KHK4083

Overview

KHK4083, developed by Concord Kirin Pharmaceutical Development Co., Ltd., is a fully humanized non-fucosylated IgG1 monoclonal antibody (mAb) specific for OX40. KHK4083 exhibits superior antagonistic activity against OX40L in vitro and exhibits anti-tumor efficacy in xenograft animal models. Currently, the safety and tolerability of KHK4083 have been evaluated in clinical phase 1/2 dose escalation studies in patients with moderate to severe atopic dermatitis.

ADCC Enhancement Technology for KHK4083

KHK4083 is a novel glycosylation engineered humanized anti-OX40 monoclonal antibody developed to meet the needs of new therapies with atopic dermatitis. The glycosylation process used to develop this agent is achieved by reducing the fucosylation in the Fc region of the mAb molecule, resulting in increased binding affinity of the agent for the FcγRIII receptor on immune effector cells.

Glycoengineering by defucosylation of immunoglobulin G oligosaccharides in the Fc region of KHK4083. Fig.1 Glycoengineering by defucosylation of immunoglobulin G oligosaccharides in the Fc region of KHK4083.

Mechanism of Action of KHK4083

OX40 (CD134, Tumor Necrosis Factor Receptor [TNFR] SF4) is a member of the TNFR family. OX40 provides a new therapeutic target as it is expressed in the diseased skin of psoriasis patients rather than healthy skin. OX40 maintains late T cell proliferation and survival by inhibiting apoptosis and induces T cell memory formation. Glycosylation modified KHK4083 is specific for OX40 and showed enhanced ADCC activity compared to a non-glycosyl engineered parent antibody. The MOA of KHK4083 is depicted as follows:

Mechanisms of action of KHK4083.Fig.2 Mechanisms of action of KHK4083. (Source: Kyowa Kirin Pharmaceutical Development, Inc.)

ADCC Activity

KHK4083

Preclinical Pharmacological Studies

KHK4083

Clinical Activity

KHK4083

KHK4083

Clinical Development Status

NCT ID Status Conditions Lead Sponsor Phase Update Time
NCT03703102 Active, not recruiting Atopic Dermatitis Kyowa Kirin Pharmaceutical Development, Inc. Phase 2 September 16, 2019

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Reference

  1. K.A. Papp.; et al. Phase I randomized study of KHK4083, an anti‐OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol. 2017, Aug; 31(8): 1324–1332.

RESOURCES

Creative Biolabs provides luciferase-based ADCC assay. This Jurkat cell based assay is pioneered by Creative Biolabs, and the methodology is very well accepted by the field. See attached ADCC Reporter Assay Protocol for further details. 

All products and services are for Research Use Only. Do Not use in humans.

CASE STUDY

ADCC Assay WT vs AfucoTM Mabs  Visit

Resource

Antibody Fc Engineering: Towards Better Therapeutics  Visit

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