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Congenital Disorders

Immune System Diseases

Endocrinology and Metabolic Disease

Antibody drug conjugate (ADC)

Biological products

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Disease Domain	Count

Endocrinology and Metabolic Disease	1
Hemic and Lymphatic Diseases	1
Immune System Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Antibody drug conjugate (ADC)	1
Biological products	1

Top 5 Target	Count

TSHR(Thyroid stimulating hormone receptor)	1
MRC2(C-type mannose receptor 2)	1

Author: Dijkxhoorn, Kim ; Budding, Kevin ; de Zeeuw, Elisabeth ; Hack, C Erik ; Meeldijk, Jan ; de Haard, Hans ; Simons, Peter J ; Boross, Peter ; Blanchetot, Christophe ; Boon, Louis ; Percier, Jean-Michel ; Yildiz, Cafer ; Silence, Karen ; Van de Walle, Inge ; Otten, Henny G ; Leusen, Jeanette H W ; Urbanus, Rolf ; Wildemann, Johanna ; Van de Ven, Liesbeth ; Cox, Linda ; Gabriels, Sofie ; Holgate, Rob

BACKGROUNDActivation of the classical and lectin pathway of complement may contribute to tissue damage and organ dysfunction of antibody-mediated diseases and ischemia-reperfusion conditions. Complement factors are being considered as targets for therapeutic intervention.OBJECTIVEWe sought to characterize ARGX-117, a humanized inhibitory monoclonal antibody against complement C2.METHODSThe mode-of-action and binding characteristics of ARGX-117 were investigated in detail. Furthermore, its efficacy was analyzed in in vitro complement cytotoxicity assays. Finally, a pharmacokinetic/pharmacodynamic study was conducted in cynomolgus monkeys.RESULTSThrough binding to the Sushi-2 domain of C2, ARGX-117 prevents the formation of the C3 proconvertase and inhibits classical and lectin pathway activation upstream of C3 activation. As ARGX-117 does not inhibit the alternative pathway, it is expected not to affect the antimicrobial activity of this complement pathway. ARGX-117 prevents complement-mediated cytotoxicity in in vitro models for autoimmune hemolytic anemia and antibody-mediated rejection of organ transplants. ARGX-117 exhibits pH- and calcium-dependent target binding and is Fc-engineered to increase affinity at acidic pH to the neonatal Fc receptor, and to reduce effector functions. In cynomolgus monkeys, ARGX-117 dose-dependently reduces free C2 levels and classical pathway activity. A 2-dose regimen of 80 and 20 mg/kg separated by a week, resulted in profound reduction of classical pathway activity lasting for at least 7 weeks.CONCLUSIONSARGX-117 is a promising new complement inhibitor that is uniquely positioned to target both the classical and lectin pathways while leaving the alternative pathway intact.

01 Aug 2015·Cancer Research

Abstract 655: The next generation of targeted toxins: A novel deimmunized sarcin ribotoxin fused with an EphA2 Abdurin binder

Author: Demartis, Anna ; Jones, Tim ; Gehlsen, Kurt R.

AbstractAbdurins are a novel antibody-like scaffold derived from the engineering of a single CH2 domain (CH2D) of IgG. The prolonged serum half-life of Abdurins, the result of retained FcRn binding, is 10-20 times longer than the serum half-life of any other protein scaffold of comparable molecular weight. Here we present data on the isolation and characterization of high affinity ABDURIN binders to the cancer target EphA2. α-Sarcin is a small (17 kDa) fungal ribonuclease produced by Aspergillus giganteus. Sarcin functions by catalytically cleaving a single phosphodiester bond in the sarcin-ricin loop, a well-defined RNA motif within the rRNA scaffold of the large ribosomal subunit. This cleavage makes the ribosome unrecognizable to elongation factors and hence, blocks protein synthesis. We have deimmunized α-sarcin (Sarcin-DI) and made several variants lacking T cell epitopes while retaining cytotoxic activity. This novel Abdurin EphA2 binder fusion with Sarcin-DI creates a new generation of targeted toxins with a longer half-life, low immunogenicity and potent tumor cell killing.Citation Format: Kurt R. Gehlsen, Anna Demartis, Tim Jones. The next generation of targeted toxins: A novel deimmunized sarcin ribotoxin fused with an EphA2 Abdurin binder. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 655. doi:10.1158/1538-7445.AM2015-655

01 Oct 2010·Self/Nonself

Immunogenicity of protein therapeutics: The key causes, consequences and challenges

Article

Author: Brooke Lumicisi ; Matthew P Baker ; Helen M Reynolds ; Christine J Bryson

The immunogenicity of protein therapeutics has so far proven to be difficult to predict in patients, with many biologics inducing undesirable immune responses directed towards the therapeutic resulting in reduced efficacy, anaphylaxis and occasionally life threatening autoimmunity. The most common effect of administrating an immunogenic protein therapeutic is the development of a high affinity anti-therapeutic antibody response. Furthermore, it is clear from clinical studies that protein therapeutics derived from endogenous human proteins are capable of stimulating undesirable immune responses in patients, and as a consequence, the prediction and reduction of immunogenicity has been the focus of intense research. This review will outline the principle causes of the immunogenicity in protein therapeutics, and describe the development of pre-clinical models that can be used to aid in the prediction of the immunogenic potential of novel protein therapeutics prior to administration in man.

100 Deals associated with Abzena (Cambridge) Ltd.

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100 Translational Medicine associated with Abzena (Cambridge) Ltd.

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Pipeline

Pipeline Snapshot as of 27 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

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