tuxobertinib (BDTX-189)

P1/2, N=91, Terminated, Black Diamond Therapeutics, Inc. | Completed --> Terminated; The development of BDTX-189 was discontinued by the sponsor.

P1/2, N=91, Completed, Black Diamond Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Sep 2022 | Trial primary completion date: Jun 2023 --> Sep 2022

STX-721 demonstrates EGFR exon 20 mutant selectivity approaching the selectivity of Osimertinib in EGFR T790M mutants, warranting further exploration of this potential best-in-class exon 20 inhibitor in the clinic. Ba/F3: proliferation selectivity vs. EGFR WT Human cells: proliferation selectivity (vs.

P1/2, N=91, Active, not recruiting, Black Diamond Therapeutics, Inc. | Recruiting --> Active, not recruiting | N=200 --> 91

While several small molecules have been approved (mobocertinib) or are in clinical development (e.g. CLN-081, BDTX-189) none have demonstrated meaningful CNS activity and they can be associated with treatment-limiting adverse events, including wild-type (WT) EGFR-mediated toxicities. LNG-451 potently suppressed EGFR phosphorylation in tumor tissue (e.g. 99%, 3 h post 50 mg/kg dose) but had minimal-to modest suppression of phospho-EGFR in large intestine tissue (e.g. 4.2%, 3h post 50 mg/kg dose) and skin tissue (e.g 1.9%, 3h post 50 mg/kg dose). Taken together, LNG-451 is a wild-type EGFR-sparing, CNS-penetrant EGFR Ex20ins inhibitor that is expected to provide strong anti‑tumor efficacy for patients with advanced/metastatic solid cancers harboring oncogenic EGFR exon 20 insertions with reduced WT EGFR-driven toxicities.

While several small molecules have been approved (mobocertinib) or are in clinical development (e.g. CLN-081, BDTX-189) none have demonstrated meaningful CNS activity and they can be associated with treatment-limiting adverse events, including wild-type (WT) EGFR-mediated toxicities. An ex vivo imaging analysis of the brain and spinal cords from all animals at the end of the study showed a dose-dependent decrease in the bioluminescent signal in both brain and spinal cords from mice treated with LNG-451 relative to the vehicle control animals. Taken together, LNG-451 is a CNS-penetrant, wild-type EGFR-sparing, EGFR Ex20ins inhibitor that is expected to provide strong anti‑tumor efficacy for patients with advanced/metastatic solid cancers harboring oncogenic EGFR exon 20 insertions with reduced WT EGFR driven toxicities.

P1/2, N=100, Ongoing, Black Diamond Therapeutics, Inc.

Enrollment began 1/2020. Research Funding: Black Diamond Therapeutics