Biomap® phenotypic profiling of two batches of originator etanercept reveals equivalent activity signatures consistent with conserved biological activity

Background: The BioMAP® platform is a complex human primary cell-based system for modelling tissue and disease states that is used to characterise drug activities based on the analyses of 148 clinically relevant biomarker readouts. Objectives: To confirm that the BioMAP phenotypic signatures of two originator etanercept (ETN) samples remained comparable over time. Methods: Two different ETN samples (ETN_1 and ETN_2) were independently profiled with a 5 year interval across a panel of 12 disease-relevant systems (3C and 4 hour [endothelial inflammation]; LPS [monocyte activation]; SAg [T cell activation]; BT [B cell activation]; BF4T and BE3C [epithelial inflammation]; CASM3C [vascular inflammation]; HDF3CGF, KF3CT, and MyoF [tissue remodelling, fibrosis]; lMphg [macrophage activation]). BioMAP systems consist of human primary cells or cocultures from healthy donors cultured in the presence of cytokines and growth factors. Protein levels, measured using immune-based methods or functional assays for cell viability and proliferation, were used to generate a BioMAP activity profile for each sample. ETN activities were annotated if they differed from the vehicle control and had an effect size >20%. The profiles of the 2 samples were compared using Pearson’s correlation. Results: BioMAP phenotypic profiling of ETN_1 versus ETN_2 samples at 10 µg/mL revealed similar signatures across 148 biomarkers in 12 disease-relevant systems. The Pearson’s correlation coefficient was 0.781, which is above the determined threshold for mechanistic similarity (r≥0.7). Key efficacy-related anti-inflammatory and immunomodulatory activities were commonly inhibited in multiple systems including tumour necrosis factor alpha (LPS and BT), interleukin (IL)−2 (BT), vascular cell adhesion molecule 1 (MyoF and lMphg), IL-8 (SAg and MyoF), and E-Selectin (SAg and lMphg). The profiles of ETN samples at 1 µg/mL in the SAg system modelling T cell activation responses also revealed statistically significant similarity in signatures (p<0.01) in both magnitude and direction across all biomarker activities (figure 1). Abstract AB0050 – Figure 1 SAg system profile of ETN_1 and ETN_2 samples at 1 μg/mL. Conclusions: The BioMAP phenotypic signatures of the ETN_1 and ETN_2 samples profiled in independent experiments using different primary cell pools remained comparable, which was consistent with conserved ETN mechanisms of action. The BioMAP platform represents a useful orthogonal approach for assessing ETN activity. Disclosure of Interest: A. O’Mahony Employee of: Eurofins DiscoverX, E. L. Berg Employee of: Eurofins DiscoverX, H. Jones Shareholder of: Pfizer, Employee of: Pfizer, B. Fitzpatrick Shareholder of: Pfizer, Employee of: Pfizer, B. Hassett Shareholder of: Pfizer, Employee of: Pfizer, S. Vicik Shareholder of: Pfizer, Employee of: Pfizer, L. Marshall Shareholder of: Pfizer, Employee of: Pfizer, K. Roshak: None declared, E. Choy Grant/research support from: Novimmune, Pfizer, Roche, UCB, Consultant for: Abbott Laboratories, Amgen, Biogen, BMS, Celgene, Chugai Pharma, Eli Lilly, GSK, Hospira, Janssen, MedImmune, Napp, Novimmune, Novartis, Pfizer, Regeneron, Roche, R-Pharm, Sanofi DOI: 10.1136/annrheumdis-2018-eular.2335 Citation: Ann Rheum Dis, volume 77, supplement Suppl, year 2018, page A1225Session: Cytokines and inflammatory mediators