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Gary J. Chellman
Charles River Laboratories
EndocrinologyPregnancyToxicityGestationBiology
21Publications
11H-index
412Citations
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Publications 21
Newest
#1H. Skaggs (Incyte)
#2Gary J. Chellman (Charles River Laboratories)H-Index: 11
Last. Gerhard F. WeinbauerH-Index: 39
view all 8 authors...
Source
#1Jeanine L. Bussiere (Amgen)H-Index: 13
#2Rhian Davies (Amgen)H-Index: 2
Last. Thomas M. Monticello (Amgen)H-Index: 3
view all 11 authors...
Abstract Calcitonin gene-related peptide (CGRP) and its receptor have been implicated as a key mediator in the pathophysiology of migraine. Thus, erenumab, a monoclonal antibody antagonist of the CGRP receptor, administered as a once monthly dose of 70 or 140 mg has been approved for the preventive treatment of migraine in adults. Due to the species specificity of erenumab, the cynomolgus monkey was used in the pharmacology, pharmacokinetics, and toxicology studies to support the clinical progra...
2 CitationsSource
#1Kary E. Thompson (BMS: Bristol-Myers Squibb)H-Index: 5
#2Deanna L. Newcomb (Charles River Laboratories)H-Index: 3
Last. Mary Ellen McNerney (BMS: Bristol-Myers Squibb)H-Index: 3
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Given concern about potential embryo-fetal harm following seminal exposure to drugs with teratogenic potential, pharmaceutical companies use theoretical calculations to estimate seminal concentrations, maternal exposure, and distribution across the placenta to the embryo-fetal compartment for risk assessment. However, it is plausible that there are additional mechanisms whereby the conceptus is exposed. In order to determine if theoretical calculations are sufficiently conservative to predict em...
3 CitationsSource
#1D.O. ClarkeH-Index: 1
#2Kim G. HilbishH-Index: 4
Last. Gary J. Chellman (Charles River Laboratories)H-Index: 11
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Abstract The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; ...
6 CitationsSource
#1William J. BreslinH-Index: 11
#2Kim G. HilbishH-Index: 4
Last. Gary J. Chellman (Charles River Laboratories)H-Index: 11
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Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B-cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by s...
3 CitationsSource
#1Gerhard F. Weinbauer (Covance)H-Index: 39
#2Christopher N. Bowman (Pfizer)H-Index: 79
Last. Gary J. Chellman (Charles River Laboratories)H-Index: 11
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Abstract Nonhuman primates (NHPs) are an important model for evaluating the potential effects of new biopharmaceuticals on male and female reproduction and pre- and postnatal development. Toxicity testing for these parameters should be conducted in NHPs only when they are the only relevant species or are critical for the human risk assessment. In general, evaluation of potential effects on male and female reproduction can be included in general toxicity studies using sexually mature animals, and...
3 CitationsSource
#1Graeme J. Moffat (Amgen)H-Index: 6
#2Rhian Davies (Amgen)H-Index: 2
Last. Ian Pyrah (Amgen)H-Index: 9
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Abstract To assess the potential for male-mediated drug transfer to their female partner and/or developing conceptus, vaginal uptake of a monoclonal antibody (mAb) biotherapeutic was assessed in cynomolgus monkeys. A human IgG2 mAb (IgG2X; bound human and cynomolgus monkey neonatal Fc-receptor, FcRn, with similar high affinity) was administered intravaginally (IvG; 100 mg/dose) to 5 pregnant cynomolgus monkeys biweekly from gestation day (gd) 21 to gd133. In all maternal samples collected before...
7 CitationsSource
#1Rogely Waite Boyce (Amgen)H-Index: 13
#2Aurore Varela (Charles River Laboratories)H-Index: 10
Last. Ian Pyrah (Amgen)H-Index: 9
view all 7 authors...
Abstract RANKL is a key regulator of bone resorption and osteoclastogenesis. Denosumab is a fully human IgG2 monoclonal antibody that inhibits bone resorption by binding and inhibiting the activity of RANKL. To determine the effects of denosumab on pre- and postnatal skeletal growth and development, subcutaneous injections of 0 (control) or 50 mg/kg/month denosumab were given to pregnant cynomolgus monkeys from approximately gestation day (GD) 20 until parturition (up to 6 doses). For up to 6 mo...
18 CitationsSource
#1Graeme J. Moffat (Amgen)H-Index: 6
#2Marc W. Retter (Amgen)H-Index: 11
Last. Gary J. Chellman (Charles River Laboratories)H-Index: 11
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Understanding species differences in the placental transfer of monoclonal antibodies is important to inform species selection for nonclinical safety assessment, interpret embryo-fetal changes observed in these studies, and extrapolate their human relevance. Data presented here for a fully human immunoglobulin G2 monoclonal antibody (IgG2X) revealed that, during organogenesis, in both the cynomolgus monkey (gestation day 35 [gd35]) and the rat (gd10) the extent of IgG2X placental transfer (approx...
20 CitationsSource
#1Jeanine L. Bussiere (Amgen)H-Index: 13
#2Ian Pyrah (Amgen)H-Index: 9
Last. Gary J. Chellman (Charles River Laboratories)H-Index: 11
view all 9 authors...
Abstract Denosumab is a monoclonal antibody that inhibits bone resorption by targeting RANKL, an essential mediator of osteoclast formation, function, and survival. Reproductive toxicity of denosumab was assessed in cynomolgus monkeys in an embryofetal development study (dosing GD20–50) and a pre-postnatal toxicity study (dosing GD20–parturition). In the embryofetal toxicity study, denosumab did not elicit maternal toxicity, fetal harm or teratogenicity. In the pre-postnatal toxicity study, ther...
21 CitationsSource
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