Vincerx Pharma Presents Data on PTEFb/CDK9 Inhibitor VIP152 in DLBCL and CLL at the 63rd American Society of Hematology Annual Meeting
VIP152 has increased selectivity and potency compared to other CDK9 inhibitors in development, consistent across DLBCL and CLL models of disease
Vincerx hosting KOL webinar today,
“The data presented at ASH show that VIP152 has increased selectivity and potency as compared with other CDK9 inhibitors in development across high-grade B cell lymphoma and chronic lymphocytic leukemia models of disease,” said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx, “The consistency of preclinical data are noteworthy, with robust effects on key biomarkers of CDK9 inhibition including the durable downregulation of RNA polymerase II as well as the sustained reduction, and near clearance of, MYC and MCL-1 mRNA and protein. These results also translate through to primary samples from patients, with VIP152 demonstrating cytotoxic activity that overcomes stromal protection in primary CLL samples, and pharmacodynamic effects on key transcriptional targets observed in blood of patients with HGBL treated with VIP152. These results suggest that the demonstrated effects of VIP152 may translate to the clinic to provide new treatment options for patients with MYC and MCL-1- driven malignancies. With these expanded mechanism data in hand, we are currently enrolling two studies, a Phase 1b expansion study in relapsed/refractory aggressive lymphoma and advanced solid tumors, and a Phase 1b dose-escalation in CLL relapsed/refractory to venetoclax and BTK inhibitors.”
Key Presentation Highlights:
Poster presentation, titled, “VIP152, a selective CDK9 inhibitor, induces complete regression of high-grade B-cell lymphoma (HGBL) models and depletion of short-lived oncogenic driver transcripts, MYC and MCL1, with a once weekly schedule” presented by
- Compared with two oral CDK9 inhibitors in development, KB-0742 and atuveciclib, at equimolar concentrations, VIP152 demonstrated more potent and durable downregulation of phospho-Serine 2 on RNA polymerase II, a key biomarker for evaluating the mechanism of action of CDK9 inhibitors (50% reduction for 24–48 hours). Additionally, depletion of short half-life MYC and MCL-1 transcript levels up to 48 hours was observed.
- VIP152 treatment conferred a shift in transcriptional program, supporting an oncogenic shock mechanism of action, and sustained robust reduction and near clearance of MYC and MCL-1 proteins in MYC overexpressing lymphoma cell lines.
- Once weekly VIP152 treatment showed antitumor efficacy as demonstrated by dose-dependent tumor regression and tumor-outgrowth control in the SU-DHL-10 (a MYC overexpressing cell line) xenograft model.
- The pharmacodynamic effect demonstrated in the blood of HGBL patients treated with VIP152 suggests that the effect may translate to the clinic. Tumor-based pharmacodynamic studies are planned to confirm these findings.
- VIP152 is currently being evaluated in HGBL patients and other MYC expressing indications in the clinic (ClinicalTrials.gov Identifier: NCT02635672).
Oral presentation titled, “VIP152 Is a Novel CDK9 Inhibitor with Efficacy in Chronic Lymphocytic Leukemia” presented by
- VIP152 shows selective CDK9 inhibition with improved activity over other CDK9 inhibitors in development including dinaciclib, KB-0742 and atuveciclib.
- VIP152 induces apoptosis in CLL cell lines and demonstrates cytotoxic activity that overcomes stromal protection of primary CLL samples.
- VIP152 disrupts transcriptomics of patient samples after a two-hour treatment, alters cellular programming and disrupts binding of CDK9 to canonical binding partners, thereby inhibiting its function.
- VIP152 weekly dosing decreases peripheral disease in a circulating tumor CLL mouse model and improves survival.
- Data support the ongoing clinical trial in CLL (ClinicalTrials.gov Identifier: NCT04978779).
Vincerx will be hosting a KOL webinar today, at
A live Q&A session will follow the formal presentations. To register for the webinar, please click here.
The poster can be accessed on the presentations section of the Vincerx website.
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Source: Vincerx Pharma, Inc.