TARGETING FGFR FOR CANCER AND RARE PEDIATRIC DISEASES.
QED Therapeutics is targeting FGFR for patients with FGFR-driven cancers and pediatric skeletal dysplasias.
Science
Fibroblast growth factor receptors, or FGFRs, are tyrosine kinase receptors on the surface of cells that link growth factor signaling 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 in the FGFR pathway can be a critical contributor to many forms of cancers, most notably cholangiocarcinoma (cancer of the bile ducts of the liver) and urothelial carcinoma (cancer of the lining of the bladder). FGFR2 genomic alterations (e.g., fusions, mutations, amplifications) are present in approximately 15% of cholangiocarcinomas, and FGFR3 genomic alterations are present in approximately 25% of advanced urothelial carcinomas, 50% of non-muscle invasive urothelial carcinomas, and up to 70% of upper tract 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 altered bone formation that can lead to nerve compression. Achondroplasia affects one out of every 20,000 live births.
ABOUT INFIGRATINIB (BGJ398)
Infigratinib (BGJ398) is an orally administered, FGFR1-3-selective tyrosine kinase inhibitor 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 FGFR2 fusions and other activating genomic alterations. In an interim analysis of 63 patients in the ongoing trial, infigratinib demonstrated a 24% confirmed overall response rate. In the subset of patients with FGFR2 fusions, there was a 30% confirmed overall response rate. The median progression free survival in the group was 6.7 months.
30%
confirmed ORR in patients with FGFR2 fusions
24%
confirmed ORR in total population
76%
disease control rate (CR+PR+SD)
6.7 mos
median progression free survival
Data on infigratinib in patients with metastatic urothelial carcinoma was recently published in Cancer Discovery. In 67 patients with a diverse group of FGFR3 genomic alterations, infigratinib demonstrated a 25% confirmed overall response rate. Patients had a median progression free survival of 3.8 months and overall survival of 7.8 months.
25%
confirmed ORR in patients with FGFR genomic alterations
42%
best overall response in total population
64%
disease control rate (CR+PR+SD)
3.8 mos
median progression free survival
To date, over 400 patients have been treated with infigratinib in numerous clinical trials with a variety of FGFR-driven diseases. For more information about infigratinib clinical trials, please visit www.clinicaltrials.gov.
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 a mouse model. Importantly, by treating the disease at its source, infigratinib demonstrated greater than 2x preclinical improvement over any previously tested intervention for achondroplasia.
Publications
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 nineteen 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.
