Vincerx Pharma presents preclinical VIP943, VIP924 posters at ASH 2023

Vincerx Pharma announced the presentation of two preclinical posters at the 65th Annual Meeting of the American Society for Hematology for VIP943, for leukemias and myelodysplastic syndrome, and VIP924, for B-cell malignancies. On-target selectivity and activity show that VIP943 is highly selective for the kinesin spindle protein target, aka EG5, versus other members of the related KIF super family. This on-target activity translates to cell cycle arrest at the G2/M phase of mitosis, resulting in apoptosis in AML cell lines. In vitro cytotoxicity assays show that most hematologic cell lines are sensitive to VIP943’s payload and that DNA alterations did not reduce its cytotoxicity. Nonhuman primate safety and toxicokinetic studies show that repeat dosing of VIP943 in cynomolgus monkeys has good overall tolerability without the myelosuppression and hepatotoxicity seen with other ADCs. This is consistent with the favorable safety profile seen to date in the VIP943 Phase 1 dose-escalation trial. Regarding “VIP924: CXCR5-KSPi ADC for B-cell malignancies,” target expression analysis in a panel of 20 human MCL samples shows that CXCR5 and CD19 expression was medium to high in all samples, while CD79b showed slightly lower expression. In vivo activity in a humanized mouse model shows that VIP924 demonstrates significant efficacy with no substantial change in body weight. In comparison, the commercially available ADCs, Polivy and Zynlonta, show no improvement in tumor growth inhibition or survival in this setting. Immunophenotyping of key immune tissues show that: VIP924 treatment yielded no difference in the percent of CD45+ cells versus the control, while the other two ADCs showed a clear reduction in CD45+ cells. VIP924 treatment reduced T-follicular helper cells in the blood, tumor and spleen; significantly increased T-regs; and had no meaningful impact on myeloid-derived suppressor cells compared with controls. Zynlonta also reduced peripheral blood Tfhs and significantly increased MDSCs compared with control. Complete blood counts show that VIP924 had minimal impact on the six elements of the CBC reported in these studies. Zynlonta reduced the levels of all cell populations in the CBC, except for platelets.