Anti-IL-17 Receptor Antibody AMG 827 Leads to Rapid Clinical Response in Subjects with Moderate to Severe Psoriasis: Results from a Phase I, Randomized,

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Anti-IL-17 Receptor Antibody AMG 827 Leads to Rapid Clinical Response in Subjects with Moderate to Severe Psoriasis: Results from a Phase I, Randomized, Placebo- Controlled Trial Kim A. Papp, Cathy Reid, Peter Foley, Rod Sinclair, David H. Salinger, Gary Williams, Hua Dong, James G. Krueger, Chris B. Russell, David A. Martin Journal of Investigative Dermatology Volume 132, Issue 10, Pages 2466-2469 (October 2012) DOI: 10.1038/jid.2012.163 Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Single doses of AMG 827 lead to rapid improvement in PASI responses. (a) Mean changes in PASI score from baseline. (b) Proportion of subjects achieving a PASI 50, PASI 75, and PASI 90 at any time during the study. IV, intravenously; PASI, Psoriasis Area and Severity Index; SD, standard deviation; SC, subcutaneously. Journal of Investigative Dermatology 2012 132, 2466-2469DOI: (10.1038/jid.2012.163) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Single doses of AMG 827 lead to rapid improvement in multiple skin biomarkers. (a) Epidermal thickness. Symbols in centers of box plots represent mean values, horizontal lines in centers of box plots represent median values, upper and lower edges of boxes represent 75th and 25th quartiles, respectively, and upper and lower error bars represent maximum and minimum values, respectively. P-values are for post-treatment level versus baseline. *P<0.001; †P<0.01; ‡P<0.05. (b) Hematoxylin and eosin stain to show epidermal thickness and immunohistochemistry staining for KRT16 and Ki67 messenger RNA (mRNA) levels in skin biopsies from a subject who received a single dose of 700mg IV AMG 827. Scale bar=0.1mm. (c) mRNA levels of keratinocyte-derived factors (upper panels) and inflammatory cytokines (lower panels). H&E, hematoxylin & eosin; IHC, immunohistochemistry; IV, intravenously; mRNA, messenger RNA; PL, placebo; SC, subcutaneously. Journal of Investigative Dermatology 2012 132, 2466-2469DOI: (10.1038/jid.2012.163) Copyright © 2012 The Society for Investigative Dermatology, Inc Terms and Conditions