Anti-Cancer Drugs Publishes Preclinical Data Demonstrating the Broad Antineoplastic Activity of Panavance’s Misetionamide (GP-2250)
Misetionamide showed broad antineoplastic activity in 15 different cancer types including multiple human cancer cell lines with no detrimental effect on normal cells
Misetionamide reduces energy metabolism by inhibiting aerobic glycolysis
BERWYN, PA, Feb. 01, 2024 (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 outcomes and quality of life for patients, today announced publication of positive data in the peer-reviewed Anti-Cancer Drugs in an article titled, “Antineoplastic Activity of GP-2250 In Vitro and in Mouse Xenograft Models.”1 The publication by Sofia et al. (2024) provided early research evidence that misetionamide exhibits a dose-dependent antineoplastic effect on both established cancer cell lines and xenograft models from patient tissues.2 Antineoplastic activity was tested in over 300 cancer cell lines using the OncoPanel® cytotoxicity assay and was further tested in eight human cancer xenograft models.
Results included a reduction of 30-40% of tumor volume in xenograft mouse models treated with misetionamide and demonstrated a reduction in the progression of tumor cell volume in multiple cancer cell lines including pancreatic and ovarian cancer suggesting a strong antineoplastic effect. Most notably in the ovarian tumor xenograft model, misetionamide produced a regression in the original tumor volume. Concentrations for IC50 and EC50 were determined as was the concentration at which a 10-fold increase in apoptosis was induced. All these concentrations have subsequently been shown to be clinically achievable in an on-going Phase 1 clinical trial. In addition, misetionamide was also shown to induce a cancer cell cycle block that would inhibit tumor cells from replicating and thus inhibiting tumor growth. The results of these studies also reinforce the results of other studies demonstrating strong synergism with other anticancer agents, including gemcitabine, bevacizumab, and PARP inhibitors. To that end, the results support the development of misetionamide as a promising new therapeutic agent with a unique mechanism of action for human cancers.
“While this paper details the early screening work in 300 human cancer lines using in vitro studies as well as 8 in vivo studies to determine if misetionamide showed any antineoplastic activity, and, if so, in which cancer cells, we were pleased that the results showed both the very broad activity in many cancer cell lines and that normal cells were not detrimentally affected, said R. Duane Sofia, PhD, Head Nonclinical Research, Panavance Therapeutics.
“The results from these studies demonstrate that misetionamide has a broad mechanism of action which could be impactful in treating most cancers. While our initial focus is on pancreatic and ovarian cancers, these studies further support the potential to pursue other cancer indications with misetionamide in the future,” said Greg Bosch, Chairman and CEO.
About Misetionamide (GP-2250)
Misetionamide is a tumor cell selective drug that is broadly active in multiple cancer models with a unique mechanism of action that suppresses cancer by disrupting its energy metabolism, leading to cancer cell death while not affecting normal cells. This activity occurs due to misetionamide’s targeting at least 3 key enzymes in the aerobic glycolysis pathway as well as downstream effects on other enzymes, transcription factors and tumor suppressor genes. Misetionamide’s inhibition of hexokinases, GAPDH (glyceraldehyde 3-phosphate dehydrogenase), and PVD (pyruvate dehydrogenase) during aerobic glycolysis greatly inhibits ATP production for cancer cells, setting up oxidative, metabolic, and hypoxic stresses within the cancer cell. Additionally, misetionamide’s inhibition of key transcription factors such as NFkB and enzymes further impair the ability for the cancer cell to provide sufficient energy for cellular reproduction for proliferation and survival. It also induces tissue hypoxia by inhibiting new blood vessel development in tumors.3
About Panavance Therapeutics
Panavance Therapeutics Inc. is a privately held, clinical-stage pharmaceutical company developing a novel oncology asset, GP-2250 (also known as misetionamide). Panavance was formed in 2021 as a US-based, wholly owned carve out of Geistlich group, a family-owned Swiss company, to focus on GP-2250 and the oncology business.
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: a Phase 2/3 study of GP-2250 for the treatment of platinum resistant ovarian cancer and a pivotal Phase 3 clinical trial as a first-line maintenance therapy for non-BRCA mutated pancreatic cancer patients. Extensive preclinical studies have demonstrated that GP-2250’s broadly anti-neoplastic MOA has the potential to be effective in additional indications, including for example melanoma, squamous cell, breast, and colorectal cancers.
1Sofia, R. Duane; Martin, Kathryn M.b; Costin, James C.c. Antineoplastic activity of GP-2250 in-vitro and in mouse xenograft models. Anti-Cancer Drugs 35(2):p 183-189, February 2024. | DOI: 10.1097/CAD.0000000000001550
2Buchholz, M; Majchrzak-Stiller, B; Hahn, S.; Vangala, D; Pfirrmann, RW; Uhi, W; et al. Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma – in vitro and in vivo. MGC Cancer 2017; 17:216.
3Majchrzak-Stiller, B.; Buchholz, M.; Peters, I.; Waschestjuk, D.; Strotmann, J.; Höhn, P.; Hahn, S.; Braumann, C.; Uhl, W.; Müller, T.; et al. GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells. J. Cell. Mol. Med. 2023, 27, 2082–2092.
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