Evaluation of forimtamig’s mode of action in an orthotopic mouse model of MM. (A) Luciferase-labeled NCI-H929 cells were injected into the femur of humanized NSG (huNSG) mice and randomized into 4 different treatment arms based on bioluminescent signals measured as photons per second (p/s); animals were treated once weekly with indicated doses of forimtamig and tumor growth was monitored over time; background signals were determined in nontumor-bearing mice; each group included 10 animals and is presented as mean + SEM. (B) Orthotopically engrafted huNSG mice (n = 5) were treated once weekly with 0.1 mg/kg forimtamig and sBCMA levels were detected in serum of animals before, 4, 24, 48, 72, and 168 hours after dosing using enzyme-linked immunosorbent assay (ELISA). (C-E) Orthotopically engrafted humanized mice (n = 40) were treated once weekly with 0.1 mg/kg forimtamig; BM, blood and serum were harvested from n = 5 animals at 4, 24, 48, 72, and 168 hours, after C1 and C2 dosing, and subjected to fluorescence-activated cell sorting (FACS) or cytokine analysis; CD8 T-cell counts in the tumor tissue (right femur) were normalized against CD8 counts from healthy BM from the same animal (left femur); naïve CD8 T cells were defined as CD62L+CD45RA+ and effector memory T cells as CD4RA−CD62L−. (F) Orthotopically engrafted huNSG mice (n = 15 animals per group) were treated once weekly with 0.5 mg/kg forimtamig flat or 0.005, 0.05, and 0.5 mg/kg SUD at C1D1, C1D8, and C1D15; serum was harvested from n = 5 animals at 10 minutes, 4 hours, and 72 hours after dosing and cytokine levels were measured by bioplex; and fold change in cytokine release was calculated by normalization to vehicle animals at the same time points. (G) Orthotopically engrafted huNSG mice (n = 15 animals per group) were treated once weekly with 0.5 mg/kg forimtamig flat or 0.005, 0.05, and 0.5 mg/kg SUD at C1D1, C1D8, and C1D15, and tumor monitored over time by bioluminescence imaging; and background signals were determined in nontumor-bearing mice. TNF-α, tumor necrosis factor α.

Evaluation of forimtamig’s mode of action in an orthotopic mouse model of MM. (A) Luciferase-labeled NCI-H929 cells were injected into the femur of humanized NSG (huNSG) mice and randomized into 4 different treatment arms based on bioluminescent signals measured as photons per second (p/s); animals were treated once weekly with indicated doses of forimtamig and tumor growth was monitored over time; background signals were determined in nontumor-bearing mice; each group included 10 animals and is presented as mean + SEM. (B) Orthotopically engrafted huNSG mice (n = 5) were treated once weekly with 0.1 mg/kg forimtamig and sBCMA levels were detected in serum of animals before, 4, 24, 48, 72, and 168 hours after dosing using enzyme-linked immunosorbent assay (ELISA). (C-E) Orthotopically engrafted humanized mice (n = 40) were treated once weekly with 0.1 mg/kg forimtamig; BM, blood and serum were harvested from n = 5 animals at 4, 24, 48, 72, and 168 hours, after C1 and C2 dosing, and subjected to fluorescence-activated cell sorting (FACS) or cytokine analysis; CD8 T-cell counts in the tumor tissue (right femur) were normalized against CD8 counts from healthy BM from the same animal (left femur); naïve CD8 T cells were defined as CD62L+CD45RA+ and effector memory T cells as CD4RA−CD62L−. (F) Orthotopically engrafted huNSG mice (n = 15 animals per group) were treated once weekly with 0.5 mg/kg forimtamig flat or 0.005, 0.05, and 0.5 mg/kg SUD at C1D1, C1D8, and C1D15; serum was harvested from n = 5 animals at 10 minutes, 4 hours, and 72 hours after dosing and cytokine levels were measured by bioplex; and fold change in cytokine release was calculated by normalization to vehicle animals at the same time points. (G) Orthotopically engrafted huNSG mice (n = 15 animals per group) were treated once weekly with 0.5 mg/kg forimtamig flat or 0.005, 0.05, and 0.5 mg/kg SUD at C1D1, C1D8, and C1D15, and tumor monitored over time by bioluminescence imaging; and background signals were determined in nontumor-bearing mice. TNF-α, tumor necrosis factor α.

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