Black Diamond Therapeutics, Inc. · NASDAQ:BDTX
Black Diamond Therapeutics — 32nd EORTC-NCI-AACR Virtual Symposium 2020
13 slides from Black Diamond Therapeutics's conference presentation, Oct 24, 2020
Slide 1: BDTX-189, a Potent and Selective Inhibitor of Allosteric EGFR and HER2 Oncogenic Mutations
BDTX-189, a Potent and Selective Inhibitor of Allosteric EGFR and HER2 Oncogenic Mutations Elizabeth Buck, PhD 32nd EORTC-NCI-AACR Virtual Symposium; October 24–25, 2020 INV-006 1
Slide 2: MasterKey Precision Medicine; Novel Cancer Therapy Against Families of Mutations
MasterKey Precision Medicine; Novel Cancer Therapy Against Families of Mutations Allosteric EGFR and HER2 oncogenic mutations represent an undrugged opportunity Our proprietary MAP (Mutation-Allostery-Pharmacology) platform enables us to: • Identify oncogenic allosteric mutations • Aggregate these m
Slide 3: The Allosteric HER2/EGFR Mutant Oncogene Family Represents an Undrugged Opportunity
The Allosteric HER2/EGFR Mutant Oncogene Family Represents an Undrugged Opportunity for MasterKey Precision Medicine MAP Scoring: An in silico approach to reveal oncogenic spectra Dimer Mutation Interface Exclusivity Structural MAP Protein Motifs Dynamics Score Conservation Mutation Landscape NGS re
Slide 4: Allosteric EGFR/HER2 Mutations Share a Unique Activation Mechanism and Are Resistant to Current Drugs
Allosteric EGFR/HER2 Mutations Share a Unique Activation Mechanism and Are Resistant to Current Drugs Allosteric mutations share a unifying Allosteric mutations confer drug resistance activation mechanism (Current-generation inactive/nonselective inhibitors) Dimer interface EGFR WT EGFR ASV HER2 WT
Slide 5: Unique Pharmacology Imparted by Protein Allostery Necessitates Cell-Based Screening in Drug Discovery
Unique Pharmacology Imparted by Protein Allostery Necessitates Cell-Based Screening in Drug Discovery Isogenic Panel of ERBB Mutants as Screen in cellular phenotypic assays Ba/F3 Transformants Screen mutant panel in Extracellular domain cellular proliferation assay 13 mutants Counterscreen vs cells
Slide 6: Potent, selective, irreversible active site inhibitor: antiproliferative IC50
BDTX-189 Antiproliferative IC50 (nM) 1 100 1000 10 A431 H292 EGFR A763-Y764insFQEA EGFR WT EGFR A767-V769dupASV EGFR A767-V769dupSVA EGFR S768-D770dupSVD EGFR D770-N771insG EGFR D770-N771insGYN EGFR D770-P772dupDNP EGFR N771-H773dupNPH EGFR P772-H773dupPH EGFR H773-V774dupHV EGFR H773-V774insAH Exon
Slide 7: BDTX-189 Achieves a Favorable Kinase Selectivity Profile
BDTX-189 Achieves a Favorable Kinase Selectivity Profile – Improved vs Current-Generation ERBB-Targeted Agents Kinase KD, nM EGFR 0.20 HER2 0.76 ERBB3 ND ERBB4 ND RIPK2 BLK 13 RIPK2 1.2 EGFR HER2 ERBB3 ERBB4 BLK 468 kinases tested BLK, B lymphocyte kinase; EGFR, epidermal growth factor receptor; HER
Slide 8: BDTX-189 Achieves a Superior Selectivity Profile vs Current-Generation Drugs
BDTX-189 Achieves a Superior Selectivity Profile vs Current-Generation Drugs Head-to-Head Assessment in Cell-Based Assays > 100 (EGFR WT/Mutant) Targeted selectivity Fold Selectivity 10 1 Poor selectivity 0.1 Poziotinib Mobocertinib/TAK788 Osimertinib Afatinib BDTX-189 CLN-081/TAS6417 Erlotinib Muta
Slide 9: Achieves Rapid and Sustained Active Site Occupancy
BDTX-189 Achieves Rapid and Sustained Active Site Occupancy Profile Supports “Hit-and-Run” PK Strategy BDTX-189 is designed to achieve rapid and sustained BDTX-189 is designed with rapid clearance to achieve target occupancy a long biological PD effect while minimizing potential toxicities Ba/F3 HER
Slide 10: Potent, Sustained Inactivation of Multiple Allosteric ERBB Mutants In Vivo
BDTX-189 Is Differentiated by Potent, Sustained Inactivation of Multiple Allosteric ERBB Mutants In Vivo PK/PD Properties Afford Target Coverage Across a Range of IC50 Values IC50, nM HER2 S310F EGFRvIII HER2 YVMA 1.2 1.5 1.2 Fraction of Control Activity (EGFRvIII Phosphorylation) EGFRvIII (Ba/F3) F
Slide 11: Dose-Dependent Regression of Allosteric HER2 and EGFR Tumors at Well-Tolerated Doses
BDTX-189 Achieves Dose-Dependent Regression of Allosteric HER2 and EGFR Tumors at Well-Tolerated Doses Dose-dependent tumor growth inhibition and Dose-dependent tumor growth inhibition regression in engineered HER2 S310F tumors and regression in PDX models b Allosteric HER2 Tumors (HER2 S310F)a EGFR
Slide 12: BDTX-189: A Mutation Spectrum-Selective MasterKey ERBB Inhibitor
BDTX-189: A Mutation Spectrum-Selective MasterKey ERBB Inhibitor Clinical Development Is Ongoing Favorable Preclinical Toxicology Profile Strong Preclinical Activity Designed to spare EGFR WT-associated toxicities Potent and selective Spectrum activity against family of mutants Dose-dependent antica
Slide 13: Thank You
THANK YOU
Black Diamond Therapeutics — 32nd EORTC-NCI-AACR Virtual Symposium 2020 on 6ix