Bridge Biotherapeutics Completes Preclinical Poster Presentation of 'BBT-207' at AACR

At the 2022 American Association for Cancer Research (AACR) Annual Meeting held in New Orleans, USA, a representative from Bridge Biotherapeutics is explaining the preclinical data of BBT-207.

[Asia Economy Reporter Chunhee Lee] Bridge Biotherapeutics announced on the 13th that it has unveiled the preclinical study results of its 4th-generation non-small cell lung cancer (NSCLC) treatment candidate ‘BBT-207’ for the first time on the international stage at the 2022 American Association for Cancer Research (AACR) Annual Meeting held in New Orleans, USA.

On the 12th (local time), Bridge Biotherapeutics presented key preclinical data from cell and animal experiments through a poster session, focusing on ▲ the inhibitory effect of BBT-207 on C797S-positive double mutations based on cell and animal studies ▲ pharmacokinetic evaluation results of BBT-207 in animal models, and introduced the tumor suppression efficacy of BBT-207 targeting C797S-positive double mutations as well as future development strategies.

BBT-207 is being developed as a novel epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that targets C797S-positive double mutations, which arise as resistance after treatment with 3rd-generation EGFR inhibitors such as Osimertinib (brand name ‘Tagrisso’) in NSCLC patients. It is also the first development candidate discovered independently by Bridge Biotherapeutics.

According to cell-based drug efficacy evaluation results, BBT-207 showed competitive inhibitory effects against double mutations including the C797S mutation, such as ‘DC (Del19/C797S)’ or ‘LC (L858R/C797S)’, which appear as resistance when 3rd-generation NSCLC drugs are used as first-line treatments, compared to existing drugs. In vitro experiments measuring the IC50 value?the drug concentration required to reduce EGFR phosphorylation activity related to cancer growth by half?showed that the IC50 values of Osimertinib for DC and LC double mutations including C797S were 304.4 nM and 573.7 nM, respectively, whereas BBT-207 showed an IC50 of 0.8 nM for both, indicating inhibitory effects on C797S double mutations at relatively lower concentrations. This EGFR phosphorylation inhibitory effect of BBT-207 was also confirmed to be competitive against C797S-positive double mutations compared to existing treatments in experiments using Ba/F3 cell lines expressing EGFR activating mutations.

Meanwhile, the inhibitory effect of BBT-207 on C797S-positive double mutations confirmed through cell-based experiments was further substantiated by tumor size observations over the dosing period in animal experiments. In animal models induced with LC including C797S, the duration of drug response was observed, confirming that BBT-207 exhibited dose-proportional antitumor efficacy. When BBT-207 was orally administered once daily at a maximum dose of 40 mg/kg, antitumor efficacy was maintained for more than two weeks. Additionally, BBT-207 demonstrated higher antitumor efficacy compared to Osimertinib against T790M-positive double mutations ‘DT (Del19/T790M)’ and ‘LT (L858R/T790M)’, as well as two oncogenic mutations (Del19, L858R), suggesting its potential for development as an initial treatment for NSCLC.

The presentation also disclosed the pharmacokinetic evaluation of BBT-207 in animal models. After a single dose of BBT-207 in various animal models including dogs and monkeys, the blood concentration of the drug was monitored, showing that blood drug exposure above the IC50 level was maintained for more than 24 hours, providing pharmacokinetic evidence supporting once-daily dosing of BBT-207.

Jimmy Jin, Vice President and Head of Discovery Biology at Bridge Biotherapeutics, stated, “As the global use of 3rd-generation targeted therapies for NSCLC treatment is gradually expanding, the demand for new drugs that can address various resistance cases such as double mutations is increasing. Based on the differentiated drug efficacy profile of BBT-207 compared to BBT-176, as presented at AACR, we will strive to provide effective NSCLC treatment solutions that inhibit a wider range of resistance mutations as soon as possible.”

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