Foghorn Therapeutics Inc. · NASDAQ:FHTX
Foghorn Therapeutics — Corporate Update (April 2024)
32 slides from Foghorn Therapeutics's corporate update, Apr 9, 2024
Slide 1: 2024 AACR and Pipeline Update
April 9, 2024 Unique biology Precision therapeutics Broad impact 2024 AACR and Pipeline Update 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: Foghorn AACR Conference Call Agenda
| Foghorn AACR Conference Call Agenda 3 Introduction Karin Hellsvik Vice President Corporate Affairs and IR Key Highlights Adrian Gottschalk President and CEO Clinical Update Dr. Alfonso Quintás-Cardama Chief Medical Officer Research Update Dr. Steve Bellon, PhD Chief Scientific Officer
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 Chromatin – compacted form of DNA inside the nucleus of the cell Chromatin Remodeling Complex – specialized multiprotein machineries that allow access to DNA Transcription Factor – proteins that
Slide 5: Foghorn at 2024 AACR
| Foghorn at 2024 AACR 5 BAF Complex BRG1 (SMARCA4) BRM (SMARCA2) Chromatin Binding Proteins CBP EP300 Significant Opportunity, Challenging Targets Developing First-in-Class Medicines Targeting the Chromatin Regulatory System Chromatin biology is implicated in up to 50% of tumors, potentially impact
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: Broad and Deep Pipeline Across a Range of Targets and Modalities
| Broad and Deep Pipeline Across a Range of Targets and Modalities 7 Modality Program Discovery Phase 1 Phase 2 Phase 3 Enzyme Inhibitors Transcription Factor Disruptors Undisclosed Protein Degraders Commercial Rights 3 Discovery Programs Undisclosed Partnered Program Undisclosed Disease Selective B
Slide 8: AACR Data Demonstrates First-in-Class Potential for Multiple Programs
| AACR Data Demonstrates First-in-Class Potential for Multiple Programs 8 • FHD-286 in combination with decitabine for the treatment of AML, now enrolling in a dose-escalation Phase 1 study • FHD-909, BRM selective inhibitor set to enter Phase 1 study (Q2 IND) targeting NSCLC; partnership with Lilly
Slide 9: Clinical Update
Dr. Alfonso Quintás-Cardama Chief Medical Officer Targeting BAF Dependency in Cancer • FHD-286 – Dual BRM/BRG1 Inhibition • FHD-909 (a.k.a. LY4050784) – Selective BRM Inhibition Clinical Update
Slide 10: Exploring BAF Dependency in Cancer with FHD-286
| Exploring BAF Dependency in Cancer with FHD-286 – Potent, Small Molecule Inhibitor Targeting BRM and BRG1 10 BAF ATPase: BRG1/BRM FHD-286 FHD 286 is an oral, daily, potent small molecule inhibitor of BRG1 and BRM AML cells known to be highly dependent on the BAF complex for proliferation and maint
Slide 11: Phase 1 Monotherapy Results: FHD-286 Induced Differentiation Across Genetic Backgrounds
| Phase 1 Monotherapy Results: FHD-286 Induced Differentiation Across a Broad Range of Genetic Backgrounds 11 Dose Level Mutations Starting CD11b% CD11b+ Fold Increase Starting CD34% CD34+ % Decrease 10mg N/A 7 9.2x 94 (71%) 7.5mg CBFB (locus at 16q22) 2 59.4x 70 (97%) 7.5mg KMT2A rearrangement 3 21
Slide 12: 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 12 FHD-286 + menin inhibitor (mtNPM1 + FLT3 ITD Luc/GFP AML PDX) 0 20 40 60 0 25 50 75 100 Days, post-infusion % S ur vi va l FHD-286 + decitabine (n=8)
Slide 13: Ongoing FHD-286 Phase 1 Multicenter Dose-Escalation with Decitabine in AML
| Ongoing FHD-286 Phase 1 Multicenter Dose-Escalation in Combination with Decitabine in AML 13 FHD-286: 1.5 mg QD + Decitabine FHD-286: 2.5 mg QD + Decitabine FHD-286: 5 mg QD + Decitabine FHD-286: 7.5 mg QD + Decitabine FHD-286: 2.5 mg QD + Decitabine FHD-286: 5 mg QD + Decitabine FHD-286: 7.5 mg Q
Slide 14: Significant Opportunity for Novel, Effective Therapy in Patients with R/R AML
| Significant Opportunity for Novel, Effective Therapy in Patients with R/R AML 14 • More than half of patients will relapse post frontline treatment • Intensive chemotherapy has been standard of care for four decades with no meaningful improvement Most cases of AML are not curable 40% of AML cases
Slide 15: FHD-909 will be the First Selective BRM Inhibitor to Enter the Clinic
| FHD-909 will be the First Selective BRM Inhibitor to Enter the Clinic 15 BRM selective inhibitor, chosen for clinical development by Lilly as part of a collaboration initiated in December 2021 BRMi IND filing anticipated Q2 2024
Slide 16: BRM Selective Inhibition Exploits Synthetic Lethal Relationship with Mutated BRG1
| BRM Selective Inhibition is a Promising Strategy to 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
Slide 17: 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 17 BRG1 mutated across a broad range of tumors Accounts for ~5% of all tumors AACR GENIE via cBioPortal
Slide 18: Patients with NSCLC Harboring BRG1 Mutations Define a High Unmet Need Population
| BRG1 mutated in up to 10% of NSCLC tumors, minimal overlap with other mutations2Overall Survival for SMARCA4wt vs SMARCA4mut1 Patients with NSCLC Harboring BRG1 Mutations Have Significantly Worse Clinical Outcomes and Define a High Unmet Need Patient Population 18 BRG1 10% KRAS 29% EGFR 26% ALK 7%
Slide 19: Research Update
AACR Data • FHD-909 – Selective BRM Inhibitor • Selective CBP Degrader • Selective EP300 Degrader Research Update Dr. Steve Bellon, PhD Chief Scientific Officer
Slide 20: FHD-909 Demonstrates Approximately 30-fold Selectivity Across 17 Cell Lines
| BRG1 WT BRG1 MUT 0.0001 0.001 0.01 0.1 1 A bs ol ut e IC 50 (μ M ) NCI-H2122 CALU6 NCI-H2172 NCI-H441 NCI-H2170 NCI-H460 NCI-H1703 NCI-H358 NCI-H2009 NCI-H1944 NCI-H1299 A549 RERFLCAI NCI-H1693 NCI-H1568 NCI-H2023 NCI-H838 BRG1 (WT) BRG1 (MUT) FHD-909 Demonstrates Approximately 30-fold Selectivity
Slide 21: FHD-909 Monotherapy Demonstrated In Vivo Activity in H2126 BRG1 Mutant NSCLC Model
| FHD-909 Monotherapy Demonstrated In Vivo Activity in H2126 BRG1 Mutant NSCLC Model; Well Tolerated 21 H2126 Efficacy H2126 Body Weight Genetic Background: BRG1 W764R, TP53 E62*, STK11-/-, CDKN2A-/-, KEAP1 R272C NOTE: All doses were well tolerated. Dosing holidays were applied at the high dose, as
Slide 22: FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across BRG1 Mutant NSCLC Models
| RERF-LC-AI Model FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across BRG1 Mutant NSCLC Models; Well Tolerated 22 A549 Model NOTE: All doses were well tolerated. Dosing holidays were applied at the high dose, as appropriate 0 7 14 21 28 200 400 600 800 1000 1200 Days of Dosing (Dose Sta
Slide 23: FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across BRG1 Mutant NSCLC Models
| FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across BRG1 Mutant NSCLC Models; Well Tolerated 23 H1793 Model • FHD 909 profiled across range of BRG1 mut xenograft models • Results ranging from impressive TGI to regression as monotherapy • All doses across models were well tolerated NOTE
Slide 24: CBP and EP300 Proteins – A Decades Long Challenge in Selectivity
| CBP and EP300 Proteins – A Decades Long Challenge in Selectivity 24 • CBP and EP300 are chromatin regulators and histone acetyltransferases • CBP and EP300 are virtually identical, thus achieving selectivity is a significant challenge • Dual targeting has revealed tolerability and safety issues Fo
Slide 25: Selective CBP Protein Degradation Demonstrates Dose Dependent Tumor Growth Inhibition
| 25 Selective CBP Protein Degradation Demonstrates Dose Dependent Tumor Growth Inhibition and/or Regression Across In Vivo Models Gastric AGS (EP300 Null) Model Bladder 639V (EP300 Null) Model Colorectal RKO (EP300 Null) Model 30 40 50 0 500 1,000 1,500 2,000 2,500 3,000 Days after Tumor Inoculatio
Slide 26: Selective CBP Degradation Does Not Show Thrombocytopenia and Spares Megakaryocytes In Vivo
| Bone Marrow Staining (In Vivo)Platelet Counts Post Two Weeks of Dosing (In Vivo) Selective CBP Degradation Does Not Show Thrombocytopenia and Spares Megakaryocytes In Vivo 26 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-CBPd, 10mg/kg,
Slide 27: Long-Acting Injectable Formulations of CBP Degrader Could Enable Less Frequent Dosing
| Long-Acting Injectable Formulations of CBP Degrader Could Enable Once Every 2 Weeks, or Less Frequent, Dosing 27 dCBP-9 PK/PD (60mg/kg, sc) dCBP-9 PK/PD (150mg/kg, sc) dCBP-59 PK/PD (150mg/kg, im) 0 24 48 72 96 120 144 168 192 216 240 264 288 312 336 360 0 25 50 75 100 125 10 100 1000 10000 Hour P
Slide 28: EP300 Degradation Demonstrates Significant Tumor Growth Inhibition in Prostate and DLBCL Models
| EP300 Degradation Demonstrates Significant Tumor Growth Inhibition in AR+ VCAP Prostate and KARPAS422 DLBCL Models 28 Prostate AR+ VCAP 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 Control Enzalutamide, 30mg/kg, QD
Slide 29: Selective EP300 Degradation Does Not Show Thrombocytopenia In Vivo
| Selective EP300 Degradation Does Not Show Thrombocytopenia In Vivo 29 Platelet Counts Post Two Weeks of Dosing (In Vivo) 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 Dual BD inhibitor, 30mg/kg, p.o, BID FHT-EP
Slide 30: Closing Remarks
Closing Remarks Adrian Gottschalk President and CEO
Slide 31: First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer
| First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer 31 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
Slide 32: Question & Answers
FCGHORN THERAPEUTICS Question & Answers