Publications by authors named "Joao N S Pereira"

M6495 is a first-in-class NANOBODY molecule and an inhibitor of ADAMTS-5, with the potential to be a disease modifying osteoarthritis drug. In order to investigate the PK/PD (pharmacokinetic and pharmacodynamic) properties of M6495, a single dose study was performed in cynomolgus monkeys with doses up to 6 mg/kg, with the goal of understanding the PK/PD properties of M6495. The neo-epitope ARGS (Alanine-Arginine-Glycine-Serine) generated by cleavage of aggrecan by ADAMTS-5 was used as a target-engagement biomarker.

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Typically, therapeutic proteins (TPs) have a low risk for eliciting meaningful drug interactions (DIs). However, there are select instances where TP drug interactions (TP-DIs) of clinical concern can occur. This white paper discusses the various types of TP-DIs involving mechanisms such as changes in disease state, target-mediated drug disposition, neonatal Fc receptor (FcRn), or antidrug antibodies formation.

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Characterization of the pharmacokinetics and biodistribution of therapeutic proteins (TPs) is a hot topic within the pharmaceutical industry, particularly with an ever-increasing catalog of novel modality TPs. Here, we review the current practices, and provide a summary of extensive cross-company discussions as well as a survey completed by International Consortium for Innovation and Quality members on this theme. A wide variety of in vitro, in vivo and in silico techniques are currently used to assess pharmacokinetics and biodistribution of TPs, and we discuss the relevance of these from an industry perspective, focusing on pharmacokinetic/pharmacodynamic understanding at the preclinical stage of development, and translation to human.

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