Misetionamide

Misetionamide-gemcitabine combination demonstrates very good safety profile and potential therapeutic benefit in the challenging treatment of pancreatic adenocarcinoma Interim results show ~40% of patients achieved either a partial response or stable disease Ongoing Phase 1 dose-selection study with final results expected in 2025 BERWYN, PA, Oct. 09, 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 the presentation of interim data from its Phase 1 clinical study evaluating misetionamide (GP-2250) in combination with gemcitabine at the 2024 Visceral Medicine Congress in Leipzig, Germany. This open label, single arm, multicenter Phase 1 dose escalation clinical trial is enrolling patients with advanced unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC) as a second line therapy for patients who have previously received a first line 5FU containing regimen (e.g. FOLFIRINOX/NALIRIFOX). The study is underway, and this interim data presented includes 49 patients across 11 cohorts. Goals are to establish safety, tolerability, and preliminary efficacy. The safety profile to date has shown zero grade ≥3 adverse events in an initial monotherapy treatment. During the combination therapy with gemcitabine, a total of 5 grade 3 events, and a total of 10 grade 4 events have been observed with all definitely attributed to gemcitabine, and one possibly attributed to misetionamide. The progression free survival of patients treated with the misetionamide-gemcitabine combination compares favorably to historical comparison to gemcitabine alone. There have been 6 partial responders (>30% tumor reduction) thus far including one partial response patient who remained on study 24 months. Anup Kasi, MD, MPH, Associate Professor, Medical Oncology, University of Kansas Cancer Center and primary investigator for the ongoing Phase 1 clinical trial, presented an update at the conference on the clinical trial data to date. “Based on the synergistic effects of misetionamide in combination with gemcitabine, with approximately 40% of patients achieving either a partial response or stable disease, and the degree of tumor regression by this drug combination, compares favorably to historical results with gemcitabine alone. Data from this interim update of the ongoing trial, including initial efficacy together with a very acceptable safety and tolerability profile, support the promise of the misetionamide-gemcitabine combination as a potential new option for the treatment of pancreatic cancer patients,” said Dr. Kasi. “We are pleased to share, for the first time, an interim look at the data from our ongoing Phase 1 dose escalation study. The trial is now at cohorts where the dose levels are in the range (on a mg/kg basis) where effectiveness was observed in the preclinical models. We continue to focus on completing the Phase 1 study with 4 US clinical trial sites and look forward to providing further clinical data updates in 2025,” said Greg Bosch, Chairman and CEO. About Panavance TherapeuticsPanavance 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 misetionamide and the oncology business. Misetionamide is a broadly active small molecule with a unique mechanism of action that inhibits two oncogenic transcription factors, c-MYC and NFκB. Acting through c-MYC, misetionamide selectively disrupts the energy metabolism of cancer cells leading to cancer cell death. Through NFκB inhibition, misetionamide inhibits cancer cells’ ability to proliferate and survive. This mechanism makes misetionamide an attractive tumor cell selective agent. The Company plans to initiate a clinical trial 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. Corporate and Investor Relations Contact Lisa DeScenzaLaVoieHealthScience(978)-395-5970ldescenza@lavoiehealthscience.com Media ContactEla WangLaVoieHealthScience(617)-582-3091ewang@lavoiehealthscience.com

Misetionamide demonstrated significant single agent activity and synergy with either PARP inhibitors (PARPi) or bevacizumab in ovarian cancer preclinical studiesProfound 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. Corporate and Investor Relations Contact Lisa DeScenzaLaVoieHealthScience(978) 395-5970ldescenza@lavoiehealthsceince.com Media ContactEla WangLaVoieHealthScience(617)-582-3091 ewang@lavoiehealthscience.com________________________________________ 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.