A Sequential Population Pharmacokinetic Model of Zilovertamab Vedotin in Patients with Hematologic Malignancies Extrapolated to the Pediatric Population.

Background And Objectives: Recently a number of antibody-drug conjugate (ADC) pharmacometric models have been reported in the literature, describing one or two ADC-related analytes. The objective of this analysis was to build a population pharmacokinetic (popPK) three-analyte ADC model to describe efficacy and safety of zilovertamab vedotin, an ROR1-targeting ADC conjugated to monomethyl auristatin E (MMAE).

Methods: Data from a phase 1 study of zilovertamab vedotin in subjects with hematologic malignancies was used in a stepwise ADC modeling strategy based on the simplified ADC popPK model proposed by Gibiansky.

Minimal brain PBPK model to support the preclinical and clinical development of antibody therapeutics for CNS diseases.

There are several antibody therapeutics in preclinical and clinical development, industry-wide, for the treatment of central nervous system (CNS) disorders. Due to the limited permeability of antibodies across brain barriers, the quantitative understanding of antibody exposure in the CNS is important for the design of antibody drug characteristics and determining appropriate dosing regimens. We have developed a minimal physiologically-based pharmacokinetic (mPBPK) model of the brain for antibody therapeutics, which was reduced from an existing multi-species platform brain PBPK model.

Guiding principles for rewilding.

There has been much recent interest in the concept of rewilding as a tool for nature conservation, but also confusion over the idea, which has limited its utility. We developed a unifying definition and 10 guiding principles for rewilding through a survey of 59 rewilding experts, a summary of key organizations' rewilding visions, and workshops involving over 100 participants from around the world. The guiding principles convey that rewilding exits on a continuum of scale, connectivity, and level of human influence and aims to restore ecosystem structure and functions to achieve a self-sustaining autonomous nature.

Design and Validation of Probes and Sensors for the Characterization of Magneto-Ionic Radio Wave Propagation on Near Vertical Incidence Skywave Paths.

This article describes the design and validation of deployable low-power probes and sensors to investigate the influence of the ionosphere and the Earth's magnetic field on radio wave propagation below the plasma frequency of the ionosphere, known as Near Vertical Incidence Skywave (NVIS) propagation. The propagation of waves that are bent downward by the ionosphere is dominated by a bi-refractive mechanism called 'magneto-ionic propagation'. The polarization of both downward waves depends on the spatial angle between the Earth's magnetic field and the direction of propagation of the radio wave.