Foghorn Therapeutics Inc. · NASDAQ:FHTX
Foghorn Therapeutics — Technical Presentation (April 2025)
37 slides from Foghorn Therapeutics's technical presentation, Apr 28, 2025
Slide 1: Targeting SMARCA2-Dependent Tumors with FHD-909 (LY4050784)
April 29, 2025 • Targeting SMARCA2-Dependent Tumors with FHD-909 (LY4050784) • Advancing Multiple Additional First-in-Class Anticancer Agents AACR April 2025 Exhibit 99.1
Slide 2: Forward Looking Statements
| Forward Looking Statements 2 This presentation contains forward-looking statements that are based on management's beliefs and assumptions and on information currently available to management. All statements other than statements of historical facts contained in this presentation are forward- looki
Slide 3: Foghorn AACR Conference Call Agenda
| Foghorn AACR Conference Call Agenda FHD-909 and Foghorn Overview Welcome FHD-909 AACR Data and Clinical Program Pipeline Programs Karin Hellsvik Vice President Investor Relations Adrian Gottschalk President and CEO Alfonso Quintás-Cardama, MD Chief Medical Officer Steve Bellon, PhD Chief Scientifi
Slide 4: FHD-909 (LY4050784) Holds Potential to Dramatically Improve Outcomes in SMARCA4-Mutated Tumors
| FHD-909 (LY4050784) Holds Potential to Dramatically Improve Outcomes in Patients with SMARCA4-Mutated Tumors 4 First-in-class highly selective oral SMARCA2 inhibitor Potential to address major unmet medical need in cancer, with initial focus on Non-Small Cell Lung Cancer (NSCLC) Highly active in p
Slide 5: FHD-909 is Being Developed in Collaboration with Lilly
| FHD-909 is Being Developed in Collaboration with Lilly; Landmark Agreement Signed in December 2021 Significant Upfront and Economics Strong Momentum and Shared Vision Ongoing Discovery Programs • $300 million cash • $80 million in Foghorn common stock at a price of $20 per share • 50/50 U.S. econo
Slide 6: FHD-909 (LY4050784): A first in class selective SMARCA2 inhibitor
Alfonso Quintás-Cardama, MD Chief Medical Officer FHD-909 (LY4050784) A first in class selective SMARCA2 inhibitor with broad potential to transform outcomes for patients with SMARCA4 mutated tumors Steve Bellon, PhD Chief Scientific Officer
Slide 7: SMARCA4 Mutations are Common: ~10% of NSCLC and Up to 5% of Solid Tumors
| SMARCA4 Mutations are Common: ~10% of NSCLC and Up to 5% of Solid Tumors 7 SMARCA4 mutated across a broad range of tumors Accounts for ~5% of solid tumors Source: AACR GENIE via cBioPortal
Slide 8: SMARCA4 Mutations are Consequential in NSCLC
| NSCLC patients with SMARCA4 mutations: ─ Poor prognosis ─ Shorter overall survival ─ Less responsive to immune checkpoint inhibitors ─ Clinically definable, high unmet need population SMARCA4 Mutated in Up to 10% of NSCLC Tumors, Minimal Overlap With Other Mutations2Overall Survival for SMARCA4wt
Slide 9: SMARCA4 and KRAS Co-Mutations Have Even Worse Outcomes
| When SMARCA4 and KRAS Mutations Co-Occur, Patients Have Even Worse Outcomes to Standard of Care Treatment In response to PD(L)-1 therapy, Patients with Co-Occurring SMARCA4 and KRAS Mutations have a Shorter ORR, PFS, and OS than Patients with only KRASmut 9 Overall Response Rate (ORR) Source: Ales
Slide 10: Selective SMARCA2 Inhibition Exploits Synthetic Lethality with Mutant SMARCA4
| Selective SMARCA2 Inhibition: Promising Strategy to Exploit Synthetic Lethal Relationship Between SMARCA2 and Mutant SMARCA4 10 No SMARCA4 Mutations SMARCA4 Mutation SMARCA4 Mutation and SMARCA2i Cell Survival Cell Death Healthy Cells Cancer Cells SMARCA4 SMARCA2 BAF Complex BAF Complex Mutant SMA
Slide 11: FHD-909 is Highly Selective for SMARCA2 over SMARCA4
| FHD-909 is Highly Selective for SMARCA2 over SMARCA4 11 FHD-909 Demonstrated Approximately 33-fold Selectivity Across SMARCA4 Mutant and Wild-Type Cell Lines In Vitro SMARCA4 WT SMARCA4 MUT 0.0001 0.001 0.01 0.1 1 Ab so lu te IC 50 (μ M ) NCI-H2122 CALU6 NCI-H2172 NCI-H441 NCI-H2170 NCI-H460 NCI-H
Slide 12: FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across SMARCA4 Mutant NSCLC Models
| FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across SMARCA4 Mutant NSCLC Models at Tolerated Doses 12 Note: All doses were well tolerated Studies were conducted in Athymic Nude or NOD SCID gamma (NSG) mice according to all IACUC guidelines. Dosing holidays were applied to the 60mg/kg F
Slide 13: FHD-909 is Positioned to Be Evaluated in Combination with Standard Therapies
| Chemotherapy Targeted Therapies FHD-909 is Positioned to Be Evaluated in Combination with Standard Therapies 2025 AACR Data FHD-909 shows significant anti-tumor activity preclinically in combination with standard therapies in NSCLC 13 Cisplatin PemetrexedPaclitaxel KRAS inhibitorsPembrolizumab
Slide 14: FHD-909 with Standard Therapies in the A549 Xenograft NSCLC Model
| FHD-909 in Combination with Standard Therapies Demonstrates Significant Activity in the A549 (SMARCA4 mutant, KRAS G12S) Xenograft NSCLC Model 14 Vehicle Control FHD-909 60mg/kg BID, PO Cisplatin 4mg/kg IP + pemetrexed 50mg/kg QDx3, IP, Q14D FHD-909 60mg/kg BID, PO + cisplatin 4mg/kg IP + pemetrex
Slide 15: FHD-909 with Standard Therapies in the RERF-LC-AI Xenograft NSCLC Model
| FHD-909 in Combination with Standard Therapies Demonstrates Significant Activity in the RERF-LC-AI (SMARCA4 mutant) Xenograft NSCLC Model 15 0 7 14 21 28 200 400 600 800 1000 1200 1400 Days of Dosing (Dose Start Day 1) Tu m or V ol um e (m m 3 ) * * * * **# # Note: * p≤0.05 for pairwise comparison
Slide 16: Synergistic Activity of FHD-909 with KRAS Inhibitors In Vitro
| Synergistic Activity Observed for FHD-909 in Combination with KRAS Inhibitors In Vitro 16 0.1 1 10 100 -20 0 20 40 60 80 100 120 FHD-909 Concentration [nM] In hi bi tio n (% ) 12.5 1.56 0.19 DMSO [olomorasib] (nM) 100 0.1 1 10 100 -20 0 20 40 60 80 100 120 FHD-909 Concentration [nM] In hi bi tio n
Slide 17: FHD-909 with KRAS Inhibitors in Co-Mutated NSCLC Xenograft Models (olomorasib)
| Combination of FHD-909 with KRAS Inhibitors Demonstrates Synergistic Activity in SMARCA4, KRAS Co-Mutated Human NSCLC Xenograft Models in vivo FHD-909 + olomorasib (KRAS G12C inh) NCI-H2030 (SMARCA4mt, KRAS G12C) 17 Vehicle Control 40mg/kg FHD-909, BID, PO Olomorasib 10mg/kg BID, PO FHD-909 40mg/k
Slide 18: FHD-909 with KRAS Inhibitors in Co-Mutated NSCLC Xenograft Models (pan-KRAS)
| Combination of FHD-909 with KRAS Inhibitors Demonstrates Synergistic Activity in SMARCA4, KRAS Co-Mutated Human NSCLC Xenograft Models in vivo FHD-909 + pan-KRAS inh A549 (SMARCA4mt, KRAS G12S) 18 Combination of FHD-909 with pan-KRAS inhibitor resulted in synergistic antitumor activity and sustain
Slide 19: FHD-909 with Pembrolizumab in Humanized Xenograft NSCLC Model
| FHD-909 in Combination with Pembrolizumab Shows Significantly Enhanced Anti-Tumor Activity in A549 CD34+ HSC Humanized Xenograft NSCLC Model 19 FHD-909 sensitized the tumor cells to pembrolizumab treatment resulting in enhanced combination activity, while pembrolizumab alone had no effect on tumor
Slide 20: A First-in-Human Phase Trial of FHD-909 in Advanced Solid Tumor Patients with SMARCA4 Mutations
| A First-in-Human Phase 1 Trial of FHD-909 in Advanced Solid Tumor Patients with SMARCA4 Mutations Phase 1a Dose Escalation Advanced solid tumors with any SMARCA4 alteration (mTPI-2 method with backfillinga) Dose Level 1 Dose Level 2 Dose Level 3 Dose Level n Phase 1b Dose Expansionb Presence of a
Slide 21: Treatment Landscape in NSCLC by Line of Therapy
| Treatment Landscape in NSCLC by Line of Therapy 21 1st Line NSCLC Pembrolizumab-based regimens Other immune checkpoint inhibitor-based regimens Chemotherapy-based regimens 2nd Line NSCLC Chemotherapy-based regimens Ramucirumab (anti-VEGF) + chemotherapy Checkpoint inhibitor monotherapy 3rd Line NS
Slide 22: Treatment Landscape in NSCLC by Line of Therapy
| Treatment Landscape in NSCLC by Line of Therapy 22 1st Line NSCLC Pembrolizumab-based regimens Other immune checkpoint inhibitor-based regimens Chemotherapy-based regimens 2nd Line NSCLC Chemotherapy-based regimens Ramucirumab (anti-VEGF) + chemotherapy Checkpoint inhibitor monotherapy 3rd Line NS
Slide 23: FHD-909 Holds the Promise of Addressing Major Unmet Medical Needs in Cancer
| FHD-909 Holds the Promise of Addressing Major Unmet Medical Needs in Cancer 23 O ve ra ll Su rv iv al (% ) Months Overall Survival for SMARCA4wt vs SMARCA4mut1 O ve ra ll Su rv iv al () % ) Source: 1 Alessi et al DOI: 10.1016/j.jtho.2023.01.091
Slide 24: Foghorn's Platform is Differentiated & Highly Productive
Foghorn’s Platform is Differentiated & Highly Productive • Selective CBP Degrader • Selective EP300 Degrader • Selective ARID1B Degrader Program Steve Bellon, PhD Chief Scientific Officer
Slide 25: Foghorn is Leading the Way in Developing Novel Medicines Targeting the Chromatin Regulatory System
| Foghorn is Leading the Way in Developing Novel Medicines Targeting the Chromatin Regulatory System 25 Chromatin – compacted form of DNA inside the nucleus of the cell Chromatin Remodeling Complexes – specialized multiprotein machines that allow access to DNA Targets: SMARCA2, ARID1B Transcription
Slide 26: CBP and EP300 Proteins – A Decades Long Challenge in Selectivity
| CBP and EP300 Proteins – A Decades Long Challenge in Selectivity 26 • 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 27: Selective CBP Degradation Results in Anti-Tumor Activity in EP300mut Solid Tumor Models
| EP300mut Lung Cancer CDX (LU99) EP300mut Bladder Cancer CDX (639V) EP300mut Gastric Cancer CDX (AGS) Selective CBP Degradation Results in Significant Anti-Tumor Activity in EP300mut Solid Tumor Models 27 CBP 0.05 nM EP300 64 nM Fold Selectivity >1000x Degrader Selectivity FHT-CBPd-59 DC50 @24h 20
Slide 28: Long-Acting Injectable Formulation Provides Anti-Tumor Activity With a Single Injection
| No Significant Difference in Platelet Counts at End of Study Tumor growth inhibition (regression) observed in EP300mut (639V) Bladder CDX Long-Acting Injectable (LAI) Formulation Provides Anti-Tumor Activity With a Single Injection 28 Company Confidential & Proprietary Information 25 30 35 40 45 5
Slide 29: Selective CBP Degrader in Combination With Standard Therapies in ER+ Breast Cancer Models
| Foghorn Selective CBP Degrader Shows Promise in Combination With Standard Therapies in Preclinical ER+ Breast Cancer Models 29 CDK4/6 Inhibitor + Fulvestrant CBP Degrader (FHT-CBPd-41) + CDK4/6 inhibitor + Fulvestrant Cancer cell growth only significantly inhibited at highest concentrations of SoC
Slide 30: Selective CBP Degrader in Combination With Standard Therapies in ER+ Breast Cancer Models
| Foghorn Selective CBP Degrader Shows Promise in Combination With Standard Therapies in Preclinical ER+ Breast Cancer Models 30 CDK4/6 Inhibitor + Fulvestrant CBP Degrader (FHT-CBPd-41) + CDK4/6 inhibitor + Fulvestrant Cancer cell growth only significantly inhibited at highest concentrations of SoC
Slide 31: EP300 Degradation Shows Anti-Proliferative Activity in Hematological Malignancies
| Anti-Tumor Activity Across Full Range of Heme Sub-Lineages (~ 70% of All Tested Cell Lines are Sensitive) EP300 Degradation Shows Anti-Proliferative Activity in Broad Range of Hematological Malignancies (~ 70% of All Tested Cell Lines are Sensitive) 31 Note: MM: Multiple Myeloma; DLBCL: Diffuse La
Slide 32: Selective EP300 Degrader Demonstrated Complete Response in Multiple Myeloma Model
| 10 15 20 25 30 0 500 1000 1500 2000 2500 3000 Days After Tumor Inoculation Tu m or V ol um e (m m ³+ S EM ) Vehicle FHT-EP300d-532, SC, 30 mg/kg (QD) FHT-EP300d-532, SC, 10 mg/kg (QD) CCS1477 (Inobrodib), PO, 20 mg/kg (QD) • Non-selective dual CBP/EP300 inhibitor shows tumor stasis, but clinical s
Slide 33: ARID1B is a Major Synthetic Lethal Target in Up to 5% of Solid Tumors
| ARID1B Paralog (ARID1A) is One of the More Frequently Mutated Genes in Cancer 33Source: Mendiratta 2021 No Approved Drug Approved Drug Foghorn Targets ARID1B is a Major Synthetic Lethal Target With Potential in Up To 5% of All Solid Tumors
Slide 34: ARID1A Mutations Represent a Significant Unmet Need Across Several Indications in Oncology
| ARID1A Mutations Represent a Significant Unmet Need Across Several Indications in Oncology 34 Uterine Bladder Stomach Cholangiocarcinoma Liver Esophageal Ovarian Colorectal Melanoma 0% 10% 20% 30% 40% Commercial Opportunity % of Patients with ARID1A Mutation
Slide 35: Foghorn is First to Report Selective Degradation of ARID1B
| Foghorn is First to Report Selective Degradation of ARID1B 35 ARID1A/B BAF Nucleosome PDB ID: 6LTJ Company Confidential & Proprietary Information • Foghorn has developed potent and selective binders • Foghorn is first to report selective degradation • Program update expected in 2025
Slide 36: Closing Remarks
Closing Remarks Adrian Gottschalk President and CEO
Slide 37: Question & Answers
FCGHORN THERAPEUTICS Question & Answers
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