, FZEC demonstrated such a bystander effect.

The ADC field is currently very competitive, over a dozen of these drugs have been approved and the world market for such agents has been estimated to be worth over $8B and expected to grow to almost $24B by 2032. 

There’s also been a flurry of deals. In early April, BioNTech inked a deal with Duality Biologics worth up to $1.5B. Soon after, Bristol Myers signed a deal worth up to $1B for Tubulis to use the biotech’s “PS conjugation platform” to develop ADCs against solid tumors. In May, Eisai inked a clinical trial collaboration worth up to $2B with Bliss Biopharmaceutical around its lead ADC BB-1701, which is in Phase I/II in China and the U.S. BB-1701 has an eribulin-payload directed against Human Epidermal Growth Factor Receptor 2 (HER2).

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 I/II study for solid tumors, and BMS’s Phase II studies for ovarian, peritoneal and fallopian tube cancers, and non-small cell lung cancer.

The payload eribulin was the first in the halichondrin class of microtubule dynamics inhibitors. 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).

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