Safety, Pharmacokinetics and Pharmacodynamics of the Selective Glucocorticoid Receptor Modulator AZD5423 after Inhalation in Healthy Volunteers

2016 ◽  
Vol 119 (6) ◽  
pp. 574-581 ◽  
Author(s):  
Viktoria Werkström ◽  
Susanne Prothon ◽  
Ella Ekholm ◽  
Carin Jorup ◽  
Staffan Edsbäcker
Keyword(s):  
Glucocorticoid Receptor ◽  
Healthy Volunteers ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Receptor Modulator

scholarly journals Safety, pharmacokinetics and pharmacodynamics of the selective glucocorticoid receptor modulator AZD7594, following inhalation in healthy Japanese volunteers

2019 ◽  
Vol Volume 13 ◽  
pp. 3845-3853
Author(s):  
Susanne Prothon ◽  
Ulrika Wählby Hamrén ◽  
Ulrika Tehler ◽  
Esther Yoon ◽  
Henrik Forsman ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Receptor Modulator

scholarly journals POS0365 ANTI-TNF GLUCOCORTICOID RECEPTOR MODULATOR ANTIBODY DRUG CONJUGATE FOR THE TREATMENT OF AUTOIMMUNE DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 412.2-413
Author(s):  
B. Stoffel ◽  
M. McPherson ◽  
A. Hernandez ◽  
C. Goess ◽  
S. Mathieu ◽  
...  
Keyword(s):  
Side Effects ◽  
Cell Surface ◽  
Glucocorticoid Receptor ◽  
Healthy Volunteers ◽  
Immune Cells ◽  
Research Support ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Receptor Modulator ◽  
Antibody Drug

Background:Glucocorticoids (GC) are potent drugs used for treating many inflammatory diseases. While GCs are effective in many immune diseases, dose and duration of administration is limited due to significant side effects. Resting immune cells have very little TNF expression on the cell surface and it is only in an activated state that TNF expression is upregulated. Upon immune cell stimulation, TNF is upregulated and although a significant amount of TNF is cleaved from an activated cell, a portion remains on the cell surface. We have observed that anti-TNF antibodies bind to transmembrane TNF (tmTNF) and undergo endocytosis to the lysosome (1). We have developed a stable antibody drug conjugate (ADC), ABBV-3373, that has a proprietary, highly potent, glucocorticoid receptor modulator (GRM) payload linked to an anti-TNF monoclonal antibody (mAb) that is able to deliver the GC payload to activated immune cells.Objectives:We hypothesized that a TNF ADC with a GRM payload would be able to deliver increased efficacy through both TNF inhibition and targeted GRM payload delivery to activated immune cells while sparing systemic glucocorticoid side effects.Methods:A mouse surrogate TNF GRM ADC was characterized in an acute in vivo contact hypersensitivity model of inflammation (CHS) and in a mouse model of collagen induced arthritis (mCIA). Additionally, the human anti-TNF GRM ADC, ABBV-3373 has been characterized in healthy volunteers.Results:In the CHS model the anti-TNF GRM ADC significantly inhibited the inflammatory response with minimal effect on systemic GC biomarkers. In mCIA a single dose of an anti-TNF GRM ADC, administered at disease onset, was able to completely inhibit arthritis for greater than 30 days while an anti-TNF mAb only partially inhibited disease. ABBV-3373, a human anti-TNF GRM ADC with a GC payload, was evaluated in a Phase 1 study in healthy volunteers. ABBV-3373 demonstrated antibody-like PK profile and ABBV-3373 did not impact cortisol levels at predicted efficacious doses while control subjects that received a single oral dose of 10 mg prednisone demonstrated expected decreases in cortisol levels.Conclusion:These data suggest that an anti-TNF ADC delivering a GRM payload into activated immune cells may provide improved efficacy in immune mediated diseases, while minimizing systemic side effects associated with standard GC treatment.References:[1]Deora, A. et al. MABs. 2017;9(4):680-695.Disclosure of Interests:Bob Stoffel Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Michael McPherson Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Axel Hernandez Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Christian Goess Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Suzanne Mathieu Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Wendy Waegell Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Shaughn Bryant Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Adrian Hobson Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Melanie Ruzek Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Yinuo Pang Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Hartmut Kupper Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Ronilda D’Cunha Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Julie Parmentier Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie, Timothy Radstake Shareholder of: AbbVie, Grant/research support from: AbbVie, Employee of: AbbVie

scholarly journals Safety, tolerability, pharmacokinetics and pharmacodynamics of a TLR7 agonist prodrug RO6870868 in healthy volunteers

2021 ◽  
Author(s):  
Joseph F. Grippo ◽  
Ilia Folitar ◽  
Sharon Passe ◽  
Qiudi Jiang ◽  
Ignacio Rodriguez ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Tlr7 Agonist

scholarly journals Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Mohammad Al‐Mahdi Al‐Karagholi ◽  
Jakob Møller Hansen ◽  
Dalia Abou‐Kassem ◽  
Anna Koldbro Hansted ◽  
Kumari Ubhayasekera ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Phase 1 ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Phase 1 Study

The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice

2014 ◽  
Vol 143 ◽  
pp. 40-48 ◽  
Author(s):  
Maria Meyer ◽  
Maria Claudia Gonzalez Deniselle ◽  
Hazel Hunt ◽  
E. Ronald de Kloet ◽  
Alejandro F. De Nicola
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Modulator
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