Misetionamide demonstrated significant single agent activity and synergy with either PARP inhibitors (PARPi) or bevacizumab in ovarian cancer preclinical studies
Profound effects on tumor metabolism, anti-angiogenic activity, protein synthesis, and DNA transcription
BERWYN, PA, Aug. 14, 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 journal, Cancer Medicine, in a manuscript titled “Mechanism and Rational Combinations with GP-2250, a Novel Oxathiazine Derivative, in Ovarian Cancer.”1 The publication by Kim, et al. (2024) at MD Anderson Cancer Center reports the research on misetionamide which demonstrated excellent monotherapy results as well as synergistic activity with PARPi’s and bevacizumab antineoplastic in ovarian cancer.
Misetionamide is a tumor cell selective small molecule drug that is broadly active in multiple cancer models. Misetionamide’s inhibition of hexokinase-2 (HK-2), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and pyruvate dehydrogenase (PVD) in 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 further impairs the ability of the cancer cell to express genes and thus sustain viability and proliferation.2
“The key findings in our research are that misetionamide exerts a profound antitumor effect when used as monotherapy as well as synergistically when used either in combination with PARP inhibitors or bevacizumab. Misetionamide also has anti-angiogenic activity that interacts synergistically with bevacizumab. Both findings, and others, strongly suggest that misetionamide in combination with PARPi or bevacizumab should be studied further as a new antitumor drug in ovarian cancers,” said Anil Sood, MD, Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center.
“This research demonstrates that misetionamide exerts major anti-cancer effects through new metabolic and transcription inhibition mechanisms. As such, misetionamide may be a promising new therapeutic approach for ovarian cancer patients, which is the fifth leading cause of female cancer death,” commented study author, Robert L. Coleman, MD, Gynecologic Oncologist, Texas Oncology.
“The results of this study support our strategy to initiate a clinical trial in ovarian cancer. The Company had a pre-IND meeting with the FDA to discuss our ovarian cancer clinical and regulatory plan in May, and we plan to pursue a Phase 1/2 proof of concept study in platinum-resistant ovarian cancer. Given the high unmet need with approximately 20,000 new cases of ovarian cancer diagnosed each year in the US alone, we are dedicated to bringing new treatment options to these patients,” said Greg Bosch, Chairman and CEO.
About Panavance Therapeutics
Panavance Therapeutics Inc. is a privately held, clinical-stage pharmaceutical company developing a novel oncology asset, misetionamide (GP-2250). 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.
Misetionamide 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 affects cancer cells’ ability for protein synthesis and DNA transcription thereby restricting cancer cell growth and proliferation. The Company plans to initiate two clinical studies: a Phase 1/2 study of misetionamide for the treatment of platinum-resistant ovarian cancer and a clinical trial as a first-line maintenance therapy for non-BRCA mutated pancreatic cancer patients. Extensive preclinical studies have demonstrated that misetionamide’s broadly anti-neoplastic MOA has the potential to be effective in additional tumor types, including melanoma, squamous cell, breast, and colorectal cancers.
For more information, please visit panavance.com and connect with the Company on Twitter, LinkedIn, and Facebook.
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1Kim MS, Glassman D, Handley KF, Lankenau Ahumada A, Jennings NB, Bayraktar E, Foster K, Joseph R, Lee S, Coleman RL, Sood AK. Mechanism and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer. Cancer Med. 2024 Aug;13(15):e70031. doi: 10.1002/cam4.70031. PMID: 39114948; PMCID: PMC11306972.
2Majchrzak-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.
