About: Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5
Creator	Chen, Gang Zhang, Qian Hu, Ying Babb, Robert Olson, William Krueger, Pamela Yuan, Ming Kamat, Vishal Xiao, Hui Liu, Nina Huang, Tammy Cao, Jingtai Cao, Marc Chen, Henry Ehrlich, George Foster, Randi Latuszek, Adrianna Liu, Yashu Lovric, Irena Morton, Lori Poueymirou, William Retter, Marc Romano, Carmelo Rosconi, Michael Springer, Carola Zambrowicz, Brian Olsen Id, Olav Rafiqueid, Ashique
Source	PMC
abstract	Complement is a key component of the innate immune system. Inappropriate complement activation underlies the pathophysiology of a variety of diseases. Complement component 5 (C5) is a validated therapeutic target for complement-mediated diseases, but the development of new therapeutics has been limited by a paucity of preclinical models to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties of candidate therapies. The present report describes a novel humanized C5 mouse and its utility in evaluating a panel of fully human anti-C5 antibodies. Surprisingly, humanized C5 mice revealed marked differences in clearance rates amongst a panel of anti-C5 antibodies. One antibody, pozelimab (REGN3918), bound C5 and C5 variants with high affinity and potently blocked complement-mediated hemolysis in vitro. In studies conducted in both humanized C5 mice and cynomolgus monkeys, pozelimab demonstrated prolonged PK and durable suppression of hemolytic activity ex vivo. In humanized C5 mice, a switch in dosing from in-house eculizumab to pozelimab was associated with normalization of serum C5 concentrations, sustained suppression of hemolytic activity ex vivo, and no overt toxicity. Our findings demonstrate the value of humanized C5 mice in identifying new therapeutic candidates and treatment options for complement-mediated diseases.
has issue date	2020-05-08(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0231892
bibo:pmid	32384086
has license	cc-by
sha1sum (hex)	4a15a507587fb51559b92df9398eb41b2b485540
schema:url	https://doi.org/10.1371/journal.pone.0231892
resource representing a document's title	Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5
has PubMed Central identifier	PMC7209288
has PubMed identifier	32384086
schema:publication	PLoS One
resource representing a document's body	covid:4a15a507587fb51559b92df9398eb41b2b485540#body_text
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