Slide 1: BDTX-1535, a CNS penetrant MasterKey inhibitor of common, uncommon and resistant EGFR mutations
BDTX-1535, a CNS penetrant MasterKey inhibitor of common, uncommon and resistant EGFR mutations, demonstrates in vivo efficacy and has potential to treat patients with NSCLC harboring osimertinib-resistant mutations with or without brain metastases Matthew C Lucas, Melinda Merchant, Matthew O’Connor
Slide 2: Expanding the Reach of Precision Medicine Through the Development of Novel MasterKey Therapies
Expanding the Reach of Precision Medicine Through the Development of Novel MasterKey Therapies Addressing significant unmet need for novel precision oncology therapies for patients with genetically defined cancers with limited treatment options Uniquely de-orphaning oncogenic mutations to develop si
Slide 3: Targeting Unmet Medical Need in EGFR-mutated NSCLC
Targeting Unmet Medical Need in EGFR-mutated NSCLC Acquired Resistance to 3rd Brain Metastasis Occurrence Intrinsic Resistance to EGFR TKIs generation EGFR TKIs with NSCLC EGFR-mutant (N=200) Never 31% At diagnosis 53% On treatment 16% Offin et al., Leonetti et al., Harrison et al., Cancer 2019 Br J
Slide 4: BDTX-1535: A Brain Penetrant, Potent Inhibitor of Oncogenic EGFR Mutations
BDTX-1535: A Brain Penetrant, Potent Inhibitor of Oncogenic EGFR Mutations
Slide 5: Optimized to Address a Wide Range of Oncogenic EGFR Mutations and Variants
Optimized to Address a Wide Range of Oncogenic EGFR Mutations and Variants EGFR Mutations of Intrinsic Resistance and Acquired EGFR Variants and Mutations Found in GBM Resistance in NSCLC Anti-proliferation Ba/F3 IC50 (nM) Anti-proliferation Ba/F3 IC50 (nM) 100 100 80 80 >10-fold selectivity vs 60 6
Slide 6: BDTX-1535 Is a CNS-penetrant Inhibitor of Canonical and Drug-Resistance Mutations
BDTX-1535 Is a CNS-penetrant Inhibitor of Canonical and Drug-Resistance Mutations Erlotinib Gefitinib Afatinib Dacomitinib Osimertinib BDTX-1535 MOA Reversible Reversible Irreversible Irreversible Irreversible Irreversible CNS Kpuu (r) 0.08 0.29 -* 0.21 0.29 0.45 EGFR-WT (H292) IC50 (nM) 878 418 29
Slide 7: BDTX-1535 Achieves Excellent Kinome Selectivity and Drug Like Properties
BDTX-1535 Achieves Excellent Kinome Selectivity and Drug Like Properties ü Not a hERG inhibitor at projected clinical concentrations EGFR ü Good blood & moderate liver stability HER2 ü Good GSH T1/2 ü Low Risk for CYP Inhibition with no TDI DDR1 ü No CYP induction ü No unique human metabolites ü Wea
Slide 8: Preclinical Data Supports Opportunity in NSCLC Harboring Osimertinib Resistant C797S
Preclinical Data Supports Opportunity in NSCLC Harboring Osimertinib Resistant C797S Retains irreversible binding against Regression in Ba/F3-EGFR Regression across range of allograft C797S mutant Exon19del /C797S Mouse allograft and EGFRvII and C595F PDX models 1000nM 34nM BDTX-1535 Osimertinib Was
Slide 9: CNS Exposure, Sustained Target Engagement and TGI in Intracranial PDX Tumors
CNS Exposure, Sustained Target Engagement and TGI in Intracranial PDX Tumors Exposure in Rat Blood, Brain, CSF >24h Inhibition of pEGFR in Ba/F3 Survival increase in Intracranial after single oral dose of 30 mg/kg Allograft Tumors expressing EGFRvIII EGFRvIII PDX Tumors Single oral dosing of BDTX-15
Slide 10: Conclusions
Conclusions Black Diamond Therapeutics is Developing BDTX-1535 as a Brain Penetrant, Potent Inhibitor of Oncogenic EGFR Mutations Excellent free drug Highly efficacious in intracranial Potential to treat patients exposure in the CNS PDX tumor model with an intact with NSCLC harboring BBB and across