Precision Oncology Medicines

Pioneering the Development of MasterKey Therapies

SEPTEMBER 2021

1 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, express or implied statements regarding our ability to advance and expand the MAP platform, the potential timing and advancement of our clinical trial and preclinical studies, including our clinical trial for BDTX-189, the timing and potential achievement of milestones to advance our product candidate pipeline, including initiation of additional investigational new drug (“IND”)- enabling studies, filing INDs and product candidate nomination, the potential commercial opportunities, including value and market, for our product candidates, and our expectations regarding our use of capital and other financial results. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Our actual future results may be materially different from what we expect due to factors largely outside our control, including the results of clinical trials, clinical trial patient enrollment, changes in regulatory requirements or decisions of regulatory authorities, commercialization plans and timelines if approved, the actions of our third party clinical research organizations, suppliers and manufacturers, and the impact that the current COVID-19 pandemic will have on our clinical trials, pre-clinical studies, and operations. 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 2020 annual report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the Securities and Exchange Commission. All information in this presentation is as of the date hereof, and we undertake no duty to update this information unless required by law. Certain information contained in this presentation relates to, or is based on, studies, publications, surveys and other data obtained from third party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.

2 Black Diamond Therapeutics Overview Expanding the Reach of Precision Medicine Through the Development of Novel MasterKey Therapies

Addressing significant unmet need for novel precision oncology therapies for patients with genetically defined cancers with limited treatment options

Significant market opportunity by uniquely de-orphaning oncogenic mutations to develop single therapies designed to inhibit specific mutation families

Our proprietary computational Mutation Allostery Pharmacology (MAP) drug discovery engine is designed to: • Analyze population-level genetic sequencing data to identify oncogenic mutations that promote cancer across tumor types • Aggregate these mutations into families • Develop a spectrum-selective (MasterKey) small molecule therapy

Robust pipeline of oral, potent and selective small molecule kinase inhibitors across a range of indications and target groups including EGFR, HER2, BRAF and FGFR

4 MAP Platform Enables Black Diamond to Develop MasterKey Therapies that Address a Significant Unmet Need for Patients with Genetically-Defined Cancers

Classic/Current Approach: Black Diamond Approach: Targeting active site kinase Targeting allosteric mutations to expand domain mutations the opportunity for precision oncology

With expanding genetic profiling of cancer patients via Next Generation Sequencing (NGS) Aggregation of mutations yields significant Targeting single mutations market opportunities for populations lacking in individual tumor types Only 9% of patients with metastatic suitable therapies cancer eligible for approved precision oncology medicines

5 Wholly-Owned Novel Classes of Precision Medicines

Drug Target Candidate Indication Discovery Optimization IND-Enabling Phase 1 Phase 2 Phase 3

Multiple solid EGFR BDTX-189 tumors (incl. HER2 NSCLC and breast) Milestone: Initiate Phase 2 Portion (2H 2021)

EGFR BDTX-1535 GBM, NSCLC

Milestone: IND (1H 2022)

BRAF Undisclosed Multiple solid tumors Milestone: IND (2022)

FGFR Undisclosed Multiple solid tumors Milestone: IND (2022)

6 MAP Platform MAP Platform Unlocks Precision Medicine Strategies With a “MasterKey”

COMPUTATIONAL BIOLOGY MAP SCORE Predict oncogenicity in silico

Harmonize NGS data Genomics Proteomics using custom-built algorithm +

Mutant A Mutant B Mutant C Mutant D BIOLOGICAL VALIDATION PHARMACOLOGY MASTERKEY THERAPY Validate novel targets and novel Identify lead candidates oncogenic mutations active against mutational families

Mutant A Mutant B Mutant C ALLOSTERY Aggregate oncogenic mutations into families 8 Mutations: Proprietary Machine Learning Used to Identify Oncogenic Mutations Previously Unknown or Thought to be Undruggable

100s Unique Mutations Prevalence(1og10) 1e−06 1e−05 1e−04 1e−03 Data 1 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

● Protein Mutation ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

● Interface Exclusivity ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

Analyze ● ● ● ● ● ● ● ● ● ● Predicted oncogenic ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 201 ● ● ●

population- ● ● ● ● ● ● mutations ● ● ● FGFR3 Mutation Pre ● ●

● MAP ● Protein ● ● ● Structural ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● level genetic ● Motifs Dynamics ● ● ● ● ● ● ● ● ● ● ● ● ●

● Score ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

sequencing ● ● ● FGFR3 AA position ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● v ● ● ● ● ● ● ● ● ● ● ● ● ● ● alence Solid T ● ● ● ● ● ● ● ● ● ● ●

● ● ● Mutation ● ● 401 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

to identify ● ● data ●

● ● ● Conservation ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

● ● ● ● Landscape ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

potential ● ● ● ● ● ● ● ● ● ● ● ● ● ● umor (GENIE) ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

● (MAP Score) (MAP ● ● ● ● ● ● ● ● ● ● ●

oncogenic ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● mutations 601 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

● ● Oncogene Prediction Oncogene ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

● ● MAP Algorithm ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 801 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

9 Allostery: MAP Platform Aggregates Allosteric Mutations Driving Similar Conformational Changes into Families

Intact cellular assays and tumor models are utilized for oncogenic validation

Structural and functional analyses allow for aggregation of mutations into families based on common

conformations Frequency (log) Frequency

10 Pharmacology: Develop Spectrum-Selective MasterKey Therapies that Inhibit an Entire Family of Allosteric Mutants

Product candidates designed to bind at the active site to selectively inhibit only the intended mutation family

11 BDTX-189 MasterKey Inhibitor Targeting Allosteric EGFR/HER2 Mutations Early Proof-of-Concept Demonstrated for BDTX-189, a MasterKey EGFR/HER2 Inhibitor

Predicted Efficacious Exposure Achieved Favorable Safety Profile

• T1/2 & AUC in-line with preclinical • Generally well-tolerated at preliminary RP2D predictions • Minimal evidence of WT-EGFR related adverse events • In-line with design principles & preclinical predictions BDTX-189

Anti-Cancer Activity Observed Phase 1/2 MasterKey-01 Trial Advancing • Early PoC in NSCLC EGFR Ex 20 ins tumors • Pivotal Phase 2 study on track to begin enrollment 2H 2021 • Early PoC in HER2 solid tumors

AUC = area under the curve; EGFR = epidermal growth factor receptor; Ex 20 ins = Exon 20 insertion; HER2 = human epidermal growth factor receptor 2; NSCLC = non-small cell

lung cancer; PoC = proof of concept; RP2D = recommended Phase 2 dose; T1/2 = half-life; WT-EGFR = wild-type EGFR 13 BDTX-189 Is a Potent and Selective MasterKey Inhibitor of a Broad Range of Allosteric EGFR/HER2 Mutational Clusters

Oncogenic MTCs for Phenotypic Activity and Selectivity v. WT-EGFR EGFR and HER2 Oncogenes for BDTX-189 Across Targeted MTCs

MTC Description WT-EGFR (A431/H292)

MTC-A EGFR Ex 20 ins M 1000 n

WT-EGFR

, 0 MTC-B HER2 Ex 20 ins 5

C WT-EGFR (A431) ranges 5- to 258-fold; avg >50-fold

e 100

MTC-C HER2 Ex 20 missense v

a r

MTC-E HER2 KD β-sheet missense e

f i

l 10 o

MTC-F HER2 KD α-loop missense r

i t

MTC-G HER2 JMD missense n 1 A HER2 MTC-D HER2 ECD missense WT MTC-A MTC-B MTC-D MTCs-C, E, F, G

ECD, extracellular domain; IC50, half maximal inhibitory concentration; KD, kinase domain; JMD, juxtamembrane domain; MTC, mutational cluster. 14 Phase 1 Portion of Masterkey-01 Study Evaluates BDTX-189 in Solid Tumors Driven by Broad Range of EGFR and HER2 Genomic Alterations MasterKey-01 Study Schemaa Part A: Phase 1 Dose Escalation (BOIN1) Part A (Phase 1) • Primary objective: Determine the Part B (Phase 2) RP2D and schedule • BID schedule also under evaluation 1 NSCLC EGFR Ex 20 ins mutations (MTC-A) Key Eligibility Criteria • Relapsed/refractory solid tumor, no 2 NSCLC HER2 Ex 20 ins & point available SOC mutations (MTCs-B or C) • Treated, asymptomatic CNS malignancy allowed Breast cancer with Allo HER2 • Prior EGFR/HER2-targeted therapy 3 mutations (MTCs-B thru F) allowed

NSCLC, cervical and biliary cancers 4 (MTC-D; includes S310F/Y) Genomic Alterations • Allosteric HER2 or HER3 mutation Solid tumor types with Allo • EGFR/HER2 Ex 20 ins mutation 5 EGFR/HER2 mutations • HER2 amplification/overexpression (MTCs-A thru G) • EGFR Ex 19 or L858R mutation

BID, twice daily; BOIN, Bayesian Optimal Interval Design; CNS, central nervous system; QD, once daily; SOC, standard of care. 1Yuan Y, et al. Clin Cancer Res. 2016;22(17):4291-4301. aFigure summarizes number of patients in Full Analysis Set (i.e., those who received at least 1 dose of study drug). bSingle dose crossover study at 400 mg. On day 5, patients begin dosing with 800 mg QD. cAdministered with meal of patient's preference. 15 Phase 1 Dose Escalation was Conducted in Heavily Pre-Treated Patients with a Diverse Array of Cancer Types and MTCs

25–400 mg QD 800 mg QD (+ FE) 800 mg QD (+ FE) 1000 mg QD 1200 mg QD Fasting Fasting Non-Fasting Non-Fasting Fasting Characteristics n = 12 n = 21 n = 9 n = 7 n = 6 Age, median (range) 64 (45-75) 65 (39-83) 59 (45-70) 63 (40-80) 57 (47-64) ECOG PS, 0/1 4/8 3/18 7/2 4/3 1/5 Race (White/Asian/Black/Other) 9/0/1/2 13/2/1/5 7/1/0/1 4/2/0/1 4/2/0/0 # of prior lines of therapy 1 line 3 4 0 1 0 2 lines 2 3 6 2 2 ≥3 lines 7 14 3 4 4 Tumor types Lung 4 9 5 0 2 Breast 1 2 0 1 2 CRC (colon, rectal) 3 0 1 1 0 Cholangiocarcinoma (bile, gall bladder) 1 2 0 0 0 Esophageal 1 1 0 0 0 Othera 2 7 3 5 2 Mutations EGFR Ex 20 ins mutations (MTC-A) 2 3 3 0 0 HER2 Ex 20 alterations (MTCs-B & C) 4 4 1 1 1 Extracellular Allo HER2 mutations 5 4 2 2 0 (MTCs-D thru G) Canonical ErbB mutations (Ex 19 del, 0 3 0 0 1 L858R) or HER3 HER2 amplified 1 5 3 2 4 Other mutations 0 2 0 0 0 Missing 0 0 0 2 0 CRC, colorectal cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; FE, food effect. aIncludes cervical, cancer of unknown primary (CUP), endometrial, kidney, liver, ovarian, prostate, pancreas, salivary, signet ring cell, urothelial, and uterine. 16 BDTX-189 Is Well Tolerated at Preliminary RP2D of 800 mg QD NF Gastrointestinal Events Predominate, Skin Disorders Are Infrequent

Dose 25-400 mg QD 800 mg QD F 800 mg QD NF 1000 mg QD NFb 1200 mg QD F Safety population, n 12 21 9 7 (5 evaluable) 6 Most Common DLTs, n ------2 2 Grade 1 TRAEs Treatment-Related Diarrhea 25% 19% 44% 57% 17% Nausea 17% 24% 33% 43% 17% Adverse Events Vomiting 18% 19% 33% 27% 17% ALT increased 8% 14% -- 14% 17% AST increased 8% 10% -- -- 17% Bilirubin increased ------14% -- Fatigue -- 5% 11% 29% -- Skin disordersa 8% 5% ------Decreased appetite 8% 5% ------Grade 2 TRAEs Diarrhea -- 24% ------Nausea -- 19% 11% -- 17% Vomiting -- 5% -- -- 50% ALT increased ------14% -- AST increased -- -- 11% 14% -- Bilirubin increased ------29% -- Fatigue 8% 14% 11% 14% 17% Skin disordersa -- -- 11% -- 17% Decreased appetite -- 10% -- 14% -- Grade 3 TRAEs Diarrhea -- 10% -- 29% 33% Nausea -- 5% 11% -- -- Vomiting -- 5% ------ALT increased -- 10% 11% -- -- AST increased -- 5% ------Bilirubin increased ------Fatigue ------14% -- Skin disordersa ------Decreased appetite ------ALT, alanine aminotransferase; AST, aspartate aminotransferase; F = fasting; NF = non-fasting. aInclude following AE terms: rash, dermatitis acneiform, rash morbilliform, dry skin, urticaria. bData incomplete as of cutoff date. Note: No grade 4 or 5 events reported. Data presented is as of April 2, 2021, unless otherwise noted. This is an ongoing study and is undergoing active data entry and cleaning. 17 Early PoC Achieved for BDTX-189 in NSCLC EGFR Ex 20 Ins Population Despite Prior Anti-EGFR/HER2 Therapy Evidence of Anti-Cancer Activity in Lung Tumors Harboring Ex 20 Ins 100 (EGFR or HER2) Oncogenes 80 Anti-cancer activity observed at 60 EGFR Ex 20 Ins HER2 Ex 20 Ins 40 ≥800mg QD among lung cancer PD SD patients expressing EGFR/HER2 Ex 20 20 SD 0 * * ins mutations -20 SD SD

From Baseline From -40 • EGFR Ex 20 ins -60 Best % Change in Change SLD % Best cPRa • 3 evaluable by RECIST -80 = ongoing (1 cPR, 1 SD, 1 PD) -100 * MTC-A MTC-A MTC-A MTC-B MTC-B MTC-B • All patients received prior ErbB Cluster Type (NSCLC)MTC-A (NSCLC)MTC-A (NSCLC)MTC-A (NSCLC)MTC-B (NSCLC)MTC-B (NSCLC)MTC-B 800 mg QD 800 mg QD targeted therapy Dosing 800 mg QD 800 mg QD 800 mg QD 800 mg QD NF NF Prior lines of therapy 1 2 2 7 1 2 • HER2 Ex 20 ins Prior EGFR/HER2 TKI therapy Osi Pozi Nera Afa Prior EGFR/HER2 mAbtherapy Ami • 3 evaluable by RECIST (3 SD) Platinum-based therapy Carbo Carbo Carbo Carbo Carbo • 2/3 received prior EGFR/HER2- I/O therapy Pembro Pembro Pembro Pembro Waterfall plot reflects data for a subset of patients from the overall waterfall plot, representing patients with NSCLC expressing targeted therapy EGFR or HER2 Ex 20 ins mutations and treated at doses of ≥800 mg QD.

afa, afatinib; ami, amivantamab; carbo, carboplatin; cPR, confirmed partial response; I/O, immuno-oncology; mAb, monoclonal antibody; nera, neratinib; NF, non-fasting; osi, osimertinib; PD, progressive disease; pembro, pembrolizumab; pozi, poziotinib; SD, stable disease; SLD, sum of longest diameters. Three patients without SLD data excluded from plot. aConfirmed after the data cut-off. 18 NSCLC EGFR Ex 20 Ins: 51-year-old Woman with 53% Tumor Reduction and Improved Diffuse Lung Disease (Confirmed PRa, on study 13+ wks)

Genomic alteration: EGFR Ex 20 ins (SVD) Treatment regimen: on study Prior therapy: • BDTX-189, 800 mg QD NF • Controlled, low-grade diarrhea • Poziotinib with PR and toxicity followed by PD • Off oxygen starting at ~9 weeks • Carboplatin and pemetrexed

Target Lesions Over Time Radiologic Scans Baseline Week 6

aConfirmed after the data cut-off. 19 Early PoC Achieved for BDTX-189 in Solid Tumors with HER2-Amp

100 Broad Spectrum Anti-Cancer Activity 80 in HER2-Amplified Cancers 60 PD 40 PD 20 0 * * Clinical activity observed at ≥800mg SD -20 SD QD among broad group of HER2- From Baseline From -40 uPR Amp expressing patients

-60 Best % Change in % Best SLD -80 • 6 evaluable patients by RECIST = ongoing -100 * cPR Amp Amp Amp (NSCLC) (1 cPR / 1 uPR / 2 SD / 2 PD) Tumor Origin (Esophageal)Esophageal Breast(Other:Pancreas pancreas) Ovary Lung CUP • 4/6 patients received prior 800 mg 1200 mg 800 mg 1200 mg 1200 mg 800 mg Dosing QD QD QD QD QD QD EGFR/HER2-directed therapy Prior Lines of Therapy 1 3 3 3 6 4 Prior EGFR/HER2 TKI Therapy Afa, Osi Tras Prior EGFR/HER2 mAb Therapy Tras Marget Pertuz Cis Carbo, Platinum-based Therapy Oxali Oxali Carbo Carbo Oxali Waterfall plot represents patients with HER2 amplification and treated at ≥800 mg QD. This includes patients from all tumor types expressing HER2 amplification.

cis, cisplatin; marget, margetuximab; oxali, oxaliplatin; pertuz, pertuzumab; tras, trastuzumab; uPR, unconfirmed partial response. Eight patients without SLD data excluded from plot. 20 Cancer of Unknown Primarya (HER2 Amplification): 73-year-old Woman with Deep and Durable Confirmed PR (on study 7+ mos)

Genomic alteration: HER2-amplification Radiologic Scans Prior therapy: b • Carbo/taxol, FOLFIRINOX, Everolimus Baseline 7 months Treatment regimen: on study • BDTX-189 800 mg daily (fasting) • No ongoing related toxicity, had brief episodes of G1 diarrhea

Target Lesions Over Time 100% regression

100% regression

aCUP presumed by the investigator of this patient to be of breast cancer, pancreato-biliary or upper gastrointestinal origin. bScans from April 23, 2021. 21 BDTX-1535 Brain-Penetrant Inhibitor of Allosteric and Canonical EGFR Mutations BDTX-1535 Is Designed to be Potent, Selective, and Brain Penetrant EGFR Inhibitor

Target Multiple EGFR Mutations Brain Penetrance • Designed to inhibit allosteric and • Brain penetrant properties as a design canonical EGFR mutations, rule to ensure adequate drug exposures including those expressed in GBM and NSCLC

BDTX-1535

Selectivity Over WT-EGFR Rapid Pre-Clinical Advancement • Demonstrated potency against • IND-enabling studies ongoing with IND allosteric EGFR mutants with selectivity anticipated in 1H 2022 vs. WT-EGFR, providing a favorable safety profile

23 BDTX-1535 Has Demonstrated Potent and Selective Inhibition of Allosteric and Canonical EGFR Variants Expressed in GBM and NSCLC

In vitro IC50 against panel of EGFR mutations indicates broad spectrum of BDTX-1535 activity

AMP, amplified; Del, deletion; EGFR, epidermal growth factor receptor; Ex, exon; GBM, glioblastoma; IC50, half maximal inhibitory concentration; WT, wild type. 24 BDTX-1535, Designed for a Brain Penetrant PK Profile, Achieved Tumor Growth Inhibition of Intracranial PDX Tumors Expressing Allosteric EGFR Mutants

Mean Plasma and Brain BDTX-1535 Achieved Complete and Imaging of GBM6 Orthotopic Brain Concentration of BDTX-1535 in Sustained Inhibition of pEGFR in Patient-Derived Xenograft (PDX) Tumors 1 Mouse (15 mg/kg PO) Allo-EGFR Mutant Expressing Tumors Expressing EGFR-Viii3 Following a Single Oral Dose2

10000 )

s 250 t

i Vehicle

80000 n u

1000 200 BDTX-1535 d

Mean [Plasma] e 60000 z

i 150 )

100 l

6 a

Mean [Brain] 0

1 m

p 100

( r

40000 R

10 o

G (

I p

1 20000 L

0.250 1.00 2.00 4.00 8.00 B Concentration (ng/mL) or (ng/g) or (ng/mL) Concentration 0 Time(h) 5 10 15 20 0 Control 4hr 8hr 10hr 12hr 24hr Days Post Implantation Kpuu = 0.265

1 PK was conducted in fasted, male Balb/C mice. Plasma was collected , prepared and analyzed by LC-MS/MS analysis. Brain homogenate samples were prepared after homogenizing brain with homogenizing solution, then

analyzed by LC-MS/MS. Kp = AUCbrain/AUCplasma. Kpuu was calculated using the formula Kpuu = Kp*Fubrain/Fuplasma. 2 Mice bearing BaF3 allograft tumors expressing EGFR-Viii treated with a single oral dose of 50mg/kg, followed by determination of phosphorylation state of EGFR at 4, 8, 10, 12 and 24 hours following dosing. 3. Bioluminescence imaging in mice expressing intracranial GBM6 patient derived tumors. Mice were treated orally with 50mg/kg of BDTX-1535 25 BRAF Program MasterKey Inhibitors Targeting Class II/III BRAF Mutations BRAF Program: MasterKey Inhibitors of Class II/III BRAF Mutations

Target Spectrum of BRAF Mutations Strong Pre-Clinical Data • Designed for potent inhibition of a • Tumor regression observed in BRAF mutant spectrum of Class II/III BRAF mouse models mutations

BRAF Program

Differentiated Profile Rapid Pre-Clinical Advancement • Paradoxical activation, which can • Lead optimization ongoing with IND lead to secondary malignancies, anticipated in 2022 avoided in pre-clinical studies

27 BRAF Program Molecules Potently Inhibited Allosteric Class II/III BRAF Mutants While Avoiding Induction of Paradoxical Activation in Early Pre-Clinical Research

Potency v. Non-Canonical Class II/III BRAF Mutants Avoidance of Paradoxical Activation

While approved drugs are known to induce paradoxical activation, BRAF program molecules did not lead to an increase in pERK in cells harboring WT-BRAF

28 BRAF Program Molecules Achieved Tumor Growth Inhibition of BRAF Mutant Mouse Models

A BRAF program molecule evidenced robust anti tumor activity in mutant BRAF dimer driven allograft models Ba/F 3 expressing BRAF KIAA 1549 or BRAF G 469 A) and BRAF V 600 E driven xenograft model (A375).

The animals treated with a BRAF program molecule showed sustained and lower pERK level in tumors compared to untreated animals (BRAF KIAA 1549 fusion data shown).

29 FGFR Program MasterKey Inhibitors Targeting FGFR2/3 Mutations FGFR Program: MasterKey Inhibitors of FGFR2/3 Mutations

Differentiated Activity Strong Pre-Clinical Approved Drugs Profile Data Drug resistant • Designed for potent Target FGFR2 • Tumor regression mutations inhibition of a spectrum observed in pre- of allosteric FGFR2/3 clinical FGFR3 mutations mutant PDX tumors Target FGFR3 Target FGFR1

FGFR Program Black Diamond Approach Target Spectrum of High Barrier to Drug FGFR2 alterations resistant mutations

Optimization Designed to Capture Rapid Pre-Clinical Strategy Efficacy Advancement Target spectrum of Spare FGFR1 for wide FGFR3 alterations therapeutic window • FGFR1-sparing • Lead optimization ongoing with IND • Activity against anticipated in 2022 gatekeeper mutations

31 FGFR2/3 Program Leads Differentiated By Broad Selectivity Profile While Sparing Wild Type FGFR1

FGFR2/3 Program Leads Demonstrated 19-40-fold Selectivity v. WT-FGFR1 FGFR2/3 Program Leads Demonstrated Improved Potency Against ATP-Site Gatekeeper Mutations 30 Pemigatinib Erdafitinib

) 20

(

5 C I 10

0 FGFR1-WT FGFR3-S249C FGFR3-Tacc3 FGFR2 (DMS-114) (UMUC14) (RT112) (SNU-16)

1000

800 BDTX-A

) BDTX-B

M 600

(

5 400

C I

200 *Gatekeeper mutants constructs in MCF10A cells: 0 FGFR3-V555X, X=M, L, F FGFR1-WT FGFR3-S249C FGFR3-Tacc3 FGFR2 (DMS-114) (UMUC14) (RT112) (SNU-16) FGFR2-V564X, X=I, F 32 FGFR2/3 Program Molecules Achieved Regression of FGFR3 Mutant PDX Tumors

UM-UC-14 (FGFR3-S249C)

1000 Efficacy in Nu/Nu mice using the UM-UC-14 Control FGFR3-S249C-driven bladder PDX model

BDTX-A 150 mpk QD - PO 3

m BDTX-A 75 mpk BID - PO

z i

s 500

r BDTX-A achieved in-vivo POC:

o m

u • BDTX-A 150 mpk PO-QD, T TGI=106% 0 0 10 20 30 • BDTX-A 75 mpk PO-BID, TGI=113% Time (Day)

33 Deep Oncology and Small Molecule Drug Discovery and Development Experience

Leadership Team Board of Directors

Ali Behbahani, M.D. General Partner, NEA

Brad Bolzon, Ph.D. Managing Director, Versant Ventures

Kapil Dhingra, M.D. Managing Member, KAPital Consulting

David M. Epstein, Ph.D. Liz Buck, Ph.D. Tommy Leggett David M. Epstein, Ph.D. President & CEO Chief Scientific Officer Chief Financial Officer CEO, Black Diamond Therapeutics

Bob Ingram – Chairman General Partner, Hatteras Ventures

Sam Kulkarni, Ph.D. CEO, CRISPR Therapeutics AG

Alex Mayweg, Ph.D. Managing Director, Versant Ventures

Garry Menzel CEO, TCR2

Brent Hatzis-Schoch, J.D. Fang Ni, Pharm.D. Karsten Witt, M.D. Rajeev Shah COO and General Counsel Chief Business Officer Interim Chief Medical Officer Managing Director, RA Capital

Mark Velleca, M.D., Ph.D. Venture Partner, Hatteras Ventures 34 The Black Diamond Vision: Precision Cancer Medicines for Every Genetically Defined Cancer

ADDRESSING PIONEERING COMMITTED Significant unmet A novel and innovative To the patient communities medical needs scientific approach we serve