Black Diamond Therapeutics, Inc. · NASDAQ:BDTX
Black Diamond Therapeutics — Corporate Update (December 2025)
38 slides from Black Diamond Therapeutics's corporate update, Dec 3, 2025
Slide 1: Developing MasterKey Therapies to Defeat Cancer Resistance
1 Black Diamond Therapeutics, Inc. Developing MasterKey Therapies to Defeat Cancer Resistance December 3, 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 Silevertinib : potential First and Best - in - Class 4 th
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 silevertinib BDTX - 4933 2L/3L NSCLC 1L NSCLC FGFR2/3 BDTX - 4876 Achondroplasia or solid tumors RAF/RAS mutant solid tumors Partnering opportunity Licensed to S
Slide 7: Silevertinib: Potential First and Best-in-Class 4th Generation EGFR TKI
7 Targets broad spectrum of EGFR classical, non - classical, and C797S resistance mutations in NSCLC, as well as EGFR oncogenic alterations in GBM Selective for mutations versus WT - EGFR to deliver favorable tolerability profile Oral small molecule with covalent MOA for potency and durability Demon
Slide 8: Silevertinib: Development in NSCLC
8 Silevertinib : Development in NSCLC
Slide 9: Silevertinib: Broad Potential to Benefit EGFRm NSCLC Patients Across Multiple Lines
9 Silevertinib : 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 Final Ph2 data expected Q2 2026 Fast Track Designation : C797S Potential for longer durati
Slide 10: Evolution of the EGFR mutation landscape over the past years
10 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
Slide 11: Addressing the Unmet Need in 1L EGFR-NCM NSCLC
11 Addressing the Unmet Need in 1L EGFR - NCM NSCLC The Problem: High Prevalence, Poor Outcomes Non - classical mutations (NCMs) are common and poorly served by current therapies Current TKIs deliver limited benefit to 1L NSCLC patients with NCMs There is a critical need for a brain penetrant and se
Slide 12: High Incidence of CNS Progression in EGFR-NCM Patients
12 NCM: non - classical mutations; 1: Kang et al Front Oncol 2023; 2: Wilcox et al Annals Oncology 2025; 3: Colclough et al Clin Can Res 2021 (afatinib and osimertinib ), data on file ( silevertinib ); Kpuu : unbound brain - to - plasma partition coefficient; 4. No head - to - head studies have been
Slide 13: Silevertinib Phase 1 Dose Escalation: Summary
13 Silevertinib 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 Radiographic responses and durable anti - tumor activity across multiple m
Slide 14: Silevertinib Preliminary Phase 2 Data in Recurrent Setting
14 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 complete 42 pts ) Cohort 1 (enro
Slide 15: Silevertinib Phase 2 Clinical Activity Across Broad Spectrum of EGFR Mutations
15 Silevertinib Phase 2 Clinical Activity Across Broad Spectrum of EGFR Mutations Found in Recurrent Post EGFR TKI Patients # includes Ex19del (E746_A750) and L858R; *Includes atypical Ex19dels with variable sensitivity to osimertinib ( Heymach et al ESMO 2024) ^ osimertinib - sensitive mutations (R
Slide 16: Silevertinib Preliminary Phase 2 Data in Frontline Setting
16 Silevertinib Preliminary Phase 2 Data in Frontline 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 EGF
Slide 17: Silevertinib in 1L NSCLC: Phase 2 Preliminary Summary
17 Silevertinib in 1L NSCLC: Phase 2 Preliminary Summary □ 43 frontline NSCLC patients presenting with 35 unique EGFR - NCMs enrolled □ 16/43 patients with brain metastases (7/16 with response evaluable CNS lesions) □ All patients were treated with silevertinib at a daily dose of 200mg based on expe
Slide 18: Silevertinib in 1L NSCLC: Patient Demographics and Baseline Characteristics
18 Silevertinib in 1L NSCLC: Patient Demographics and Baseline Characteristics 1L EGFR - NCM (N=43) 200mg QD silevertinib (conducted in the United States and Canada) 70.3 (44 - 91) Age in years, median (range) 12 (28) / 31 (72) Male / Female, N (%) 21 (49) / 22 (51) ECOG 0/1, N (%) 18 (42) / 25 (58)
Slide 19: Silevertinib 1L NSCLC Preliminary Waterfall Plot: 60% ORR, 86% CNS ORR
19 Silevertinib 1L NSCLC Preliminary Waterfall Plot: 60% ORR, 86% CNS ORR 2186 2247 2297 2288 2229 2210 2292 2296 2286 2298 2274 2305 2287 2221 2304 2295 2293 2214 2232 2299 2256 2276 2262 2294 2285 2300 2275 2209 2278 2261 2283 2303 2163 2302 2260 2165 2290 2279 2282 2281 Patient ID - 100 - 91.0 -
Slide 20: Silevertinib 1L NSCLC: Reduction of EGFRm VAF for all Evaluable Patients
20 Silevertinib 1L NSCLC: Reduction of EGFRm VAF for all Evaluable Patients VAF measured at C3D1 for all patients except for 2196 (EOT measurement) and 2279 (C5D1 measurement) as C3D1 samples were not ava ilable. VAF in ctDNA evaluated using Guardant Health G360 assay. 1. Patients with compound muta
Slide 21: Silevertinib 1L NSCLC Preliminary Swimmer Plot: Encouraging Durability
21 Silevertinib 1L NSCLC Preliminary Swimmer Plot: Encouraging Durability 1. Patients with compound mutations are classified as “PACC” if at least one PACC mutation is present. CNS Non - classical Mutation Structure function group 1 Patient ID T, NT G719A PACC 2165 L747_K754delinsQQ Classical Like 2
Slide 22: Silevertinib 1L NSCLC Preliminary Spider Plot: Encouraging Depth and Durability
CONFIDENTIAL | 22 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 Months on Treatment % c h a n g e i n S o D 2247 2260 2276 2261 2165 2163 2186 2210 2209 2214 2221 2229 2232 2256 2262 2274 2279 2278 2283 2286 2282 2285 2288 2287 2281 3 pts
Slide 23: CNS response in 1L NSCLC Patient: 77% Reduction in Brain Target Lesion
23 -100.0 -80.0 -60.0 -40.0 -20.0 0.0 20.0 (-2 wk) 1.4 mo 2.6 mo 4.2 mo % SoD change CNS response in 1L NSCLC Patient: 77% Reduction in Brain Target Lesion LN - lymph node; SoD= Sum of diameters per RECIST 1.1 Baseline 4 Target Lesions 1 brain, 1 lung, 2 liver SoD = 91 mm Screening Cycle 7 C7 C5 C3
Slide 24: Silevertinib Exhibits a Tolerability Profile Consistent with the EGFR TKI Class
24 Silevertinib 200 mg (n=43 1L NSCLC pts) Grade ≥ 3 Any Grade Adverse Event 19% 95% Rash or Acne 9% 77% Stomatitis 19% 74% Diarrhea 5% 72% Paronychia 0 19% Dry Skin 0 5% ALT Increase 56% TRAE Grade≥3 12% SAEs 84% Dose interruption 77% Dose reduction 9% AE Leading to DC Silevertinib Exhibits a Toler
Slide 25: Silevertinib: Key Takeaways from Phase 2 Data
25 Silevertinib: Key Takeaways from Phase 2 Data Silevertinib achieves a 60% ORR and shows promising initial durability across a patient population presenting with a broad range of 35 unique non - classical mutations Robust responses in patients with brain metastases: CNS ORR of 86% (potentially 100
Slide 26: Silevertinib: Development in Glioblastoma
26 S ilevertinib : Development in Glioblastoma
Slide 27: Treatment of EGFR-Driven GBM Requires Inhibition of Complex EGFR Mutations
27 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. 3. EGFRvIII expression based upon Noeuveglise et al ESMO OPEN 2022, French et al Neuro - Oncology 2019, Weller et al Lancet Oncology 2
Slide 28: Silevertinib: Potential to Overcome Limitations of Prior Attempts to Drug EGFR in GBM
28 Silevertinib: Potential to Overcome Limitations of Prior Attempts to Drug EGFR in GBM Lessons From Past Failures Silevertinib MOA=mechanism of action; CNS=Central Nervous System; WT=Wild - Type; GBM=Glioblastoma Multiforme; NSCLC=Non - Small Cell Lung Cancer Potent MasterKey preclinical inhibitio
Slide 29: Silevertinib: Potential to Address Deficiencies of Other EGFR Therapies
29 silevertinib Other EGFR Targeted Therapies gefitinib erlotinib osimertinib depatuximab dacomitinib afatinib paradoxical activation paradoxical activation paradoxical activation paradoxical activation Silevertinib: Potential to Address Deficiencies of Other EGFR Therapies Potency and paradoxical a
Slide 30: EGFRvIII: Covalent Homodimers Promote Potent Oncogenic Activity in GBM
30 EGFRvIII : Covalent Homodimers Promote Potent Oncogenic Activity in GBM • In EGFR WT extracellular domain cysteines are paired through intramolecular interactions; there are no free cysteines 1 • EGFRvIII is a genomic mutation resulting in a free unpaired Cys - 307 at the extracellular dimer inte
Slide 31: Silevertinib Demonstrates Potent Preclinical Inhibition of EGFRvIII
31 Silevertinib Demonstrates Potent Preclinical Inhibition of EGFRvIII and Other Alterations that are Co - Expressed with EGFRvIII Silevertinib potently inhibits EGFRvIII and co - expressed EGFR mutations present in GBM Dosing period GBM6 PDX (EGFRvIII & EGFR - Amp) Day 6 – Day 17 Silevertinib durab
Slide 32: Encouraging Data for Silevertinib in GBM Trials to Date
32 Encouraging Data for Silevertinib in GBM Trials to Date Wen et al ASCO 2024, Sanai et al ASCO 2024, Sanai et al EANO 2024, Sanai et al SNO 2024, Sanai et al AACR 2025, and Sanai et al EANO 2025 * 27 dose escalation patients presented at ASCO 2024, an additional 14 patients were dosed at 200mg pri
Slide 33: Silevertinib 200mg QD Tolerability Profile in GBM: Generally Well-Tolerated
33 Ivy Phase 1 (n=21 )^ BDTX Phase 1 (n=17)* Any Grade Grade ≥3 Any Grade Adverse Event NA 6% 82% Rash or Acne NA 0% 41% Diarrhea NA 0% 24% Stomatitis NA 0% 12% Paronychia NA 6% 6% ALT Increase NA 0 0% Dry Skin 28.6% 35% TRAE Grade≥3 4.8% 6% SAEs 28.6% 29 % Dose interruption 0% 6% Dose reduction 0%
Slide 34: Phase 0/1 IST in Recurrent GBM Patients: Silevertinib Exceeds Targeted Exposure
34 Phase 0/1 IST in Recurrent GBM Patients: Silevertinib Exceeds Targeted Exposure in Non - Contrast Enhancing Regions of Brain Tumors Sanai et al EANO 2025. NE = non - enhancing, E = enhancing, CSF = cerebral spinal fluid Exposure in GBM tumors exceeds IC50 for targeted mutations (measure d in pati
Slide 35: Newly Diagnosed GBM Patient Journey: Limited Options for Patients
35 AT: adjuvant therapy after radiation; CRT: chemoradiation; HR: hazard ratio; M: methylated; MGMT: methylguanine methyltransferas e; mos : months; UM: unmethylated; PD: progressive disease Newly Diagnosed GBM Patient Journey: Limited Options for Patients Newly diagnosed GBM (MRI) 4 - 8 weeks Surge
Slide 36: Design Principles: Randomized Phase 2 Trial in Newly Diagnosed GBM
36 Design Principles: Randomized Phase 2 Trial in Newly Diagnosed GBM Focus on combination of silevertinib with TMZ (vs. TMZ alone) in unmethylated patients • Area of highest unmet medical need • Preclinical data support combining TMZ and silevertinib ; no anticipated DDI/safety concerns Randomize p
Slide 37: Randomized Phase 2 of Silevertinib + TMZ in Newly Diagnosed GBM
37 SLV: silevertinib ; TMZ: temozolomide; ND – newly diagnosed; BICR: Blinded Independent Central Review; IDMC: Independent Data Monitoring Committee Randomized Phase 2 of Silevertinib + TMZ in Newly Diagnosed GBM R 1:1 PART 1: SLV+TMZ safety run - in ≤12 pts COMPLETION OF CHEMORADIATION Control arm
Slide 38: Advancing Pipeline Across Multiple Oncology Indications
38 Advancing Pipeline Across Multiple Oncology Indications Target Drug Candidate Indication Pre - clinical Phase 1 Phase 2 Phase 3 EGFR RAF silevertinib BDTX - 4933 2L/3L NSCLC 1L NSCLC FGFR2/3 BDTX - 4876 Achondroplasia or solid tumors RAF/RAS mutant solid tumors Partnering opportunity Licensed to
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