Afuco™ Anti-Human IL23A ADCC Recombinant Antibody (BI 655066), ADCC Enhanced (CAT#: AFC-403CL)

Figure 1 IL23 was injected into the skin of the mouse ear every 24 h for 4 consecutive days.

Mice were given a single intraperitoneal dose of vehicle or 1 mg/kg antibody 1 h before the first IL23 injection. Twenty-four hours after the last IL23 injection, the ear thickness was measured and ear tissue was harvested for cIL17 and IL22 measurement by ELISA. Values are the mean +/− SEM. Statistical analysis by ANOVA.

Singh, S., Kroe-Barrett, R. R., Canada, K. A., Zhu, X., Sepulveda, E., Wu, H., ... & Amodeo, L. M. (2015, July). Selective targeting of the IL23 pathway: generation and characterization of a novel high-affinity humanized anti-IL23A antibody. In MAbs (Vol. 7, No. 4, pp. 778-791). Taylor & Francis.

Figure 2 Hydrogen/Deuterium Exchange Mass Spectrometry.

P19 peptides identified and their extents of exchange with BI 655066, as compared to control. All peptides showing exchange differences are found within the p19 subunit. The y-axis shows the calculated exchange normalized per amide.

Singh, S., Kroe-Barrett, R. R., Canada, K. A., Zhu, X., Sepulveda, E., Wu, H., ... & Amodeo, L. M. (2015, July). Selective targeting of the IL23 pathway: generation and characterization of a novel high-affinity humanized anti-IL23A antibody. In MAbs (Vol. 7, No. 4, pp. 778-791). Taylor & Francis.

Figure 3 Pharmacokinetics of BI 655066 in cynomolgus monkeys following a single 1 mg/kg intravenous (IV) or subcutaneous (SC) dose.

Serum concentrations were measured using an IL23-capture ELISA. Data are the mean ± SD of three monkeys per dose route. Bioavailability was estimated to be>70%, and the half-life (9–12 days) was similar after intravenous or subcutaneous administration.

Singh, S., Kroe-Barrett, R. R., Canada, K. A., Zhu, X., Sepulveda, E., Wu, H., ... & Amodeo, L. M. (2015, July). Selective targeting of the IL23 pathway: generation and characterization of a novel high-affinity humanized anti-IL23A antibody. In MAbs (Vol. 7, No. 4, pp. 778-791). Taylor & Francis.

Figure 4 Mean PASI percentage improvement from baseline over 24 weeks.

Mean improvements in PASI scores for patients receiving intravenous (IV) or subcutaneous (SC) BI 655066 are shown. For the intravenous BI 655066 group, there were 24 subjects to week 12 and 23 subjects thereafter; a patient originally allocated to the 5 mg/kg BI 655066 group was lost to follow-up because of relocation, and discontinued after week 12. For the BI 655066 subcutaneous group, there were 15 subjects throughout.

Krueger, J. G., Ferris, L. K., Menter, A., Wagner, F., White, A., Visvanathan, S., ... & Solinger, A. (2015). Anti–IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology,136(1), 116-124.

Figure 5 Changes in expression of genes/proteins in key pathophysiologic pathways in psoriatic lesion development and maintenance after administration of a single dose of BI 655066.

A, Representative skin biopsy specimens from a single patient treated with subcutaneous BI 655066 at a dose of 0.25 mg/kg (baseline and week 8) stained for specific markers, including K16 and Ki67, S100A7, neutrophil gelatinase lipocalin, β-defensin 2, DC-LAMP, CD11c, and CD3. B, Heat map showing FC expression (change from baseline to week 8) in a subset of 60 genes (significantly increased in lesional vs nonlesional skin) from a published RNA-seq analysis in patients with moderate-to-severe psoriasis15 that are overall normalized by treatment with BI 655066 (purple) versus placebo (green). The scale shows log2 FC in expression of each gene, with red representing FC increase and blue representing FC decrease.

Krueger, J. G., Ferris, L. K., Menter, A., Wagner, F., White, A., Visvanathan, S., ... & Solinger, A. (2015). Anti–IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology,136(1), 116-124.

Figure 6 Response rates for ASAS40, ASAS20, ASAS 5/6 and ASAS partial remission during double-blind and escape treatment and follow-up periods.

Clinical response rates over time for double-blind and escape treatment periods. ASAS40 (panel A), ASAS20 (panel B), ASAS 5/6 (panel C) and partial remission (panel D). NRI was used for missing data. Number of patients entering the double-blind treatment were: placebo: n=40; 18 mg risankizumab: n=40; 90 mg risankizumab: n=39; and 180 mg risankizumab: n=40. Patients entering escape treatment received 180 mg risankizumab; responses shown for the escape period are by the original randomised treatment (placebo: n=26; 18 mg risankizumab: n=21; 90 mg risankizumab: n=23; 180 mg risankizumab: n=26). ASAS, Assessment in SpondyloArthritis International Society; NRI, non-responder imputation.

Baeten, D., Østergaard, M., Wei, J. C. C., Sieper, J., Järvinen, P., Tam, L. S., ... & Pamulapati, C. (2018). Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Annals of the rheumatic diseases,77(9), 1295-1302.

Figure 7 Change from baseline in ASDAS-CRP, CRP and BASDAI over time to week 12.

Change from baseline in ASDAS-CRP (panel A), CRP (mg/L) (panel B) and BASDAI (panel C) over time to week 12. Median (IQR) changes are shown (observed). The values under each plot are the number of patients per treatment arm with a valid measurement at the specified time point. *P=0.0229 and p=0.0101 for median change in ASDAS-CRP for 18 mg and 180 mg risankizumab, respectively, versus placebo at week 12. ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score-CRP; BASDAI, Bath Ankylosing Spondylitis Disease Activity Score; CRP, C reactive protein.

Baeten, D., Østergaard, M., Wei, J. C. C., Sieper, J., Järvinen, P., Tam, L. S., ... & Pamulapati, C. (2018). Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Annals of the rheumatic diseases,77(9), 1295-1302.