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) [1]. FGFR2 genomic alterations (e.g., fusions, mutations, amplifications) are present in at least 15% of cholangiocarcinomas [2], and FGFR3 genomic alterations are present in approximately 20% of advanced urothelial carcinomas [3], 50% of non-muscle invasive urothelial carcinomas [4], and up to 70% of upper tract urothelial carcinomas [5].

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 approximately one out of every 15,000 live births [6].

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 conduct clinical trials to evaluate the safety and efficacy of the product for multiple FGFR-driven diseases, including cancers and skeletal dysplasias.

Infigratinib remains investigational and is currently under study in a single arm, open-label Phase 2 trial for the treatment of chemotherapy-refractory cholangiocarcinoma (bile duct cancer) with FGFR2 fusions and other activating genomic alterations [7]. In an interim analysis of 71 patients in the ongoing trial with FGFR2 fusions/translocations, the confirmed overall response rate (cORR) was 27% for all patients with the potential for confirmation (n=67) and an additional 57% experienced stable disease as their best response, resulting in a disease control rate of 84%. For patients who had received one or fewer prior treatment regimens, the cORR was 39% (n=28), whereas patients who had received two or more treatment regimens had a cORR of 18%. Median progression free survival was 6.8 months and median overall survival was 12.5 months. In the interim analysis, the most common treatment-emergent adverse events (all grades) included hyperphosphatemia (73%), fatigue (49%), stomatitis (45%), alopecia (38%) and constipation (35%). Most adverse events were expected based on infigratinib’s mechanism of action. The trial remains open and is currently enrolling.

27%

confirmed ORR in patients with FGFR2 fusions*

33%

best overall response in patients with FGFR2 fusions*

84%

disease control rate (CR+PR+SD)*

6.8 mos

median progression free survival*

Data on infigratinib from a completed study in patients with metastatic urothelial carcinoma was recently published in Cancer Discovery [8]. In 67 patients with a diverse group of FGFR3 genomic alterations, infigratinib demonstrated a 25% confirmed overall response rate in a single arm, open-label, Phase 1 expansion cohort. Patients had a median progression free survival of 3.8 months and overall survival of 7.8 months. In this final analysis, the most common treatment-emergent adverse events (all grades) included hyperphosphatemia (46%), elevated creatinine (42%), fatigue (37%), constipation (37%), and anemia (36%).

*In patients with potential for confirmation (patients completed [or discontinued prior to] 6 cycles)

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

In addition to its clinical data in FGFR-driven cancer, in preclinical research, 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 had a corrective effect on pathological hallmarks of achondroplasia in a mouse model [9]. Importantly, in this research, infigratinib demonstrated greater than 2x preclinical improvement when compared to published data for previously tested interventions for achondroplasia [10, 11].

To date, infigratinib has been administered to more than 600 patients with a variety of FGFR-driven diseases in more than half a dozen clinical trials [7, 8, 12]. Infigratinib is an investigational product that has not been approved by FDA, and further evaluation of the product remains ongoing. For more information about infigratinib clinical trials, please visit www.clinicaltrials.gov. Currently, QED Therapeutics does not have a formal expanded access program in place and considers requests for expanded access only on a case-by-case basis. Inquiries regarding expanded access may be sent to info@qedtx.com. We anticipate acknowledging receipt of your message within 5 business days. Patients seeking to enroll in open clinical studies should visit www.clinicaltrials.gov for information regarding ongoing studies and current study site locations.

References

About Us

QED Therapeutics, a subsidiary of BridgeBio Pharma, is a biotechnology company focused on precision medicine for FGFR-driven diseases. Our lead investigational candidate is infigratinib, an orally administered FGFR1-3 tyrosine kinase inhibitor that has shown meaningful clinical activity in patients with chemotherapy-refractory cholangiocarcinoma FGFR2 fusions and metastatic urothelial carcinoma with FGFR3 genomic alterations. QED is also evaluating infigratinib in preclinical studies for the treatment of achondroplasia and other skeletal dysplasias. We plan to conduct further clinical trials to evaluate infigratinib in additional FGFR-driven tumor types and rare disorders.

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.

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