Afuco™ Anti-Human Hla ADCC Recombinant Antibody (MEDI4893), ADCC Enhanced (CAT#: AFC-343CL)

Figure 1 Anti-alpha toxin IgG and neutralizing antibody levels in serum. Each sample was tested in duplicate.

Anti-AT IgG (a) and neutralising antibody (b) in IU per millilitre of serum samples were summarised in mean and standard deviation in log scale for each treatment group at each visit time point. Upon administration of MEDI4893, serum anti-AT IgG and neutralising antibody levels increased; the highest levels were observed at the end of infusion. The magnitude of increase from the baseline to the peak levels correlated with MEDI4893 dose.

Ruzin, A., Wu, Y., Yu, L., Yu, X. Q., Tabor, D. E., Mok, H., ... & Esser, M. T. (2018). Characterisation of anti-alpha toxin antibody levels and colonisation status after administration of an investigational human monoclonal antibody, MEDI4893, against Staphylococcus aureus alpha toxin. Clinical & translational immunology, 7(1), e1009.

Figure 2 Anti-alpha toxin IgG and neutralising antibody levels in the upper respiratory tract.

Anti-AT IgG and anti-AT neutralising antibody levels in the upper respiratory tract were measured on days 1 (MEDI4893 predose), 8 and 31. These antibody levels were MEDI4893 dose-dependent and reached a plateau by day 8. Each sample was tested in duplicate. Anti-AT IgG (a) and neutralising antibody (b) in IU per millilitre of nasal wash samples were summarised in mean and standard deviation in log scale for each treatment group at each visit time point. The dashed line represents the LLOQ of the assay, and LLOQ/2 was used for measurements below the LLOQ.

Ruzin, A., Wu, Y., Yu, L., Yu, X. Q., Tabor, D. E., Mok, H., ... & Esser, M. T. (2018). Characterisation of anti-alpha toxin antibody levels and colonisation status after administration of an investigational human monoclonal antibody, MEDI4893, against Staphylococcus aureus alpha toxin. Clinical & translational immunology, 7(1), e1009.

Figure 3 Changes in nasal Staphylococcus aureus colonisation relative to baseline in subject groups.

The changes in PCR cycle threshold (Ct) values and culture scores relative to baseline (pre-infusion, day 1) were monitored over the course of 360 days. The results showed no consistent dose-dependent MEDI4893-mediated effect on nasal S. aureus colonisation. Two nasal swabs, one from each nostril, were collected per study subject. One swab was used for S. aureus identification and enumeration by culture, another swab was used for Cepheid Xpert SA Nasal Complete PCR assay. Changes from the baseline measurement of S. aureus colonisation in PCR Ct values (a) and culture scores (b) of nasal swab samples were summarised in mean and standard deviation for each treatment group at each visit time point. The dashed line at 0 represents no change from baseline.

Ruzin, A., Wu, Y., Yu, L., Yu, X. Q., Tabor, D. E., Mok, H., ... & Esser, M. T. (2018). Characterisation of anti-alpha toxin antibody levels and colonisation status after administration of an investigational human monoclonal antibody, MEDI4893, against Staphylococcus aureus alpha toxin. Clinical & translational immunology, 7(1), e1009.

Figure 4 MEDI4893 pharmacokinetics in healthy adult volunteers. Dashed line represents the target concentration of 211 µg/mL, the EC90 from a S. aureus murine pneumonia model.

Yu, X. Q., Robbie, G. J., Wu, Y., Esser, M. T., Jensen, K., Schwartz, H. I., ... & Jafri, H. S. (2017). Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-Staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrobial agents and chemotherapy, 61(1), e01020-16.

Figure 5 (A) Baseline serum anti‒alpha-toxin neutralizing antibody. (B) Correlation between serum MEDI4893 concentrations and anti‒alpha-toxin neutralizing activity. AT = alpha-toxin.

Yu, X. Q., Robbie, G. J., Wu, Y., Esser, M. T., Jensen, K., Schwartz, H. I., ... & Jafri, H. S. (2017). Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-Staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrobial agents and chemotherapy, 61(1), e01020-16.