Data presented at the American Association for Cancer Research (AACR) Annual Meeting 2023
GP-2250’s antineoplastic effects on ovarian cancer cells include inhibition of glycolysis via modulation of HK2 activity in addition to GAPDH and NFkB down regulation and expression and inhibition of HIF-1α induced VEGF secretion
GP-2250, alone and in combination with poly ADP-ribose polymerases (PARP) inhibitors as well as bevacizumab demonstrated profound antitumor efficacy
BERWYN, Pa., April 17, 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 outcomes and quality of life for the patients that receive them, today announced that positive data from the Company’s tumor cell selective and broadly active small molecule with a unique mechanism of action, GP-2250 (misetionamide), was presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19, 2023, at the Orange County Convention Center in Orlando, FL.
The poster titled, Mechanisms and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer was presented by Mark S. Kim, Ph.D., Assistant Professor of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center and Anil Sood, M.D., Vice Chair for Translational Research in the Departments of Gynecologic Oncology and Cancer Biology and co-director of the Center for RNA Interference and Non-Coding RNA at MD Anderson as part of the Novel Antitumor Agents 2 session. The poster outlined the mechanism of action and the biological effects of GP-2250 using in vitro and in vivo models.
“The data generated by GP-2250 to date has continued to demonstrate promising treatment potential for cancers. These findings are encouraging and provide valuable insight as we advance the development of GP-2250 for the treatment of ovarian cancer. Of particular note, these new data indicate that GP-2250 monotherapy exerts profound effects on tumor metabolism and, when taken in combination with PARP inhibitors or bevacizumab, showed enhanced anti-tumor efficacy compared with any agent alone. With this growing body of data, we look forward to further evaluating GP-2250’s potential in the treatment of ovarian cancer,” commented Greg Bosch, Chairman and CEO of Panavance Therapeutics.
Dr. Sood commented, “There remains a significant unmet need in treatment options for ovarian cancer. The findings from these preclinical studies evaluating GP-2250 in combination with the current standards of care are incredibly encouraging as we continue to explore GP-2250 as a potential treatment option. With these promising preclinical data in hand and the validation of these findings for continued clinical development, we look forward to further evaluating the potential of GP-2250 to provide a much needed solution for patients in need.”
For the study, researchers from MD Anderson conducted in vitro experiments including MTT assay, Annexin V/PI assay, colony formation assay, reverse-phase protein array (RPPA), and HRLC/IC analysis to determine the biological activity of GP-2250 and investigate the mechanism of action. In vivo experiments were carried out to determine the therapeutic efficacy of GP-2250 alone and in combination with standard-of-care drugs (e.g., paclitaxel, cisplatin topotecan, PARP inhibitors and the antiangiogenic drug, bevacizumab (Avastin®). Additionally, researchers conducted an in vivo pharmacodynamic experiment using the OVCAR8 mouse model, which demonstrated that a dose of 500 mg/kg GP-2250 was the most effective in downregulating AKT and mTOR expression.
Data Highlights:
- GP-2250 montherapy preclinical results demonstrated significant reductions in ovarian cancer tumor weight and number of tumor nodules, which were comparable to the results of PARP inhibitors and bevacizumab.
- In vivo therapy experiment demonstrated that the combination of GP-2250 and each of the PARP inhibitors tested (olaparib, niraparib, and rucaparib) as well as bevacizumab showed a significant reduction of tumor weights and tumor nodules compared to a control group or the monotherapy groups.
- GP-2250’s mechanism of action inhibited hypoxia-inducible factor-1α, AKT, and mTOR activation and expression level as revealed in RPPA analyses.
- Ultra-high resolution mass spectrometry (HRMS) analysis also revealed that hexokinase-2 activity and expression was significantly reduced by GP-2250 treatment.
- GP-2250 reduced GAPDH and HK2 impacting glycolysis and ATP synthesis in ovarian cancer cells.
The presented poster is now available on the Publications page of the Resource section of the Company’s website (panavance.com).
Panavance is currently advancing the development of GP-2250 towards multiple registration directed clinical studies including a Phase 2/3 for the treatment of ovarian cancer in combination with leading anti-cancer agents. These registration studies are expected to start in 2024.
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.
For more information, please visit panavance.com and connect with the Company on Twitter and LinkedIn.
References and links to websites have been provided for convenience, and the information contained on any such website is not a part of, or incorporated by reference into, this press release. Panavance is not responsible for the contents of third-party websites.
Forward Looking Statements
This press release contains “forward-looking statements” that are based on Panavance’s current expectations and subject to inherent uncertainties, risks and assumptions that are difficult to predict, including, without limitation, Panavance’s ability to execute its business plan and fund its ongoing business activities as planned, Panavance’s ability to develop and commercialize its product candidates, Panavance’s expectations related to results of clinical trials and studies, and Panavance’s ability to obtain FDA approval of GP-2250. Forward-looking statements may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. Forward-looking statements contained in this press release are made as of this date, and Panavance undertakes no duty to update such information except as required under applicable law.
Investor Relations Contact
JTC Team, LLC
Jenene Thomas
833-475-8247
panavance@jtcir.com
