Foghorn Therapeutics Inc. · NASDAQ:FHTX
Foghorn Therapeutics — Investor Presentation (February 2024)
35 slides from Foghorn Therapeutics's investor presentation, Feb 8, 2024
Slide 1: Unique biology, Precision therapeutics, Broad impact
February 2024 Unique biology Precision therapeutics Broad impact Exhibit 99.1
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
| 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: FHD-286 Demonstrated Differentiation Across a Broad Range of Genetic Backgrounds
| FHD-286 Demonstrated Differentiation Across a Broad Range of Genetic Backgrounds 10 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 11: 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 11 Patient Background: • 47-year-old male, secondary AML • Abnormal karyotype: Del (7Q), Inv (3),
Slide 12: Meaningful Clinical Benefit in Heavily Pre-Treated Patient
| Absolute Neutrophil Count (ANC) Peripheral Blast Count Meaningful Clinical Benefit in Heavily Pre-Treated Patient 12 100% 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 13: Pre-Clinical Data Demonstrate Significant Combination Potential in AML
| FHD-286 + decitabine (MLL-AFP + FLT3 TKD Luc/GFP PDX) Pre-Clinical Data Demonstrate Significant Combination Potential with Multiple Agents in AML 13 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 14: 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 15: BRM Selective Inhibitor FHD-909 IND Targeted in Q2'24
| BRM Selective Inhibitor FHD-909 IND Targeted in Q2’24, BRM Selective Degrader Continues Late-Stage Pre-Clinical Development 15 BRM Selective Inhibitor (FHD-909) BRM Selective Degrader Biology Exploit the synthetic lethal relationship between BRM and mutated BRG1 Stage IND submission planned in Q2’
Slide 16: BRM Selective Inhibition Exploits Synthetic Lethal Relationship With Mutated BRG1
| BRM Selective Inhibition and Degradation Exploit the Synthetic Lethal Relationship Between BRM and Mutated BRG1 16 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 17: BRM Selective Inhibitor Demonstrates PK/PD and In Vivo Efficacy
| BRM Selective Inhibitor Demonstrates PK/PD and In Vivo Efficacy in a BRG1 Mutant Lung CDX Model 17 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 18: BRM Selective Degrader Achieves Complete BRM Degradation
| BRM Selective Degrader Achieves Complete BRM Degradation and Cell Growth Inhibition 18 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 19: Selective EP300 Protein Degrader For CBP Mutated and EP300 Dependent Cancers
Selective EP300 Protein Degrader For CBP Mutated and EP300 Dependent Cancers
Slide 20: Summary: Selective EP300 Protein Degrader
| Summary: Selective EP300 Protein Degrader for CBP Mutant & EP300 Dependent Cancers 20 * 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 21: EP300 Degradation Results in Significant Tumor Growth Inhibition
| EP300 Degradation Results in Significant Tumor Growth Inhibition in AR+ VCAP Prostate and KARPAS422 DLBCL Models 21 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 22: Selective Degradation of EP300 and CBP Does Not Show Thrombocytopenia in Mice
| Platelet Counts Post Two Weeks of Dosing (In-Vivo) Selective Degradation of EP300 and CBP Does Not Show Thrombocytopenia in Mice at Relevant Doses 22 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 23: Selective CBP Protein Degrader For EP300 Mutated Cancers
Selective CBP Protein Degrader For EP300 Mutated Cancers
Slide 24: Summary: Selective CBP Protein Degrader for EP300 Mutated Cancers
| Summary: Selective CBP Protein Degrader for EP300 Mutated Cancers 24* 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 25: CBP Degrader Tumor Growth Inhibition in Colorectal and Bladder Models
| Colorectal RKO (EP300 Null) Model Selective CBP Protein Degrader Result in Significant Tumor Growth Inhibition in Colorectal and Bladder EP300 Null Models 25 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 26: Selective CBP Protein Degrader Result in Tumor Regression in Gastric Models
| Selective CBP Protein Degrader Result in Tumor Regression in Gastric EP300 Null Models 26 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 27: Long-Acting Injectable Formulations of CBP Degrader
| CBP Degrader Plasma Concentration Long-Acting Injectable Formulations of CBP Degrader Could Enable Once Every 2 Weeks (or Better) Dosing Frequency 27 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 28: Selective ARID1B Protein Degrader For ARID1A Mutated Cancers
Selective ARID1B Protein Degrader For ARID1A Mutated Cancers
Slide 29: ARID1B is a Major Synthetic Lethal Target
| ARID1B is a Major Synthetic Lethal Target Implicated in Up To 5% of All Solid Tumors 29* 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 30: Targeting ARID1B 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 30 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 31: 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 32: Foghorn's Novel Approach to Drugging Transcription Factors
| Foghorn’s Novel Approach to Drugging Transcription Factors Enabled by Its Protein Production and Discovery Capabilities 32 • 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 33: Transcription Factors Bind to BAF Directly with High Specificity
| Transcription Factors Bind to BAF Directly with High Degree of Specificity; Unique Insights into Where and How Transcription Factors Bind 33 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 34: Broad and Deep Pipeline Across a Range of Targets and Modalities
| Broad and Deep Pipeline Across a Range of Targets and Modalities 34 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 35: First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer
| First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer 35 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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