Foghorn Therapeutics Inc. · NASDAQ:FHTX
Foghorn Therapeutics — Investor Presentation (February 2021)
37 slides from Foghorn Therapeutics's investor presentation, Feb 16, 2021
Slide 1: Targeting the Chromatin Regulatory System
Exhibit 99.1 Targeting the Chromatin Regulatory System A Product Platform with Potential to Impact Millions of Patients February 16, 2021Exhibit 99.1 Targeting the Chromatin Regulatory System A Product Platform with Potential to Impact Millions of Patients February 16, 2021
Slide 2: Precision Oncology: Novel Biology with Breadth and Depth
Precision Oncology: Novel Biology with Breadth and Depth Large Market Potential / Precision Approach Experienced Leadership Team • Expertise across drug discovery, clinical development • Biology implicated in up to 50% of cancer potentially and commercialization impacting ~2.5 million patients • Ove
Slide 3: On Track for Entry Into the Clinic with First Two Programs
On Track for Entry Into the Clinic with First Two Programs Precision Oncology / Breadth and Depth Global Program / Target Modality Discovery IND-enabling Phase 1 Phase 2 Phase 3 Rights AML FHD-286 Enzyme inhibitor (BRG1 / BRM) Uveal melanoma FHD-609 Protein degrader Synovial sarcoma (BRD9) Enzyme in
Slide 4: Our Gene Traffic Control Platform Makes It Possible to Understand and Drug Genetic Dependencies
Our Gene Traffic Control Platform Makes It Possible to Understand and Drug Genetic Dependencies within the Chromatin Regulatory System Integrated, Scalable, Efficient – Repeatable Paradigm Production of Discovery and Translation to Clinic Chromatin Regulatory Target Identification Targeted Protein O
Slide 5: Experienced Leadership Team with Industry Leading Advisors and Investors
Experienced Leadership Team with Industry Leading Advisors and Investors SENIOR LEADERSHIP TEAM Adrian Gottschalk, President & CEO Carl Decicco, Ph.D., CSO Sam Agresta, M.D., M.P.H., CMO Michael LaCascia, CLO Development through commercialization in >200 drugs transitioned to the clinic, Global drug
Slide 6: The Chromatin Regulatory System Orchestrates Gene Expression
The Chromatin Regulatory System Orchestrates Gene ExpressionThe Chromatin Regulatory System Orchestrates Gene Expression
Slide 7: The Chromatin Regulatory System Orchestrates Gene Expression
The Chromatin Regulatory System Orchestrates Gene Expression Two Major Components Work in Concert - Chromatin Remodeling Complexes and Transcription Factors 1 3 Work together to orchestrate Once chromatin unpacked, gene expression gene expression can occur Chromatin Chromatin remodeling Transcriptio
Slide 8: Breakdowns in the Chromatin Regulatory System Lead to Disease
Breakdowns in the Chromatin Regulatory System Lead to Disease Mutations in Chromatin Remodeling Complex Result in Abnormal Gene Expression Mutated or Overexpressed TF Hijacks Chromatin Remodeling Complex to Wrong Location DISEASE DISEASE 8Breakdowns in the Chromatin Regulatory System Lead to Disease
Slide 9: Chromatin Regulatory System Implicated in Over 50% of Cancers
Chromatin Regulatory System Implicated in Over 50% of Cancers Potentially Impacting Over 2.5M Patients 28 Chromatin Remodeling BAF Complex and Associated Transcription Factors Complexes and >1,000 TFs + BAF Complex Subunits Estimate >100 Transcription Mutated and Dysregulated Factors Associated with
Slide 10: Mutations Lead to Disease Specific Genetic Dependencies on the Chromatin Regulatory System
Mutations Lead to Disease Specific Genetic Dependencies on the Chromatin Regulatory System Novel Targets Tailored Drugging Approaches Enzymatic Inhibitors: Highly selective and allosteric Mutations in Chromatin small molecule inhibitors Remodeling Complexes ATP ADP Targeted Protein Degradation: Tran
Slide 11: Pursuing a Precision Oncology Approach
Pursuing a Precision Oncology Approach Each Program is Based on a Genetically Defined Dependency Mutation / Target Patient Program Genetic Dependency Drug Approach Abberation Population* AML Elevated BRG1 expression BRG1 (20,000) Enzymatic Inhibitor FHD-286 SOX10 / MITF / BAF Uveal Melanoma GNAQ/GNA
Slide 12: FHD-286: Clinical Entry Point - AML and Uveal Melanoma
FHD-286: Clinical Entry Point - AML and Uveal Melanoma FHD-286 is a Potent, Selective, Allosteric, Small Molecule Inhibitor of the BRG1 and BRM subunits of the BAF complexFHD-286: Clinical Entry Point - AML and Uveal Melanoma FHD-286 is a Potent, Selective, Allosteric, Small Molecule Inhibitor of th
Slide 13: FHD-286 Targets Abnormal Dependencies on BAF in Cancer
FHD-286 Targets Abnormal Dependencies on BAF in Cancer BAF Chromatin Remodeling Complex • BRG1/BRM ATPase Target / Approach • Small molecule, allosteric, oral enzymatic inhibitor • Acute myelogenous leukemia (AML) • Uveal melanoma Indications • Indication expansion work ongoing in multiple solid tum
Slide 14: Therapeutic Rationale for AML: Blast Cells Dependent on BRG1-BAF
Therapeutic Rationale for AML: Blast Cells Dependent on BRG1-BAF Cancerous blast Intervention cells rely on elevated decreases BRG1- BRG1-BAF BAF activity expression BRG1 BRG1 expression expression level level Disease State Treatment with FHD-286 Differentiation HSC Loss of blast phenotype / AML bla
Slide 15: FHD-286 Treatment of Patient-Derived AML Samples: Differentiation and Cytoreduction
Treatment with FHD-286 of Patient-Derived AML Tumor Samples was Associated with both Differentiation and Cytoreduction Patient #1 Sample BM-de novo AML Patient #2 Sample BM-secondary AML Patient #3 Sample BM-secondary AML Exposure-dependent differentiation effect and cytoreduction (Cytoreduction is
Slide 16: Dose-Dependent Tumor Growth Inhibition with FHD-286 in AML CDX Models
Dose-Dependent Tumor Growth Inhibition Observed with FHD-286 Treatment in AML CDX Models Tumor Volume Body Weight 120 1250 1000 110 750 100 MV4-11 500 CDX Model 90 (FLT3 ITD, MLL-AF4) 250 0 80 0 7 14 21 0 7 14 21 Days Post Treatment Days Post Treatment Tumor Volume Body Weight 3200 120 2400 110 OCI-
Slide 17: Therapeutic Rationale for Uveal Melanoma
Therapeutic Rationale for Uveal Melanoma: Dependency on Overexpression of the MITF / SOX10 Transcription Factors and the BAF Complex Inhibiting BRG1/BRM to shut down the abnormal TF interaction with the BAF complex Biology Validation of Dependency and Approach MITF ChIPseq Over 85% of uveal melanoma
Slide 18: FHD-286 Dose-Dependent Tumor Regression in Uveal Melanoma CDX Models
FHD-286 was Associated with Dose-Dependent Tumor Regression in Uveal Melanoma CDX Models at Tolerated Doses Tumor Volume Body Weight MP-46 uveal melanoma 1200 120 CDX model 900 110 • Dose-dependent tumor growth 600 100 inhibition 300 90 • Well tolerated 0 80 0 7 14 21 28 0 7 14 21 28 Days Post Treat
Slide 19: FHD-286 Clinical Development Plan
FHD-286 Clinical Development Plan Our Understanding of the Biology and Target allows for the Selection of Focused Patient Populations CLINICAL PLAN AML & Uveal Melanoma FIH Phase 1 Studies Relapsed / Refractory AML Potential for entry into definitive efficacy trials in AML Metastatic Uveal Melanoma
Slide 20: FHD-609: Clinical Entry Point – Synovial Sarcoma
FHD-609: Clinical Entry Point – Synovial Sarcoma FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complexFHD-609: Clinical Entry Point – Synovial Sarcoma FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex
Slide 21: FHD-609 Targets and Degrades the BRD9 Subunit of BAF
FHD-609 Targets and Degrades the BRD9 subunit of BAF which is Required for Synovial Sarcoma Cells to Survive Selective, Potent BRD9 Targeted Protein Degrader • BRD9 Target / BRD9 subunit Approach • Intravenous Protein Degrader • Synovial Sarcoma Initial Indication Mutation / • SS18-SSX1 / SSX2 / SSX
Slide 22: Robust in vivo Activity in Synovial Sarcoma Model and BRD9 Degradation
Robust in vivo Activity Observed in Synovial Sarcoma Model and BRD9 Degradation Associated with FHD-609 Treatment Weekly Dosing of FHD-609 Achieved Sustained BRD9 Degradation • Sustained BRD9 Degradation SY01 Synovial Sarcoma CDX Model • Mutation: SS18-SSX2 • Inhibited tumor growth • Dose dependent
Slide 23: Superior Tumor Growth Inhibition of FHD-609 versus Ifosfamide and Pazopanib
Superior Tumor Growth Inhibition of FHD-609 in a Synovial Sarcoma Model as Compared to Ifosfamide and Pazopanib Tumor Volume Body Weight ASKA CDX Model 2800 120 • Mutation: SS18-SSX1 2100 110 • Superior tumor growth inhibition compared to ifosfamide and pazopanib 1400 100 • Complete suppression obse
Slide 24: FHD-609 Clinical Development Plan
FHD-609 Clinical Development Plan Our Understanding of the Biology and Target allows for the Selection of Focused Patient Populations CLINICAL PLAN Synovial Sarcoma FIH Phase 1 Synovial Sarcoma Potential for entry into definitive Metastatic Synovial Sarcoma expansion cohorts efficacy trials in synov
Slide 25: On Track for Entry Into the Clinic with First Two Programs
On Track for Entry Into the Clinic with First Two Programs Precision Oncology / Breadth and Depth Global Program / Target Modality Discovery IND-enabling Phase 1 Phase 2 Phase 3 Rights AML FHD-286 Enzyme inhibitor (BRG1 / BRM) Uveal melanoma FHD-609 Protein degrader Synovial sarcoma (BRD9) Enzyme in
Slide 26: Selective BRM Modulators for BRG1 Mutated Cancers
Selective BRM Modulators for BRG1 Mutated Cancers Enzymatic Inhibitor and Protein Degrader ProgramsSelective BRM Modulators for BRG1 Mutated Cancers Enzymatic Inhibitor and Protein Degrader Programs
Slide 27: BRG1 Mutations Create a Genetic Dependency on BRM
BRG1 Mutations Create a Genetic Dependency on BRM Selective BRM Modulators Overview • BRM Target / • Enzymatic inhibitor Approach • Targeted protein degrader • BRG1 mutated cancers (e.g., NSCLC), 30+ Indication cancers with BRG1 mutations BRM Mutation / • BRG1 Aberration Stage • Pre-clinical New Pat
Slide 28: BRG1 Mutated in ~5% of All Tumors
BRG1 Mutated in ~5% of All Tumors – Potential Broad Addressable Patient Populations BRG1 mutated across range of tumors Accounts for ~5% of all tumors BRG1 mutated in up to 10% of NSCLC tumors, minimal overlap with other mutations 28BRG1 Mutated in ~5% of All Tumors – Potential Broad Addressable Pat
Slide 29: 20X Selective BRM Inhibitor and Targeted Protein Degrader Discovered
20X Selective BRM Inhibitor and Targeted Protein Degrader Discovered from Gene Traffic Control Platform Selective BRM Modulators Enzyme assay using BRG1 and Enzyme assay using BRG1 and BRM Cellular assays for BRG1 BRM subunits containing full BAF complexes and BRM BRM Selective Inhibitor Program • P
Slide 30: Selective ARID1B Protein Degrader for ARID1A Mutated Cancers
Selective ARID1B Protein Degrader for ARID1A Mutated CancersSelective ARID1B Protein Degrader for ARID1A Mutated Cancers
Slide 31: ARID1A – Most Mutated Subunit in BAF Complex – Creates Dependency on ARID1B
ARID1A – Most Mutated Subunit in BAF Complex – Creates Dependency on ARID1B Selective ARID1B Protein Degrader Overview ARID1A • ARID1B Target / Approach • Targeted Protein Degrader Indication • ARID1A mutated cancers • ARID1A mutations (e.g., Mutation / ovarian, endometrial, Aberration colorectal, b
Slide 32: ARID1B Highlights Broad Potential of Foghorn Gene Traffic Control Platform
ARID1B Highlights Broad Potential of Foghorn Gene Traffic Control Platform Biology Drugging Strategy Highly purified • ARID1A is the most highly • Platform produces BAF ARID1B-BAF mutated subunit of the BAF complexes and Complex complex in cancer subcomplexes containing either ARID1A or ARID1B at •
Slide 33: Novel Approach to Targeting Transcription Factors
Novel Approach to Targeting Transcription Factors Disrupting Transcription Factor – Chromatin Remodeling Complex InteractionsNovel Approach to Targeting Transcription Factors Disrupting Transcription Factor – Chromatin Remodeling Complex Interactions
Slide 34: A New Approach to Drugging Transcription Factors
A New Approach to Drugging Transcription Factors Enabled by Proprietary Ability to Purify and Synthesize Chromatin Regulatory System Components Foghorn’s Focus TFs are compelling drug targets… • Highly involved in gene expression • Implicated in range of cancers and other Potential druggable sites d
Slide 35: Transcription Factor-Chromatin Remodeling Complex Interactions
Transcription Factor-Chromatin Remodeling Complex Interactions Unique Insights in Where and How Transcription Factors Bind TF #1 TF #2 TF #3 TF #4 KD = 21 nM KD = 125 nM KD = 351 nM KD = 94 nM 400 250 350 400 300 200 300 300 250 150 200 200 200 150 100 100 100 100 50 50 0 0 0 0 0.1 1 10 100 1000 100
Slide 36: Highly Scalable Approach and Significant Unmet Medical Need
Highly Scalable Approach and Significant Unmet Medical Need Potential to drug > 100 TFs associated with BAF • >100 TFs estimated associated with BAF • Foghorn pursuing multiple TFs in parallel TF #X Primary HTS • HTS on full BAF complex + TF target of >330K Median + 3s = 37.5% compounds Selected hit
Slide 37: On Track for Entry Into the Clinic with First Two Programs
On Track for Entry Into the Clinic with First Two Programs Precision Oncology / Breadth and Depth Global Program / Target Modality Discovery IND-enabling Phase 1 Phase 2 Phase 3 Rights AML FHD-286 Enzyme inhibitor FHD-286: Early Clinical Data (Q4 2021) (BRG1 / BRM) Uveal melanoma FHD-609 Protein deg
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