Targeting FGFR for rare pediatric diseases and cancer.
Journal of Clinical Oncology; Javle, M. et al.; 2017
QED Therapeutics is targeting FGFR for patients with fusion-driven cancers and pediatric skeletal dysplasias.
Science
Fibroblast growth factor receptors or FGFRs, are tyrokine kinase receptors on the surface of cells that link growth factor signalling with the downstream PI3K/AKT and MAPK pathways to regulate cellular proliferation and survival. The FGFR family has four members (encoded by the FGFR1-4 genes).
Overactivity of these pathways is a critical contributor to many forms of cancers, most notably cholangiocarcinoma (bile duct cancer) and urothelial carcinoma (bladder cancer). FGFR2 fusions are present in 13% of cholangiocarcinomas, and FGFR3 mutations are present in 64% of non-muscle invasive urothelial carcinomas.
In achondroplasia, activating mutations in FGFR3 suppress proliferation and maturation of growth plate chondrocytes, leading to shortened bones. Complications can be severe, with an increased risk of death during infancy and the potential for compressed bone formation that can lead to nerve compression. Achondroplasia affects one out of every 20,000 live births.
ABOUT INFIGRATINIB (BGJ398)
Infigratinib (BGJ398) is a best-in-class, FGFR-selective, orally-administered investigational new drug in clinical development for the treatment of patients with FGFR-driven cancers. QED Therapeutics acquired the worldwide rights to infigratinib from Novartis for use in all applications and will develop the compound as a treatment for multiple FGFR-driven diseases, including cancers and achondroplasia.
Infigratinib is currently under study in a Phase 2 trial for the treatment of chemotherapy-refractory cholangiocarcinoma (bile duct cancer) with FGFR-fusions. In an early analysis of 63 patients in the ongoing trial, infigratinib demonstrated a 30.2% overall response rate. Of the subset of patients with FGFR2 fusions, there was a 39.6% overall response rate. To date, over 350 patients have been treated with infigratinib in numerous clinical trials. For more information about infigratinib clinical trials, please visit www.clinicaltrials.gov.
For information on the clinical trial currently enrolling in cholangiocarcinoma, please email DHill@QEDTx.com.
In addition to its clinical data in FGFR-driven cancer, infigratinib has demonstrated potential in pediatric skeletal dysplasias, including achondroplasia. In the early work published in the Journal of Clinical Investigation, researchers demonstrated that low doses of infigratinib corrected pathological hallmarks of achondroplasia in mouse models. Importantly, by treating the disease at its source, infigratinib demonstrated greater than 2x improvement over any previously tested intervention for achondroplasia.
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QED IS A MEMBER OF THE BRIDGEBIO FAMILY
BridgeBio is a clinical-stage biotech company developing novel, genetically targeted therapies to improve the lives of patients. The BridgeBio approach combines a traditional focus on drug development with a unique corporate model, allowing rapid translation of early stage science into medicines that treat disease at its source. Founded in 2015 by a team of industry veterans, the company has built a robust portfolio of fifteen transformative assets, each housed in its own subsidiary, ranging from pre-clinical to late stage development in multiple therapeutic areas including oncology, cardiology, dermatology and endocrinology. The company’s focus on scientific excellence and rapid execution aims to translate today’s discoveries into tomorrow’s medicines.
