Eisai and Bristol Myers Squibb Enter Global Strategic Collaboration for Best-in-Class FRα-Targeting ADC MORAb-202
Jun 19, 2021 04:51
CST Updated
04:51
Eisai
Pharmaceutical Product R&D and Manufacturer
Bristol-Myers Squibb
Biopharmaceutical and Nutritional Product R&D and Sales
MORAb-202 (Image sourced from the literature—PMID: 30262588)
June 18, 2021 /BioonBIOON/ -- Eisai and Bristol-Myers Squibb (BMS) jointly announced that they have reached an agreement on the joint development and commercialization of the antibody-drug conjugate (ADC) MORAb-202(farletuzumab-[Mal-PEG2-Val-Cit-PAB-eribulin]) entered into an exclusive global strategic collaboration agreement.
MORAb-202 is Eisai's first ADC. It is an ADC targeting folate receptor alpha (FRα), combining Eisai's internally developed antibody farletuzumab (a humanized anti-FRα IgG1 monoclonal antibody) and Eisai's internally developed anticancer agent eribulin, with the two connected via an enzymatically cleavable linker,The drug-to-antibody ratio (DAR) is 4.0. After MORAb-202 enters target FRα-positive cancer cells, the linker is enzymatically cleaved, releasing eribulin from the antibody, thereby exerting antitumor activity. Furthermore, in non-clinical studies, MORAb-202 demonstrated a bystander effect, exhibiting antitumor activity against FRα-negative cancer cells surrounding FRα-positive cancer cells.
MORAb-202 is a potentially best-in-class FRα ADC with a favorable pharmacological profile, demonstrating single-agent activity in patients with advanced solid tumors. Currently, Eisai is investigating MORAb-202 for the treatment of FRα-positive solid tumors (including endometrial cancer, ovarian cancer, lung cancer,Breast Cancer): a Japanese Phase I clinical study and a US Phase I/II clinical study. The two companies plan to enter the registrational development stage for the asset as early as next year.
Eribulin Chemical Structure (Image sourced from literature—PMID: 25838395)
The payload of MORAb-202, eribulin (brand name: Halaven, generic name: eribulin), is the first halichondrin-class microtubule dynamics inhibitor, with a novel mechanism of action.Structurally, eribulin is a simplified synthetic analogue of halichondrin B. Halichondrin B is a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to inhibit cell division by suppressing the growth phase of microtubule dynamics. In cancer cells, this mechanism can lead to prolonged and irreversible mitotic arrest, ultimately resulting in cell death.
To date, Halaven has been approved in more than 75 countries worldwide for the treatment of breast cancer and liposarcoma (soft tissue sarcoma in Japan).In China, Halaven (Chinese brand name: Hai Le Wei; generic name: eribulin mesylate) was approved by the National Medical Products Administration (NMPA) in July 2019., indicated for the treatment of patients with locally recurrent or metastatic breast cancer who have previously received at least two chemotherapy regimens (including anthracyclines and taxanes). In January 2020, Halaven was launched in China.
Under the agreement, Eisai and Bristol-Myers Squibb will co-develop and commercialize MORAb-202 in the following collaboration territories: Japan and China; Asia-Pacific countries*; the United States; Canada; Europe, including the European Union and the United Kingdom; and Russia. Bristol-Myers Squibb will be solely responsible for the development and commercialization of the drug in territories outside the collaboration regions. Eisai will continue to be responsible for the global manufacturing and supply of MORAb-202.
Under the financial terms of the agreement, Bristol-Myers Squibb will pay Eisai $650 million, which includes $200 million for Eisai's R&D expenses. Eisai is also eligible to receive up to $2.45 billion in potential future development, regulatory, and commercial milestone payments. The parties will share profits, R&D, and commercialization costs within the collaboration territory, and Bristol-Myers Squibb will pay Eisai royalties on sales outside the collaboration territory. Eisai is expected to record sales of MORAb-202 in Japan, China, Asia-Pacific countries, Europe, and Russia. Bristol-Myers Squibb is expected to record sales of MORAb-202 in the United States and Canada.
Haruo Naito, Chief Executive Officer of Eisai, stated: “MORAb-202 combines an antibody discovered internally at Eisai with a payload, leveraging the company’s advanced chemical capabilities. The drug is characterized by its payload, eribulin, a product of our modern synthetic organic chemistry that has already contributed to the treatment of patients with breast cancer and soft tissue sarcoma. Our collaboration with Bristol-Myers Squibb will accelerate the development of MORAb-202, with the aim of delivering a potentially effective treatment option to patients worldwide.”
Bristol-Myers Squibb Chairman and Chief Executive Officer Giovanni Caforio said: "The global collaboration with Eisai represents an important strategic fit for Bristol-Myers Squibb, as it expands our leadership in oncology by providing a differentiated asset that complements our extensive solid"Tumorportfolio, and leveraged our extensive internal development expertise. We look forward to collaborating with Eisai to bring this potential therapy to patients in need as soon as possible."(Bioon.com)