Afuco™ Anti-Human MMP9 ADCC Recombinant Antibody (GS-5745), ADCC Enhanced (CAT#: AFC-513CL)

Figure 1 Efficacy endpoints.

The proportion of patients achieving [A] EBS clinical remission, [B] MCS response, [C] endoscopic response, and [D] mucosal healing at Week 8. [E] Change from baseline in partial MCS over time. [A–D] Values indicate percentage of patients per treatment group achieving response. Error bars indicate upper and lower 95% confidence interval. [E] Data represented as mean with error bars indicating SD. EBS clinical remission defined as endoscopic subscore of 0 or 1, rectal bleeding score of 0, and ≥1-point decrease in stool frequency to achieve a subscore of 0 or 1; MCS response defined as reduction of ≥3 points and at least 30% from baseline with decrease in rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of 0 or 1; endoscopic response defined as endoscopic subscore of 0 or 1; mucosal healing defined as elimination of ulcers/erosion, elimination of crypt destruction, elimination of intraepithelial neutrophils, elimination of lamina propria neutrophils, and reduction in lamina propria chronic inflammatory cells to at most a mild increase. Partial MCS comprised subscores from rectal bleeding, stool frequency, and PGA. aPatients with mucosal healing at baseline were excluded from the analysis. EBS, endoscopy/bleeding/stool; MCS, Mayo clinical score; PGA, physician's global assessment; Q2W, every 2 weeks; QW, weekly; SD, standard deviation.

Sandborn, W. J., Bhandari, B. R., Randall, C., Younes, Z. H., Romanczyk, T., Xin, Y., ... & Sundy, J. S. (2018). Andecaliximab [Anti-matrix Metalloproteinase-9] Induction Therapy for Ulcerative Colitis: A Randomised, Double-Blind, Placebo-Controlled, Phase 2/3 Study in Patients With Moderate to Severe Disease. Journal of Crohn's and Colitis,12(9), 1021-1029.

Figure 2 Mean plasma concentration vs time curves for andecaliximab Q2W and QW.

Error bars indicate SD. Arrows indicate drug administration for Q2W dosing. All PK samples were collected before dosing on respective treatment days. For the 150 mg Q2W group, the Week 8 concentration was determined 2 weeks following the previous dose, whereas Week 1 and Week 5 concentrations were determined 1 week following the previous dose. PK, pharmacokinetic; Q2W, every 2 weeks; QW, weekly; SD, standard deviation.

Sandborn, W. J., Bhandari, B. R., Randall, C., Younes, Z. H., Romanczyk, T., Xin, Y., ... & Sundy, J. S. (2018). Andecaliximab [Anti-matrix Metalloproteinase-9] Induction Therapy for Ulcerative Colitis: A Randomised, Double-Blind, Placebo-Controlled, Phase 2/3 Study in Patients With Moderate to Severe Disease. Journal of Crohn's and Colitis,12(9), 1021-1029.

Figure 3 GS-5745 demonstrate noncompetitive inhibition of MMP9: Antibody-mediated inhibition of MMP9 activity was assessed at multiple concentrations of substrate (a fluorogenic peptide).

Marshall, D. C., Lyman, S. K., McCauley, S., Kovalenko, M., Spangler, R., Liu, C., ... & Mikels-Vigdal, A. (2015). Selective allosteric inhibition of MMP9 is efficacious in preclinical models of ulcerative colitis and colorectal cancer. PloS one,10(5), e0127063.