Black Diamond Therapeutics, Inc. · NASDAQ:BDTX
Black Diamond Therapeutics — Investor Presentation (April 2022)
38 slides from Black Diamond Therapeutics's investor presentation, Apr 25, 2022
Slide 1: Pioneering the Development of MasterKey Therapies
1 Black Diamond Therapeutics, Inc. Pioneering the Development of MasterKey Therapies APRIL 2022
Slide 2: Important Notice and Disclaimers
2 Important Notice and Disclaimers This presentation contains “forward - looking statements” of Black Diamond Therapeutics, Inc . (“Black Diamond,” “we” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995 . These forward - looking statements include, but are not limi
Slide 3: Black Diamond Therapeutics Overview
Black Diamond Therapeutics Overview
Slide 4: Proprietary MAP drug discovery engine overview
4 Our proprietary MAP drug discovery engine is designed to: • Predict and validate novel oncogenic mutant families from population level tumor genomics • Pioneer mutant family conformation - based MasterKey drug design • Provide opportunities beyond oncology and small molecules MasterKey therapies a
Slide 5: MasterKey Approach Designed to Address Overlooked Mutation Families
5 Black Diamond’s MasterKey Approach Designed to Address Overlooked Mutation Families Classic/Current Approach: Targeting active site kinase domain mutations With expanding genetic profiling of cancer patients via Next Generation Sequencing (NGS) Mutation families yield significant market opportunit
Slide 6: Wholly-Owned Novel MasterKey Precision Medicines
6 Wholly - Owned Novel MasterKey Precision Medicines Target Drug Candidate Indication Discovery Optimization IND - Enabling Phase 1 Phase 2/3 Global Rights EGFR BDTX - 1535 EGFR - driven GBM & NSCLC ± CNS mets BRAF BDTX - 4933 BRAF - driven solid tumors ± CNS mets FGFR Undisclosed FGFR3 - driven sol
Slide 7: MAP Drug Discovery Engine
yy" 3 MAP Drug Discov) ey” a& BLACK DIAMOND THERAPEUTICS
Slide 8: MAP Drug Discovery Engine Unlocks Precision Medicine with a MasterKey
8 Validate novel oncogenic driver mutations and targets Develop MasterKey inhibitors against mutation families Proprietary MAP scoring in silico MAP Drug Discovery Engine Unlocks Precision Medicine with a “ MasterKey ” Genomics Proteomics + Employ structural and dynamic methods to identify oncogenic
Slide 9: A Scaled Approach to Extract Oncogenic MasterKey Mutation Families
9 MAP Drug Discovery Engine: A Scaled Approach to Extract Oncogenic MasterKey Mutation Families Population level clinical mutation landscape Thousands Computational in - silico oncogenicity prediction Hundreds amino acid position prevalence amino acid position prevalence Oncogene amino acid position
Slide 10: Conformation Based Drug Design Enabled by MAP Engine
10 WILD TYPE MASTERKEY MUTATION FAMILIES MasterKey Inhibitors designed to exploit this vulnerability MasterKey mutations drive global conformation change Conformation Based Drug Design Enabled by MAP Drug Discovery Engine
Slide 11: BDTX-1535 Brain-Penetrant Inhibitor of GBM and NSCLC MasterKey EGFR Mutations
BDTX - 1535 Brain - Penetrant Inhibitor of GBM and NSCLC MasterKey EGFR Mutations
Slide 12: BDTX-1535: Oral, Brain Penetrant, Selective Inhibitor of Oncogenic EGFR
12 BDTX - 1535: Oral, Brain Penetrant, Selective Inhibitor of Oncogenic EGFR MasterKey Mutations Designed to treat patients harboring EGFR oncogenic MasterKey mutations Irreversible Designed with selectivity versus WT - EGFR to deliver favorable safety profile Selective Designed to be brain penetran
Slide 13: Current EGFR TKIs Do Not Extend PFS in Patients with GBM Mutations
13 1 Van den Bent et al JCO 2009 2 Capuzzo et al Lancet 2010 GBM Mutations Time (months) p=0.003 PFS (%) GBM Trial 1 Erlotinib in WT - EGFR GBM Patients Erlotinib in EGFR - vIII GBM Patients Current EGFR TKIs Do Not Extend PFS in Patients with GBM Mutations Erlotinib Placebo Time (months) PFS (%) HR
Slide 14: Potential for Unwanted Paradoxical Activation of GBM Mutations by Reversible EGFR TKIs
14 Black Diamond Revealed the Potential for Unwanted Paradoxical Activation of GBM Mutations by Reversible EGFR TKIs PK=Pharmacokinetics; PD=Pharmacodynamics; PDX=Patient - Derived Xenografts The oncogenic conformation of mutant EGFR in GBM is a locked dimer Reversible TKIs can stimulate the activit
Slide 15: BDTX-1535 Addresses Unique Pharmacology of EGFR Mutations in GBM
15 BDTX - 1535 Addresses Unique Pharmacology of EGFR Mutations in GBM to Achieve Sustained Inhibition and Activity in Preclinical Models Kp uu Partition Coefficient Calculation: AUC brain:blood x plasma Fu/brain Fu; QD= quaque die (once a day) 12 14 16 18 0 25 50 75 100 Days Post Implantation P r o
Slide 16: BDTX-1535 Optimized to Address Wide Range of Oncogenic EGFR Mutations
16 H 2 9 2 A 4 3 1 E G F R v I I I E G F R v I I E G F R v V I E G F R R 1 0 8 K E G F R R 2 2 2 C E G F R C 2 3 1 F E G F R A 2 8 9 T E G F R A 2 8 9 V E G F R C 5 9 5 S E G F R G 5 9 8 V E G F R S 6 4 5 C 0 20 40 60 80 100 120 A n t i P r o l i f e r a t i v e I C 5 0 ( n M ) H 2 9 2 A 4 3 1 D 7 6
Slide 17: BDTX-1535 Designed to Inhibit EGFR Intrinsic and Acquired Resistance Mutations in NSCLC
17 BDTX - 1535 Designed to Potently Inhibit EGFR Intrinsic and Acquired Resistance Mutations in NSCLC Intrinsic Resistance Mutations Designed for potent & selective inhibition across mutant families Osimertinib Altered Covalent Interaction Altered P - loop Interaction C797S G719X Gefitinib Acquired
Slide 18: BDTX-1535 Achieves Dose-dependent Tumor Regression in EGFR Mouse Models
18 BDTX - 1535 Achieves Dose - dependent Tumor Regression in EGFR Mouse Models, Including Acquired Resistance Mutation C797S BDTX - 1535 retains irreversible binding against C797S mutant BDTX - 1535 demonstrates dose - dependent tumor regression in EGFR Ex19del + C797S and L858R + C797S tumor models
Slide 19: BDTX-1535 Promotes Regression Across Range of GBM & NSCLC Tumor Models
19 EGFR AMP EGFR AMP EGFR vII EGFR AMP EGFR Ex19del EGFR C595F EGFR G719C EGFR AMP EGFR Ex19del EGFR L858R +C797S EGFR Ex19del +C797S BDTX - 1535 Promotes Regression Across Range of GBM & NSCLC Tumor Models Expressing MasterKey EGFR Mutations & EGFR Amplification In Vivo Tumor Models - 100 100 % Reg
Slide 20: BDTX-1535: Biomarker-Driven First-in-Human Phase 1 Study Design
20 BDTX - 1535: Focused, Biomarker - Driven First - in - Human Phase 1 Study Design RP2D Dose Escalation EGFR Alterations EGFR Intrinsic Resistance Mutations RP2D=Recommended Phase 2 Dose EGFR Acquired Resistance Mutations • Global trial • Bayesian optimal interval design
Slide 21: Large Addressable Patient Population Harboring MasterKey Mutations Across GBM and NSCLC
21 ~ 160,500 Sources: Epidemiology data from EvaluatePharma Addressable Patient Population (US / EU / Japan / China) Classical Acquired Resistance EGFRmut 11,700 Intrinsic Resistance EGFRmut 139,700 Classical EGFRmut 9,100 EGFRmut Newly Diagnosed GBM 36,400 24,700 EGFRmut Recurrent GBM ~ 61,100 Larg
Slide 22: BDTX-1535 Well Positioned to Address Unmet Needs in EGFR Mutant GBM/NSCLC
22 BDTX - 1535 is Well Positioned to Address Unmet Needs in EGFR Mutant GBM/NSCLC Potent & selective inhibition of EGFR mutations (Avg IC 50 ~3nM) that drive intrinsic and acquired resistance to current generation TKIs • Irreversible inhibition of GBM mutations to avoid paradoxical activation • Irre
Slide 23: BDTX-4933 Brain-Penetrant Inhibitor of Class I, II, & III MasterKey BRAF Mutations
BDTX - 4933 Brain - Penetrant Inhibitor of Class I, II, & III MasterKey Oncogenic BRAF Mutations
Slide 24: BDTX-4933: Oral, Brain Penetrant Inhibitor of Oncogenic BRAF Mutations
24 BDTX - 4933: Oral, Brain Penetrant Inhibitor of Oncogenic BRAF Mutations BDTX - 4933 Designed for potent and selective inhibition of Class I, II, and III BRAF mutations MasterKey Family Inhibits dimerized RAF kinases and avoids paradoxical activation Avoids Paradoxical Activation Designed to be b
Slide 25: BRAF Alterations Drive Oncogenesis Through Hyperactivation of MAP Kinase Pathway
25 • MAPK signaling is a central pathway regulating cellular proliferation, cell - cycle progression, and survival • Hyperactivation responsible for >40% of human cancer cases • Activating BRAF alterations are associated with various cancers including melanoma and NSCLC • Currently approved BRAF inh
Slide 26: BDTX-4933 Designed to Avoid Paradoxical Activation
26 BDTX - 4933 Designed to Deliver Superior Activity by Avoiding Paradoxical Activation Independent of Context • Paradoxical activation occurs through activation of the non - inhibited RAF molecule in dimer ― Limits efficacy through secondary malignancies and/or cutaneous toxicities • Approved BRAF
Slide 27: BDTX-4933 Exhibits Strong Anti-Tumor Activity Across All BRAF Mutation Classes
27 BDTX - 4933 Exhibits Strong Anti - Tumor Activity Across All BRAF Mutation Classes in In Vivo Models BRAF Class II Mutant Tumor Model BRAF Class III Mutant Tumor Model BRAF Class I Mutant Tumor Model 0 5 10 15 20 0 500 1000 1500 2000 Days (post treatment) T u m o r V o l u m e ( m m 3 ) Vehicle B
Slide 28: NRAS-mutant Driven Cancers: Additional Clinical Opportunity for BDTX-4933
28 NRAS - mutant Driven Cancers: Additional Clinical Opportunity for BDTX - 4933 -10 -8 -6 -4 0 2 4 6 8 NRAS Q61L , HRAS G13D Concentration Log[M] p E R K N o r m a l i z e d t o D M S O Encorafinib Belvarafenib BDTX-4933 • NRAS - mutant melanoma represent ~20% of melanomas • Acquired NRAS mutations
Slide 29: BDTX-4933 Designed to be Brain Penetrant to Treat CNS Disease
29 • CNS metastasis occurs in ~30 - 40% 1 of BRAF driven cancers • ~17,000 2 patients/year in the US • BRAF mutations drive primary CNS tumors (e.g., g lioma ) in ~1,500 2 patients/year in the US • Currently approved therapies are not brain penetrant BDTX - 4933 Designed to be Brain Penetrant to Tre
Slide 30: BDTX-4933 Is Brain Penetrant and Exhibits Robust Activity in CNS Disease Models
30 Day 0 Day 15 BDTX - 4933 prolongs survival in BRAF - V600E intracranial tumor model Vehicle BDTX - 4933 3 mpk Belvarafenib 15 mpk BDTX - 4933 Is Brain Penetrant and Exhibits Robust Activity in Treating CNS Disease in in vivo models BDTX - 4933 10 mpk BDTX - 4933 BDTX - 4933
Slide 31: BDTX-4933: Potential Best-in-Class MasterKey Inhibitor
31 BDTX - 4933: Potential Best - in - Class , Masterkey Inhibitor For A Greater Number Of Patients With Overlooked Oncogenic Mutations Sources: EvaluatePharma Epi and GENIE/TCGA 47,500 NRAS Melanoma 51,600 BRAF Class II/III alt. Solid Tumors 91,810 BRAF V600 Solid Tumors Addressable US / EU / JP Pat
Slide 32: FGFR2/3 Selective Inhibitor Program
FGFR2/3 Selective Inhibitor Program
Slide 33: BDTX-FGFR: Oral, Selective Small-Molecule FGFR2 & FGFR3 Inhibitor
33 BDTX - FGFR: Oral, Selective Small - Molecule FGFR2 & FGFR3 Inhibitor BDTX - FGFR Potency against families of FGFR2 & FGFR3 alterations and amplifications Unique Activity Profile Robust in vivo efficacy demonstrated in bladder (FGFR3) and gastric (FGFR2) xenograft models without hyperphosphatemia
Slide 34: a& BLACK
a& BLACK DIAMOND THERAPEUTICS
Slide 35: Deep Oncology and Small Molecule Drug Discovery and Development Experience
35 Deep Oncology and Small Molecule Drug Discovery and Development Experience David M. Epstein, Ph.D. President & CEO Liz Buck, Ph.D. Chief Scientific Officer Brent Hatzis - Schoch, J.D. COO and General Counsel Leadership Team Board of Directors Ali Behbahani , M.D. General Partner, NEA Kapil Dhingr
Slide 36: Cash Runway Expected to Enable Multiple Upcoming Milestones
36 Cash Runway Expected to Enable Multiple Upcoming Milestones • BDTX - 1535 clinical data update in 2023 • BDTX - 4933 IND filing in 1H 2023 • FGFR program development candidate nomination in 2022 • Undisclosed program development candidate nomination in 2023 • $209mm in cash, cash equivalents and
Slide 37: Expanding the Reach of Precision Medicine Through MasterKey Therapies
37 Expanding the Reach of Precision Medicine Through the Development of MasterKey Therapies Our proprietary MAP drug discovery engine is designed to: • Predict and validate novel oncogenic mutant families from population level tumor genomics • Pioneer mutant family conformation - based MasterKey dru
Slide 38: Thank You
Thank You Partnership: partnership@bdtx.com Investors: investors@bdtx.com Media: media@bdtx.com
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