Black Diamond Therapeutics, Inc. · NASDAQ:BDTX
Black Diamond Therapeutics — Investor Presentation (January 2022)
39 slides from Black Diamond Therapeutics's investor presentation, Jan 10, 2022
Slide 1: Pioneering the Development of MasterKey Therapies
1 Black Diamond Therapeutics, Inc. Pioneering the Development of MasterKey Therapies JANUARY 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 limited to,
Slide 3: Black Diamond Therapeutics Overview
Black Diamond Therapeutics Overview
Slide 4: Expanding Precision Medicine Through the Development of MasterKey Therapies
4 Expanding 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 drug design • Provi
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 Classes of Precision Medicines
6 Wholly-Owned Novel Classes of Precision Medicines Target Drug Candidate Indication Discovery Optimization IND-Enabling Phase 1 Phase 2 Phase 3 EGFR BDTX-1535 GBM, NSCLC ± CNS mets EGFR HER2 BDTX-189 NSCLC, breast BRAF Undisclosed Targeted solid tumors ± CNS mets FGFR Undisclosed Targeted solid tum
Slide 7: a& BLACK
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 m
Slide 9: MAP Drug Discovery Engine: 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 p
Slide 10: MasterKey Inhibitors designed to exploit this vulnerability
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 MasterKey Mutations
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 penetrant to
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 Trial1 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=0.10
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 The oncogenic conformation of mutant EGFR in GBM is a locked dimer 0 12 24 36 48 0 1 2 3 4 5 Time (hrs) F r a c t i o n o f C o n t r o l P h o s p h o r y l a t i o n Reversible TKIs
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 Kpuu Partition Coefficient Calculation: AUCbrain: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 b a b
Slide 16: BDTX-1535 Optimized to Address a Wide Range of Oncogenic EGFR MasterKey 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 Potently 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 Resi
Slide 18: BDTX-1535 Achieves Dose-dependent Tumor Regression in EGFR Mouse Models
18 BDTX-1535 retains irreversible binding against C797S mutant BDTX-1535 demonstrates dose-dependent tumor regression in EGFR Ex19del / C797S tumor model BDTX-1535 Achieves Dose-dependent Tumor Regression in EGFR Mouse Models, Including Acquired Resistance Mutation C797S Osimertinib BDTX-1535 Washou
Slide 19: BDTX-1535 Promotes Regression Across Range of GBM & NSCLC PDX Tumors
19 EGFR AMP EGFR AMP EGFR vII EGFR AMP EGFR Ex19del EGFR C595F EGFR G719C EGFR AMP EGFR Ex19del EGFR Ex19del +C797S BDTX-1535 Promotes Regression Across Range of GBM & NSCLC PDX Tumors Expressing MasterKey EGFR Mutations & EGFR Amplification PDX Models -100 100 % Regression -10 10 AMP=Amplification
Slide 20: BDTX-1535: Focused, Biomarker-Driven First-in-Human Phase 1 Study Design
20 BDTX-1535: Focused, Biomarker-Driven First-in-Human Phase 1 Study Design Selected Patient Population • GBM Patients with EGFR alterations • NCSLC Patients with EGFR intrinsic resistance mutations • NCSLC Patients with acquired EGFR resistance mutations RP2D Dose Escalation EGFR MasterKey Mutation
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 Large
Slide 22: BDTX-1535 is 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 IC50 ~3nM) that drive intrinsic and acquired resistance to current generation TKIs • Irreversible inhibition of GBM mutations to avoid paradoxical activation • Irrever
Slide 23: BDTX-189 Inhibitor Targeting MasterKey EGFR/HER2 Mutations
BDTX-189 Inhibitor Targeting MasterKey EGFR/HER2 Mutations
Slide 24: BDTX-189: MasterKey EGFR/HER2 Inhibitor, Early Proof-of-Concept Demonstrated
24 BDTX-189: MasterKey EGFR/HER2 Inhibitor, Early Proof-of-Concept Demonstrated FDA endorsed RP2D 800 mg QD non-fasting PK in-line with preclinical predictions RP2D Achieved Anti-tumor activity in NSCLC EGFR Ex20ins and in HER2 amplified solid tumors Activity Observed Well-tolerated, minimal evidenc
Slide 25: BDTX-189 is a Potent and Selective Inhibitor Across EGFR/HER2 MasterKey Mutation Family
25 BDTX-189 is a Potent and Selective Inhibitor Across EGFR/HER2 MasterKey Mutation Family EC domain 17 mutants JM domain 2 mutants Ex 20 ins 24 mutants Kinase domain 18 mutants A 4 3 1 H 2 9 2 E G F R A 7 6 3 - Y 7 6 4 i n s F Q E A E G F R A 7 6 7 - V 7 6 9 d u p A S V E G F R A 7 6 7 - V 7 6 9 d
Slide 26: MasterKey-01 Dose Escalation Complete; Safety Expansion Enrolling
26 MasterKey-01 Dose Escalation Complete; Safety Expansion Enrolling Recommended Phase 2 Dose (RP2D) • 800 mg QD non-fasting • Well tolerated, no DLTs at RP2D • Most common AE grade 1 diarrhea, no AE ≥ grade 2 • Low rate of rash Safety Summary • Safety dataset dose escalation QD cohorts n=59* • n=18
Slide 27: Improved Selectivity Drives Improved Safety
27 Targeted selectivity E r l o t i n i b P o z i o t i n i b A f a t i n i b O s i m e r t i n i b C L N - 0 8 1 / T A S 6 4 1 7 M o b o c e r t i n i b / T A K 7 8 8 B D T X - 1 8 9 0.1 1 10 100 F o l d S e l e c t i v i t y ( E G F R W T / M u t a n t ) > Poor selectivity Improved Selectivity Dri
Slide 28: NSCLC EGFR Ex Ins: 53% Tumor Reduction at Week 12
28 Radiologic Scans NSCLC EGFR Ex 20 Ins: 51-year-old Woman with 53% Tumor Reduction at Week 12 and Improved Diffuse Lung Disease SLD=Sum of longest diameter; PR=partial response; PD=progressive disease Genomic alteration: EGFR Ex20ins (SVD), HER2-amp Prior therapy: • Poziotinib with PR and toxicity
Slide 29: Early PoC Achieved for BDTX-189 in Solid Tumors with HER2-Amp
29 Early PoC Achieved for BDTX-189 in Solid Tumors with HER2-Amp with Deep and Durable Confirmed PR Observed Radiologic Scans Genomic alteration: HER2-amplification Prior therapy: • Carbo/taxol, FOLFIRINOX, Everolimus Response to BDTX-189: • BDTX-189 800 mg QD fasting • Had brief episodes of Grade 1
Slide 30: BRAF Program Oral, Brain Penetrant, MasterKey Inhibitor
BRAF Program Oral, Brain Penetrant, MasterKey Inhibitor
Slide 31: BDTX-BRAF: Oral, Brain Penetrant, Inhibitor of Oncogenic BRAF Mutations
31 BDTX-BRAF: Oral, Brain Penetrant, Inhibitor of Oncogenic BRAF Mutations BDTX-BRAF 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 brai
Slide 32: BDTX-BRAF: Designed with Potential Best-In-Class Target Product Profile
32 BDTX-BRAF: Designed with Potential Best-In-Class Target Product Profile Potent Inhibition of All Three Class I / II / III BRAF Mutations Brain Penetration High incidence of CNS metastasis among tumors express BRAF mutations (lung, melanoma) High prevalence of BRAF mutations in primary CNS maligna
Slide 33: BDTX-BRAF Exhibits Strong Anti-Tumor Activity Across All BRAF Mutation Classes
33 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 BDTX-BRAF (10 mpk) Belvarafenib (15 mpk) BDTX-BRAF (3 mpk) 0 3 6 9 12 0 500 1000 1500 2000 Days (post treatment) T u m o r V o l u m e ( m m 3 ) Encorafenib (60 mpk) Vehicle BDTX-BRAF (3 mpk) 0 5 10 15
Slide 34: BDTX-BRAF Is Brain Penetrant and Exhibits Robust Activity in CNS Disease Models
34 Day 0 Day 15 BDTX-BRAF prolongs survival in BRAF-V600E intracranial tumor model Vehicle BDTX-BRAF 3 mpk Belvarafenib 15 mpk BDTX-BRAF Is Brain Penetrant and Exhibits Robust Activity in Treating CNS Disease in in vivo models BDTX-BRAF 10 mpk
Slide 35: BDTX BRAF: Potential Best-in-Class MasterKey Inhibitor For More Patients
35 BDTX BRAF: 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 Patient Po
Slide 36: Corporate Overview
Corporate Overview a& BLACK DIAMOND THERAPEUTICS
Slide 37: Deep Oncology and Small Molecule Drug Discovery and Development Experience
37 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 Brad Bolzon, Ph
Slide 38: Expanding Precision Medicine Through the Development of MasterKey Therapies
38 Expanding 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 drug design • Prov
Slide 39: a& BLACK
a& BLACK DIAMOND THERAPEUTICS
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