GAPDH

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.

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. For more information, please visit panavance.com and connect with the Company on Twitter, LinkedIn, and Facebook. ________________________________________ 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. Corporate and Investor Relations Contact Lisa DeScenza LaVoieHealthScience (978) 395-5970 ldescenza@lavoiehealthsceince.com Media Contact Sara Krane LaVoieHealthScience (617) 865-2197 skrane@lavoiehealthscience.com

Misetionamide is effective in targeting and killing BRAF-mutated melanoma cells while preserving normal cellsBRAF-mutated melanoma accounts for approximately 50% of all melanomas BERWYN, PA, Nov. 21, 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 patients, today announced publication of positive data in the peer-reviewed International Journal of Molecular Sciences in a manuscript titled, “In Vitro Experiments on the Effects of GP-2250 on BRAF-Mutated Melanoma Cell Lines and Benign Melanocytes.”1 The publication by Gambichler, et al. (2023) details the anti-tumor activity of the GAPDH inhibitor misetionamide (GP-2250) in BRAF-mutated melanoma cell lines and benign melanocytes. Mutated BRAF is a potent oncogene involved in sending signals inside cells which are involved in directing cell growth and is overexpressed in melanomas, non-small cell lung cancer, and other tumor types. 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.2 This study demonstrated that misetionamide may be a promising add-on therapy in BRAF-mutated melanomas, which account for approximately 50% of all melanomas. “Given the anti-tumor activity observed in misetionamide as recently published from our studies in Merkel cell carcinoma cells as well as in cutaneous squamous cell carcinoma cell lines, I was eager to study the impact in BRAF-melanoma due to its GAPDH inhibition. The results demonstrated that misetionamide is able to downregulate the gene and protein expression of aberrant tumorigenic pathways in melanoma cell lines and could represent a promising therapy for tumors such as melanoma,” said Prof. Thilo Gambichler, former Head of the Skin Cancer Center of the Ruhr-University Bochum. This research was conducted at Skin Cancer Center Ruhr-University, Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Germany with support from the Company. Results of this preclinical study showed misetionamide has anti-neoplastic effects in BRAF-mutated melanoma cell lines regarding tumor cell viability, proliferation, and apoptosis/necrosis. These findings also extend the mechanism of action activity of misetionamide to include STAT, COX2, and NOTCH 1,2, and 3 in melanoma cells in addition to the known effects on GAPDH, Hexokinases, NFkB, and others. The team studied three melanoma cell lines and one primary melanocyte cell line (Ma-Mel-61a, Ma-Mel-86a, SH-4, and ATCC-PCS-200-013, respectively) which were exposed to different misetionamide doses. All three melanoma cell lines (Ma-Mel-62a, Ma-Mel-86a, SH-4) showed a dose-dependent response to misetionamide during BrDU testing and the MTT viability assays, whereas proliferation as well as viability were drastically reduced by a misetionamide concentration of 500 μmol/L. “We are very excited to see the cancer cell killing benefits of misetionamide demonstrated in this study. These results further broaden the mechanism of action into yet another potential oncology target in BRAF-mutated melanoma. The high incidence of BRAF-mutated melanoma of approximately 50% indicates that it could be an attractive therapeutic target in addition to the company’s current focus on pancreatic and ovarian cancers,” said Greg Bosch, Chairman and CEO. About Panavance TherapeuticsPanavance 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 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 ContactSara KraneLaVoieHealthScience(617) 865-2197skrane@lavoiehealthscience.com ________________________________________1Gambichler, Thilo & Harnischfeger, Friederike & Skrygan, Marina & Majchrzak-Stiller, Britta & Buchholz, Marie & Müller, Thomas & Braumann, Chris. (2023). In Vitro Experiments on the Effects of GP-2250 on BRAF-Mutated Melanoma Cell Lines and Benign Melanocytes. International Journal of Molecular Sciences. 24. 15336. 10.3390/ijms242015336. 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.