Foghorn Therapeutics Inc. · NASDAQ:FHTX
Foghorn Therapeutics — Investor Presentation (March 2024)
37 slides from Foghorn Therapeutics's investor presentation, Mar 7, 2024
Slide 1: Unique biology, Precision therapeutics, Broad impact
March 2024 Unique biology Precision therapeutics Broad impact Exhibit 99.2
Slide 2: Forward Looking Statements
| Forward Looking Statements 2 This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “could,” “may,” “m
Slide 3: First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer
| First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer 3 Large Market Potential Chromatin biology is implicated in up to 50% of tumors, potentially impacting ~2.5 million patients Foghorn’s current pipeline potentially addresses more than 500,000 of these patients Major Strategic
Slide 4: Unique Insights into Chromatin Biology to Prosecute Untapped Area for Novel Targets and Therapeutics
| Unique Insights into Chromatin Biology to Prosecute Untapped Area for Novel Targets and Therapeutics 4 Novel Targets Guided by Genetic Dependencies Tailored Drugging Approaches Transcription Factor Mutations / Overexpression Chromatin Remodeling Complex Mutations / Overexpression Helicases & Other
Slide 5: Foghorn's Validated Gene Traffic Control Platform
| Foghorn’s Validated Gene Traffic Control© Platform Enables an Integrated, Scalable, Efficient and Repeatable Paradigm 5 Deep mechanistic understanding of the chromatin regulatory system Biology first, small molecule modality agnostic Targeting Disease Selective Therapeutics What to Drug: Identify
Slide 6: Broad and Deep Pipeline Across a Range of Targets and Modalities
| Broad and Deep Pipeline Across a Range of Targets and Modalities 6 Modality Program Discovery Phase 1 Phase 2 Phase 3 Enzyme Inhibitors Transcription Factor Disruptors Undisclosed Protein Degraders Commercial Rights FHD-286 (BRG1/BRM) FHD-909 (Selective BRM) 3 Discovery Programs Undisclosed Partne
Slide 7: FHD-286: Dual BRM/BRG1 Inhibition Targeting BAF Dependency in Cancer
FHD-286: Dual BRM/BRG1 Inhibition Targeting BAF Dependency in Cancer FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex
Slide 8: Exploring BAF Dependency in Cancer with FHD-286
| Exploring BAF Dependency in Cancer with FHD-286 – Potent, Small Molecule Inhibitor Targeting BRM and BRG1 8 Clinical and pre-clinical data demonstrate broad- based differentiation across AML and multiple solid tumors BAF ATPase: BRG1/BRM FHD-286: • Allosteric modulation inhibiting the activity of
Slide 9: First-in-Class Broad-Based Differentiation Agent With Significant Combination Potential in AML
| First-in-Class Broad-Based Differentiation Agent With Significant Combination Potential in AML 9 Completed Phase I Monotherapy Safety and Efficacy Results Ongoing Phase I Combination StudySignificant Opportunity • ~27,000 drug treated relapsed and/or refractory (R/R) AML patients* • No broad diffe
Slide 10: Study Design for FHD-286 Phase 1 Dose-Escalation in Combination with Decitabine in AML
| Study Design for FHD-286 Phase 1 Multicenter Dose-Escalation in Combination with Decitabine in AML 10 Target Indication: • R/R AML Treatment Plan & Dose Escalation: • 3+3 escalation design • Oral FHD-286, QD, 28-day cycles • Standard decitabine dose schedule Key Objectives Primary • Safety/Tolerab
Slide 11: FHD-286 Demonstrated Differentiation Across a Broad Range of Genetic Backgrounds
| FHD-286 Demonstrated Differentiation Across a Broad Range of Genetic Backgrounds 11 Dose Level Mutations Cytogenetics Risk Starting CD11b% Max CD11b% CD11b+ Fold Change Starting CD34% Min CD34% CD34+ % Decrease 10mg N/A Adverse 7 62 9.2x 94 27 (71%) 7.5mg CBFB (locus at 16q22) 2 94 59.4x 70 2 (97%
Slide 12: Bone Marrow Aspirate: Clear Evidence of Differentiation
| Bone Marrow Aspirate: Clear Evidence of Differentiation Bone Marrow Blast Reduction from 40% to 6% Clear Signs of Differentiation in Heavily Pre-Treated, Secondary AML Patient with Abnormal Karyotype 12 Patient Background: • 47-year-old male, secondary AML • Abnormal karyotype: Del (7Q), Inv (3),
Slide 13: Meaningful Clinical Benefit in Heavily Pre-Treated Patient
| Absolute Neutrophil Count (ANC) Peripheral Blast Count Meaningful Clinical Benefit in Heavily Pre-Treated Patient 13 100% 0% 50% 10 5 10/13/21 10/24/21 11/4/21 11/14/21 11/25/21 12/6/21 0 Initiation of FHD 286 1st SCT 2nd SCT Patient Background: • 25-year-old male, treatment-related AML • KMT2A re
Slide 14: Pre-Clinical Data Demonstrate Significant Combination Potential with Multiple Agents in AML
| FHD-286 + decitabine (MLL-AFP + FLT3 TKD Luc/GFP PDX) Pre-Clinical Data Demonstrate Significant Combination Potential with Multiple Agents in AML 14 FHD-286 + BET inhibitor (mtNPM1 + FLT3 ITD Luc/GFP AML PDX) FHD-286 + menin inhibitor (mtNPM1 + FLT3 ITD Luc/GFP AML PDX) FHD-286 + cytarabine (MV4,
Slide 15: Selective BRM Modulators For BRG1 Mutated Cancers
Selective BRM Modulators For BRG1 Mutated Cancers FHD-286 is a Potent, Selective, Allosteric, Small Molecule Inhibitor of the BRG1 and BRM subunits of the BAF complex
Slide 16: BRM Selective Inhibitor FHD-909 IND Targeted in Q2'24, BRM Selective Degrader Continues Pre-Clinical Development
| BRM Selective Inhibitor FHD-909 IND Targeted in Q2’24, BRM Selective Degrader Continues Late-Stage Pre-Clinical Development 16 BRM Selective Inhibitor (FHD-909) BRM Selective Degrader Biology Exploit the synthetic lethal relationship between BRM (SMARCA2) and mutated BRG1 (SMARCA4) Stage IND submi
Slide 17: BRM Selective Inhibition and Degradation Exploit the Synthetic Lethal Relationship Between BRM and Mutated BRG1
| BRM Selective Inhibition and Degradation Exploit the Synthetic Lethal Relationship Between BRM and Mutated BRG1 17 No BRG1 Mutations BRG1 Mutation BRG1 Mutation and BRMi Cell Survival Cell Death Healthy Cells Cancer Cells BRG1 BRM BAF Complex BRM BAF Complex Mutant BRG1 BAF Complex BRMi • BRG1 mut
Slide 18: BRG1 is Mutated in Up to 10% of NSCLC; Up to 5% of Solid Tumors
| BRG1 is Mutated in Up to 10% of NSCLC; Up to 5% of Solid Tumors 18 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
Slide 19: BRM Selective Inhibitor Demonstrates PK/PD and In Vivo Efficacy in a BRG1 Mutant Lung CDX Model
| BRM Selective Inhibitor Demonstrates PK/PD and In Vivo Efficacy in a BRG1 Mutant Lung CDX Model 19 PK/PD Body Weight LossA549-BRG1 Mutant NSCLC Model BRG1 cellular IC50 BRM cellular IC50 0 5 10 15 1 10 100 1,000 Time (h) M ea n U nb ou nd Pl as m a C on ce nt ra tio n (n M ) 10 20 30 40 0 500 1,00
Slide 20: BRM Selective Degrader Achieves Complete BRM Degradation and Cell Growth Inhibition
| BRM Selective Degrader Achieves Complete BRM Degradation and Cell Growth Inhibition 20 Degraders Cause Time- and Dose-Dependent BRM Degradation Antiproliferative Effects in A549 Mutant NSCLC Model A549 Ten-Day Proliferation AssayBRM/BRG1 HIBIT Data BRM BRG1 % D eg ra da tio n Concentration (uM) 0.
Slide 21: Selective CBP Protein Degrader For EP300 Mutated Cancers
Selective CBP Protein Degrader For EP300 Mutated Cancers
Slide 22: Summary: Selective CBP Protein Degrader for EP300 Mutated Cancers
| Summary: Selective CBP Protein Degrader for EP300 Mutated Cancers 22* Per year incidence in the U.S., EU5, Japan Target / Approach • CREB binding protein (CBP) • Targeted protein degrader Initial Indication • EP300 mutated cancers (e.g., subsets of bladder, colorectal, breast, gastric and lung can
Slide 23: Selective CBP Protein Degrader Results in Significant Tumor Growth Inhibition in Colorectal and Bladder EP300 Null Models
| Colorectal RKO (EP300 Null) Model Selective CBP Protein Degrader Result in Significant Tumor Growth Inhibition in Colorectal and Bladder EP300 Null Models 23 Bladder 639V (EP300 Null) Model 30 40 50 -20 -10 0 10 20 Days after Tumor Inoculation B od y W ei gh t C ha ng e (% ) 30 40 50 0 500 1,000 1
Slide 24: Selective CBP Protein Degrader Results in Tumor Regression in Gastric EP300 Null Models
| Selective CBP Protein Degrader Result in Tumor Regression in Gastric EP300 Null Models 24 Gastric AGS (EP300 Null) Model 20 30 40 50 60 -20 -10 0 10 20 B od y w ei gh t C ha ng e (% ) Days after Tumor Inoculation 20 30 40 50 60 0 500 1,000 1,500 Days After Tumor Inoculation Tu m or V ol um e (m m
Slide 25: Long-Acting Injectable Formulations of CBP Degrader Could Enable Dosing Once Every 2 Weeks
| CBP Degrader Plasma Concentration Long-Acting Injectable Formulations of CBP Degrader Could Enable Once Every 2 Weeks (or Better) Dosing Frequency 25 0 100 200 300 400 0 2,000 4,000 6,000 8,000 Time (hours) C on cn et ra tio n (n g/ m l) CBPd - 9, SC, 150 mg/kg CBPd - 9, IM, 150 mg/kg
Slide 26: Selective EP300 Protein Degrader For CBP Mutated and EP300 Dependent Cancers
Selective EP300 Protein Degrader For CBP Mutated and EP300 Dependent Cancers
Slide 27: Summary: Selective EP300 Protein Degrader for CBP Mutant & EP300 Dependent Cancers
| Summary: Selective EP300 Protein Degrader for CBP Mutant & EP300 Dependent Cancers 27 * Per year incidence in the U.S., EU5, Japan Target / Approach • E1A binding protein p300 (EP300) • Targeted protein degrader Initial Indications • AR+ Prostate • DLBCL • Bladder, melanoma, others Mutation / Aber
Slide 28: EP300 Degradation Results in Significant Tumor Growth Inhibition in Prostate and DLBCL Models
| EP300 Degradation Results in Significant Tumor Growth Inhibition in AR+ VCAP Prostate and KARPAS422 DLBCL Models 28 Prostate AR+ VCAP Model DLBCL KARPAS422 (CBP Null) Model 5 10 15 20 25 30 35 40 45 50 0 500 1,000 1,500 2,000 Days After Tumor Inoculation Tu m or V ol um e (m m ³ + S EM ) Vehicle C
Slide 29: Selective Degradation of EP300 and CBP Does Not Show Thrombocytopenia in Mice at Relevant Doses
| Platelet Counts Post Two Weeks of Dosing (In-Vivo) Selective Degradation of EP300 and CBP Does Not Show Thrombocytopenia in Mice at Relevant Doses 29 PLT (x109cells/L) 0 500 1,000 1,500 2,000 2,500 Study Day 14 Pl at el et s (X 10 3 c el ls /u L) Vehicle FHT-EP300d, 50mg/kg, sc, BID FHT-CBPd, 10mg
Slide 30: Selective ARID1B Protein Degrader For ARID1A Mutated Cancers
Selective ARID1B Protein Degrader For ARID1A Mutated Cancers
Slide 31: ARID1B is a Major Synthetic Lethal Target Implicated in Up To 5% of All Solid Tumors
| ARID1B is a Major Synthetic Lethal Target Implicated in Up To 5% of All Solid Tumors 31* Per year incidence in the U.S., EU5, Japan Target / Approach • ARID1B • Targeted protein degrader Initial Indication • ARID1A mutated cancers Mutation / Aberration • ARID1A mutations (e.g., ovarian, endometria
Slide 32: Targeting ARID1B for ARID1A Mutated Cancers is Enabled by Foghorn's Unique Biology and Discovery Capabilities
| Targeting ARID1B for ARID1A Mutated Cancers is Enabled by Foghorn’s Unique Biology and Discovery Capabilities 32 Gene Traffic Control Platform Protein Degrader Capabilities Program Status • Platform produces BAF complexes and subcomplexes containing either ARID1A or ARID1B at scale • Enables propr
Slide 33: Transcription Factors: A Novel Approach
Transcription Factors A Novel Approach FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex
Slide 34: Foghorn's Novel Approach to Drugging Transcription Factors
| Foghorn’s Novel Approach to Drugging Transcription Factors Enabled by Its Protein Production and Discovery Capabilities 34 • Highly involved in gene expression • Implicated in range of cancers and other diseases • Featureless surface: no druggable binding pocket • Tight interactions with DNA: undr
Slide 35: Transcription Factors Bind to BAF Directly with High Degree of Specificity
| Transcription Factors Bind to BAF Directly with High Degree of Specificity; Unique Insights into Where and How Transcription Factors Bind 35 Mass spec. foot-printing Pull-down assays Foghorn’s collection of BAF sub-complexes and domains Biophysical Biochemical Structural AUC / SPR / ITC TR-FRET /
Slide 36: Broad and Deep Pipeline Across a Range of Targets and Modalities
| Broad and Deep Pipeline Across a Range of Targets and Modalities 36 Modality Program Discovery Phase 1 Phase 2 Phase 3 Enzyme Inhibitors Transcription Factor Disruptors Undisclosed Protein Degraders Commercial Rights FHD-286 (BRG1/BRM) FHD-909 (Selective BRM) 3 Discovery Programs Undisclosed Partn
Slide 37: First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer
| First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer 37 Large Market Potential Chromatin biology is implicated in up to 50% of tumors, potentially impacting ~2.5 million patients Foghorn’s current pipeline potentially addresses more than 500,000 of these patients Major Strategi
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