Maridebart cafraglutide Clinical Bispecific, Immunoconjugate

Antibody Information

Entry ID	282
INN	Maridebart cafraglutide
Status	Clinical
Drug code(s)	AMG 133, MariTide
Brand name	None
mAb sequence source	mAb human
General Molecular Category	Bispecific, Immunoconjugate
Format, general category	Full length Ab
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	GLP-1 peptides
Discovery method/technology	None

Therapeutic information

Target(s)	GIPR, GLP-1R
Indications of clinical studies	Type 2 Diabetes Mellitus, Obesity
Primary therapeutic area	Metabolic disorders

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Phase 3
Status	Active
Start of clinical phase (IND filing or first Phase 1)	August 07, 2020
Start of Phase 2	January 30, 2023
Start of Phase 3	March 01, 2025
Date BLA/NDA submitted to FDA
Year of first approval (global)	None
Date of first US approval
INN, US product name	None
US or EU approved indications	None

Company information

Company	Amgen
Licensee/Partner	None
Comments about company or candidate	NCT06858878 Phase 3 in Type 2 Diabetes Mellitus started in Mar 2025. NCT06858839 Phase 3 in obesity started in Mar 2025 Nov. 26, 2024: Amgen announced positive data at 52 weeks in a double-blind, dose-ranging Phase 2 study with MariTide (NCT05669599); Amgen Announces "MARITIME," a Phase 3 Clinical Development Program in Obesity and Obesity-Related Conditions. https://investors.amgen.com/static-files/0176d78e-920b-45b3-b9cc-a727e58e80da NCT06660173 Phase 2 in Type 2 Diabetes Mellitus started in Oct 2024. NCT05669599 is a Phase 2 Randomized, Placebo-controlled, Double-blind, Dose-ranging Study to Evaluate the Efficacy, Safety and Tolerability of AMG 133 in Adult Subjects With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus started in Jan 2023. Included as Phase 1 in pipeline dated July 28, 2020: https://www.amgenpipeline.com/-/media/Themes/Amgen/amgenpipeline-com/amgenpipeline-com/PDF/amgen-pipeline-chart.pdf
Full address of company	Thousand Oaks, California, United States North America United States of America https://www.amgen.com/

Description/comment

AMG 133 is a bispecific glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist and glucagon-like peptide-1 (GLP-1) receptor agonist molecule. AMG 133 mimics the agonist effects of GLP-1 and antagonizes the effects of glucose-dependent insulinotropic polypeptide (GIP). The genetic findings by deCODE and others led Amgen to start working on a first-in-class antibody-based multispecific molecule currently dubbed AMG 133, with a novel mechanism of action that simultaneously activates the GLP-1 receptor and inhibits GIPR. To create AMG 133, researchers started with an antibody that blocks GIPR. To this antibody backbone, they then added two modified GLP-1 peptides that activate the GLP-1 receptor. (https://www.amgen.com/stories/2022/12/targeting-obesity-using-biology-not-behavior)
AMG 133 (maridebart cafraglutide) is a bispecific molecule engineered by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers. https://doi.org/10.1038/s42255-023-00966-w

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None