BERWYN, PA — Panavance Therapeutics Inc. announced the recent publication of positive data from a preclinical study evaluating GP-2250 for the treatment of pancreatic neuroendocrine carcinoma. The manuscript titled, “New Therapy Options for Neuroendocrine Carcinoma of the Pancreas—The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo1,” was published in the peer-reviewed journal, Cancers.
GP-2250 is the Company’s broadly active, tumor cell selective cancer therapeutic with a unique mechanism of action that, as demonstrated in preclinical research, suppresses cancer cells by disrupting their energy metabolism—bringing about cancer cell death.
“Neuroendocrine carcinoma of the pancreas is an aggressive form of neuroendocrine tumors which continue to increase in incidence but not in survival rates. There remains an urgent, unmet need to establish new therapy regimens and concepts with better tolerability. This study was the first to evaluate the effects of GP-2250 on pancreatic neuroendocrine tumors and we are very pleased with the encouraging results demonstrated. While we are currently evaluating GP-2250 in a Phase 1 clinical trial for the treatment of pancreatic ductal adenocarcinoma, these results add valuable insight to our growing body of data as we advance our clinical program,” commented Greg Bosch, Chairman and CEO of Panavance Therapeutics. “We believe GP-2250 is well-positioned as a potential effective therapy in oncology and are dedicated to advancing its clinical development as quickly and efficiently as possible.”
For this preclinical study conducted by a research team at St. Josef-Hospital, Ruhr-University Bochum, with support from the Company, the cytotoxic effects of monotherapy GP-2250 and gemcitabine, as well as the combination therapy of both, were studied in vitro using an MTT-assay on the QGP-1 and BON-1 cell lines, along with in vivo studies on a murine xenograft model of QGP-1 and a patient-derived xenograft model (PDX) of Bo99. In vitro, both monotherapy gemcitabine and GP-2250 showed a dose-dependent cytotoxicity.
“We are very pleased with the results from this study. In addition to the effects of GP-2250 and gemcitabine in these models, chemoresistance to gemcitabine is a well-described problem, developing within weeks after initiation. The treatment of pancreatic neuroendocrine carcinoma with the combination of GP-2250 and gemcitabine resulted in a renewed response following a treatment break, while monotherapy with gemcitabine led to the development of resistance after 30 days of treatment. Overcoming this hurdle presents a substantial opportunity towards providing patients with a potential treatment option that improves both the survival and quality of life for patients,” added Prof. Dr. med. Chris Braumann, Chief of General, Visceral & Vascular Surgery, University of Duisburg-Essen, Germany and Scientific Advisor to Panavance.
Results of the study showed that GP-2250 demonstrated strong synergism in combination with gemcitabine, and the combination therapy proved to be highly effective in vitro and in vivo on both an established cell line and a patient-derived xenograft model of pancreatic neuroendocrine tumors. While the monotherapy with gemcitabine achieved stable disease in a patient-derived xenograft model and progressive disease in QGP-1 cells, the combination therapy of GP-2250 and gemcitabine even led to partial response according to the RECIST and thereby led to a significant decrease in tumor volume in comparison to the monotherapy with gemcitabine (p < 0.001). No development of secondary resistances was observed for the combination treatment.
Results are consistent with the findings of prior studies involving pancreatic ductal adenocarcinoma cells and the combination therapy with gemcitabine and GP-2250. This additional analysis suggests that GP-2250 may be valuable not only in pancreatic ductal adenocarcinoma but also in pancreatic neuroendocrine tumors.
Panavance is initially advancing development of GP-2250 for the treatment of pancreatic ductal adenocarcinoma cancer, and has active preclinical studies in numerous other cancers including ovarian cancer. Additionally, the Company believes GP-2250 has the potential for expanded use in several areas of oncology treatments and potentially other clinical states.
1 Buchholz M, Strotmann J, Majchrzak-Stiller B, Hahn S, Peters I, Horn J, Müller T, ö-Umlaut P, Uhl W, Braumann C. New Therapy Options for Neuroendocrine Carcinoma of the Pancreas—The Emergent Substance GP-2250 and Gemcitabine Prove to Be Highly Effective without the Development of Secondary Resistances In Vitro and In Vivo. Cancers. 2022; 14(11):2685. https://doi.org/10.3390/cancers14112685
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