Fig. 6: VIS832 treatment efficacy as monotherapy and in combination with btz in a murine model of disseminated human MM.

a In vivo work plan. CB-17 SCID mice injected with MM1S-luc cells by i.v. route at day 0 were randomized on day 14 as the first day of dosing twice weekly with vehicle control (VC, PBS), VIS832 (4āmg/kg), btz (1āmg/kg), or combination of VIS832 and btz (nā=ā9 mice per group). Tumor burden was assessed by whole body BLI and quantified by IVIS imaging. Treatment was discontinued at day 53 (dosing phase), followed by a three-week washout period with end of study at day 73. b Group efficacy data. Disseminated tumor burden was reported as BLIā±āSEM at each time point. Tumor growth was significantly inhibited starting at day 36 in VIS832 or btz vs. VC groups; the combination-treated vs. VC groups. (at Day 36, VIS832 vs. VC, Pā<ā0.0001; btz vs. VC, Pā=ā0.0001; VIS832ā+ābtz vs. VC, Pā<ā0.0001; VIS832 vs. VIS832ā+ābtz, Pā<ā0.0001; btz vs. VIS832ā+ābtz, Pā<ā0.0001; VIS832 vs. btz, Pā=ā0.0004, by Tukeyās multiple comparison test). c KaplanāMeier survival curves. The percentage of survival was defined as mice surviving to a pre-determined euthanasia criterion related to disease-related morbidity such as weight loss >20%, severely impaired central nervous system function, severely impaired movement, or loss of righting reflexes. VIS832 significantly increased the median overall survival of animals, and VIS832 with btz completely eradicated MM tumors, with all mice tumor-free (VC, 30d; VIS832ā>ā60d; btz, 42d; VIS832ā+ābtz, >73d) (VIS832 vs. VC, Pā<ā0.0001; btz vs. VC, Pā=ā0.0004; VIS832ā+ābtz vs. VC, Pā<ā0.0001; VIS832 vs. VIS832ā+ābtz, Pā<ā0.02; btz vs. VIS832ā+ābtz, Pā<ā0.0001; VIS832 vs. btz, Pā=ā0.02).