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Data indicate that GP-2250 has anti-neoplastic effects in virus-negative MCC cells as evidenced by tumor cell viability, proliferation and migration
GP-2250 demonstrated ability to downregulate protein expression of aberrant tumorigenic pathways in virus-negative MCC cell lines
BERWYN, Pa., June 29, 2023 (GLOBE NEWSWIRE) — Panavance Therapeutics Inc. (“Panavance” or the “Company”), a clinical-stage pharmaceutical company advancing the development of a novel oncology therapeutic intended to improve the effectiveness of cancer treatments and quality of life for the patients that receive them, today announced the publication of positive preliminary data in a manuscript titled, “The effect of GP‑2250 on cultured virus‑negative Merkel cell carcinoma cells: preliminary results1,” in the peer-reviewed Journal of Cancer Research and Clinical Oncology.
The objective of the preclinical study was to investigate the effects of GP-2250 on Merkel cell polyomavirus (MCPyV)-negative MCC cells. Patients with MCPyV-negative MCC have a much lower 5-year survival rate than MCPyV-positive cancer.
Greg Bosch, Chairman and CEO of Panavance Therapeutics commented, “We are encouraged by these preclinical findings in this rare, aggressive form of skin cancer. These preliminary results demonstrating the effectiveness of GP-2250 on MCC represent the second neuroendocrine cancer in which GP-2250 has shown effectiveness, the other one being pancreatic neuroendocrine cancer.”
“To date, the effects of GP-2250 have been studied in malignant skin cancers such as MCC and cutaneous squamous cell carcinoma, however this study is the first time a more in-depth evaluation of the anti-neoplastic effects of GP-2250 in virus-negative MCC cell lines was conducted. This study was able to show that GP-2250 has significant, dose-dependent cytotoxic effects on MCC cells as well as reduced cancer cell proliferation and migration. We are extremely encouraged by these results as they add to our growing body of data and further support our belief in the potential of GP-2250 as an important treatment of a broad range of cancers,” added Prof. Dr. med. Chris Braumann, Chief of General, Visceral & Vascular Surgery, University of Duisburg-Essen, Germany; Head of Molecular and Clinical Research at Ruhr-University of Bochum, Germany; and Scientific Advisor to Panavance.
A research team at St. Josef-Hospital, Ruhr-University Bochum, Germany with support from the Company, studied three cell lines (MCC13, MCC14.2, MCC26) which were exposed to different GP-2250 doses. GP-2250’s effects on cell viability, proliferation and migration were evaluated by means of MTT, BrdU, and scratch assays, respectively. Flow cytometry was performed for the evaluation of apoptosis and necrosis. Western blotting was implemented for the determination of AKT, mTOR, STAT3 and Notch1 protein expression.
Results of the study showed that cell viability, proliferation and migration decreased with increasing GP-2250 doses. Flow cytometry revealed a dose response to GP-2250 in all three MCC cell lines. While the viable fraction decreased, the share of necrotic and in a smaller amount the apoptotic cells increased. Regarding Notch1, AKT, mTOR and STAT3 expression a comparatively time- and dose-dependent decrease of protein expression in the MCC13 and MCC26 cell lines was observed. By contrast, Notch1, AKT, mTOR and STAT3 expression in MCC14.2 was scarcely altered or even increased by the three dosages of GP-2250 applied.
About Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine carcinoma, associated with the Merkel cell polyomavirus (MCPyV) in 80% of cases. The remaining 20% is associated with high rates of ultraviolet (UV)-induced mutations. There are roughly 2,000 new cases of MCC per year in the United States, most often developing in older people. Long-term sun exposure or a weak immune system may increase the risk of developing MCC. MCC tends to grow fast and to spread quickly, and treatment options often depend on whether the cancer has spread beyond the skin.
About Panavance Therapeutics
Panavance Therapeutics Inc. is a privately-held, clinical-stage pharmaceutical company developing a novel oncology platform focused on improving the outcomes and quality of life for cancer patients. Panavance, a US Delaware company, is located in Berwyn, PA. It was founded in 2021 and is a subsidiary of Swiss privately held Ed. Geistlich Söhne AG für Chemische Industrie. Panavance’s lead program, misetionamide (also known as GP-2250), is a tumor cell selective and broadly active small molecule with a unique dual mechanism of action of selectively disrupting the energy metabolism of cancer cells leading to cancer cell death as well as impacting nuclear factor-κB (“NFκB”) which effects cancer cells’ ability for protein synthesis and DNA transcription thereby restricting cancer cell growth and proliferation. The Company is advancing towards the initiation of two registration directed clinical studies expected to start in 2024: a Phase 2/3 study of GP-2250 for the treatment of ovarian cancer and a pivotal Phase 3 clinical trial as a first-line maintenance therapy for non-BRCA mutated pancreatic cancer patients, a population for which there are no FDA approved agents. GP-2250’s unique mechanism of action and extensive preclinical data supports broad oncology utility with the potential to be effective in additional indications, including melanoma, squamous cell, breast and colorectal cancers.
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1 Gambichler, T., Majchrzak-Stiller, B., Peters, I. et al. The effect of GP-2250 on cultured virus-negative Merkel cell carcinoma cells: preliminary results. J Cancer Res Clin Oncol (2023). https://doi.org/10.1007/s00432-023-04960-3