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Item 7.01 Regulation FD Disclosure.
On April 25, 2022, Black Diamond Therapeutics, Inc. (the “Company”) issued a press release titled, “Black Diamond Therapeutics Announces Pipeline Prioritization and Workforce Realignment” and updated its corporate presentation for use in meetings with investors, analysts and others. A copy of the press release and a copy of the corporate presentation are furnished as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form 8-K.
The information furnished under this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 9.01. | Exhibits |
| (d) Exhibits | |
| 99.1 | Press Release issued by the Company, dated April 25, 2022, furnished herewith. |
| 99.2 | Corporate Presentation of the Company, dated April 25, 2022, furnished herewith. |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL Document). |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| April 25, 2022 | BLACK DIAMOND THERAPEUTICS, INC. | |
| By: | /s/ Brent Hatzis-Schoch | |
| Name: Brent Hatzis-Schoch | ||
| Title: Chief Operating Officer and General Counsel | ||
Exhibit 99.1
Black Diamond Therapeutics Announces Pipeline Prioritization and Workforce Realignment
| – Strategic areas of focus on development of BDTX-1535 and BDTX-4933 as well as MAP platform enabled small molecule drug discovery efforts – |
| – Company to discontinue development of BDTX-189 and reduce workforce to extend its cash runway into 3Q 2024, supporting execution of key milestones – |
CAMBRIDGE, Mass. and NEW YORK, April 25, 2022 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, today announced that it is realigning its resources to focus on key near-term value drivers and to extend its cash runway into the third quarter of 2024, supporting the execution of important clinical and preclinical milestones.
“Black Diamond’s mission of expanding the reach of precision cancer medicines through the development of our novel MasterKey therapies is at the core of our daily work, and we believe that our MAP discovery engine offers a novel approach to addressing major unmet needs within the oncology treatment landscape,” said David Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. “In order to increase our operational efficiency and execute on our mission, we have made the difficult decision to reduce our workforce by approximately 30%. We are incredibly grateful to every member of the Black Diamond team who has helped to advance MasterKey therapies for the many patients in need of new therapeutic options as well as to the patients and investigators involved in the clinical trial of BDTX-189. The actions announced today enable us to focus and strengthen our organizational priorities, reduce our operating expenses, and continue to invest in value generating clinical development activities to bring us to the next inflection points for BDTX-1535 and BDTX-4933.”
Black Diamond has discontinued the development of BDTX-189 and realigned its workforce to focus on progressing its pipeline through important upcoming milestones for BDTX-1535, BDTX-4933 and discovery efforts. Since its announcement regarding the status of BDTX-189 in January 2022, the Company has been reviewing the development program for BDTX-189, an orally available, irreversible small molecule inhibitor targeting oncogenic driver mutations of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) kinases, while continuing to enroll patients in the safety expansion cohort of the Phase 1 study. As part of its strategic review, Black Diamond has decided to discontinue development of the program due to the rapid evolution of the treatment landscape in non-small cell lung cancer (NSCLC) harboring either EGFR or HER2 Exon 20 insertion mutations.
Black Diamond is aligning its operational and scientific efforts on two priority programs, in addition to its discovery efforts.
BDTX-1535
| · | BDTX-1535 is designed as a potent, selective, brain-penetrant and irreversible MasterKey inhibitor of EGFR mutations expressed in glioblastoma multiforme and of intrinsic and acquired resistance EGFR mutations to third generation EGFR inhibitors in NSCLC. |
| · | Black Diamond initiated the Phase 1 study of BDTX-1535 in the first quarter of 2022 and expects to provide a clinical data update in 2023. |
BDTX-4933
| · | BDTX-4933 is a central nervous system (CNS)-penetrant BRAF inhibitor against a family of Class I, II, III canonical and non-canonical mutations being developed for the treatment of patients with or without brain tumors driven by oncogenic BRAF mutations. BDTX-4933 is designed to be highly selective and potent, with the ability to avoid paradoxical activation. |
| · | Black Diamond initiated investigational new drug (IND)-enabling studies in the first quarter of 2022 and expects to submit an IND for BDTX-4933 in the first half of 2023. |
Discovery Efforts
| · | Black Diamond will continue the advancement of its discovery efforts generated from its Mutation-Allostery-Pharmacology (MAP) Drug Discovery Engine focused on predicting and validating novel oncogenic mutant families from population level tumor genomics. Black Diamond anticipates announcing a development candidate for its FGFR program in 2022 in addition to disclosing a new small molecule development candidate in 2023. |
About Black Diamond
Black Diamond Therapeutics is a precision oncology medicine company pioneering the development of novel MasterKey therapies. Black Diamond is addressing the significant unmet need for novel precision oncology therapies for patients with genetically defined cancers who have limited treatment options. Black Diamond is built upon a deep understanding of cancer genetics, onco-protein function, and drug discovery. The Company’s proprietary Mutation-Allostery-Pharmacology, or MAP drug discovery engine, is designed to allow Black Diamond to analyze population-level genetic sequencing tumor data to predict and validate oncogenic mutations that promote cancer across tumor types as MasterKey mutations. Black Diamond discovers and develops selective MasterKey therapies against these families of oncogenic mutations. Black Diamond was founded by David M. Epstein, Ph.D., and Elizabeth Buck, Ph.D. For more information, please visit www.blackdiamondtherapeutics.com.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the planned realignment of resources and pipeline prioritization, the ongoing development of BDTX-1535 and BDTX-4933, including timing of upcoming milestones, the nomination of a development candidate for the Company’s FGFR program and the Company’s cash runway. Any forward-looking statements in this statement are based on management’s current expectations 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. Risks that contribute to the uncertain nature of the forward-looking statements include those risks and uncertainties set forth in the Company’s 2021 annual report on Form 10-K filed with the United States Securities and Exchange Commission and its other filings filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Contacts
For Investors:
Julie Seidel
investors@bdtx.com
For Media:
Kathy Vincent
(310) 403-8951
media@bdtx.com
Exhibit 99.2
1 Black Diamond Therapeutics, Inc. Pioneering the Development of MasterKey Therapies APRIL 2022
2 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 drug discovery engine, the potential timing and advancement of our clinical trial and preclinical studies, including the timing of clinical data updates for BDTX - 1535 and the timing of filing investigational new drug (“IND”) application for BDTX - 4933 , the timing and potential achievement of additional milestones to advance our product candidate pipeline, including development candidate nomination for our FGFR 2 / 3 program and our undisclosed target program, and our cash runway . 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 2021 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 .
Black Diamond Therapeutics Overview
4 Our proprietary MAP drug discovery engine is designed to: • Predict and validate novel oncogenic mutant families from population level tumor genomics • Pioneer mutant family conformation - based MasterKey drug design • Provide opportunities beyond oncology and small molecules MasterKey therapies address oncogene mutation families; providing precision oncology medicines to greater numbers of patients with genetically defined tumors Clinical and late - preclinical pipeline of MasterKey inhibitors derived from our MAP drug discovery engine targeting oncogenic ErbB1/2, BRAF, FGFR2/3 and additional undisclosed targets BDTX - 1535 : a brain - penetrant, mutant selective, irreversible inhibitor of EGFR in Phase 1 for the treatment of patients with GBM and NSCLC driven by EGFR intrinsic & acquired resistance mutations BDTX - 4933 : a brain - penetrant inhibitor of Class I, II, and III oncogenic BRAF mutations in IND - enabling studies Expanding the Reach of Precision Medicine Through the Development of MasterKey Therapies
5 Black Diamond’s MasterKey Approach Designed to Address Overlooked Mutation Families Classic/Current Approach: Targeting active site kinase domain mutations With expanding genetic profiling of cancer patients via Next Generation Sequencing (NGS) Mutation families yield significant market opportunities for populations lacking suitable precision therapies Black Diamond Approach: Targeting mutation families to expand the opportunity for precision oncology Less than 15% patients 1 with metastatic cancer eligible for approved precision oncology medicines Targeting single mutations in individual tumor types 5 1 Haslam, A., et al. Annals Oncology Vol 32, Issue 7, p926 - 932; July 2021
6 Wholly - Owned Novel MasterKey Precision Medicines Target Drug Candidate Indication Discovery Optimization IND - Enabling Phase 1 Phase 2/3 Global Rights EGFR BDTX - 1535 EGFR - driven GBM & NSCLC ± CNS mets BRAF BDTX - 4933 BRAF - driven solid tumors ± CNS mets FGFR Undisclosed FGFR3 - driven solid tumors Un - disclosed Undisclosed Solid tumors Clinical Data (2023) IND (1H 2023) Development Candidate (2022) Development Candidate (2023)
MAP Drug Discovery Engine
8 Validate novel oncogenic driver mutations and targets Develop MasterKey inhibitors against mutation families Proprietary MAP scoring in silico MAP Drug Discovery Engine Unlocks Precision Medicine with a “ MasterKey ” Genomics Proteomics + Employ structural and dynamic methods to identify oncogenic mutation families Masterkey Therapy Oncogenicity Prediction Biological Validation Drug Discovery Conformation - based drug design
9 MAP Drug Discovery Engine: A Scaled Approach to Extract Oncogenic MasterKey Mutation Families Population level clinical mutation landscape Thousands Computational in - silico oncogenicity prediction Hundreds amino acid position prevalence amino acid position prevalence Oncogene amino acid position prevalence Experimentally validated oncogenic MasterKey mutations Tens Mutational Lollipop Plot
10 WILD TYPE MASTERKEY MUTATION FAMILIES MasterKey Inhibitors designed to exploit this vulnerability MasterKey mutations drive global conformation change Conformation Based Drug Design Enabled by MAP Drug Discovery Engine
BDTX - 1535 Brain - Penetrant Inhibitor of GBM and NSCLC MasterKey EGFR Mutations
12 BDTX - 1535: Oral, Brain Penetrant, Selective Inhibitor of Oncogenic EGFR MasterKey Mutations Designed to treat patients harboring EGFR oncogenic MasterKey mutations Irreversible Designed with selectivity versus WT - EGFR to deliver favorable safety profile Selective Designed to be brain penetrant to treat CNS tumors Brain Penetrant BDTX - 1535 Phase 1 study in patients with either GBM or NSCLC, with and without CNS tumors Clinical Stage CNS=Central Nervous System; WT=Wild - Type; GBM=Glioblastoma Multiforme; NSCLC=Non - Small Cell Lung Cancer
13 1 Van den Bent et al JCO 2009 2 Capuzzo et al Lancet 2010 GBM Mutations Time (months) p=0.003 PFS (%) GBM Trial 1 Erlotinib in WT - EGFR GBM Patients Erlotinib in EGFR - vIII GBM Patients Current EGFR TKIs Do Not Extend PFS in Patients with GBM Mutations Erlotinib Placebo Time (months) PFS (%) HR=0.10 (0.04 - 0.25) log - rank p<0.0001 NSCLC Trial 2 Kinase Domain Mutations EGFR TKIs Extend PFS in Patients with Kinase Domain Mutations Reversible EGFR Inhibitors Show Potentially Detrimental Pharmacology in EGFR Driven GBM TKIs=Tyrosine Kinase Inhibitors.
14 Black Diamond Revealed the Potential for Unwanted Paradoxical Activation of GBM Mutations by Reversible EGFR TKIs PK=Pharmacokinetics; PD=Pharmacodynamics; PDX=Patient - Derived Xenografts The oncogenic conformation of mutant EGFR in GBM is a locked dimer Reversible TKIs can stimulate the activity of mutant EGFR in GBM PDX tumors expressing EGFRvIII paradoxical activation Single dose in vivo PK/PD study 10 -10 10 -8 10 -6 10 -4 -0.4 0.0 0.4 0.8 1.2 1.6 2.0 [erlotinib] (M) P r o l i f e r a t i o n ( f o l d g r o w t h ) LoDi-EGFR (EGFR-Viii) KD-EGFR (E746-A750) 10 -10 10 -8 10 -6 10 -4 -0.4 0.0 0.4 0.8 1.2 1.6 2.0 [erlotinib] (M) P r o l i f e r a t i o n ( f o l d g r o w t h ) LoDi-EGFR (EGFR-Viii) KD-EGFR (E746-A750) EGFRvIII (GBM) EGFR Ex19del (NSCLC) Inhibitors against EGFR mutants in GBM should be potent, selective & irreversible to avoid paradoxical activation
15 BDTX - 1535 Addresses Unique Pharmacology of EGFR Mutations in GBM to Achieve Sustained Inhibition and Activity in Preclinical Models Kp uu Partition Coefficient Calculation: AUC brain:blood x plasma Fu/brain Fu; QD= quaque die (once a day) 12 14 16 18 0 25 50 75 100 Days Post Implantation P r o b a b i l i t y o f S u r v i v a l GBM6 Vehicle Control N=10 BDTX-1535 50mpk BDTX - 1535 (50mpk QD) vehicle Average oral unbound brain fraction ( Kp uu ) = 0.55 in Rats Control 4hr 8hr 10hr 12hr 24hr 0 20000 40000 60000 80000 p E G F R ( p 1 0 6 8 ) Single dose in vivo PK/PD study (50mpk) Complete & sustained inhibition of pEGFR / pERK Increased survival of intracranial PDX tumors
16 H 2 9 2 A 4 3 1 E G F R v I I I E G F R v I I E G F R v V I E G F R R 1 0 8 K E G F R R 2 2 2 C E G F R C 2 3 1 F E G F R A 2 8 9 T E G F R A 2 8 9 V E G F R C 5 9 5 S E G F R G 5 9 8 V E G F R S 6 4 5 C 0 20 40 60 80 100 120 A n t i P r o l i f e r a t i v e I C 5 0 ( n M ) H 2 9 2 A 4 3 1 D 7 6 1 Y E 7 0 9 A E 7 0 9 G G 7 1 9 A G 7 1 9 C G 7 1 9 D G 7 1 9 R G 7 1 9 S S 7 6 8 I E 7 4 6 _ A 7 5 0 d e l + S 7 6 8 I E G F R E x 1 9 d e l E x 1 9 d e l + C 7 9 7 S E G F R L 8 5 8 R E G F R L 8 5 8 R + C 7 9 7 S 0 20 40 60 80 100 120 A n t i P r o l i f e r a t i v e I C 5 0 ( n M ) BDTX - 1535 Optimized to Address a Wide Range of Oncogenic EGFR MasterKey Mutations and Amplification in GBM and NSCLC Anti - proliferation Ba/F3 IC 50 ( nM ) Anti - proliferation Ba/F3 IC 50 ( nM ) GBM mutations Intrinsic resistance mutations Classical & acquired resistance mutations (EGFR Amp) Selectivity over WT - EGFR Selectivity over WT - EGFR EGFR WT (EGFR Amp) Potency against EGFR variants and mutations prevalent in GBM Potency against EGFR mutations of intrinsic resistance and acquired resistance in NSCLC Average IC 50 = 3.8 nM Average IC 50 = 3.5 nM IC50=half maximal inhibitory concentration EGFR WT
17 BDTX - 1535 Designed to Potently Inhibit EGFR Intrinsic and Acquired Resistance Mutations in NSCLC Intrinsic Resistance Mutations Designed for potent & selective inhibition across mutant families Osimertinib Altered Covalent Interaction Altered P - loop Interaction C797S G719X Gefitinib Acquired Resistance Mutations Designed to covalently target C797 & C797S
18 BDTX - 1535 Achieves Dose - dependent Tumor Regression in EGFR Mouse Models, Including Acquired Resistance Mutation C797S BDTX - 1535 retains irreversible binding against C797S mutant BDTX - 1535 demonstrates dose - dependent tumor regression in EGFR Ex19del + C797S and L858R + C797S tumor models Osimertinib BDTX - 1535 Washout Washout Control0 4.0 10.024.0 Control0 0.5 1 2 0 20 40 60 80 100 % p E G F R ( E x 1 9 d e l + C 7 9 7 S ) Time after washout (hrs) 1 2 3 4 5 6 7 8 9 10 11 0 200 400 600 800 Days After Dosing Start M e a n T u m o r V o l u m e m m ^ 3 Vehicle Control BDTX-1535 40 mpk Osimertinib 25 mpk Ex19del + C797S L858R + C797S
19 EGFR AMP EGFR AMP EGFR vII EGFR AMP EGFR Ex19del EGFR C595F EGFR G719C EGFR AMP EGFR Ex19del EGFR L858R +C797S EGFR Ex19del +C797S BDTX - 1535 Promotes Regression Across Range of GBM & NSCLC Tumor Models Expressing MasterKey EGFR Mutations & EGFR Amplification In Vivo Tumor Models - 100 100 % Regression - 10 10 AMP=Amplification
20 BDTX - 1535: Focused, Biomarker - Driven First - in - Human Phase 1 Study Design RP2D Dose Escalation EGFR Alterations EGFR Intrinsic Resistance Mutations RP2D=Recommended Phase 2 Dose EGFR Acquired Resistance Mutations • Global trial • Bayesian optimal interval design
21 ~ 160,500 Sources: Epidemiology data from EvaluatePharma Addressable Patient Population (US / EU / Japan / China) Classical Acquired Resistance EGFRmut 11,700 Intrinsic Resistance EGFRmut 139,700 Classical EGFRmut 9,100 EGFRmut Newly Diagnosed GBM 36,400 24,700 EGFRmut Recurrent GBM ~ 61,100 Large Addressable Patient Population Harboring MasterKey Mutations Across GBM and NSCLC
22 BDTX - 1535 is Well Positioned to Address Unmet Needs in EGFR Mutant GBM/NSCLC Potent & selective inhibition of EGFR mutations (Avg IC 50 ~3nM) that drive intrinsic and acquired resistance to current generation TKIs • Irreversible inhibition of GBM mutations to avoid paradoxical activation • Irreversible binding to C797 and C797S acquired resistance in NSCLC • Regression across panel of in vivo tumor models harboring EGFR mutations in GBM and NSCLC Robust brain penetration to treat patients with EGFR mutations and CNS tumors • Unbound brain fraction ( Kp uu ) = 0.55 in rat; activity demonstrated in intracranial GBM model Favorable drug like properties • Prolonged blood stability • Projected t 1/2 of 15 hours for QD dosing t 1/2 =half - life; IC 50 =half maximal inhibitory concentration
BDTX - 4933 Brain - Penetrant Inhibitor of Class I, II, & III MasterKey Oncogenic BRAF Mutations
24 BDTX - 4933: Oral, Brain Penetrant Inhibitor of Oncogenic BRAF Mutations BDTX - 4933 Designed for potent and selective inhibition of Class I, II, and III BRAF mutations MasterKey Family Inhibits dimerized RAF kinases and avoids paradoxical activation Avoids Paradoxical Activation Designed to be brain penetrant to treat CNS tumors Brain Penetrant IND - enabling studies initiated Status
25 • MAPK signaling is a central pathway regulating cellular proliferation, cell - cycle progression, and survival • Hyperactivation responsible for >40% of human cancer cases • Activating BRAF alterations are associated with various cancers including melanoma and NSCLC • Currently approved BRAF inhibitors only address Class I V600 mutations and lack CNS activity No approved drugs ABERRANT BRAF SIGNAING NORMAL RAS/BRAF SIGNAING BRAF Alterations Drive Oncogenesis Through Hyperactivation of the MAP Kinase Pathway Class I Mutants Class II Mutants Class III Mutants
26 BDTX - 4933 Designed to Deliver Superior Activity by Avoiding Paradoxical Activation Independent of Context • Paradoxical activation occurs through activation of the non - inhibited RAF molecule in dimer ― Limits efficacy through secondary malignancies and/or cutaneous toxicities • Approved BRAF inhibitors demonstrate paradoxical activation • Some investigational “paradox breaker” agents demonstrate context - dependent paradoxical activation Encorafenib Vemurafenib BDTX - 4933 paradoxical activation -10 -9 -8 -7 -6 -5 0 1 2 3 4 WT BRAF, NRAS Q61R Concentration Log[M] p E R K N o r m a l i z e d t o D M S O -11 -10 -9 -8 -7 -6 -5 0 1 2 3 4 WT BRAF, NRAS WT Concentration Log[M] p E R K N o r m a l i z e d t o D M S O c o n t r o l Avoidance of Paradoxical Activation Concentration Concentration
27 BDTX - 4933 Exhibits Strong Anti - Tumor Activity Across All BRAF Mutation Classes in In Vivo Models BRAF Class II Mutant Tumor Model BRAF Class III Mutant Tumor Model BRAF Class I Mutant Tumor Model 0 5 10 15 20 0 500 1000 1500 2000 Days (post treatment) T u m o r V o l u m e ( m m 3 ) Vehicle BDTX-BRAF (10 mpk) Belvarafenib (15 mpk) BDTX-BRAF (3 mpk) BDTX - 4933 BDTX - 4933 0 3 6 9 12 0 500 1000 1500 2000 Days (post treatment) T u m o r V o l u m e ( m m 3 ) Encorafenib (60 mpk) Vehicle BDTX-BRAF (3 mpk) BDTX - 4933 BDTX - 4933 Daily oral dosing
28 NRAS - mutant Driven Cancers: Additional Clinical Opportunity for BDTX - 4933 -10 -8 -6 -4 0 2 4 6 8 NRAS Q61L , HRAS G13D Concentration Log[M] p E R K N o r m a l i z e d t o D M S O Encorafinib Belvarafenib BDTX-4933 • NRAS - mutant melanoma represent ~20% of melanomas • Acquired NRAS mutations associated with BRAF inhibitor use and brain metastases • Clinical proof of concept: Belvarafenib demonstrated ORR 44% in NRAS - mutant melanoma trial Oncogenic NRAS mutations induce RAF dimerization and pathway activation BRAFi resistance RAF dimerization Created by BioRender
29 • CNS metastasis occurs in ~30 - 40% 1 of BRAF driven cancers • ~17,000 2 patients/year in the US • BRAF mutations drive primary CNS tumors (e.g., g lioma ) in ~1,500 2 patients/year in the US • Currently approved therapies are not brain penetrant BDTX - 4933 Designed to be Brain Penetrant to Treat CNS Disease 1 Management of brain metastases in melanoma - UpToDate 2 EvaluatePharma Epi for incidence by tumor type (2021, US), publications and GENIE/TCGA datasets for mutation prevalence by tumor type Brain Tumor
30 Day 0 Day 15 BDTX - 4933 prolongs survival in BRAF - V600E intracranial tumor model Vehicle BDTX - 4933 3 mpk Belvarafenib 15 mpk BDTX - 4933 Is Brain Penetrant and Exhibits Robust Activity in Treating CNS Disease in in vivo models BDTX - 4933 10 mpk BDTX - 4933 BDTX - 4933
31 BDTX - 4933: Potential Best - in - Class , Masterkey Inhibitor For A Greater Number Of Patients With Overlooked Oncogenic Mutations Sources: EvaluatePharma Epi and GENIE/TCGA 47,500 NRAS Melanoma 51,600 BRAF Class II/III alt. Solid Tumors 91,810 BRAF V600 Solid Tumors Addressable US / EU / JP Patient Population ~ 190,910 BDTX Is Growing The Addressable Patient Population By De - Orphaning of Overlooked Mutations # of Known Oncogenic Mutations # of BDTX MAP Engine De - orphaned Oncogenic Mutations Growing +
FGFR2/3 Selective Inhibitor Program
33 BDTX - FGFR: Oral, Selective Small - Molecule FGFR2 & FGFR3 Inhibitor BDTX - FGFR Potency against families of FGFR2 & FGFR3 alterations and amplifications Unique Activity Profile Robust in vivo efficacy demonstrated in bladder (FGFR3) and gastric (FGFR2) xenograft models without hyperphosphatemia Preclinical PoC Designed to be FGFR1 & FGFR4 sparing, allowing maximum efficacy while minimizing dose limiting toxicities Selective Development candidate anticipated in 2022 Status
Corporate Overview
35 Deep Oncology and Small Molecule Drug Discovery and Development Experience David M. Epstein, Ph.D. President & CEO Liz Buck, Ph.D. Chief Scientific Officer Brent Hatzis - Schoch, J.D. COO and General Counsel Leadership Team Board of Directors Ali Behbahani , M.D. General Partner, NEA Kapil Dhingra, M.D. Managing Member, KAPital Consulting Wendy Dixon, Ph.D. Former Global Marketing Head, Bristol Myers Squibb David M. Epstein, Ph.D. CEO, Black Diamond Therapeutics, Inc. 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 Rajeev Shah Managing Director, RA Capital Mark Velleca , M.D., Ph.D. CEO, StrideBio , Inc. Karsten Witt, M.D. Interim Chief Medical Officer Fang Ni, Pharm.D. Chief Business Officer and Chief Financial Officer Elizabeth L. Montgomery Chief People Officer
36 Cash Runway Expected to Enable Multiple Upcoming Milestones • BDTX - 1535 clinical data update in 2023 • BDTX - 4933 IND filing in 1H 2023 • FGFR program development candidate nomination in 2022 • Undisclosed program development candidate nomination in 2023 • $209mm in cash, cash equivalents and investments as of December 31, 2021 • Cash runway into 3Q 2024 Strong balance sheet Upcoming program milestones
37 Expanding the Reach of Precision Medicine Through the Development of MasterKey Therapies Our proprietary MAP drug discovery engine is designed to: • Predict and validate novel oncogenic mutant families from population level tumor genomics • Pioneer mutant family conformation - based MasterKey drug design • Provide opportunities beyond oncology and small molecules MasterKey therapies address oncogene mutation families; providing precision oncology medicines to greater numbers of patients with genetically defined tumors Clinical and late - preclinical pipeline of MasterKey inhibitors derived from our MAP drug discovery engine targeting oncogenic ErbB1/2, BRAF, FGFR2/3 and additional undisclosed targets BDTX - 1535 : a brain - penetrant, mutant selective, irreversible inhibitor of EGFR in Phase 1 for the treatment of patients with GBM and NSCLC driven by EGFR intrinsic & acquired resistance mutations BDTX - 4933 : a brain - penetrant inhibitor of Class I, II, and III oncogenic BRAF mutations in IND - enabling studies
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