On April 8, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported a poster presentation of preclinical and preliminary clinical data on VIP152, the Company’s PTEFb/CDK9 inhibitor, in gynecologic cancer cell lines and in patients with gynecologic malignancies, respectively, at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held virtually and in New Orleans, Louisiana from April 8-13, 2022 (Press release, Vincerx Pharma, APR 8, 2022, View Source [SID1234611694]).

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"The preclinical data presented at AACR (Free AACR Whitepaper) demonstrate sensitivity of gynecologic cancer cell lines with MYC and/or MYCN genetic alterations to VIP152," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx, "Our findings demonstrate that VIP152 monotherapy inhibits tumor growth in an ovarian cancer xenograft model in mice. We believe these preclinical data are noteworthy and translate through to primary tissue samples from patients with ovarian or endometrial cancer showing significant reduction in MYC protein expression ex vivo, and, in the blood of patients with gynecologic cancer, a downregulation of CDK9-regulated genes MYC, MCL1, and PCNA mRNA expression after VIP152 treatment."

"Additionally, our preliminary VIP152 monotherapy clinical results as of March 2022 demonstrated an early signal in patients with gynecologic malignancies who have had multiple lines of prior therapy," continued Dr. Hamdy. "In our ongoing first-in-human study, 3 out of 3 patients with MYC-amplified gynecologic cancer had stable disease at first assessment, as well as 1 out of 4 patients with ovarian cancer unselected for MYC. These results, together with our findings presented at ASH (Free ASH Whitepaper) last year, suggest that VIP152 has the potential to provide new treatment options for patients across various MYC and MCL-1- driven tumor types. We are continuing to enroll patients in our Phase 1b expansion study across multiple tumor types including hematologic malignancies."

Key Presentation Highlights:

Poster presentation, titled, "VIP152, a selective CDK9 inhibitor, demonstrates sensitivity in gynecologic cell lines that are cisplatin sensitive or resistant and delivers in vivo antitumor efficacy" presented by Melanie Frigault, Ph.D., Vice President of Translational Medicine, Vincerx, include:

A 10-fold range of sensitivity to VIP152 was observed in cisplatin-sensitive and cisplatin-resistance ovarian, uterus, uterus/cervix, and vulva cancer cell lines demonstrating the cytotoxic effects of VIP152.
High tumor mutation burden (TMB) is identified as a feature associated with VIP152 in the most sensitive quartile of gynecologic cell lines and will be validated in an independent cohort.
Antitumor efficacy was observed following a single 17.5 mg/kg dose of VIP152 monotherapy as demonstrated by tumor growth inhibition in the A2780 ovarian cancer xenograft model.
VIP152 treatment administered on an intermittent treatment schedule (once weekly), showed predictable pharmacokinetic properties and conferred a shift in transcriptional program, supporting an oncogenic shock mechanism of action, with significant reduction in MYC protein expression in patient-derived ovarian and endometrial cancer tissues samples as well as a downregulation of CDK9-regulated genes MYC, MCL, and PNCA mRNA expression in the blood of patients with gynecologic cancer.
Four out of seven patients with gynecologic cancers treated with VIP152 had stable disease, including all 3 of the MYC-amplified patients, at their first assessment. One patient remains on treatment. Although duration on monotherapy treatment is short, we believe this is a signal that warrants further exploration including in combination studies.
Neutropenia is an on-target (CDK9) toxicity via downregulation of MCL1 and is monitorable and manageable with supportive care. Once weekly dosing of VIP152 allows for recovery of neutrophils before the next dose.
Data support the ongoing Phase 1 clinical trial of VIP152 (ClinicalTrials.gov Identifier: NCT02635672).
The poster can be accessed on the presentations section of the Vincerx website.