Black Diamond Therapeutics, Inc. · NASDAQ:BDTX
Black Diamond Therapeutics — Investor Presentation (March 2025)
38 slides from Black Diamond Therapeutics's investor presentation, Mar 19, 2025
Slide 1: Developing MasterKey Therapies to Defeat Cancer Resistance
1 Black Diamond Therapeutics, Inc. Developing MasterKey Therapies to Defeat Cancer Resistance March 19, 2025
Slide 2: Forward-Looking Statements
2 Forward - Looking Statements This presentation contains forward looking statements of Black Diamond Therapeutics, Inc (“we,” “us,” “our”) within the meaning of the Private Securities Litigation Reform Act of 1995 . Forward looking statements include all statements that are not historical facts, an
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 BDTX - 1535: best/first - in - class 4 th - generation EG
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
Slide 6: Advancing Pipeline Across Multiple Oncology Indications
6 Advancing Pipeline Across Multiple Oncology Indications Target Drug Candidate Indication Pre - clinical Phase 1 Phase 2 Phase 3 EGFR RAF BDTX - 1535 BDTX - 4933 2L/3L NSCLC 1L NSCLC FGFR2/3 BDTX - 4876 Achondroplasia or solid tumors RAF/RAS mutant solid tumors Final Phase 2 data expected H1 2026 P
Slide 7: MasterKey: Potential First and Best-in-Class 4th Generation EGFR TKI
7 Targets a broad spectrum of EGFR classical, non - classical, and C797S resistance mutations BDTX - 1535 MasterKey BDTX - 1535: Potential First and Best - in - Class 4th Generation EGFR TKI for Patients with EGFRm NSCLC and GBM Selective for mutations versus WT - EGFR to deliver favorable tolerabil
Slide 8: Evolution of the EGFR mutation landscape
8 Evolution of the EGFR mutation landscape over the past 20 years NGS revolution Mutation specific sequencing 2005 (2/3L) 2013 2015 2018 2024 T790M resistance C797S resistance Non - classical drivers Classical drivers L858R / Ex19del R ealization of EGFR non - classical mutations (NCMs) Treatments S
Slide 9: 23-30% of Newly Diagnosed EGFRm NSCLC Patients Carry Non-Classical Mutations
9 23 - 30% of newly diagnosed EGFRm NSCLC express non - classical mutations Classical and non - classical driver mutations are d istributed across EGFR structure 23 - 30% of Newly Diagnosed EGFRm NSCLC Patients Carry Non - Classical Mutations (NCMs); Not Adequately Addressed by Current Therapies 1.
Slide 10: Real World Treatment Data Highlights Significant Unmet Need
CONFIDENTIAL | 10 Heymach et al ESMO 2024 Real World Treatment Data Highlights Significant Unmet Need for Patients with Newly Diagnosed EGFR - NCM NSCLC 0 20 40 60 80 100 % of Patients Treated Afatinib Chemo+/ - I/O Osimertinib Afatinib Afatinib: 8.0 months Chemo +/ - I/O: 4.2 months Time (Months) T
Slide 11: Osimertinib and afatinib deliver limited PFS benefit in NCMs
CONFIDENTIAL | 11 * GuardantInform data derived from collaboration with Guardant Health – data on file at BDTX. UNICORN - 2024: Okuma et al JAMA Oncology 2024. UNI CORN - 2023: Bar et al JTO 2023. ARTICUNO: Pizzutilo et al ESMO Open 2024, mPFS for all NCM represents data for Group A TKI naïve patien
Slide 12: 200mg Achieves Coverage of the EGFR Mutation Spectrum
12 200mg PK data from Phase 1 dose escalation trial* 1 00mg BDTX - 1535 Achieves Coverage of the EGFR Mutation Spectrum at the Well - Tolerated Oral Dose of 200mg QD * Cmax doses plotted for human PK. PK d ata adapted from poster at EORTC/AACR/NCI International Conference on Molecular Targets and Ca
Slide 13: Potently Targets NCMs Less Sensitive to Osimertinib
CONFIDENTIAL | 13 BDTX - 1535 Potently Targets NCMs Which Are Less Sensitive to Osimertinib l oss of potency Osimertinib: weak against most NCMs (most commonly expressed NCMs shown) BDTX - 1535: potent against NCM spectrum (most commonly expressed NCMs shown) Pre - clinical data; EGFR mutations are
Slide 14: Frontline L858R Patients with EGFR-NCMs Discontinue Quickly Following Osimertinib
14 Real World Data Demonstrate Frontline L858R Patients Presenting with EGFR - NCMs Discontinue Quickly Following Osimertinib Therapy Poor performance for osimertinib in the context of L858R + NCM NSCLC A spectrum of NCMs co - occur together with L858R EGFR - NCMs frequently p resent as compound m u
Slide 15: Phase 1 Dose Escalation: Summary
15 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 tolerability profile at 200 mg (similar to osimertinib ) Radiographic responses and durable anti - tumor a
Slide 16: Phase 2 Data in Recurrent Setting
16 BDTX - 1535 Preliminary Phase 2 Data in Recurrent Setting Patients with non - classical driver mutations after ≤2 prior lines of therapy with osimertinib as the preferred prior EGFR TKI Patients with acquired resistance C797S after ≤2 prior lines of therapy with osimertinib as the only prior EGFR
Slide 17: Recurrent EGFRm NSCLC: PACC-NCM and C797S Resistance Mutations
17 In Recurrent EGFRm NSCLC, Patients Most Frequently Present with PACC - NCM and C797S Resistance Mutations Classical mutation Non - classical mutation (including PACC - NCM) C797S Resistance 1 . Rotow JK, et al. Journal of Thoracic Oncology , 2023. Under selective pressure, patients acquire / accu
Slide 18: Favorable Tolerability Profile
18 0 10 20 30 40 50 60 70 80 90 100 Rash Diarrhea Stomatitis Weight decr Paronychia Nausea Fatigue Alopecia Vomiting Pruritus BDTX - 1535: Favorable Tolerability Profile Patients Randomized to 200mg Starting Dose Treatment Related Adverse Events (TRAE) ≥ 10% Patients Rash includes rash, rash maculo
Slide 19: Patient Demographics and Baseline Characteristics
19 *1 patient had 3 prior lines prior lines of treatment (incl. amivantamab ) BDTX - 1535: 200 mg Patient Demographics and Baseline Characteristics Efficacy evaluable patients (N=27) Baseline Characteristics 62 (41, 82) Age, median (range) 19 (70%) Female 16 (59%) ECOG PS 1 6 (22%) CNS metastases at
Slide 20: Phase 2: Patient Treatment Summary
20 Phase 2: Patient Treatment Summary 8 Response evaluable per protocol 27 3 Efficacy evaluable Patients with PACC - NCMs and/or C797S 22 19 Exclusion criteria mutations ID’d by C1D1 liquid biopsy >1 prior EGFR - targeted therapy 2 3 36% Preliminary ORR 42% Preliminary ORR Patients without on - targ
Slide 21: Phase 2 Preliminary Waterfall Plot
21 -100 -80 -60 -40 -20 0 20 40 60 B e s t % S o D c h a n g e 1015-212 4 BDTX - 1535 Phase 2 Preliminary Waterfall Plot Preliminary ORR 42% in patients w ith PACC - NCM and/or C797S uCR cPR SD uPR uPR cPR cPR SD cPR uPR SD SD SD SD SD SD SD PD Best response 33 41 55 46 40 29 63 71 75 77 24 159 51 4
Slide 22: Months on Treatment Swimmer Plot
22 0 1 2 3 4 5 6 7 8 9 10 11 26 25 23 22 21 18 17 14 13 12 11 10 9 8 7 6 5 2 1 Months on Treatment P t I D PD SD PR Best response Prior Therapy EGFR Mutation(s) Pt ID 2nd 1st C797S Non - classical Classical cPR Osi+C+pem+bev Osi C797S L833V L858R 2110 cPR HER3 - DXd Osi L718V L858R 2115 uCR C+pac Os
Slide 23: Patient 2152: Unconfirmed Complete Response and Remains on Therapy
23 Patient 2152: Unconfirmed Complete Response and Remains on Therapy Data from September 23, 2024 disclosure LN= lymph node, SoD = Sum of diameters per RECIST 1.1 Absent Present Pleura Present Absent/Normal Present LN - pleura Present Absent Present Brain Present PR 200 mg PR PR PR Baseline CR Abse
Slide 24: Eradicates EGFRm Alleles and Drives ctDNA Clearance
24 2179 2110 2097 Patient ID PR PR PR BDTX - 1535 Eradicates EGFRm Alleles and Drives ctDNA Clearance Eradication of targeted variant alleles and reduction of ctDNA are early predictors of PFS 1 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 2 4 6 8 C1D1 C3D1 %ctDNA clearance %VAF of EGFRm C797S E746_
Slide 25: Patient Mutation Profiles by Type
25 # includes Ex19del (E746_A750) and L858R; *Includes atypical Ex19dels with variable sensitivity to osimertinib ( Heymach et al ESMO 2024) ^ osimertinib - sensitive mutations (Robichaux et al Nature 2021, Heymach et al ESMO 2024) ; osi = osimertinib C797S Other NCMs* PACC NCMs Classical # Patient
Slide 26: Key Takeaways from Phase 2 Data in Recurrent NSCLC Patients
26 BDTX - 1535: Key Takeaways from Phase 2 Data in Recurrent NSCLC Patients BDTX - 1535 has a well - tolerated safety profile at 200mg once daily BDTX - 1535 achieves RECIST responses and shows promising initial durability across patients presenting with a broad - range of non - classical mutations
Slide 27: Phase 2 Status
27 BDTX - 1535 Phase 2 Status Patients with non - classical driver mutations after ≤2 prior lines of therapy with osimertinib as the preferred prior EGFR TKI Patients with acquired resistance C797S after ≤2 prior lines of therapy with osimertinib as the only prior EGFR TKI Cohort 2 (enrollment compl
Slide 28: Current Treatment Landscape for EGFRm NSCLC
28 Ami: Amivantamab Laz: Lazertinib 1 st line Locally advanced/metastatic EGFRm NSCLC 2 nd line 3 rd line Platinum Doublet +/ - Ami Platinum Doublet Docetaxel Docetaxel Osimertinib +/ - Platinum Doublet Ami + Laz Afatinib FDA label for 3 NCM Platinum Doublet Osimertinib NCCN Only Classical EGFRm Non
Slide 29: Well-Positioned for Success in Frontline EGFR-NCM NSCLC
29 Infusion - based regimens BDTX - 1535 monotherapy Intravenous Route of administration Oral once daily High rates of grade 3 AEs Safety and tolerability Generally well - tolerated Classical Mutation coverage Classical + non - classical Burdensome Patient QoL Opportunity for high QoL for year(s) BD
Slide 30: Broad Potential to Benefit EGFRm NSCLC Patients Across Multiple Lines of Therapy
30 BDTX - 1535: Broad Potential to Benefit EGFRm NSCLC Patients Across Multiple Lines of Therapy 1L non - classical mutations Recurrent setting with EGFR - resistance mutations Adjuvant/post - adjuvant 1L L858R (+) Topline Ph2 results Sept’24 Potential for longer duration of therapy, including: • No
Slide 31: Opportunity in Glioblastoma
31 BDTX - 1535: Opportunity in Glioblastoma
Slide 32: Treatment of EGFR-Driven GBM Requires Inhibition of Complex EGFR Mutations
32 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 33: Potential to Overcome Limitations of Prior Attempts to Drug EGFR in GBM
33 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 34: Encouraging Data in the Recurrent Setting; Initiating Phase 0/1b in Newly Diagnosed GBM
34 Encouraging Data for BDTX - 1535 in the Recurrent Setting; Initiating Phase 0/1b Trial in Newly Diagnosed GBM Patients Wen et al ASCO 2024, Sanai et al ASCO 2024, Sanai et al EANO 2024, Sanai et al SNO 2024, and Sanai et al AACR 2025 Ph 1 Dose Escalation in 2L+ ▪ 27 patients with recurrent diseas
Slide 35: Phase 0/1 Trial in Recurrent GBM: Exceeds Targeted Exposure
CONFIDENTIAL | 35 Phase 0/1 Trial in Recurrent GBM Patients: BDTX - 1535 Exceeds Targeted Exposure in Non - Contrast Enhancing Regions of Brain Tumors Sanai et al SNO 2024. NE = non - enhancing, E = enhancing, CSF = cerebral spinal fluid Exposure in GBM tumors exceeds IC50 for targeted mutations Dec
Slide 36: Phase 0/1b IST in Newly Diagnosed GBM Patients
CONFIDENTIAL | 36 Phase 0/1b IST in Newly Diagnosed GBM Patients: Potential to Deliver Data to Guide Future Registrational Study Phase 0/1b study: enrolling up to 48 patients with confirmed presence of EGFR alterations BDTX - 1535 as monotherapy for 5 days prior to resection Days 1 - 5 Newly diagnos
Slide 37: Anticipated Milestones Q2 2025 – 1H 2026
37 BDTX - 1535: Anticipated Milestones Q2 2025 – 1H 2026 Final Phase 2 results 2Q25 3Q25 4Q25 1H26 1L NSCLC GBM 2L /3L NSCLC Financial Summary as of December 31, 2024 Servier upfront for BDTX - 4933 Cash runway into Q4 2027 Phase 0/1 data in recurrent patients at AACR (IST at Ivy) Initial Phase 2 re
Slide 38: Thank You
Thank You Partnership: partnership@bdtx.com Investors: investors@bdtx.com Media: media@bdtx.com
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