misetionamide (GP-2250) / Geistlich Pharma AG, Panavance Therap - LARVOL DELTA

Trial to Evaluate Safety and Tolerability of GP-2250 in Combination With Gemcitabine (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: Geistlich Pharma AG | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Jun 2026 | Trial primary completion date: Sep 2024 ➔ Jun 2026

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Panavance Therapeutics Announces Promising Misetionamide (GP-2250) Phase 1 Clinical Trial Interim Findings in Pancreatic Cancer at BIO 2025 (The Manila Times) - P1 | N=64 | NCT03854110 | Sponsor: Geistlich Pharma AG | "The Phase 1 dose escalation trial has demonstrated encouraging findings of the novel agent misetionamide (GP-2250), an inhibitor of c-MYC and NFκB, two major oncogenic transcription factors, as well as an antiangiogenic transcription factor, HIF1α, as second-line therapy in combination with gemcitabine....The combination of misetionamide and gemcitabine has been very well tolerated, with no new or exacerbated toxicities evident compared with those expected of gemcitabine alone.

P1 data • Pancreatic Cancer

Interim open-label phase 1 results of misetionamide (GP-2250): A small molecule antineoplastic targeting three major transcription factors. (ASCO 2025) - P1 | "GP-2250/gemcitabine combination therapy showed encouraging safety and tolerability and favorable PFS outcomes compared to gemcitabine alone. These promising results in a historically difficult to treat pancreatic cancer population warrant progress to later-stage studies. This study is funded by Geistlich Pharma AG."

Clinical • P1 data • Infectious Disease • Neutropenia • Oncology • Pain • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pneumonia • Respiratory Diseases • Solid Tumor • MYC

Panavance Announces New Discovery that Misetionamide Directly Inhibits Oncogenic Transcription Factor c-MYC (GlobeNewswire) - "Panavance Therapeutics Inc...announced positive data confirming misetionamide (GP-2250) directly inhibits the transcription factors c-MYC and NFkB, highlighting its potential to target various forms of cancer....In preclinical studies, misetionamide demonstrated robust efficacy in reducing tumor size and prolonging survival rates in animal models of cancers such as ovarian, pancreatic, melanoma, squamous cell, breast, and colorectal cancers. The results show that misetionamide not only hinders tumor growth but also enhances the effectiveness of existing chemotherapy treatments."

Preclinical • Breast Cancer • Colorectal Cancer • Melanoma • Ovarian Cancer • Pancreatic Cancer • Squamous Cell Carcinoma

Panavance Therapeutics Provides Update on Phase 1 Clinical Trial of Misetionamide in Pancreatic Cancer at 2024 Visceral Medicine Congress (GlobeNewswire) - P1 | N=64 | NCT03854110 | Sponsor: Geistlich Pharma AG | "Panavance Therapeutics Inc...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....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....Ongoing Phase 1 dose-selection study with final results expected in 2025."

P1 data • Pancreatic Adenocarcinoma

Mechanism and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer. (PubMed, Cancer Med) - "Taken together, our data indicate that GP-2250 exerts profound effects on tumor metabolism and, in combination with PARP inhibitors or bevacizumab, showed promising anti-tumor efficacy. These findings could have implications for the clinical development of GP-2250."

Journal • Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • HIF1A • HK2

Panavance Therapeutics Announces Foundational Publication of Misetionamide (GP-2250) in Ovarian Cancer in the Journal, Cancer Medicine (GlobeNewswire) - "Panavance Therapeutics Inc...announced publication of positive data in the peer-reviewed journal, Cancer Medicine...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."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Maintenance Therapy for Pancreatic Cancer, a New Approach Based on the Synergy between the Novel Agent GP-2250 (Misetionamide) and Gemcitabine. (PubMed, Cancers (Basel)) - "Furthermore, GP-2250 reduced the ratio of tumor-initiating CD133+ markers on the surface of PDAC cells in spheroid cultures, indicating a possible mechanism for the synergistic effect of both substances. Considering the high tolerability of GP 2250, these results may open up a new approach to maintenance therapy with GP-2250/Gemcitabine combination following nab-Paclitaxel plus Gemcitabine as first-line treatment."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD133

Maintenance Therapy for Pancreatic Cancer, a New Approach Based on the Synergy between the Novel Agent GP-2250 (Misetionamide) and Gemcitabine (Multidisciplinary Digital Publishing Institute) - "...In a PDX maintenance setting following two weeks of treatment with nab-Paclitaxel plus Gemcitabine, the combination of GP-2250 plus Gemcitabine resulted in outstanding tumor control (ATR: 79%) compared to treatment with Gemcitabine alone (ATR: 60%). Furthermore, GP-2250 reduced the ratio of tumor-initiating CD133+ markers on the surface of PDAC cells in spheroid cultures, indicating a possible mechanism for the synergistic effect of both substances."

Preclinical • Pancreatic Cancer

Trial to Evaluate Safety and Tolerability of GP-2250 in Combination With Gemcitabine (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Geistlich Pharma AG | Trial completion date: Aug 2024 ➔ Dec 2024 | Trial primary completion date: Mar 2024 ➔ Sep 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

The synergy between the agent GP-2250 and Gemcitabine as a new maintenance therapy approach for pancreatic cancer in a PDX mouse model (DKK 2024) - P1 | "In view of its high tolerability, the use of the GP-2250/ Gemcitabine combination in maintenance therapy following nab-Paclitaxel/Gemcitabine as first-line treatment appears as a highly promising drug combination therapy. 1. Buchholz M. et.al."

Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Increasing the cytotoxic effectivity of 5FU, Irinotecan and Oxaliplatin on pancreatic cancer cells through combination with the novel anticancer agent GP-2250 in vitro (DKK 2024) - "As part of a clinical Phase I trial, the substance is currently administered in combination with Gemcitabine after FOLFIRNOX treatment... The results form a solid foundation for further in vivo studies to validate the synergy and to get a first assessment of the toxicity."

Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Anti-Cancer Drugs Publishes Preclinical Data Demonstrating the Broad Antineoplastic Activity of Panavance’s Misetionamide (GP-2250) (GlobeNewswire) - "Panavance Therapeutics Inc...today announced publication of positive data in the peer-reviewed Anti-Cancer Drugs...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...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 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.'"

Preclinical • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

Antineoplastic activity of GP-2250 in-vitro and in mouse xenograft models. (PubMed, Anticancer Drugs) - "GP-2250 demonstrated cytotoxic activity in vitro and reduced the tumor volume in a variety of human cancer cell lines in a xenograft mouse model. Given these results, as well as evidence of synergism with other anticancer drugs, GP-2250 shows promise as a new therapeutic agent for treating human cancers and is being evaluated in a phase 1 dose-escalation study (NCT03854100)."

Journal • Preclinical • Oncology

International Journal of Molecular Sciences Publishes Preclinical Data of Panavance’s Misetionamide (GP-2250) in Melanoma (GlobeNewswire) - "Panavance Therapeutics Inc...today announced publication of positive data in the peer-reviewed International Journal of Molecular Sciences....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....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....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."

Preclinical • Melanoma • Oncology • Skin Cancer • Solid Tumor

In Vitro Experiments on the Effects of GP-2250 on BRAF-Mutated Melanoma Cell Lines and Benign Melanocytes. (PubMed, Int J Mol Sci) - "GP-2250 is able to downregulate the gene and protein expression of aberrant tumorigenic pathways in melanoma cell lines. Since GP-2250 is a GAPDH inhibitor, the substance may be a promising combination therapy for tumors presenting the Warburg effect, such as melanoma."

Journal • Preclinical • Cutaneous Melanoma • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • ANXA5 • BRAF • GAPDH • STAT3

Panavance to Present at the BIO Investor Forum (GlobeNewswire) - "Panavance Therapeutics Inc...announced it will present at the BIO Investor Forum on Tuesday, October 17 at 10 a.m. PT. Greg Bosch, Chairman and CEO will present an overview of Panavance and update on the development of Panavance’s lead product candidate, misetionamide, a highly selective yet broadly active cancer therapeutic with a unique mechanism of action that suppresses cancer by disrupting its energy metabolism, leading to cancer cell death through a number of validated mechanisms. A Phase 1 study is currently recruiting in pancreatic cancer. Greg will share Panavance’s recent accomplishments and its upcoming planned milestones."

Clinical data • Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Trial to Evaluate Safety and Tolerability of GP-2250 in Combination With Gemcitabine (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Geistlich Pharma AG | Trial completion date: Dec 2022 ➔ Aug 2024 | Trial primary completion date: Dec 2022 ➔ Mar 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Journal of Cellular and Molecular Medicine Publishes Preclinical Data of Panavance’s GP-2250 to treat Pancreatic Cancer (GlobeNewswire) - "Panavance Therapeutics Inc...announced publication of positive data in the peer-reviewed Journal of Cellular and Molecular Medicine in a manuscript...Results of the preclinical study showed that at the lowest dose of GP-2250 tested (250 μM), a significant decrease in ATP was apparent at 6 hours in both pancreatic cancer cell lines. The decrease in ATP preceded the loss of cell viability. A further decrease in ATP was apparent at the same time point with 500 μM of GP-2250 in both cell lines. These findings of a drug-induced deficit of ATP show an inhibition of energy metabolism by GP-2250....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."

New P2/3 trial • New P3 trial • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells. (PubMed, J Cell Mol Med) - "The upregulation of p53 concomitant with an excess of ROS supported apoptosis. Thus, the anticancer activity of GP-2250 is a result of disruption of energy metabolism and inhibition of tumour promotion by NF-κB."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BCL2 • CCND1 • GAPDH

Panavance Therapeutics Announces Publication of Encouraging Preclinical Data Evaluating GP-2250 for the Treatment of Merkel Cell Carcinoma (MCC) (GlobeNewswire) - "Results of the study showed that cell viability, proliferation and migration decreased with increasing GP-2250 doses. Flow cytometry revealed a dose response to GP-2250 in all three MCC cell lines. While the viable fraction decreased, the share of necrotic and in a smaller amount the apoptotic cells increased. Regarding Notch1, AKT, mTOR and STAT3 expression a comparatively time- and dose-dependent decrease of protein expression in the MCC13 and MCC26 cell lines was observed."

Preclinical • Merkel Cell Carcinoma • Oncology • Skin Cancer • Solid Tumor

The effect of GP-2250 on cultured virus-negative Merkel cell carcinoma cells: preliminary results. (PubMed, J Cancer Res Clin Oncol) - "The present study indicates GP-2250 having anti-neoplastic effects in MCPyV-negative tumor cells in regard to viability, proliferation, and migration. Moreover, the substance is capable of downregulating protein expression of aberrant tumorigenic pathways in MCPyV-negative MCC cells."

IO biomarker • Journal • Tumor mutational burden • Endocrine Cancer • Genetic Disorders • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • NOTCH1 • STAT3 • TMB

Oxathiazinane derivatives display both antineoplastic and antibacterial activity: a structure activity study. (PubMed, J Cancer Res Clin Oncol) - "Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Infectious Disease • Oncology • Pancreatic Cancer • Solid Tumor

Mechanisms and rational combinations with gp-2250, a novel oxathiazine derivative, in ovarian cancer (AACR 2023) - "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, and poly ADP-ribose polymerases (PARP) inhibitors. We investigated the cytotoxic effect of GP-2250 in 10 ovarian cancer cell lines and found that HRD ovarian cancer cells (e.g., Kuramochi, OVCAR4, and OVCAR8) were more vulnerable to GP-2250 than HRP ovarian cancer cells (e.g., A2780 and OVCAR5). Taken together, our data indicate that GP-2250 exerts profound effects on tumor metabolism and combination with PARP inhibitors or bevacizumab showed promising anti-tumor efficacy. These findings could have implications for the clinical development of GP-2250."

Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • HIF1A • HK2

Panavance Therapeutics Announces Positive Preclinical Data Demonstrating GP-2250 Single-Agent and Combination Activity for the Treatment of Ovarian Cancer (GlobeNewswire) - "Panavance Therapeutics...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....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."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor