Bridge Biotherapeutics Files IND for Lung Cancer Drug Targeting EGFR Resistance Mutation

NEW YORK – Bridge Biotherapeutics said on Thursday that the company filed an Investigational New Drug Application with both the US Food and Drug Administration and the Ministry of Food and Drug Safety in Korea in order to start clinical studies of its targeted lung cancer drug candidate BBT-176.

The drug is designed to tackle EGFR C797S resistance mutations that arise in NSCLC patients after treatment with third-generation tyrosine kinase inhibitors (TKIs).

Non-small cell lung cancer (NSCLC) accounts for over 80 percent of lung cancers. Mutations that disrupt the normal functions of the epidermal growth factor receptor (EGFR) are well-known cancer drivers. TKIs targeting these EGFR mutations have improved treatment outcomes for NSCLC patients compared to chemotherapy. But most patients who respond to TKIs eventually develop resistance. 

One of the more common resistance mutations is EGFR T790M. A few years ago, the FDA approved osimertinib (AstraZeneca's Tagrisso) for metastatic lung cancer patients who had stopped responding to an EGFR inhibitor due to a T790M mutation. Subsequently, the agency also approved osimertinib for the front-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. 

However, the EGFR C797S mutation has emerged as a common mechanism of acquired resistance to third generation TKIs. For example, the p.C797S mutation has been observed in 22 to 40 percent of osimertinib-treated patients. The C797S mutation was also reported to mediate resistance to other third generation TKIs, according to a study published in Oncotarget. 

BBT-176 has shown strong antitumor efficacy in xenograft models with C797S triple mutations: Del19/T790M/C797S and L858R/T790M/C797S. It also has demonstrated promising activity in combination with anti-EGFR antibodies. 

Bridge Biotherapeutics plans to start dose-escalation studies in Korea next year, then expand clinical studies across Korea and the US. The Phase I/II study in NSCLC patients will gauge the safety, tolerability, and efficacy of the drug candidate.  

BBT-176 was discovered by the Korea Research Institute of Chemical Technology and was licensed to Seongnam, South Korea-based Bridge Biotherapeutics in December 2018.