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Precision Oncology Medicines 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 9 mutations Predicted oncogenic oncogenic Predicted (MAP Score) (MAP Oncogene Prediction Oncogene Protein Dynamics Mutation Exclusivity Mutation Landscape MAP Score MAP Algorithm MAP Prevalence(1og10) 1e−06 1e−05 1e−04 1e−03 Data 1 1 ● ● ● Protein ● ● ● ● ● ● ● ● ● ● ● ● ● Interface ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● Conservation ● ● ● ● ● ● ● ● ● ● ● ● Motifs ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● Structural ● ● ● ● ● ● ● 201 ● ● ● ● ● ● ● ● ● ● ● ● FGFR3 Mutation Pre ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● FGFR3 AA position ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● v ● ● ● ● ● ● ● Mutations ● ● ● ● ● ● ● alence Solid T ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 401 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● umor (GENIE) ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 601 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● : Proprietary Machine Learning Used to Identify Oncogenic Oncogenic Identify to Used Learning Machine Proprietary : ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 100s 100s Unique ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● - ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 801 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● utations to identifyto Analyze Analyze Mutations Previously Unknown or Thought to be Undruggable be to Thought or Unknown Previously Mutations M potential potential oncogenic oncogenic mutations sequencing population level genetic genetic level data 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
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