S267: Properdin-Blocking Antibodies Attenuate Complement Alternative Pathway Activation Triggered by Cell-Free Heme in Sickle Cell Disease Models

Maciel, Thiago; Cofiell, Roxanne; Carvalho, Caroline; Allali, Slimane; Rignault, Rachel; Bennet, A.; Dai, Y.; Tamburini, Paul P.; Gasteyger, Christoph; Hermine, O.; Kim, S. K.

doi:10.1097/01.hs9.0000843960.95232.5f

HemaSphere

2022

DOI: 10.1097/01.hs9.0000843960.95232.5f

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S267: Properdin-Blocking Antibodies Attenuate Complement Alternative Pathway Activation Triggered by Cell-Free Heme in Sickle Cell Disease Models

Thiago Maciel

Roxanne Cofiell

Caroline Carvalho

et al.

Abstract: Book distributed under the Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) which allows third parties to download the articles and share them with others as long as they credit the author and the Abstract Book, but they cannot change the content in any way or use them commercially.

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Characterization of the bispecific VHH antibody tarperprumig (ALXN1820) specific for properdin and designed for low-volume administration

Tamburini,

Pedersen,

Devore

et al. 2024

mAbs

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The bispecific antibody tarperprumig (ALXN1820) was developed as a treatment option for diseases involving dysregulated complement alternative pathway (AP) activity that could be administered in small volumes, either subcutaneously or intravenously. Tarperprumig incorporates a C-terminal variable domain of a heavy chain only antibody (VHH) that binds properdin (FP) connected via a flexible linker to an N-terminal VHH that binds human serum albumin (HSA). The purified bispecific VHH antibody exhibits an experimental molecular weight average of 27.4 kDa and can be formulated at > 100 mg/mL. Tarperprumig binds tightly to FP and HSA with sub-nanomolar affinity at pH 7.4 and can associate simultaneously with FP and HSA to form a ternary complex. Tarperprumig potently and dose-dependently inhibits to completion in vitro AP-dependent complement C5b-9 formation, AP-dependent hemolysis, and the AP deposition of C3, FP and C9. X-ray crystallography revealed that the isolated FP-binding VHH recognizes the thrombospondin repeat 5 domain of FP, thereby preventing FP from binding to the AP convertase owing to severe steric hindrance. Tarperprumig cross-reacts with cynomolgus monkey FP and serum albumin. In summary, tarperprumig exhibits properties tailored for subcutaneous administration and is currently in clinical development for the treatment of complement AP-related disorders.

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Characterization of the bispecific VHH antibody tarperprumig (ALXN1820) specific for properdin and designed for low-volume administration

Tamburini,

Pedersen,

Devore

et al. 2024

mAbs

View full text Add to dashboard Cite

show abstract

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S267: Properdin-Blocking Antibodies Attenuate Complement Alternative Pathway Activation Triggered by Cell-Free Heme in Sickle Cell Disease Models

Abstract: Book distributed under the Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) which allows third parties to download the articles and share them with others as long as they credit the author and the Abstract Book, but they cannot change the content in any way or use them commercially.

Cited by 1 publication

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Characterization of the bispecific VHH antibody tarperprumig (ALXN1820) specific for properdin and designed for low-volume administration

Characterization of the bispecific VHH antibody tarperprumig (ALXN1820) specific for properdin and designed for low-volume administration

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