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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.

An international research team has discovered a new way to effectively treat cancer, by using nutrients to reactivate suppressed metabolic pathways in cancer cells. An international research team has discovered a new way to effectively treat cancer, by using nutrients to reactivate suppressed metabolic pathways in cancer cells. The researchers used a common amino acid, tyrosine, packaged as a nanomedicine, to change the metabolism of melanoma, a deadly skin cancer, and prevent cancer growth. Australia has the highest rate of skin cancer in the world. This new approach could be combined with current therapies to better treat melanoma. The technique also has the potential to treat other types of cancer. The study, Nutrient-delivery and metabolism reactivation therapy for melanoma, was led by Professor Wenbo Bu from Fudan University and Professor Dayong Jin from the University of Technology Sydney, and recently published in the journal Nature Nanotechnology. Tyrosine has limited bioavailability in living organisms. However, the researchers used a new nanotechnology technique to package it into tiny particles called nanomicelles, which are attracted to cancer cell membranes, and break down easily, boosting absorption. The research team then tested the innovative treatment in mice and in human-derived melanoma cells in the lab and found that the tyrosine nanomicelles reactivated dormant metabolic pathways, triggered melanin synthesis, and inhibited tumour growth. "Uncontrolled rapid growth is a key feature that distinguishes cancer cells from normal cells. In cancer cells some metabolic pathways are over-activated, and others are suppressed, to create the environment necessary for rapid spread," said Professor Jin. "While a few metabolism-based drugs for cancer have been developed previously, such as aromatase inhibitors impeding estrogen synthesis in breast cancer and HK2 inhibitors targeting glycolysis in various cancers, these work by suppressing over-activate metabolic pathways," he said. "Our research shows for the first time that cancer can be stopped by reactivating metabolic pathways that are dormant. And this can be done using simple nutrients, such as amino acids, sugars, and vitamins, which are safe, readily available and well tolerated," said Professor Bu. Different types of cancer will respond to different nutrients. Melanoma cells develop from melanocytes -- skin cells that produce melanin. Tyrosine is needed to produce melanin and it can stimulate melanin production, hence its effectiveness with melanoma. The reactivation of melanin synthesis forces the melanoma cell to reduce glycolysis, the process of converting sugar to energy, which is believed to be the mechanism for its anti-cancer effect. Melanoma cells are also susceptible to heat stress. The researchers found that by combining tyrosine nanomicelle treatment with near-infrared laser treatment, they were able to eradicate melanoma in mice after six days and it did not reoccur during the study period. The findings suggest a promising a new frontier in the use of nanomedicine for cancer therapy.

J&J’s asset works by delivering an actinium-based radioligand which emits high-energy short-range alpha particles. Image credit: Shutterstock/Jurik Peter. Johnson & Johnson ’s (J&J) prostate cancer radiotherapy JNJ-6420 outlook was hampered by safety issues that resulted in four deaths in a Phase I trial, despite the drug demonstrating promising efficacy in treating prostate cancer. Recommended Buyer's Guides Buyer's Guide Leading Guide to Compliance Software for the Pharmaceutical Industry Buyer's Guide Top Guide for Drug Delivery Systems The safety and efficacy results were announced as part of an abstract submitted to the American Society of Clinical Oncology (ASCO) Annual Meeting ahead of a data presentation at the event, which is scheduled to take place from 31 May to 4 June. JNJ-6420 is an anti-hK2 antibody-based targeted radiotherapy that works by delivering an actinium-based radioligand. This payload emits high-energy short-range alpha particles that target cancer cells. In the Phase I trial (NCT04644770), out of 57 patients who had intravenously received JNJ-6420 at 150 μCi or higher, 35 had Grade 3 or higher treatment-emergent adverse events (TEAEs), with 21 experiencing serious treatment-emergent adverse events (TEAE). The abstract highlighted thrombocytopenia and interstitial lung disease (ILD) as TEAEs of note due to repeated dosing. Nine patients left the trial due to treatment-related adverse events (TRAE), and four TRAEs resulted in death. See Also: Agios sells vorasidenib US royalties for $905m BIOSECURE “grandfather” amendment softens impact of US-China trade ban The radiotherapy’s safety and preliminary clinical were evaluated in the Phase I study, along with determining doses for progression into Phase II studies. According to ClinicalTrials.gov , metastatic castration-resistant prostate cancer patients who have previously undergone treatment with at least one prior androgen receptor targeted therapy were enrolled in the trial. Whilst the drugmaker deals with the apparent high toxicity, the abstract reported “prolonged clinical, biochemical, and radiographic responses” in patients receiving the drug at 150 μCi and higher. Out of the 57 patients, three had a confirmed objective response rate, including one complete response and two partial responses. Data demonstrated a PSA50 response rate of 45.6%, a measure of prostatic-specific antigen. This biomarker is important in prostate cancer as a PSA response is associated with prolonged overall survival. Radiotherapy dollars J&J is part of a growing number of pharma companies pursuing radiopharmaceutical candidates. Bristol Myers Squibb announced its arrival on the scene with a $3.6bn acquisition of RayzeBio – the latter’s assets also use actinium-based payloads. Eli Lilly followed its $1.4bn Point Biopharma deal last year with a $1.1bn partnership with Aktis Oncology just last week. AstraZeneca entered the arena in March 2024 with a $2bn takeover deal for Fusion Pharmaceuticals . Novartis is spearheading the field with its lutetium-based prostate cancer treatment Pluvicto. The drug generated sales of $980m in 2023 and is predicted to surpass the $4.3bn mark by 2030, according to GlobalData’s Pharma Intelligence Centre. GlobalData is the parent company of Pharmaceutical Technology. The big pharma doubled down on this space earlier this month, spending a potential $1.7bn to acquire Mariana Oncology.