NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.
NBTXR3 is being evaluated primarily in locally advanced head and neck squamous cell carcinoma (HNSCC). A Nanobiotix-sponsored phase 1 dose escalation and dose expansion study has produced consistently favorable safety data and early signs of efficacy, and a phase 3 global registrational study is planned to launch in 2021.NBTXR3 is also being studied by Nanobiotix in an immuno-oncology development program, beginning with a Nanobiotix-sponsored phase 1 clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.
Head and neck cancers include cancers of the oral cavity, pharynx, larynx, paranasal sinuses and nasal cavity, and salivary glands. Tobacco use, heavy alcohol use, human papillomavirus (HPV) infection, Epstein-Barr virus infection, poor oral hygiene and certain industrial exposures increase the risk of H&N cancer. The five-year survival rate for patients with oral and oropharyngeal caner is approximately 65%. In China, there are approximately 140,000 newly diagnosed head and neck cancer patients each year.
LianBio plans to initially develop NBTXR3 in China for the treatment of HNSCC. LianBio intends to participate in Nanobiotix’s planned global Phase 3 registrational study evaluating NBTXR3 for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy. LianBio also plans to join future Nanobiotix registrational studies across indications and therapeutic combinations, including potentially immunotherapy.
Infigratinib (BGJ398) is an investigational, orally administered FGFR1-3 tyrosine kinase inhibitor in development for the treatment of patients with FGFR-driven diseases, including cholangiocarcinoma (bile duct cancer) and urothelial carcinoma (bladder cancer).
Genetic aberrations (e.g., fusions/translocations, mutations, and amplifications) involving fibroblast growth factor receptors (FGFRs) occur in approximately 7% of cancers, most notably cholangiocarcinoma (bile duct cancer, or CCA) and urothelial carcinoma (bladder cancer) as well as gastric cancer.
Currently, there are an estimated 78,000 newly diagnosed CCA and an estimated 694,000 newly diagnosed cases of gastric cancer in mainland China. FGFR2 fusion occurs in ~10%-16% of cholangiocarcinoma tumors globally and FGFR2 amplification occurs in about ~5% of gastric cancers in Chinese patients.
LianBio is pursuing the study of infigratinib in first-line cholangiocarcinoma in mainland China as part of QED’s PROOF global Phase 3 study. LianBio is also undertaking a Phase 2a study of infigratinib in gastric cancer and exploratory studies for other FGFR-driven tumors.
BBP-398 is an allosteric SHP2 inhibitor designed to inhibit wild-type SHP2, offering the potential to treat the variety of tumors that rely on SHP2 activity for proliferation and survival. SHP2 binds to RTKs and immune checkpoint receptors to regulate their signaling.
Signaling pathways that regulate cell proliferation and survival are often altered in cancer. SHP2 is a protein tyrosine phosphatase that positively regulates RTK MAPK signaling, one of the most important pathways in promoting tumor growth in many types of cancer and upregulation of MAPK signaling is a common mechanism of resistance to targeted therapies. Additionally, SHP2 has a role in regulating immune checkpoint inhibition, whereby tumors can suppress patients’ anti-tumor immune responses. Thus, targeting SHP2 may offer a potential new approach to manage these difficult to treat cancers.
Treatment-resistant and other difficult to treat cancers with mutations in the MAPK pathway are highly prevalent in mainland China and other Asian markets. Non small cell lung cancer (NSCLC) and other lung cancers, colorectal and pancreatic cancers together account for over 40% of tumors in China and mutations such as EGFR, KRAS and BRAF occur to varying degrees in these tumor types. For example, EGFR mutations occur in ~50% of Chinese lung cancers, but only ~20% of US lung cancers. Although KRAS mutations occur in only ~38% of Chinese colorectal cancers compared to ~56% of US colorectal cancers; the total number of patients impacted in China exceeds that of the US given the large population.
Lianbio is undertaking Phase 1b combo escalation studies in China for BBP-398 in combination with various agents.