Empasiprubart Clinical Naked monospecific

Antibody Information

Entry ID	320
INN	Empasiprubart
Status	Clinical
Drug code(s)	ARGX-117
Brand name	None
mAb sequence source	mAb human
General Molecular Category	Naked monospecific
Format, general category	Full length Ab
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	TBD
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	None

Therapeutic information

Target(s)	Complement C2
Indications of clinical studies	Multifocal Motor Neuropathy, Dermatomyositis, Delayed Graft Function, Multifocal Motor Neuropathy, Phase 1 is in healthy volunteers
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)	March 01, 2020
Start of Phase 2	February 01, 2022
Start of Phase 3	January 15, 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	argenx
Licensee/Partner	None
Comments about company or candidate	NCT06742190 Phase 3 in Multifocal Motor Neuropathy started in Jan 2025. NCT06284954 Phase 2 in Dermatomyositis due to start in Sep 2024. NCT05907096 Phase 2 in Delayed Graft Function started in Feb 2024. NCT05405361 Phase 2 started in Jan 2023. NCT05225675 is a Phase 2 study to Evaluate the Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 2 Dose Regimens of ARGX-117 in Adults With Multifocal Motor Neuropathy NCT04532125 is a First-In-Human, Randomized, Double-Blinded, Placebo-Controlled Trial in Healthy Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Ascending Intravenous and Subcutaneous Doses of ARGX-117 Co-mixed With rHuPH20 May 14, 2020: argenx is sponsoring a Phase 1 trial in collaboration with Ghent University Hospital to evaluate ARGX-117 as a potential treatment for acute respiratory distress syndrome (ARDS), a frequent and serious complication associated with COVID-19. Both classical and lectin pathways of complement system are active in ARDS; by targeting C2, an important component of both pathways, ARGX-117 could inhibit downstream inflammatory responses associated with ARDS. Oct 24, 2019: A Clinical Trial Application (CTA) is on track to be filed by end of 2019 with first-in-human trial expected to start in first quarter of 2020. ARGX-117 is a next-generation complement-targeting antibody against C2, an important component of both the classical and lectin pathways in the complement cascade. ARGX-117 was developed under a collaboration with the University Medical Center Utrecht/Broteio Pharma and was exclusively licensed by argenx in 2018. First-in-human clinical studies are expected to start in the first quarter of 2020. ARGX-117 is a highly differentiated therapeutic antibody equipped with argenx’s proprietary Fc engineering technology NHance® that addresses a novel target in the classic pathway of the complement cascade. With a potentially differentiated mechanism of action, ARGX-117 represents a broad pipeline opportunity across several autoantibody-mediated indications and may have a synergistic effect with lead autoimmune compound ARGX-113
Full address of company	1101 EB Amsterdam, Netherlands Europe Netherlands https://www.argenx.com/contact-us

Description/comment

ARGX-117 is engineered as a human IgG1 anti-C2 “sweeping” antibody. Generally, serum proteins like antibodies, are transported from the serum into the cell’s endosome then to the lysosome where they are degraded. ARGX-117 is designed with an Fc backbone that is equipped with the proprietary NHance™ mutation, which is intended to enhance the binding of the antibody to FcRn in the endosome and prevent the antibody going into the lysosome for degradation. By binding to the Sushi-2 domain of C2, ARGX-117 prevents the formation of the C3 proconvertase, the C4bC2 complex, and inhibits both CP and LP activation upstream of C3.
(1) ARGX-117 binds at its variable domain to the target C2 with high affinity in the serum but lower affinity in the endosome due to the pH and Ca2+ dependent nature of the binding.
(2) The lower affinity allows C2 to dissociate from ARGX-117 in the endosome and cycle into the lysosome for destruction (3).
(4) ARGX-117 still bound to FcRn can cycle back to circulation and bind new C2 – repeating the cycle in a “sweeping” manner to continuously destroy the C2 target. With sweeping recycling properties, it is expected that ARGX-117 will remain longer in circulation and can remove several C2 molecules from circulation resulting in enhanced C2 clearance from the bloodstream.

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None