Astegolimab Clinical Naked monospecific

Antibody Information

Entry ID	1209
INN	Astegolimab
Status	Clinical
Drug code(s)	RO7187807, MSTT1041A, RG6149, AMG282
Brand name	None
mAb sequence source	mAb human
General Molecular Category	Naked monospecific
Format, general category	Full length Ab
Format details	None
Isotype (Fc)	IgG2
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	None

Therapeutic information

Target(s)	IL-33R
Indications of clinical studies	Atopic Dermatitis, Chronic Obstructive Pulmonary Disease, COVID-19, Asthma, Chronic Rhinosinusitis With Nasal Polyps
Primary therapeutic area	Immune-mediated / inflammatory 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 15, 2013
Start of Phase 2	September 15, 2016
Start of Phase 3	December 29, 2022
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	Genentech
Comments about company or candidate	Roche plans regulatory submission in COPD in 2025 (https://assets.cwp.roche.com/f/176343/x/14b2fa29c8/irp240424.pdf) NCT05878769 Phase 3 study in COPD started in June 2023. Listed as Phase 3 in Roche Q1 2023 update. NCT05595642 Phase 2/3 ARNASA study in COPD started in Dec 2022. April 2021: Roche has cut a series of experimental lung drugs from its pipeline, including two midstage COVID-19 assets. The first drug, an Amgen-licensed anti-ST2 antibody known as astegolimab (aka RG6149), works by stopping the binding of IL-33 to ST2. This has already flopped in asthma, like so many other IL-33s, but the Swiss giant thought it could help COVID patients with pneumonia. The trial was started last year and was slated to end in January; presumably, the results were not good, as Roche said in its first-quarter results presentation (PDF) today that it has been “removed from phase 2.” NCT04386616 Phase 2 study in COVID-19 pneumonia not yet recruiting when posted on May 13, 2020. Listed as Phase 2 in Roche pipeline dated July 25, 2019. NCT02918019 Phase 2 study started in Sep 2016 completed in July 2019. NCT03615040 Phase 2 study in COPD exacerbation started recruiting in Oct 2018. Listed as advanced to Phase 2 in Roche pipeline dated Oct 2, 2016. Jan 2016: Genentech plans to run Phase II trials of the antibody to treat asthma and chronic obstructive pulmonary disease (COPD), but did not provide a timeline. NCT01928368 recruiting as of Oct 2013
Full address of company	Thousand Oaks, California, United States North America United States of America https://www.amgen.com/

Description/comment

AMG 282 is a human antibody that inhibits binding of IL-33 to the ST2 receptor. immunoglobulin G2-kappa, anti-[Homo sapiens IL1RL1
(interleukin 1 receptor like 1, DER4, FIT-1, growth stimulation expressed 2 gene, ST2, IL33R)], Homo sapiens monoclonal antibody; gamma2 heavy chain Homo sapiens (1-447) [VH
(Homo sapiens IGHV5-51*01 (95.9%) -(IGHD) - IGHJ6*01(94.1%)) [8.8.14] (1-121) -Homo sapiens IGHG2*01 (100%) (CH1 (122-219), hinge 1-12 (220-231), CH2 (232-340), CH3 (341-445), CHS (446-447)) (122-447)], (223-214')-disulfide with kappa light chain Homo sapiens (1'-214') [V-KAPPA (Homo sapiens IGKV1-33*01 (97.9%) -IGKJ4*01 (100.0%)) [6.3.9] (1'-
107') -Homo sapiens IGKC*01 (100%), Km3 A45.1 (153), V101 (191) (108'-214')]; dimer (223-223":224- 224":227-227":230-230")-tetrakisdisulfide, produced in Chinese Hamster Ovary (CHO) cells, glycoform alfa immunomodulator.

Additional information

Anticipated events	Regulatory submission planned in 2025
Factor(s) contributing to discontinuation	None