Minireview Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper

ABSTRACT An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody. As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. To identify the key absorption, distribution, metabolism, and excretion (ADME) issues worth examining when developing an ADC and to find optimal scientifically based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an ADC ADME working group in early 2014. This white paper contains observations from the working group and provides an initial framework on issues and approaches to consider when evaluating the ADME of ADCs

Breeding on the leading edge of a northward range expansion: differences in morphology and the stress response in the arctic Gambel's white-crowned sparrow

Individuals at the forefront of a range shift are likely to exhibit phenotypic traits that distinguish them from the population breeding within the historic range. Recent studies have examined morphological, physiological and behavioral phenotypes of individuals at the edge of their range. Several studies have found differences in the hypothalamic-pituitary-adrenal (HPA) axis activity in response to acute restraint stress in individuals at the range limits. HPA axis activation leads to elevations in glucocorticoids that regulate physiology and behavior. Here we compare the hormonal profiles and morphometrics from Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) breeding at the northern limit of the population's range to those birds breeding within the historic population range. Birds breeding at the northern limit experienced a harsher environment with colder temperatures; however, we found no differences in arthropod prey biomass between the northern limit and more southern (historic) sites. Males at the northern limit had higher body condition scores (mass corrected for body size) compared to individuals within the historic range, but no differences were found in beak and tarsus lengths, wing chord, muscle profile or fat stores. In males during the pre-parental stage, before breeding commenced, HPA axis activity was elevated in birds at the northern limit of the range, but no differences were found during the parental or molt stages. Females showed no differences in HPA axis activity during the parental stage. This study suggests that "pioneering" individuals at the limits of their breeding range exhibit physiology and morphology that are distinct from individuals within the historic range

Assessment of the Current Approaches for ADME Characterization of Antibody-Drug Conjugates and Recommendations for Best Practices: An Industry White Paper

An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a drug molecule covalently conjugated to a carrier monoclonal antibody (mAb). As the number of ADCs in various stages of preclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches for ADC ADME characterization. In order to seek alignment on the strategy and find the most optimal experimental systems, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an “ADC ADME working group” in early 2014. This White Paper contains observations and recommendations from the working group

Current Approaches for ADME Characterization of Antibody-Drug Conjugates: An Industry White Paper Running Title Current Approaches for ADME Characterization of ADCs

Abstract An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody (mAb). As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. In order to identify the key ADME issues worth examining when developing an ADC and to find optimal scientifically-based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an "ADC ADME working group" in early 2014. This White Paper contains observations from the working group and provides an initial framework on issues and approaches to consider when evaluating the ADME of ADCs. DMD # 68049