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

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