Drug intelligence / Profile preview

M9140 + 5-fluorouracil + folinic acid + bevacizumab

Development stage
Phase 1
Lead developer
Merck KGaA
Modality
Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous
01

Overview

A combination regimen of three components: \n- **M9140**, a first-in-class antibody-drug conjugate (ADC) targeting CEACAM5, conjugated via a β-glucuronide linker to the cytotoxic payload exatecan (a topoisomerase 1 inhibitor). M9140 is designed to selectively deliver exatecan to tumor cells overexpressing CEACAM5, resulting in targeted cytotoxicity and a high "bystander effect" due to released exatecan permeating neighboring cells. \n- **5-fluorouracil (5-FU)**, a small molecule antimetabolite that interferes with DNA synthesis by inhibiting thymidylate synthase, leading to cell cycle arrest and apoptosis. \n- **Folinic acid (leucovorin)**, a reduced folate used to enhance the cytotoxic effect of 5-FU by stabilizing its binding to thymidylate synthase. \n- **Bevacizumab**, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), inhibiting tumor angiogenesis and thereby impeding tumor growth and metastasis. \nThe regimen is under investigation for the treatment of advanced or metastatic colorectal cancer, particularly in patients who have received multiple prior lines of therapy.

Other names
5-fluorouracilfolinic acidM9140 antibody-drug conjugateM-9140 antibody-drug conjugateM 9140 antibody-drug conjugateanti-CEACAM5 exatecan ADCanti-CEACAM-5 exatecan ADCanti-CEACAM 5 exatecan ADC
02

Targets

CEACAM5 (Carcinoembryonic antigen related cell adhesion molecule 5)TS (Thymidylate synthase)VEGFA (Vascular endothelial growth factor A)

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