NeuroMab™ Anti-FGFR3 BBB Shuttle Antibody(NRZP-1022-ZP3903)

Figure 1 R3Mab blocks FGF/FGFR3 interaction.

R3Mab selectively binds human FGFR3. Human FGFR1-4 Fc chimeric protein was immobilized and incubated with increasing amounts of R3Mab. Detection of specific binding using an anti-human Fab antibody

Figure 2 R3Mab inhibits Ba/F3 cell proliferation driven by wild-type and mutant FGFR3.

Figure 3 Inhibition of FGFR3 and MAPK phosphorylation by R3Mab in Ba/F3-FGFR3-IIIbWT stable cells.

Figure 4 Epitope mapping of R3Mab and crystal structure of the complex between R3Mab Fab fragment and IgD2-D3 of human FGFR3-IIIb.

Epitopes identified by binding of 13 peptides spanning IgD2-D3 of human FGFR3 to R3Mab.

Figure 5 R3Mab inhibits proliferation, clonogenic growth, and FGFR3 signaling in bladder cancer cells expressing wild-type or mutant FGFR3S249C.

Figure 6 R3Mab reduces the steady-state level of disulfide-linked FGFR3S249C dimers by pushing the dimer-monomer equilibrium toward the monomeric state.

Figure 7 R3Mab inhibits bladder cancer cell xenograft growth and Ba/F3-FGFR3S249C allograft growth.

Effect of R3Mab on growth of pre-established RT112 bladder cancer xenografts compared to vehicle control. n = 10 per group.

Figure 8 R3Mab inhibits bladder cancer cell xenograft growth and Ba/F3-FGFR3S249C allograft growth.

Effect of R3Mab on growth of pre-established UMUC-14 bladder cancer xenografts, n = 10 per group

Figure 9 ADCC contributes to the antitumor efficacy of R3Mab in a t(4;14)-positive multiple myeloma model.

Effect of R3Mab on the growth of pre-established OPM2.

Figure 10 R3Mab inhibits proliferation and FGFR3 signaling in bladder cancer cells harboring wild-type or mutant FGFR3S249C.

(Panel A) Inhibition of cell viability by R3Mab in the bladder cancer cell line RT4. Cell viability was assessed with CellTiter-Glo (Promega) after 96 hours of incubation with the antibody. Error bars represent SEM. (Panel B) Blockade of FGF1-in Activation of FGFR3 signaling by R3Mab (15 ug/ml) in bladder cancer cell line RT4.

Figure 11 Effects of endocytosis inhibitors on the internalization of R3Mab and FGFR3S249C dimers in UMUC-14 cells.

Effects of endocytosis inhibitors on R3Mab internalization. UMUC-14 cells, pretreated with various endocytosis inhibitors or DMSO for 1 hr at 37°C, were incubated with R3Mab.

Figure 12 Effect of R3Mab on the proliferation of t(4;14)+ multiple myeloma cells.

Inhibition of [3H]-thymidine incorporation by UTMC-2 cells by R3Mab. UTMC-2 cells were grown in media containing R3Mab or a control antibody.

Figure 13 Cell surface expression levels of FGFR3 in myeloma and bladder cancer cells.

Cell surface FGFR3 expression in myeloma cells and bladder cancer cells was assessed by FACS analysis. Cells were stained with phycoerythrin-conjugated mouse monoclonal antibody against human FGFR3 (FAB766P, R&D Systems) or phycoerythrin-conjugated isotype control mouse IgGl (BD Pharmingen).

Figure 14 Effect of R3Mab or its DANA mutant on the growth of transplanted tumor of bladder cancer cells.

Effect of R3Mab and its DANA mutants (50 mg/kg each) on the growth of pre-established RT112 tumors. (FIG. 24B) Effect of R3Mab and its DANA mutants (50 mg/kg each) on growth of pre-established UMUC-14 tumors. Error bars represent SEM.

Figure 1 shows the neutralizing activity of several MSPRO Fabs in a proliferation assay using FDCP-FR3.