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1 Black Diamond Therapeutics, Inc. Developing MasterKey Therapies to Defeat Cancer Resistance November 6, 2025
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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, and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward looking statements contained in this presentation include, but are not limited to, statements regarding our future financial or business performance, conditions, plans, prospects, trends or strategies and other financial and business matters, the continued development and advancement of silevertinib, the progress, timing and success of our clinical trials of silevertinib and any of our future product candidates, including the availability, timing and announcement of data and results of such trials, our ability to replicate results achieved in our preclinical studies or clinical trials, the expected timing for regulatory feedback and the disclosure of potential registrational pathways for silevertinib, the potential of silevertinib to address the unmet medical need for newly diagnosed non-small cell lung cancer (“NSCLC”) patients with non-classical EGFR mutations and benefit patients with NSCLC across multiple lines of therapy, the potential future development plans for silevertinib in NSCLC and glioblastoma, the competitive landscape and market for silevertinib or any of our other current or future product candidates, our ability to maintain our intellectual property portfolio, and the timing and success of our development and commercialization of our product candidates, including our ability to establish and maintain collaborations or strategic relationships. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by law, we assume no obligation to update these forward looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward looking statements, even if new information becomes available in the future. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward looking statements, see the section entitled “Risk Factors” in our most recent annual report on Form 10-K filed with the Securities and Exchange Commission (the “SEC”), as well as discussions of potential risks, uncertainties, and other important factors in our other subsequent filings with the SEC. In addition, we have not conducted any head to head studies comparing our product candidates to any third party drug products or candidates, whether investigated or approved. Information regarding other drug products in this presentation is meant to provide context for illustrative purposes only. Because there are no head to head studies, no conclusions should be made based on cross study comparisons. Recipients are cautioned not to place undue reliance on these forward looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. This presentation also contains information using industry publications that generally state that the information contained therein has been obtained from sources believed to be reliable, but such information may not be accurate or complete. While we are not aware of any misstatements regarding the information from these industry publications, we have not independently verified any of the data from third party sources nor have we ascertained the underlying economic assumptions relied on therein.
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3 Cancer is a Complex and Ever-Evolving Disease Currenttargeted therapies were designed against a limitedsubset 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 approach aims to provide one solution for many mutations and expand addressable patient population Our oral therapies are designed so that patients have the opportunity for a longer, healthier, active life
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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: best/first- in-class 4th-generation EGFRi in Ph2 for NSCLC, additional opportunity in GBM Pipeline of oral, brain penetrant drug candidates selectively targeting families of oncogenic mutations Multiple clinical catalysts including silevertinib Phase 2 data in 1L NSCLC patients in Q4 2025 Lean organization with runway into 4Q 2027; ended Q3 2025 with $135.5M
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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 types Potent against broad mutation families (including drug resistance mutations) Selective targeting to deliver well-tolerated therapies
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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 Servier* GBM Final Ph2 data expected H1 2026 FDA Fast Track Designation for C797S+ Patients Initial Phase 0 PD data expected in newly diagnosed patients H1 2026 Ph2 ORR/preliminary duration of treatment data Q4 2025 Ph2 PFS data and FDA feedback expected H1 2026 Exploring partnering opportunities for pivotal development *BDTX eligible for $710M in development and commercial milestones + royalties
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7 16 158 194 0 0 0 69 69 69 167 167 167 5 80 157 147 28 31 16 158 194 189 210 214 200 240 250 69 69 69 167 167 167 226 226 226 Targets broad spectrum of EGFR classical, non-classical, and C797S resistance mutations Selective for mutations versus WT-EGFR to deliver favorable tolerability profile Oral small molecule with covalent MOA for potency and durability Demonstrated pharmacologically relevant exposure in brain tumor tissue and CNS responses in NSCLC Phase 2 ongoing in both recurrent and frontline EGFRm NSCLC; Phase 0/1 in newly diagnosed GBM; over 200 patients treated since Phase 1 initiation in 2022 Initial indications in frontline non-classical EGFRm NSCLC and EGFR+ GBM represent $2bn+ peak opportunity, with potential to expand to other lines of therapy Silevertinib: Potential First and Best-in-Class 4th Generation EGFR TKI MasterKey Spares WT-EGFR Covalent Brain-Penetrant Robust Clinical Activity Significant Commercial Potential
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8 Evolution of the EGFR mutation landscape over the past 20 years NGS revolutionMutation specific sequencing 2005 (2/3L) 2013 2015 2018 2024 T790M resistance C797S resistance Non-classical drivers Classical drivers L858R / Ex19del Realization of EGFR non -classical mutations (NCMs) Treatments Sequencing practices Classical EGFR mutations described Mutation landscape Silevertinib: opportunity to address unmet need for non-classical drivers and C797S resistance mutations silevertinib (1L) (2L) (1L) The EGFR Mutational Landscape in NSCLC has Evolved, Revealing a Broad Spectrum of Unaddressed Non-Classical Oncogenic Driver & Drug Resistance EGFR Mutations silevertinib (1/2/3L)
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9 23-30% of newly diagnosed EGFRm NSCLC express non-classical mutationsClassical and non-classical driver mutations are distributed across EGFR structure 23-30% of Newly Diagnosed EGFRm NSCLC Patients Carry Non -Classical Mutations (NCMs); Not Adequately Addressed by Current Therapies 1. Borgeaud M. JTO 2024 2. Robichaux J, Nature 2021 Dardenne et al AACR 2024 and Heymachet al ESMO 2024 Black Diamond Therapeutics analyses of 94,939 sequencing reports from treatment naïve NSCLC Non-Classical Classical: L858R and Exon19del Adapted from Du et al. 2023. Analysis of the AACR GENIE database of 22,050 cases of NSCLC 23% 30% Ectodomain- Juxtamembrane (non-classical) PACC2 & others (non-classical) 50+ mutations 60+ mutations R108X R222X A289X C598X S645X … E709X G719X T725M L754E L747X S768I V769X L861X L833X … Non-Classical Exon20ins Classical Current therapies do not adequately address non-classical EGFR mutations1
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CONFIDENTIAL | 10Heymach 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 AfatinibChemo+/- I/OOsimertinib Afatinib Afatinib: 8.0 months Chemo +/- I/O: 4.2 months Time (Months) Time on Treatment (Survival Probability) 0.0 0.2 0.4 0.6 0.8 1.0 15 11 11 20 4 6Osimertinib 0 90 104 5 54 38 Osimertinib: 6.0 months 10 27 19 Chemo +/- I/O 20 14325 95 44 Afatinib: 16.7% Chemo +/- I/O: 60.1% Osimertinib: 19.4% Chemotherapy used in ~60% of 1L patients, with osimertinib and afatinib used for the remainder Median time on treatment for 1L NCM NSCLC is < 8 months
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11 16 158 194 0 0 0 69 69 69 167 167 167 5 80 157 147 28 31 16 158 194 189 210 214 200 240 250 69 69 69 167 167 167 226 226 226 Addressing the Unmet Need in 1L EGFR-NCM NSCLC The Problem: High Prevalence, Poor Outcomes Non-classical mutations are common and poorly served by current therapies ▪ 23–30% of newly diagnosed EGFRm NSCLC patients have non-classical mutations ▪ NCMs are highly diverse (~100 variants*), often co-expressed or structurally complex ▪ ~60% receive chemotherapy; median 1L treatment duration is ≤8 months Current TKIs deliver limited benefit to 1L NSCLC patients with NCMs There is a critical need for a brain penetrant and selective TKI to address NCM spectrum Limitations of Current Therapies Silevertinib is brain penetrant and demonstrates high potency across the spectrum of NCMs ▪ Potential to address all major EGFRm NSCLC settings—classical, non-classical, and resistant ▪ Maintains activity where osimertinib loses potency (e.g., G719X, E709X, S768I) ▪ Demonstrates CNS activity ▪ Mutant-selective profile with potential to reshape 1L EGFR-NCM treatment The Opportunity: Silevertinib mPFS >15 mo and ORR >60% in 1L EGFR-NCM NSCLC would be clear win for silevertinib vs. current therapies Mutation Type Osimertinib mPFS Afatinib mPFS All NCMs 7.0mo (n=55) 9.4mo (n=40) ARTICUNO (2024) UNICORN (2024) 10.6mo(n=70) 6.1mo (CNS; n=17) ACHILLES (2025) Kang et al 2023 Three common NCMs in afatinib FDA label G719X S768I L861Q 5.1mo (n=20) 9.4mo (n=10) 16.0mo(n=12) UNICORN (2024) UNICORN (2023) 9.5mo (n=44) ACHILLES (2024) Other NCMs 4.0mo (n=27) ARTICUNO(2024) 8.6mo (n=6) ACHILLES (2024) Classical mutations Ex19del L858R 21.4mo 14.4mo FLAURA(2021) 13.7mo 9.6mo LUX-Lung 6 (2014) *Guarda ntInformdata derived from collaboration with Guardant Health – data on file at BDTX. UNICO RN-2024: Okuma et al JAMA Oncology 2024. UNICORN-2023: Bar et al JTO 2023. ARTICUNO: Pizzutiloet al E SMO O pen 2024, mPFSfor all NCM represents data for Group A TKI naïve patients, mPFSfor other NCMs is for n=27 pa tients, for whom all but 2 were TKI-naive. FLAURA: Soria et al NEJM 2018. Afatinib mPFSfrom ACHILLES Sato et al ASCO 2024. mo= months
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12 NCM: non-classical mutations; 1: Kang et al, 2023; 2: Wilcox et al, 2025; 3: Colclough et al Clin Can Res 2021 (afatinib and osimertinib), data on file (BDTX-1535) High Incidence of CNS Metastases on Frontline Afatinib or Osimertinib in Patients with EGFR-NCM NSCLC: Potential for Better Activity with Silevertinib Silevertinib delivers best-in-class brain penetration3 Incidence of CNS metastases on 1L osimertinib2 Incidence of CNS failure on 1L afatinib1
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13 100mg SilevertinibAchieves Coverage of the EGFR Mutation Spectrum at the Well-T olerated Oral Dose of 200mg QD *Cmax doses plotted for human PK. PK data adapted from poster at EORTC/AACR/NCI International Conference on Molecular Targets and Cancer Therapeutics, October 2023. Dardenne et al AACR 2024 WT L858R Ex19del Ex19del+S768I L858R+A859S L858R+A289V L858R+L62R L858R+EGFRvIII L858R+G598V L858R+S784F L858R+S784S L858R+E709K L858R+E709V L858R+R108K L858R+V834L K754E L833V T725M A763insLQEA S811F L861Q L861R A763insFQEA S784F G719A G719S L833V G724S L747P L747S E709K I740dupIPVAIK R776H E709A E709V E709G S768I V769L V769M E709Q G779F L833F E709-T710delinsD L718Q G719C+S768I L858R+L747S E709A+G719S E709K+G719S S768I+V769L L858R+L718V G719A+R776C L858R+S768I L858R+L792H Ex19del+L718Q S768I+V774M V1097I G719C P772L Q812R G719A+R776C G719D D761Y G719R G719A+L861R S720F G779C V774insPR I744_K745insKIPVAI R222C R108K A289T EGFRvVI (Del 12-13) V689M G598V C595S EGFRvVII (Del 14-15) C231F S645C A289V EGFRvIII (Del 2-8) EGF:Sept14 fusion Ex19del+C797S L858R+C797S 0 20 40 60 80 100 120 Proliferation (IC50) nM L858R+ Non-Classical Classical-Like P-Loop and αC-Helix Compressing (PACC) Other Non-Classical Ecto- and Juxtamembrane Domain PACC Alone PACC Complex EGFR Non-Classical MutationsClassical EGFR-WT C797S PK data from Phase 1 dose escalation trial* 200mg
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CONFIDENTIAL | 14 Silevertinib Potently Targets NCMs Which Are Less Sensitive to Osimertinib loss of potency Osimertinib: weak against most NCMs (most commonly expressed NCMs shown) Silevertinib: potent against NCM spectrum (most commonly expressed NCMs shown) Pre-clinical data; EGFR mutations are engineered in Ba/F3 cells Silevertinib: potent against NCMs co-expressed with L858R (co-expressed NCMs shown) G719C L858R Ex19del L861Q G719A L747P E709A S768I G719S E709K E709V G719C L858REx19del L861Q G719A L747P E709AS768I G719S E709K E709V EGFR mutations frequently associated with L858R osimertinib silevertinib
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15 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 present as compound mutations together with the classical L858R mutation NCMs more frequently co-occur with L858R vs Ex19del L858R Ex19dels 0 2 4 6 8 10 12 14 % of cases with EGFR Non-Classical mutation E709X V834L R776X L833XS768I L62R A289X Others T725M R108K 10 15 0.0 0.2 0.4 0.6 0.8 1.0 Ex19del: 14.7 months L858R: 10.8 months 0 1,054 642 62 5 664 360 25 438 217 14 291 130 10 20 185 70 5 L858R + NCM: 5.0 months Time on Treatment (Survival Probability) Time (Months)Heymach et al ESMO 2024
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16 Silevertinib Phase 1 Dose Escalation: Summary Mutation Matched Phase 1 Study Inclusion Criteria Once-daily dosing delivers sufficient exposure to inhibit EGFR mutations Manageable EGFR TKI tolerability profile at 200 mg (similar to osimertinib) Radiographic responses and durable anti-tumor activity across multiple mutation families ctDNA reduction confirms loss of mutant alleles, which is predictive of clinical benefit 1 Data at EORTC 2023 Ph 1 NSCLC Key Data Takeaways • Primary objective: PK and safety • Secondary objective: Anti-tumor activity Dose Escalation Completed: 15 mg QD to 400 mg QD 15 mg QD 25 mg QD 50 mg QD 100 mg QD 200 mg QD 300 mg QD 400 mg QD Recurrent GBM Cohort EGFR alterations at resection/diagnosis Wild-type isocitrate dehydrogenase (IDH) Recurrent NSCLC Cohort EGFR mutations at the time of progression: – Non-classical driver, OR – Acquired resistance C797S Progression after EGFR TKI Exclusion of EGFR T790M, Ex20ins, KRAS mutations, cMET amplification • Target coverage and clinical activity at ≥ 100 mg, MTD at 300 mg 1. Thompson, JC., et al., British Journal of Cancer, 2023.
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17 Silevertinib 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 TKI Cohort 2 (enrollment complete 42 pts) Cohort 1 (enrollment complete 41 pts) Patients with non-classical driver mutations and no prior treatment Cohort 3 (enrollment complete 43 pts) 1st Line 2nd/3rd Line Initial data on 27 pts reported Sept 2024 ORR/preliminary duration of treatment data Q4 2025
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18 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 / accumulate EGFR resistance mutations osimertinib therapy PACC-NCMs and C797S are major mechanisms of on-target EGFR resistance in patients post osimertinib1 Recurrent Newly Diagnosed EGFRm NSCLC Dardenne et al. AACR 2024. Heymach et al. ESMO 2024. ClassicalNon-classical Exon 20
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19 0 10 20 30 40 50 60 70 80 90 100 Rash Diarrhea Stomatitis Weight decr Paronychia Nausea Fatigue Alopecia Vomiting Pruritus Silevertinib: Favorable Tolerability Profile Patients Randomized to 200mg Starting Dose Treatment Related Adverse Events (TRAE) ≥ 10% Patients Rash includes rash, rash maculo-papular, rash pustular, dermatitis acneiform. AEs in greater than two patients % of patients (n=20) Grade 1-2 Grade 3 Data from June 2024 in cohort 1 and 2 patients Data Summary • No grade 3/4 diarrhea • No liver enzyme elevation • No QTc prolongation • 1/20 patient discontinued • 4/20 patients dose reduced No new safety/ tolerability signals observed to date
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20*1 patient had 3 prior lines prior lines of treatment (incl. amivantamab) Silevertinib: 200 mg Patient Demographics and Baseline Characteristics Baseline Characteristics Efficacy evaluable patients (N=27 from cohorts 1 and 2) Age, median (range) 62 (41, 82) Female 19 (70%) ECOG PS 1 16 (59%) CNS metastases at baseline 6 (22%) Visceral metastases at baseline 9 (33%) Prior lines of anticancer treatment* 1 2 14 (52%) 12 (44%) Mutation Stratification Cohort 1 (NCMs) Cohort 2 (C797S) 15 (56%) 12 (44%) Data from September 23, 2024 disclosure
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21 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-target resistance mutation Data from September 23, 2024 disclosure
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22 -100 -80 -60 -40 -20 0 20 40 60 Best % SoD change 1015-212 4 SilevertinibPhase 2 Preliminary Waterfall Plot Preliminary ORR 42% in patients with PACC-NCM and/or C797S Best response PD SD SD SD SD SD SD SD uPR cPR SD cPR cPR uPR uPR SD cPR uCR Sum Target Lesion (mm) 22 89 48 46 46 51 159 24 77 75 71 63 29 40 46 55 41 33 *Retrospective liquid and tissue biopsy NGS testing; Pt 2118 withdrew consent prior to first scan (see patient in swimmer plot) O-osimertinib; A- afatinib; C- carboplatin, Cis – cisplatin, Pem- pemetrexed; Pac- paclitaxel; B- bevacizumab; HER3-Dxd- patritumabderuxtecan; Patient ID 2199 2124 2160 2197 2169 2158 2181 2184 2198 2179 2172 2115 2097 2208 2207 2195 2110 2152 mEGFR* Classical L858R L858R E19del L858R L858R Ex19del Ex19del L858R NCM E709A E19delinsD R108K K745N Ex19Ins- IPVAIK K745N L747_P753 delinsS L747_A750 delinsP G719A S768I L747_P753 delinsS L718V G930R Y1016C G719A S768I L718V V774M S768I L747_A755 delinsSKD L833V G719S S768I C797S C797S C797S C797S C797S C797S C797S C797S C797S C797S Prior 1L Duration, months O 19.6 O 1.5 O 25.8 O 20.8 O 22.8 O 23.5 O+Cis+Pem 1.4 Osi 19.0 O+B 67.5 C+pac 1.3 O 5.1 O 24.9 O 38.3 A 13.9 O 14.1 O 15.8 O 50.0 O 8.5 Prior 2L Duration, months O+C+Pem 6.4 O+C+Pac 6.9 O+C+Pem 4.0 Osi 16.8 O+C+Pem 3.0 HER3-Dxd 0.8 O+C+Pem+ B 26.6 C+Pac 1.8 Off-Pathway Detected RTK MAPK PI3K RTK TK/MAPK Cohort 1- NCM: 4/9 pts w/ responses Cohort 2- C797S: 4/10 pts w/ responses Remains on therapy Data from September 23, 2024 disclosure
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23 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 Pt ID PD SD PR Pt ID EGFR Mutation(s) Prior Therapy Best responseClassical Non-classical C797S 1st 2nd 2110 L858R L833V C797S Osi Osi+C+pem+bev cPR 2115 L858R L718V Osi HER3-DXd cPR 2152 G719S; S768I Osi C+pac uCR 2158 L747_A750delinsP C797S Osi SD 2160 L858R R108K C797S Osi SD 2097 Exon 19del C797S Osi cPR* 2169 L747_P753delinsS C797S Osi SD 2172 G719A; S768I Osi Osi+C+Pem SD 2179 L858R Y1016C C797S C+pac Osi cPR 2181 G719A; S768I Osi+C+pem Osi+C+pac SD 2184 Exon 19del C797S Osi SD 2124 E709_T710delinsD Osi SD 2195 Exon 19del C797S Osi SD 2197 K745_E746insIPVAIKK745N Osi Osi+pem+C SD 2199 L858R E709A Osi PD 2198 L718V; L747_P753delinsS; G930R Osi+bev Osi+C+pem uPR 2207 L747_A755delinsSKD C797S Osi uPR 2208 V774M; S768I Afatinib uPR 2118 L747_T751del; V834L C797S Osi C+pem/CPI WC Ongoing uCR N=19 in swimmer plot, including Pt 2118 who withdrew consent (WC) prior to first scan *Patient discontinued (pneumonitis) Silevertinib Phase 2 Preliminary Swimmer Plot Encouraging durability with 14 out of 19 patients still on therapy Mean follow-up: 4.7 months Data from September 23, 2024 disclosure
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24 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 Pleura Present Present Absent LN- pleura Present Present Absent/Normal Brain Present Present Absent PR 200 mg PR PR PRBaseline CR Brain Present Present Absent 1 Target Lesion Omentum SoD = 33 mm 5 Non-Target lesions -100.0 -80.0 -60.0 -40.0 -20.0 0.0 20.0 (-1 mo) 1.5 mo 3 mo 4.5 mo 6.0 mo 7.5 mo % SoD change Mutations and Prior Therapies Mutations: 2 NCMs: G719S and S768I Prior Therapies: 1L osimertinib 8 months 2L carbo/pem 2 months Screening C7D1 Mesentery Present Present Absent
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25 Patient ID 2097 2110 2179 PR PR PR SilevertinibEradicates EGFRm Alleles and Drives ctDNA Clearance Eradication of targeted variant alleles and reduction of ctDNA are early predictors of PFS1 -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_A750del ctDNA -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 3 C1D1 C3D1 %ctDNA clearance %VAF of EGFRm C797S L833V L858R ctDNA -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 2 4 6 8 C1D1 C3D1 %ctDNA clearance %VAF of EGFRm C797S L858R Y1016C ctDNA Of 8 patients with PRs, ctDNA testing on 3 patients shown above, insufficient DNA on 2 patients, and pending testing on 3 patients 1. Thompson, JC., et al., British Journal of Cancer, 2023 Data from September 23, 2024 disclosure
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26 # 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 Patient ID Classical# PACC NCMs Other NCMs* C797S 2195 Exon 19del C797S 2184 Exon 19del C797S 2097 Exon 19del C797S 2110 L858R L833V C797S 2160 L858R R108K C797S 2179 L858R Y1016C C797S 2158 L747_A750delinsP^ C797S 2169 L747_P753delinsS^ C797S 2207 L747_A755delinsSKD^ C797S 2118 L747_T751del^; V834L C797S 2115 L858R L718V 2199 L858R E709A 2152 G719S; S768I 2172 G719A; S768I 2181 G719A; S768I 2124 E709_T710deInsD 2197 K745_E746insIPVAIK K745N 2208 V774M; S768I 2198 L718V L747_P753delinsS^; G930R 2203 L747P_P753delinS^ 2101 L861Q^ 2188 L861R^; L62R 9 pts with PACC-NCMs 10 pts with C797S 3 pts with other NCMs All mutations identified with common practice NGS Silevertinib Phase 2 Clinical Activity Across Broad Spectrum of EGFR Mutations Found in Recurrent Post EGFR TKI Patients Preliminary ORR of 42% in 19 patients with PACC-NCM or C797S mutations Pts w/ PR Data from September 23, 2024 disclosure • Patients with osi-sensitive NCMs without any EGFR resistance mutations. • silevertinibexpected to deliver benefit in patients with these mutations in 1L setting.
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27 Silevertinib: Key Takeaways from Phase 2 Data in Recurrent NSCLC Patients Silevertinib has a well-tolerated safety profile at 200mg once daily Silevertinib achieves RECIST responses and shows promising initial durability across patients presenting with a broad-range of non-classical mutations including PACC and C797S Silevertinib achieves RECIST responses in brain metastases Silevertinib has also demonstrated brain penetrance in a Phase 0/1 trial of patients with recurrent GBM Data in recurrent NSCLC patients highlight favorable properties for continued development in newly-diagnosed patients with NCMs
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28 Silevertinib 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 complete 42 pts) Cohort 1 (enrollment complete 41 pts) Patients with non-classical driver mutations and no prior treatment Cohort 3 (enrollment complete 43 pts) 1st Line 2nd/3rd Line Final data expected H1 2026 ORR/preliminary duration of treatment data Q4 2025
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29 Current Treatment Landscape for EGFRm NSCLC 1st line Locally advanced/metastatic EGFRm NSCLC 2nd line 3rd line Osimertinib +/- Platinum DoubletAmi + Laz Afatinib FDA label for 3 NCM Platinum Doublet Osimertinib NCCN Only Classical EGFRm Non-classical EGFRm Platinum Doublet +/- Ami Docetaxel Platinum Doublet Docetaxel Ami: AmivantamabLaz: Lazertinib Silevertinib 1L NCMs Silevertinib Recurrent (2L+) On Target Progression via EGFR Mutations (e.g., C797S, PACC-NCMs) Dato-DXd (2L+)
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30 Silevertinib monotherapy Infusion-based regimens Oral once daily Route of administration Intravenous Generally well-tolerated Safety and tolerability High rates of grade 3 AEs Classical + non-classical Mutation coverage Classical Opportunity for high QoL for year(s) Patient QoL Burdensome Silevertinib: Well-Positioned for Success in Frontline EGFR-NCM NSCLC No head-to-head study has been conducted between silevertinib monotherapy and chemo-based combination regimens.
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31 Silevertinib: Broad Potential to Benefit EGFRm NSCLC Patients Across Multiple Lines of Therapy 1L non-classical mutationsRecurrent setting with EGFR resistance mutations Adjuvant/post-adjuvant 1L L858R Final Ph2 data H1 2026 Fast Track Designation: C797S Potential for longer duration of therapy, including: • Non-classical adjuvant setting • 1L patients with EGFR- resistance mutations post-adjuvant osimertinib Highly potent vs. L858R alone and co-expressed non- classical mutations Targeting OS benefit in EGFR L858R NSCLC ~5,000 – 11,000 ~18,000 – 22,000 ~7,000 – 14,000 ~27,000 – 30,000 Ph2 ORR/preliminary duration of treatment data Q4 2025 Ph2 PFS data and FDA feedback expected H1 2026 Data Monitor Pharma Intelligence; Zhang Oncotarget2016; HeymachESMO 2024; Kantar Treatment Architecture; Rotow JTO 2023; BDTX Internal Data Analysis; Foundation Med AACR 2023; Bertoli Int J Mol Sci 2019; Piotrowska Annals of Oncology 2022 Estimated Addressable Patients in G7 Countries
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32 Silevertinib: Opportunity in Glioblastoma
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33 1. Saadeh, F., et al., The International Journal of Biological Markers, 2018 2. Real world evidence data from Tempus Labs analysis of 2,540 GBM patient samples. 3. EGFRvIIIexpression based upon Noeuveglise et al ESMO OPEN 2022, French et al Neuro-Oncology 2019, Weller et al Lancet Oncology 2017 Treatment of EGFR-Driven GBM Requires Inhibition of Complex EGFR Mutations, Particularly EGFRvIII: Potent Preclinical Inhibition by Silevertinib Of all GBM patients express EGFRvIII, which has been demonstrated to be a potent oncogenic driver ~30% 3 ~40% 2 ~50% 1 Of all GBM patients have more than one oncogenic EGFR alteration Of all GBM patients carry oncogenic EGFR alterations ~7,000 GBM patients in the US are diagnosed each year with EGFR mutations that have been shown in preclinical studies to be inhibited by silevertinib
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34 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 inhibition of co-occurring EGFR alterations and amplification Heterogenic expression of EGFR oncogenic alterations within tumors Covalent MOA and no paradoxical activation Paradoxical activation of EGFR GBM oncogenes induced by reversible inhibitors Spares WT-EGFR in normal cells while retaining potent activity against EGFR alterations Poor tolerability driven by on target WT-EGFR activity Brain-penetrant to treat CNS tumors Low brain exposure due to a lack of CNS penetrance
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35 Silevertinib Demonstrates Potent Preclinical Inhibition of EGFRvIII and Other Alterations That Can Be 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 durably inhibits EGFRvIII activity in vivo following a single oral dose Silevertinib is efficacious in an intracranial PDX model with EGFRvIII Control 4hr 8hr 10hr 12hr 24hr 0 20000 40000 60000 80000pEGFR (p1068) Ba/F3 allograft (EGFRvIII) Durable inhibition of pEGFR following single oral 50mg/kg dose of silevertinib BDTX data on file and presented at AACR 2023 Annual Meeting. Phenotypic IC50 reflects cellular antiproliferative IC50 corrected for protein binding. GBM6 PDX study conducted at UCSF neuro oncology core facility; 50mg/kg silevertinib dosed orally over the indicated dosing period.
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36 Encouraging Data for Silevertinib in the Recurrent Setting; Initiated Phase 0/1 IST 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, Sanai et al AACR 2025, and Sanai et al EANO 2025 Ph 1 Dose Escalation in 2L+ ▪ 27 patients with recurrent disease ▪ Generally well tolerated @ 200mg ▪ Preliminary efficacy/RANO response Confirmed safety Data at ASCO 2024 Initial PD data expected H1 2026 Ph0 PD data, and potential Ph1 OS readout ▪ Up to 48 newly diagnosed patients ▪ Pre/post tx biopsies and PD (Ph 0) ▪ Treatment phase and OS (Ph 1) Phase 0/1 IST in 1L Data at ASCO/EANO/SNO 2024 AACR/EANO 2025 Confirmed brain exposure ▪ 24 patients with recurrent disease ▪ Demonstrated brain exposure ▪ Preliminary PD/efficacy Phase 0/1 IST in 2L+ Encouraging clinical activity in recurrent setting
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CONFIDENTIAL | 37 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 (measured in patients dosed 5 days @ 200mg QD) Decreased pEGFR vs. pretreatment archival tissue phosphoEGFR
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CONFIDENTIAL | 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 Servier* GBM Final Ph2 data expected H1 2026 FDA Fast Track Designation for C797S+ Patients Initial Phase 0 PD data expected in newly diagnosed patients H1 2026 Ph2 ORR/preliminary duration of treatment data Q4 2025 Ph2 PFS data and FDA feedback expected H1 2026 Exploring partnering opportunities for pivotal development *BDTX eligible for $710M in development and commercial milestones + royalties
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