Black Diamond Therapeutics, Inc. · NASDAQ:BDTX
Black Diamond Therapeutics — Investor Presentation (January 2024)
42 slides from Black Diamond Therapeutics's investor presentation, Jan 4, 2024
Slide 1: Developing MasterKey Therapies to Defeat Cancer Resistance
1 Black Diamond Therapeutics, Inc. Developing MasterKey Therapies to Defeat Cancer Resistance January 2024
Slide 2: Forward-Looking Statements
2 Forward - Looking Statements Statements contained in this presentation regarding matters that are not historical facts are “forward - looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 . Because such statements are subject to risks and uncertainties, act
Slide 3: Cancer is a Complex and Ever-Evolving Disease
3 Cancer is a Complex and Ever - Evolving Disease Current targeted therapies were designed against a limited subset of oncogenic mutations Increasing adoption of liquid biopsies reveals a broader set of oncogenic mutations We are Developing MasterKey Therapies to Defeat Cancer Resistance MasterKey a
Slide 4: Black Diamond Therapeutics At-a-Glance
4 Black Diamond Therapeutics At - a - Glance Clinical - stage company advancing MasterKey therapies designed to expand the addressable patient population Experienced team with deep understanding of cancer biology and oncology drug development Lead asset BDTX - 1535 shows durable clinical responses i
Slide 5: MasterKey: One Solution for Many Mutations
5 MasterKey : One Solution for Many Mutations Expanded addressable patient population Black Diamond Approach: Targeting families of oncogenic mutations Limited addressable patient population 5 Brain penetrant to treat CNS disease Traditional Approach: Targeting single mutations in individual tumor t
Slide 6: Advancing Wholly Owned Pipeline Across Multiple Oncology Indications
6 Advancing Wholly Owned Pipeline Across Multiple Oncology Indications Target Drug Candidate Indication Pre - clinical Phase 1 Phase 2 Phase 3 EGFR RAF BDTX - 1535 BDTX - 4933 NSCLC GBM KRAS mutant NSCLC Undisclosed Multiple Solid tumors FGFR2/3 BDTX - 4876 Achondroplasia or solid tumors RAF/RAS mut
Slide 7: EGFR MasterKey Inhibitor with Clinical Proof-of-Concept
7 Targets EGFR classical drivers, non - classical drivers, and resistance mutations WT=Wild - Type; MOA=mechanism of action; CNS=Central Nervous System; NSCLC=Non - Small Cell Lung Cancer BDTX - 1535 MasterKey BDTX - 1535: EGFR MasterKey Inhibitor with Clinical Proof - of - Concept Selective for mut
Slide 8: Clinical Proof-of-Concept Achieved in NSCLC, Promising GBM Data
8 EGFR Altered Glioblastoma (GBM) EGFR Mutant Non - Small Cell Lung Cancer (NSCLC) Phase 1 topline data demonstrated promising activity Clinical proof - of - concept achieved BDTX - 1535: Clinical Proof - of - Concept Achieved in NSCLC, Promising GBM Data
Slide 9: Summary of NSCLC Data
9 BDTX - 1535: Summary of NSCLC Data
Slide 10: Addresses the Most Clinically Relevant EGFR Mutations in NSCLC
10 BDTX - 1535 Addresses the Most Clinically Relevant EGFR Mutations in NSCLC: Classical / Non - Classical Drivers and C797S Resistance Evolution of the EGFR mutation landscape over the past 20 years NGS revolution Mutation specific sequencing 2005 1G EGFR T (2/3L) 1G EGFR T (1L) 2013 3G EGFR TKI (2
Slide 11: Real-World Data Confirms ~90% of Patients Receive 1L Osimertinib
11 1. Real world treatment patterns and outcomes in patients with advanced non - small cell lung cancer (NSCLC) post - EGFR tyrosine kinas e inhibitor (TKI) therapy Source: AACR 2023 Poster 2. Adapted from Rotow , JK., et al., Journal of Thoracic Oncology, 2023. Real - World Data Confirms ~90% of Pa
Slide 12: Potent Preclinical Inhibition of EGFR Mutations vs Osimertinib
12 BDTX - 1535 potently targets >50 EGFR oncogenic mutations BDTX - 1535: Potent Preclinical Inhibition of Classical and Non - Classical Driver Mutations and C797S Resistance vs Osimertinib; Superior Brain Exposure Data adapted from AACR 2023 Poster; non - classical driver formerly referred to as in
Slide 13: Phase 1 Dose Escalation: Summary
13 BDTX - 1535 Phase 1 Dose Escalation: Summary Mutation Matched Phase 1 Study Inclusion Criteria Once - daily dosing delivers sufficient exposure to inhibit EGFR mutations M anageable EGFR TKI safety profile at 200 mg (similar to osimertinib ) Radiographic responses and durable anti - tumor activit
Slide 14: Phase 1 Dose Escalation Patient Characteristics
14 BDTX - 1535 - 101 Phase 1 Dose Escalation Patient Characteristics NSCLC GBM 0 2 4 6 8 10 12 14 16 15 25 50 100 200 300 400 Patients enrolled Dose, mg QD NSCLC GBM Patient Enrollment Patient Characteristics All Treated Age, mean (range) 64 (46, 81) Female 18 (67%) ECOG PS 0 7 (26%) 1 20 (74%) Prio
Slide 15: Dose Escalation Treatment Emergent Adverse Events: Well-Tolerated Profile
15 15 - 50 m(N=10) 100 mg (N=5) 200 mg (N=12) 3 00 mg (N=15) 400 mg (N= 12 ) Treatment emergent adverse events (TEAEs) occurring in ≥6% patients; All patients in 300 mg cohort received rash prophylaxis Rash group terms: rash, rash maculo - papular, dermatitis acneiform Dose Escalation Treatment Emer
Slide 16: Linear Plasma PK Profile Supports Daily Dosing
16 Data from Poster at EORTC/AACR/NCI International Conference on Molecular Targets and Cancer Therapeutics October 2023 **IC 50 of EGFR alterations in GBM is average IC 50 of most prevalent EGFR mutations tested in BaF3 cells *IC 50 of EGFR C797S is average of IC 50 of Exon19del/C797S and L858R/ C7
Slide 17: NSCLC Dose Escalation Patients Reflect Real World EGFR Mutation Landscape
17 NSCLC Dose Escalation Patients Reflect Real World EGFR Mutation Landscape Post Osimertinib Data from Poster at EORTC/AACR/NCI International Conference on Molecular Targets and Cancer Therapeutics October 2023 20 of 27 patients with 2 or more mutations Classical driver mutations Non - classical dr
Slide 18: Phase 1 Dose Escalation: 13 Response-Evaluable NSCLC Patients
18 Adapted from Poster at EORTC/AACR/NCI International Conference on Molecular Targets and Cancer Therapeutics October 2023 Efficacy Evaluable Group Patients receiving starting dose <100mg Discontinuation prior to post - baseline tumor assessment Non - measurable disease No tumor assessment at the t
Slide 19: Radiographical Responses in Efficacy Evaluable Patients
19 On treatment Osi = Osimertinib; Afa = Afatinib; Gefi = Gefitinib; Daco = Dacomitinib; Erlo = Erlotinib; CPI = Checkpoint inhibitor, C = Chemotherapy; # - mutations were absent on confirmatory test; * uPR =unconfirmed partial response - patient had a PR on a post - baseline scan, but a radiologist
Slide 20: Response Evaluable Patients by Dose, Mutation and Prior Therapy
20 Assigned Dose (QD) Baseline EGFR Mutation Prior Therapy Response Evaluable Classical Non - classical Acquired 1 st 2 nd >2 line 25 mg Exon 19del C797S Osi SD a 50 mg Exon 19del C797S Osi SD b G719A, L861Q CPI, Afa Osi HER3 - ADC NM a , c 100 mg L858R L718Q, C797S Osi PR d L858R Osi C C No b 200 m
Slide 21: Drives Clearance of Mutant EGFR VAF and Plasma ctDNA
CONFIDENTIAL | 21 -100 -80 -60 -40 -20 0 20 % ctDNA change Assigned Dose, mg QD 200 400 50 100 200 200 200 200 200 400 Retrospective EGFR mutation testing at baseline EGFRm not detected Ex19Del, C797S Ex19Del, C797S L858R L748Q C797S E746_S752 delinsV, C797S Ex19Del, C797S L747
Slide 22: Clinical Benefit in a Non-Response Evaluable Patient With CNS Disease
22 1. L861Q was reported by local testing at screening, but not detected in baseline and post - dose samples by central testing Data from Poster at EORTC/AACR/NCI International Conference on Molecular Targets and Cancer Therapeutics October 2023 ; VAF – variant allelic fraction Clinical Benefit in a
Slide 23: Phase 2 Trial Enrolling in 1L and 2L/3L NSCLC
23 BDTX - 1535: Phase 2 Trial Enrolling in 1L and 2L/3L NSCLC • 2L/3L patients enrolling at 100 mg QD and 200 mg QD • ORR primary endpoint • Phase 2 data in 2L/3L patients expected Q3 2024 • FDA Fast Track Designation granted for 2L EGFRm/C797S • End of Phase 1 FDA feedback received, 1L cohort initi
Slide 24: Well Positioned Across All Lines of Therapy for EGFRm NSCLC
24 BDTX - 1535 Well Positioned Across All Lines of Therapy for EGFRm NSCLC Classical Driver Mutations (L858R, Del19) ~ 85% of patients Non - classical Driver Mutations (G719X, S786I, etc.) ~13% of patients ~32 - 42k 2027 Estimated EGFRm Incidence (G7) ~56 - 74k ~46 - 61k Resectable / Adjuvant Settin
Slide 25: Opportunity in Glioblastoma
25 BDTX - 1535: Opportunity in Glioblastoma
Slide 26: Treatment of EGFR-Driven GBM Requires Inhibition of Complex EGFR Mutations
26 1. Saadeh, F., et al., The International Journal of Biological Markers, 2018 . 2. Real world evidence data from Tempus Labs a nal ysis of 2,540 GBM patient samples Treatment of EGFR - Driven GBM Requires Inhibition of Complex EGFR Mutations: Potent Preclinical Inhibition by BDTX - 1535 Of all ECD
Slide 27: Potent Preclinical Inhibition of Oncogenic GBM EGFR Alterations vs. Osimertinib
27 BDTX - 1535 Demonstrates Potent Preclinical Inhibition of Oncogenic GBM EGFR Alterations vs. Osimertinib and Superior Brain Exposure BDTX - 1535 Exhibits Superior Brain Exposure Kpuu (rat) BDTX - 1535 0.51 0.21 Osimertinib Amplification Truncations Variants EGFR - AMP EGFR - AMP EGFR vIII EGFR vI
Slide 28: Potential to Overcome Limitations of Prior Attempts to Drug EGFR in GBM
28 BDTX - 1535: Potential to Overcome Limitations of Prior Attempts to Drug EGFR in GBM Lessons From Past Failures BDTX - 1535 MOA=mechanism of action; CNS=Central Nervous System; WT=Wild - Type; GBM=Glioblastoma Multiforme; NSCLC=Non - Small Cell Lung Cancer Potent MasterKey inhibition of co - occu
Slide 29: Opportunity in Newly Diagnosed EGFRm GBM Patients
29 1. Schäfer, J. Transl . Med. 2019; 2. Wang, Nat. Genet. 2016; 3. Johnson, Science 2014; 4. López , Acta Neuropathol . 2019; 5. Weller, Neuro - Oncology 2013; 6. Audureau , J. Neurooncol . 2018; EGFR Driver Status Often Evolves During Treatment Fresh biopsy tissue used for testing Up - to - date t
Slide 30: Promising Clinical Activity in Heavily Pre-treated GBM Patients
30 Promising Clinical Activity in Heavily Pre - treated GBM Patients From Dose Escalation Portion of Phase 1 Study x Well tolerated , with favorable plasma PK x Of 22 efficacy evaluable heavily pre - treated GBM patients • 3 patients on therapy longer than 10 months ─ 1 remains on therapy at 15 mont
Slide 31: Immediate Next Steps and 2024 Milestones in GBM
31 BDTX - 1535 in GBM: Immediate Next Steps and 2024 Milestones Anticipated Upcoming Milestones 2L patients receive 5 days of dosing with BDTX - 1535 as monotherapy Surgical resection following day 5 of dosing CNS PK/PD evaluated in resected tissue and CSF Window of Opportunity (WOO) Study Overview
Slide 32: GBM Development Path Designed for Sequential De-Risking
32 BDTX - 1535 GBM Development Path Designed for Sequential De - Risking 2L patients receive 5 days of dosing with BDTX - 1535 as monotherapy Window of Opportunity (WOO) Study Overview CNS=Central Nervous System; CSF=Cerebrospinal fluid Dose Escalation PK + EGFR Status Registration potential ▪ Recur
Slide 33: Summary: NSCLC and GBM Opportunities
33 BDTX - 1535 Summary: NSCLC and GBM Opportunities Robust near - term commercial opportunity in 2L and 1L NSCLC Emerging potential in GBM Differentiated profile F irst and potential best - in - class 4 th gen EGFR TKI Robust clinical POC in a heavily pre - treated Phase 1 NSCLC population • 5 cPR +
Slide 34: BDTX-4933: Potential Best-in-Class Brain-Penetrant RAF MasterKey Inhibitor
BDTX - 4933: Potential Best - in - Class Brain - Penetrant RAF MasterKey Inhibitor
Slide 35: BDTX-4933: Oral, Brain-Penetrant, RAF MasterKey Inhibitor
35 Potent preclinical inhibition of BRAF, KRAS, and NRAS alterations (“RAF - RAS clamp”) BDTX - 4933 MasterKey BDTX - 4933: Oral, Brain - Penetrant, RAF MasterKey Inhibitor Designed to target oncogenic conformation of RAF and avoid paradoxical activation Unique Pharmacology Designed to be brain pene
Slide 36: MAPK Pathway Mutations Among the Most Common Oncogenic Mutations in Cancer
36 MAPK Pathway Mutations Affecting KRAS/NRAS/BRAF are Among the Most Common Oncogenic Mutations in Cancer BRAF Class II/III Solid Tumors BRAF V600 Solid Tumors KRAS G12D NSCLC KRAS G12V NSCLC KRAS G13X NSCLC KRAS G12C NSCLC Source: EvaluatePharma, TCGA, GENIE - 11 NRAS Melanoma Addressable US / EU5
Slide 37: Multiple Opportunities for BDTX-4933
37 1. Zhang, W., Cell Res. (2002); 2. Yuan, J., J Hematol Oncol 13, 113 (2020); 3. Yao Z, Cancer Cell (2015); 4. Karoulia Z, Cancer Cell (2016); 5. J. Wang, Pharmacol. Res. 129, 414 – 423 (2018); 6. H. Ellens, Drug Metab. Dispos. 45, 646 – 656 (2017); 7. R. K. Mittapalli, J. Pharmacol. Exp. Ther. 34
Slide 38: BDTX-4933 Demonstrates Potent Preclinical Inhibition of BRAF/RAS and KRAS Mutations
38 Cell Proliferation IC50 Mutation BDTX - 4933 Naporafenib Belvarafenib Exarafenib Encorafenib BRAF Class I V600E BRAF Class II & non - V600 BRAF fusion BRAF fusion L597V L245F BRAF indel NRAS NRAS Q61K NRAS Q61L Not available NRAS BRAF WT Paradoxical Activation Potent and selective
Slide 39: Focused, Biomarker-Driven Phase 1 Trial Initiated
39 RP2D • Bayesian optimal interval design • Mutations and alterations confirmed by local tests BDTX - 4933: Focused, Biomarker - Driven Phase 1 Trial Initiated Data Anticipated in Q4 2024 NSCLC with KRAS mutations/BRAF alterations Dose Escalation
Slide 40: Potential for NSCLC Franchise
40 BDTX - 1535 and BDTX - 4933: Potential for NSCLC Franchise EGFR mutant 1 st Line 2 nd Line 3 rd Line Pan - KRAS KRAS mutant G12C Non - Classical G719X, L861X, etc Classical driver L858R/Del19 cMET amp / non - EGFR alterations Complex EGFR Mutations C797S, Complex EGFR Mutations Off - Label Osi /
Slide 41: Anticipated 2024 Key Milestones
41 Anticipated 2024 Key Milestones Q1 Q2 Q3 Q4 Phase 2 initiation in 1L non - classical patients Phase 2 results in 2L/3L patients Potential pivotal trial initiation in 2L patients Potential randomized trial in newly diagnosed patients Phase 1 results BDTX - 1535 EGFRm NSCLC BDTX - 4933 KRASm NSCLC
Slide 42: Thank You
Thank You Partnership: partnership@bdtx.com Investors: investors@bdtx.com Media: media@bdtx.com
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