Bridge Biotherapeutics, Inc. announced that the preclinical data poster of BBT-207 was unveiled at the American Association for Cancer Research (AACR) 2022 being held from April 8-13, 2022. BBT-207, a novel fourth-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) currently under IND-enabling preclinical development, is the company's first internally discovered drug candidate with potent activity and efficacy against a broad range of EGFR mutations in non-small cell lung cancer (NSCLC), including C797S double mutations which arise after third-generation EGFR TKI treatment. During the poster presentation, the company highlighted the potent anti-tumor efficacy of BBT-207, observed through both in-vitro and in-vivo studies.

Biochemical and cellular in-vitro efficacy data showed that BBT-207 is highly potent against EGFR C797S double mutations inclusive of Del19/C797S (DC) and L858R/C797S (LC) as well as driver mutations including Del19 and L858R. The results obtained from the in-vitro biochemical study demonstrated that the IC50 for EGFR tyrosine kinase inhibition activity was achieved at 0.8 nM against DC and LC double mutations, while Osimertinib showed 304.4 nM and 573.7 nM. Further, an in-vitro study utilizing Ba/F3 cell lines showed that BBT-207 is mutant selective and has minimal effect on wild-type EGFR.

The poster also highlighted the pharmacokinetics (PK) data of BBT-207 in animal models, which showed that the plasma concentrations of the drug candidate remained above the IC50 (0.7-11.8 ng/mL) and IC90 values (5.2-39.9 ng/mL, unpublished) for triple, double, and single mutations in Ba/F3 cell lines. In addition, in-vivo efficacy studies have shown that BBT-207 boasts robust efficacy and induced tumor regressions over 14 days in both single (driver) mutations and C797S double mutations, when dosed at 40mg/kg QD. Further, BBT-207 demonstrated dose dependent tumor regression efficacy against T790M double mutations, which indicates the potential of BBT-207 as a broad-spectrum frontline treatment for NSCLC.

Bridge Biotherapeutics is also developing BBT-176, a fourth-generation EGFR TKI candidate that is designed to inhibit C797S triple mutations. As third-generation EGFR TKIs, such as Osimertinib, have emerged as first-line treatments for EGFR-mutant NSCLC, Bridge Biotherapeutics has reinforced its oncology pipelines by nominating BBT-207 in November 2021, as the first internally-discovered EGFR TKI inhibiting C797S double mutations. Armed with BBT-176 and BBT-207, the company aims to offer NSCLC patients comprehensive treatment solutions.