UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): February 16, 2021
Foghorn Therapeutics Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-39634 | 47-5271393 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| 500 Technology Square, Ste 700 Cambridge, MA |
02139 | |
| (Address of principal executive offices) | (Zip Code) |
(Registrant’s telephone number, including area code): (617) 245-0399
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
| Common Stock, $0.0001 par value per share | FHTX | The Nasdaq Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 7.01 | Regulation FD Disclosure. |
Foghorn Therapeutics Inc. (the “Company”) is furnishing as Exhibit 99.1 to this Current Report on Form 8-K a presentation, dated February 16, 2021, which the Company intends to use from time to time in meetings with or presentations to investors.
The information in this Item 7.01 (including Exhibit 99.1 attached hereto) is being furnished and 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 filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Investor Presentation, dated February 16, 2021 | |
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.
| FOGHORN THERAPEUTICS INC. | ||
| By: | /s/ Allan Reine | |
| Allan Reine, M.D. | ||
| Chief Financial Officer | ||
Date: February 16, 2021
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
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 • Over 220 drug candidates into the clinic and over 30 drugs approved Novel Biology and Targets Multiple Drugging Approaches • Targeting the chromatin regulatory system • Synthetic lethality • Integrated and scalable platform • Protein degradation • Chromatin remodeling complexes, transcription factors, • Transcription factor disruptors and other components Potential applications beyond oncology in diseases including virology, autoimmune disease and neurology 2Precision 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 • Over 220 drug candidates into the clinic and over 30 drugs approved Novel Biology and Targets Multiple Drugging Approaches • Targeting the chromatin regulatory system • Synthetic lethality • Integrated and scalable platform • Protein degradation • Chromatin remodeling complexes, transcription factors, • Transcription factor disruptors and other components Potential applications beyond oncology in diseases including virology, autoimmune disease and neurology 2
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 inhibitor BRG1 mutated Selective BRM & protein degrader cancers ARID1A mutated Selective ARID1B Protein degrader cancers Partnered program Transcription factor disruptor (undisclosed) ® Gene Traffic Control Platform Using our proprietary Gene Traffic Control platform, we have identified additional genetically determined dependencies to drug using enzymatic inhibitors, protein degraders and transcription factor disruptors 3On 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 inhibitor BRG1 mutated Selective BRM & protein degrader cancers ARID1A mutated Selective ARID1B Protein degrader cancers Partnered program Transcription factor disruptor (undisclosed) ® Gene Traffic Control Platform Using our proprietary Gene Traffic Control platform, we have identified additional genetically determined dependencies to drug using enzymatic inhibitors, protein degraders and transcription factor disruptors 3
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 Optimization of and Identification of System Components And Validation Degradation Chemical Matter Biomarkers at Scale & Proprietary Assays 4Our 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 Optimization of and Identification of System Components And Validation Degradation Chemical Matter Biomarkers at Scale & Proprietary Assays 4
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 approval experience, Former GC, Vertex Pharmaceuticals, global law multiple therapeutic areas across >25 20 approvals 3 drug approvals and compliance experience, 2 drug approvals drug programs Steve Bellon, Ph.D., SVP, Drug Discovery Allan Reine, M.D., CFO Carlos Costa, SVP, HR Fanny Cavalie, SVP, Business & Operations 20+ years in industry drugging novel targets, 15 years biotech investor and public 20+ years worldwide experience across Global development through launch for >20 drugs, incl. bromo platform at Constellation multiple countries and regions portfolio and BD strategy experience company CFO BOARD OF DIRECTORS SCIENTIFIC AND OTHER ADVISORS Doug Cole, M.D. Adrian Gottschalk Charles Sawyers, M.D. David Schenkein, M.D. Flagship Pioneering – Foghorn President & CEO MSKCC, HHMI – SAB Chair General Partner, GV Board Chair; Founder Jose Baselga, M.D., Ph.D. Cigall Kadoch, Ph.D. Gerald Crabtree, M.D. Tony Kouzarides, Ph.D. Gurdon Institute – University of Cambridge AstraZeneca R&D Oncology Dana-Farber, Broad, HMS; Founder Stanford, HHMI; Founder Scott Biller, Ph.D. Adam Koppel, M.D., Ph.D. Faheem Hasnain Ian Smith Bain Capital Life Sciences Gossamer Bio, Chair of Mirati Former COO Vertex Pharmaceuticas, Former CSO and Strategic Advisor, Agios Chair of Solid Bio., Chair of ViaCyte Simba Gill, Ph.D. Michael Mendelsohn, M.D. Craig Peterson, Ph.D. Cardurion Pharmaceuticals Professor UMass Medical School Evelo Biosciences, Partner at Flagship Pioneering 5Experienced 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 approval experience, Former GC, Vertex Pharmaceuticals, global law multiple therapeutic areas across >25 20 approvals 3 drug approvals and compliance experience, 2 drug approvals drug programs Steve Bellon, Ph.D., SVP, Drug Discovery Allan Reine, M.D., CFO Carlos Costa, SVP, HR Fanny Cavalie, SVP, Business & Operations 20+ years in industry drugging novel targets, 15 years biotech investor and public 20+ years worldwide experience across Global development through launch for >20 drugs, incl. bromo platform at Constellation multiple countries and regions portfolio and BD strategy experience company CFO BOARD OF DIRECTORS SCIENTIFIC AND OTHER ADVISORS Doug Cole, M.D. Adrian Gottschalk Charles Sawyers, M.D. David Schenkein, M.D. Flagship Pioneering – Foghorn President & CEO MSKCC, HHMI – SAB Chair General Partner, GV Board Chair; Founder Jose Baselga, M.D., Ph.D. Cigall Kadoch, Ph.D. Gerald Crabtree, M.D. Tony Kouzarides, Ph.D. Gurdon Institute – University of Cambridge AstraZeneca R&D Oncology Dana-Farber, Broad, HMS; Founder Stanford, HHMI; Founder Scott Biller, Ph.D. Adam Koppel, M.D., Ph.D. Faheem Hasnain Ian Smith Bain Capital Life Sciences Gossamer Bio, Chair of Mirati Former COO Vertex Pharmaceuticas, Former CSO and Strategic Advisor, Agios Chair of Solid Bio., Chair of ViaCyte Simba Gill, Ph.D. Michael Mendelsohn, M.D. Craig Peterson, Ph.D. Cardurion Pharmaceuticals Professor UMass Medical School Evelo Biosciences, Partner at Flagship Pioneering 5
The Chromatin Regulatory System Orchestrates Gene ExpressionThe 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 Transcription Factor complex Normal gene expression Right genes Chromatin – compacted 2 form of DNA inside the TF’s guide chromatin remodeling nucleus of the cell complexes to the right locations 7The 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 Transcription Factor complex Normal gene expression Right genes Chromatin – compacted 2 form of DNA inside the TF’s guide chromatin remodeling nucleus of the cell complexes to the right locations 7
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 Mutations in Chromatin Remodeling Complex Result in Abnormal Gene Expression Mutated or Overexpressed TF Hijacks Chromatin Remodeling Complex to Wrong Location DISEASE DISEASE 8
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 just in Cancer the BAF Complex 9Chromatin 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 just in Cancer the BAF Complex 9
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: Transcription Factor Bi-functional protein degraders for Mutations / Overexpression targets with no enzymatic activity Potential Mutations that Impinge on Transcription Factor druggable the Chromatin Regulatory Disruptors: sites Disrupt interactions between System chromatin remodeling complexes and transcription factors 10Mutations 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: Transcription Factor Bi-functional protein degraders for Mutations / Overexpression targets with no enzymatic activity Potential Mutations that Impinge on Transcription Factor druggable the Chromatin Regulatory Disruptors: sites Disrupt interactions between System chromatin remodeling complexes and transcription factors 10
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/GNA11 complex (5,000) Synovial Sarcoma Protein Degrader FHD-609 SS18-SSX1, SSX2, SSX4 BRD9 (>1,800) BRG1 mutated cancers Enzymatic Inhibitor / Protein Selective BRM BRG1 BRM Degrader (>100K) ARID1A mutated cancers Protein Degrader Selective ARID1B ARID1A ARID1B (>175K) Specific TF – Chromatin Transcription Factor Disruptor Transcription Factors Various Various Remodeling Complex *U.S., EU5, Japan 11Pursuing 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/GNA11 complex (5,000) Synovial Sarcoma Protein Degrader FHD-609 SS18-SSX1, SSX2, SSX4 BRD9 (>1,800) BRG1 mutated cancers Enzymatic Inhibitor / Protein Selective BRM BRG1 BRM Degrader (>100K) ARID1A mutated cancers Protein Degrader Selective ARID1B ARID1A ARID1B (>175K) Specific TF – Chromatin Transcription Factor Disruptor Transcription Factors Various Various Remodeling Complex *U.S., EU5, Japan 11
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 the BRG1 and BRM subunits of the BAF complex
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 tumors • AML: BRG1 elevated in blast cells Mutation / Aberration • Uveal Melanoma: GNAQ/GNA11 mutated UM is driven by an abnormal dependency on BAF BRG1 BRM Program Status • On track for clinical data as early as Q4’21 BRG and BRM Subunits • AML: Over 20,000 relapsed and/or New Patients refractory patients Impacted • BRM/BRG1 is the engine (ATPase) of the BAF chromatin / year* • Uveal melanoma: Over 5,000 patients remodeling complex • BRG1 & BRM are highly similar proteins * US, EU5, Japan 13FHD-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 tumors • AML: BRG1 elevated in blast cells Mutation / Aberration • Uveal Melanoma: GNAQ/GNA11 mutated UM is driven by an abnormal dependency on BAF BRG1 BRM Program Status • On track for clinical data as early as Q4’21 BRG and BRM Subunits • AML: Over 20,000 relapsed and/or New Patients refractory patients Impacted • BRM/BRG1 is the engine (ATPase) of the BAF chromatin / year* • Uveal melanoma: Over 5,000 patients remodeling complex • BRG1 & BRM are highly similar proteins * US, EU5, Japan 13
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 blasts stuck in BAF-dependent proliferative phase Apoptosis 14Therapeutic 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 blasts stuck in BAF-dependent proliferative phase Apoptosis 14
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 equivalent to standard of care) Total Blasts Differentiation-like Blasts Immature Blasts Patient #1 Sample: Example of exposure-dependent differentiation effect 15Treatment 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 equivalent to standard of care) Total Blasts Differentiation-like Blasts Immature Blasts Patient #1 Sample: Example of exposure-dependent differentiation effect 15
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-AML2 1600 100 CDX Model (MII-AF6, DNMT3a mut.) 800 90 0 80 0 7 14 21 0 7 14 21 Days Post Treatment Days Post Treatment 16 3 3 Tumor Volume (mm ) Tumor Volume (mm ) Body Weight Change (%) Body Weight Change (%)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-AML2 1600 100 CDX Model (MII-AF6, DNMT3a mut.) 800 90 0 80 0 7 14 21 0 7 14 21 Days Post Treatment Days Post Treatment 16 3 3 Tumor Volume (mm ) Tumor Volume (mm ) Body Weight Change (%) Body Weight Change (%)
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 cancers have GNAQ or GNA11 mutations MITF SOX10 ChIPseq SOX10 17Therapeutic 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 cancers have GNAQ or GNA11 mutations MITF SOX10 ChIPseq SOX10 17
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 Treatment Days Post Treatment Tumor Volume Body Weight 900 120 92-1 uveal melanoma 750 CDX model 110 600 • Dose-dependent tumor growth 450 100 inhibition 300 90 • Tumor regression at 1.5 mg/kg, 150 PO, QD 0 80 0 5 10 15 20 0 5 10 15 20 • Well tolerated Days Post Treatment Days Post Treatment 18 3 3 Tumor Volume (mm ) Tumor Volume (mm ) Body Weight Change (%) Body Weight Change (%)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 Treatment Days Post Treatment Tumor Volume Body Weight 900 120 92-1 uveal melanoma 750 CDX model 110 600 • Dose-dependent tumor growth 450 100 inhibition 300 90 • Tumor regression at 1.5 mg/kg, 150 PO, QD 0 80 0 5 10 15 20 0 5 10 15 20 • Well tolerated Days Post Treatment Days Post Treatment 18 3 3 Tumor Volume (mm ) Tumor Volume (mm ) Body Weight Change (%) Body Weight Change (%)
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 Expansion cohorts Trial Design in AML, UM and Potential for entry into definitive efficacy • “3 + 3” accelerated titration design trials in metastatic uveal melanoma potentially other • Retrospective biomarker analysis to indications further evaluate safety and efficacy • Assess safety, PK, biomarkers and Potential for Indication Expansion Beyond AML and UM efficacy Early clinical data as early as Q4 2021 19FHD-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 Expansion cohorts Trial Design in AML, UM and Potential for entry into definitive efficacy • “3 + 3” accelerated titration design trials in metastatic uveal melanoma potentially other • Retrospective biomarker analysis to indications further evaluate safety and efficacy • Assess safety, PK, biomarkers and Potential for Indication Expansion Beyond AML and UM efficacy Early clinical data as early as Q4 2021 19
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
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 / SSX4 protein fusions Aberration Upcoming • IND submission Q2 2021 Milestones SS18-SSX1 / SSX2 / New Patients SSX4 mutated subunit • Synovial Sarcoma: Over 1,800 Impacted patients / year / year* • BRD9 is required for the survival of synovial sarcoma cells * US, EU5, Japan 21 BRD9 Dependency ScoreFHD-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 / SSX4 protein fusions Aberration Upcoming • IND submission Q2 2021 Milestones SS18-SSX1 / SSX2 / New Patients SSX4 mutated subunit • Synovial Sarcoma: Over 1,800 Impacted patients / year / year* • BRD9 is required for the survival of synovial sarcoma cells * US, EU5, Japan 21 BRD9 Dependency Score
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 BRD9 degradation correlated with anti-tumor activity 22Robust 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 BRD9 degradation correlated with anti-tumor activity 22
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 observed 700 90 over 30 days at 2 mg/kg of FHD- 609 0 80 0 10 20 30 40 0 7 14 21 28 Days Post Treatment Days Post Treatment 23 3 Tumor Volume (mm ) % Body Weight ChangeSuperior 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 observed 700 90 over 30 days at 2 mg/kg of FHD- 609 0 80 0 10 20 30 40 0 7 14 21 28 Days Post Treatment Days Post Treatment 23 3 Tumor Volume (mm ) % Body Weight Change
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 synovial sarcoma SMARCB-1 Trial design: deleted tumors and potentially other • “3+3” Design indications • Patients: Synovial cell sarcoma • Primary endpoints: Assess safety, PK, efficacy and biomarkers Biomarkers: • SS18-SSX1, SS18-SSX2 or SS18-SSX4 translocation IND submission expected in Q2 2021 24FHD-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 synovial sarcoma SMARCB-1 Trial design: deleted tumors and potentially other • “3+3” Design indications • Patients: Synovial cell sarcoma • Primary endpoints: Assess safety, PK, efficacy and biomarkers Biomarkers: • SS18-SSX1, SS18-SSX2 or SS18-SSX4 translocation IND submission expected in Q2 2021 24
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 inhibitor BRG1 mutated Selective BRM & protein degrader cancers ARID1A mutated Selective ARID1B Protein degrader cancers Partnered program Transcription factor disruptor (undisclosed) Gene Traffic Control® Platform Using our proprietary Gene Traffic Control platform, we have identified additional genetically determined dependencies to drug using enzymatic inhibitors, protein degraders and transcription factor disruptors 25On 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 inhibitor BRG1 mutated Selective BRM & protein degrader cancers ARID1A mutated Selective ARID1B Protein degrader cancers Partnered program Transcription factor disruptor (undisclosed) Gene Traffic Control® Platform Using our proprietary Gene Traffic Control platform, we have identified additional genetically determined dependencies to drug using enzymatic inhibitors, protein degraders and transcription factor disruptors 25
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
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 Patients Impacted • > 100,000 BRG1 / year* * US, EU5, Japan 27 BRM Dependency ScoreBRG1 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 Patients Impacted • > 100,000 BRG1 / year* * US, EU5, Japan 27 BRM Dependency Score
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 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 28
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 • Panel showing biochemical selectivity of a 20X more selective inhibitor of BRM vs. BRG1 BRM Selective Degrader Program • Selective BRM degrading molecules led to the degradation of over 75% of BRM while leaving BRG1 unchanged 2920X 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 • Panel showing biochemical selectivity of a 20X more selective inhibitor of BRM vs. BRG1 BRM Selective Degrader Program • Selective BRM degrading molecules led to the degradation of over 75% of BRM while leaving BRG1 unchanged 29
Selective ARID1B Protein Degrader for ARID1A Mutated CancersSelective ARID1B Protein Degrader for ARID1A Mutated Cancers
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, bladder and other cancers) ARID1B Stage • Pre-clinical New Patients Impacted • > 175,000 / year* * US, EU5, Japan 31 ARID1B Dependency ScoreARID1A – 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, bladder and other cancers) ARID1B Stage • Pre-clinical New Patients Impacted • > 175,000 / year* * US, EU5, Japan 31 ARID1B Dependency Score
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 • ~5% of all tumors harbor scale ARID1B ARID1A mutations including; endometrial • Status: Validating hits from cancer (~40%), bladder multiple High Throughput cancer (~25%) and ovarian Screens (~15%) • Synthetic lethal relationship with ARID1B • Developing protein degraders to ARID1B 32ARID1B 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 • ~5% of all tumors harbor scale ARID1B ARID1A mutations including; endometrial • Status: Validating hits from cancer (~40%), bladder multiple High Throughput cancer (~25%) and ovarian Screens (~15%) • Synthetic lethal relationship with ARID1B • Developing protein degraders to ARID1B 32
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
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 diseases …but historically difficult to target • Featureless surface: no druggable binding pocket • Tight interactions with DNA: Historical undruggable affinities Focus Foghorn has a new approach focusing on interaction with BAF ▪ Druggable binding pockets ▪ Druggable affinities 34A 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 diseases …but historically difficult to target • Featureless surface: no druggable binding pocket • Tight interactions with DNA: Historical undruggable affinities Focus Foghorn has a new approach focusing on interaction with BAF ▪ Druggable binding pockets ▪ Druggable affinities 34
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 10000 0.01 0.1 1 10 100 1000 0.1 1 10 100 1000 10000 0.1 1 10 100 1000 10000 MITF (nM) SPI1 (nM) MYOD1 (nM) FoxA1 (nM) TF #1 (nM) TF #2 (nM) TF #3 (nM) TF #4 (nM) Transcription Factors (TF): 35 RU RU RU RUTranscription 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 10000 0.01 0.1 1 10 100 1000 0.1 1 10 100 1000 10000 0.1 1 10 100 1000 10000 MITF (nM) SPI1 (nM) MYOD1 (nM) FoxA1 (nM) TF #1 (nM) TF #2 (nM) TF #3 (nM) TF #4 (nM) Transcription Factors (TF): 35 RU RU RU RU
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 hits • Approach highly scalable and potential broad (~3500 compounds) application – other chromatin remodeling complexes and other diseases • Merck collaboration to drug single specified transcription factor target TF #Y • $425 million in up-front, research, development Primary HTS and sales-based milestones of >250K • Up to low double-digit royalties on product sales compounds 36Highly 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 hits • Approach highly scalable and potential broad (~3500 compounds) application – other chromatin remodeling complexes and other diseases • Merck collaboration to drug single specified transcription factor target TF #Y • $425 million in up-front, research, development Primary HTS and sales-based milestones of >250K • Up to low double-digit royalties on product sales compounds 36
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 degrader Synovial sarcoma FHD-609: IND Submission (Q2 2021) (BRD9) Enzyme inhibitor BRG1 mutated Selective BRM & protein degrader cancers ARID1A mutated Selective ARID1B Protein degrader cancers Partnered program Transcription factor disruptor (undisclosed) Gene Traffic Control® Platform Using our proprietary Gene Traffic Control platform, we have identified additional genetically determined dependencies to drug using enzymatic inhibitors, protein degraders and transcription factor disruptors 37On 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 degrader Synovial sarcoma FHD-609: IND Submission (Q2 2021) (BRD9) Enzyme inhibitor BRG1 mutated Selective BRM & protein degrader cancers ARID1A mutated Selective ARID1B Protein degrader cancers Partnered program Transcription factor disruptor (undisclosed) Gene Traffic Control® Platform Using our proprietary Gene Traffic Control platform, we have identified additional genetically determined dependencies to drug using enzymatic inhibitors, protein degraders and transcription factor disruptors 37