Foghorn Therapeutics Inc. · NASDAQ:FHTX
Foghorn Therapeutics — Investor Presentation (January 2026)
63 slides from Foghorn Therapeutics's investor presentation, Jan 12, 2026
Slide 1: Unique biology, Precision therapeutics, Broad impact
Unique biology Precision therapeutics Broad impact FHTX January 2026 NASDAQ LISTED
Slide 2: Forward Looking Statements
2 | Forward Looking Statements This currently presentation available contains to management forward.- looking All statements statements other that than are statements based on of management’s historical facts beliefs contained and assumptions in this presentation and on are information forward-looki
Slide 3: Foghorn is a Leader in Chromatin Biology
Foghorn is a Leader in Chromatin Biology, Successfully Drugging Challenging Targets Multi-billion $ First-and-Best-in-Class Selective Target Strategic Partnership: Opportunities Approaches Engagement Multiple Programs Targeting chromatin Unlocking Innovating selective Leveraging a proven regulation
Slide 4: Chromatin Regulatory System Orchestrates Gene Expression
Chromatin Remodeling Complexes – specialized multiprotein machines that Chromatin – compacted Transcription Factors – proteins allow access to DNA form of DNA inside the that help turn specific genes “on” or Targets: SMARCA2, ARID1B nucleus of the cell “off” by working in concert with the chromatin
Slide 5: Foghorn's Platform Has Delivered Precision First-in-Class Therapeutics
2. Chemistry, Biochemistry & Formulations Track record Track record with previously of delivering undruggable targets precision therapeutics Foghorn’s Platform Has Delivered Precision First-in-Class Therapeutics, and is Poised to Unlock New Biology 1. Chromatin Biology Deep mechanistic understanding
Slide 6: Precision Therapies with Potential for Multi-Billion Dollar Opportunities
Modality Program and Partner Disease Discovery Pre-Clinical Phase 1 Anticipated Milestones FHD-909* SMARCA4-mutant cancers (e.g., NSCLC) Ph 1 Monotherapy Data; Enzyme (Selective SMARCA2) Confidential Inhibitors Partnered** Transition to Lilly; Undisclosed Undisclosed Confidential Transition to Lilly
Slide 7: FHD-909 Developed in Collaboration with Lilly
FHD-909 is Being Developed in Collaboration with Lilly; Landmark Agreement Signed in December 2021 Significant Upfront and Strong Momentum and Ongoing Discovery Economics Shared Vision Programs • $300 million cash • $80 million in Foghorn common stock at a price of $20 per share • 50/50 U.S. economi
Slide 8: Developing First-in-Class Precision Medicines Targeting Major Unmet Needs in Cancer
Large Market Well-Potential Funded Chromatin biology is $158.9 million in cash and implicated in up to 50% of equivalents (unaudited) tumors, potentially (as of 12/31/2025) impacting ~2.5 million patients Cash runway into 2028 Foghorn’s current pipeline Shares outstanding: potentially addresses appr
Slide 9: Selective SMARCA2 Program
For SMARCA4-mutant Cancers Selective SMARCA2 Program • FHD-909 (LY4050784) – Selective SMARCA2 Inhibitor 9
Slide 10: Selective SMARCA2 Inhibitor FHD-909 and Degrader
Selective SMARCA2 Selective SMARCA2 Inhibitor FHD-909* Degrader Exploit the synthetic lethal relationship between SMARCA2 and Biology mutated SMARCA4 SMARCA2: Clinical-stage FHD-909 Selective SMARCA2 Inhibitor and Preclinical Selective SMARCA2 Degrader Phase 1 monotherapy dose escalation Advancing t
Slide 11: Selective SMARCA2 Inhibition Exploits Synthetic Lethality
Selective SMARCA2 Selective SMARCA2 Inhibitor FHD-909* Degrader Exploit the synthetic lethal relationship between SMARCA2 and Biology mutated SMARCA4 SMARCA2: Clinical-stage FHD-909 Selective SMARCA2 Inhibitor and Preclinical Selective SMARCA2 Degrader Phase 1 monotherapy dose escalation Advancing t
Slide 12: SMARCA4 Mutated Across a Broad Range of Tumors
SMARCA4 mutated across a broad range of tumors Accounts for ~5% of solid tumors 12 | SMARCA4 is Mutated in Up to 10% of NSCLC; Up to 5% of Solid Tumors AACR GENIE via cBioPortal
Slide 13: Goal to Become First-Line Treatment for SMARCA4-mutated NSCLC
FHD-909: Overall Goal is to Become a First-Line Treatment for SMARCA4-mutated NSCLC Relevant treatment regimens in each line of therapy for metastatic NSCLC* 1st Line NSCLC Pembrolizumab-based regimens Other immune checkpoint 2nd Line NSCLC inhibitor-based regimens Chemotherapy-based Chemotherapy-ba
Slide 14: Significant Unmet Need
Significant Unmet Need 21.9% 15.0 months 8.1 months 6.1 months 2.7 months 1L (SMARCA4 WT) 1L (SMARCA4 Mut) Significant Unmet Medical Need in NSCLC Metastatic Setting for SMARCA4 Patients Frontline NSCLC Metastatic – PD1 + Chemo1 Response Rate (%) PFS (months) OS (months) 39.1% Significant Unmet Need
Slide 15: SMARCA4 Mutations are Consequential in NSCLC
SMARCA4 10% KRAS 29% EGFR 26% ALK 7% Survival(%) RET 4% MET 7% Overall SMARCA4 Mutations are Consequential – in NSCLC, Patients with Mutated SMARCA4 Have Significantly Worse Clinical Outcomes Overall Survival for SMARCA4wt vs SMARCA4mut1; Frontline Metastatic NSCLC w/ Chemoimmunotherapy SMARCA4 Muta
Slide 16: Co-occurring SMARCA4 and KRAS Mutations Have Worse Outcomes
When SMARCA4 and KRAS Mutations Co-Occur, Patients Have Even Worse Outcomes to Standard of Care Treatment Overall Response Rate (ORR) Progression-Free Survival (PFS) Overall Survival (OS) Median PFS, months (95% CI) Median OS, months (95% CI) P = 0.03 KRAS mut + SMARCA4 wt (n:159): 4.1 (2.8–6.0) KRA
Slide 17: First-in-Human Phase 1 Trial of FHD-909
A First-in-Human Phase 1 Trial of FHD-909 in Advanced Solid Tumor Patients with SMARCA4 Mutations Phase 1b Dose Expansionb Phase 1a Dose Escalation Presence of a Known or Likely Loss of Function of SMARCA4 Advanced solid tumors with any Cohort A1 SMARCA4 alteration (mTPI-2 method with backfillinga)
Slide 18: Degrader Programs
Degrader Programs • Selective CBP Degrader • Selective EP300 Degrader • Selective ARID1B Degrader 18
Slide 19: Developing a Portfolio of Novel and Selective Degraders
• EP300-mutant and CBP-dependent Cancers • Mutated in up to 5% of all • CBP-mutant and EP300-solid tumors dependent Cancers • Anti-tumor activity demonstrated including • First to demonstrate robust • Potential across range of promising potential in ER+ and selective degradation of heme malignancies
Slide 20: CBP and EP300 Proteins: A Decades-long Challenge in Selectivity
• Dysregulation of CBP and EP300 has been implicated in multiple cancers • Dual targeting has revealed tolerability and safety issues CBP and EP300 Proteins – A Decades-long Challenge in Selectivity CBP and EP300 Biology • CBP and EP300 are highly homologous, paralog histone acetyltransferases regul
Slide 21: Selective CBP Degrader, FHT-171
Selective CBP Degrader, FHT-171 For EP300-mutant and CBP-dependent Cancers 21
Slide 22: Selective CBP Degrader Summary
• CREB binding protein (CBP) • Targeted protein degrader • Preclinical • IND-ready in 2026 • Highly selective and potent • Increased tolerability relative to non-selective compounds • Long-acting formulation • Compelling combination potential Summary: Selective CBP Degrader for CBP-dependent & EP300
Slide 23: FHT-171 Disrupts ER Signaling and Inhibits Tumor Cell Growth
Robust & Potent CBP Degradation …Leads to Reduced Expression of ER …Resulting in Cancer Cell and its Target Genes Growth Inhibition CBP degradation in MCF7 cells(24h) 1nM FHT-171 treated MCF7 (7d) MCF7 colony formation assay (14d) FHT-171 [nM] DC90 = 0.3577 nM MCF7 Super Enhancer genes 0 0.017 0.05
Slide 24: FHT-171 Anti-tumor Efficacy in Resistant ER+ Breast Cancer Models
FHT-171 Demonstrates Anti-tumor Efficacy as a Monotherapy in Standard-of-care Resistant ER+ Breast Cancer Models ER+ Metastatic Breast Cancer CDX ER+ Metastatic Breast Cancer PDX ER+ Metastatic Breast Cancer PDX (ST941C; ESR1m) (ST4887B, ESR1 wt) (ST4680D, ESR1m) 3000 1000 1000 SEMSEM SEM 800——750—+
Slide 25: FHT-171 Shows No Impact on Platelet Counts
FHT-171 Shows No Impact on Platelet Counts and Spared Megakaryocytes Platelet Counts Post Two Weeks of Dosing Human Megakaryocyte Cell Viability Assay (In Vivo – Control Mice) (In Vitro**) Vehicle 2,500 FHT-171, 10mg/kg, SC, QD Dual BD inhibitor, (GNE-781), 30mg/kg, PO, BID Dual BD inhibitor (CCS147
Slide 26: FHT-171: Potent and Selective CBP Degrader
FHT-171 CBP Kinetics Dmax: 97% Max Rate: 3.2 hr-1 DC50: 30pM FHT-171 EP300 Kinetics Dmax: 5% Max Rate: N/A 100nM CBPd-171/DMSO 3hr Log2FC FHT-171: Potent and Selective CBP Degrader FHT-171 Rapidly and Potently Degrades CBP, but not its Paralog EP300 Global Proteomics Confirms that FHT-171 is Selecti
Slide 27: CBP Degraders in EP300-mutant Bladder and Gastric Models
EP300mut Bladder Cancer CDX (639V) EP300mut Gastric Cancer CDX (AGS) EP300mut Gastric Cancer PDX (ST020326) 3000 Vehicle 1,500 Vehicle 1,500 FHT-CBPd-59, 10mg/kg (QD) Vehicle FHT-CBPd-59, 3 mg/kg (BID) FHT-CBPd-41, 5mg/kg (QD) SEM) 2500 FHT-CBPd-59, 3mg/kg (QD) + FHT-CBPd-59,10 mg/kg (QD) FHT-CBPd-5
Slide 28: Long-Acting Injectable Formulation of CBPd-171
Long-Acting Injectable Formulation of CBPd-171 Enables Weekly Sub-Cutaneous (SC) Delivery Tumor Growth Inhibition Observed in EP300mut (AGS) Gastric Model (Daily Injections and SC weekly LAI Injection) 1500 Vehicle CBPd-171, 3mpk, QD s.c SEM) CBPd-171 LAI, 25mpk, QW s.c + 1000 (mm³ Volume 500 Tumor
Slide 29: Selective EP300 Degrader
Selective EP300 Degrader For CBP-mutant and EP300-dependent Cancers 29
Slide 30: Selective EP300 Degrader Summary
Asset Description Initial Opportunity (U.S.) EP300-Dependent Target / • E1A binding protein p300 (EP300) Hematological Incidence* Approach Malignancies • Targeted protein degrader MM 31K • Broad range of heme malignancies Indications focused on MM and DLBCL • AR+ prostate • Bladder, melanoma, others
Slide 31: EP300 Degradation Activity in Hematological Malignancies
EP300 Degradation Shows Anti-Proliferative Activity in Broad Range of Hematological Malignancies Anti-Tumor Activity Across Full Range of Heme Sub-Lineages (~ 70% of All Tested Cell Lines are Sensitive) MM: Multiple Myeloma; DLBCL: Diffuse Large B-Cell Lymphoma; AML: Acute Myeloid Leukemia; BL: Burk
Slide 32: EP300 Degrader Efficacy in MM, DLBCL and Prostate CDX Models
Multiple Myeloma (MM1S) CDX DLBCL (KARPAS422) CDX AR+ Prostate (VCaP) CDX 2,00 3,000 2,000 Vehicle Vehicle Vehicle Enzalutamide, PO, 30mg/kg (QD) FHT-EP300d—53, SC, 10mg/kg (QD) FHT-EP300d—32, SC, 10mg/kg (BID) 2,500 SEM) FHT-EP300d—32, SC, 50mg/kg (BID) SEM) FHT-EP300d—53, SC, 30mg/kg (QD) SEM) 1,5
Slide 33: Selective EP300 Degradation Gives Significant Responses and Spares Platelets
Selective EP300 Degradation Results in Significant Responses In Vivo, and Spares Platelets (inobrodib) • The max efficacious dose for inobrodib results in stasis with daily dosing. However, inobrodib use in the clinic is limited by thrombocytopenia, which requires dosing holidays • Selective EP300 d
Slide 34: No Change in Platelets, Red Blood Cells or Neutrophils
No Change in Platelets, Red Blood Cells or Neutrophils Following 14 Days of Daily Dosing in Immunocompetent Mice Selective EP300 Degrader Spares Platelets, Red Blood Cells and Neutrophils 2000 1500 1283.3 1172.7 1000 500 Vehicle 20 EP300d-351, 30mpk, QD, s.c 15 10.8 10 8.8 5.6 5 3.3 0 0.5 0.9 ) ) )
Slide 35: VHL-based EP300 Degrader Active in IMiD Resistant Cell Lines
VHL-based Selective EP300 Degrader Maintains Activity in IMiD Resistant Cell Lines dEP300-9 pomalidomide lenalidomide dEP300-9 mezigdomide iberdomide Resistant MM1S cell lines were developed through 5–6 months of in vitro exposure to gradually increasing concentrations of lenalidomide, pomalidomide,
Slide 36: EP300 Degrader Efficacy in Pomalidomide-Resistant Myeloma Model
Pomalidomide-Resistant Multiple Myeloma CDX (MM1S-PomR) Treated with EP300d-007 Selective EP300 Degrader Shows Superior Efficacy Compared to Pomalidomide and Inobrodib in an IMiD Resistant Multiple Myeloma Model 4000 SEM 3000— +/ 3 ) 2000 (mm 1000 Vehicle Pomalidomide, 10mpk, QD, p.o. CCS1477 (Inobr
Slide 37: EP300d-007 Rapidly and Potently Degrades EP300
EP300d-007 Rapidly and Potently Degrades EP300, but Not its Paralog CBP EP300d-007: Potent and Selective EP300 Degrader Global Proteomics Confirms that EP300d-007 is Selective Dmax: 97% Max Rate: 2.2 hr-1 DC50: 3 nM Dmax: 15% Max Rate: N/A 333nM EP300d-007/DMSO 6hr Log2FC 37 |
Slide 38: Selective ARID1B Degrader
Selective ARID1B Degrader For ARID1A-mutant Cancers 38
Slide 39: ARID1B is a Major Synthetic Lethal Target
Asset Description Initial Opportunity (U.S.) ARID1A mut. ARID1A mut. Incidence* Frequency Incidence Target / • ARID1B Approach • Targeted protein degrader Endometrial cancers 66K 38% 25K ARID1B is a Major Synthetic Lethal Target with Potential in Up To 5% of All Solid Tumors Stage / Next • Preclinic
Slide 40: ARID1B: Drugging a Previously Undruggable Target
• Large and highly unstructured protein ~ 240 kDa • No known enzymatic function • Member of large, multi-subunit complex • High sequence homology (~60%) to ARID1A ARID1B: Drugging A Previously Undruggable Target Drug Targeting Considerations Approach • Discover binders to ARID1B • Use binders to dev
Slide 41: Cereblon and VHL-based Degraders Progressed in Parallel
Maximum Optionality Achieved Through Progression of Both Cereblon and VHL-based Degraders in Parallel VHL CEREBLON 41 |
Slide 42: Robust ARID1B Degradation Across Multiple Cell Lines
IMMUNOBLOT HiBiT – ENDPOINT HiBiT – KINETICS HT-1376 (Bladder) HCT116 (Colorectal) HCT116 (Colorectal) Units 120 100 kDa 80 ARID1B 60 280 Control) Luminescence(% 40 20 Vinculin 116 Relative 0 0 4 8 12 16 20 24 Time (hr) 24 hours 24 hours 20 µM 2.5 µM 10 µM 1.25 µM 5 µM DMSO Selective ARID1B Degrader
Slide 43: ARID1B Degradation is On-Mechanism Via Ubiquitin-Proteasome System
ARID1B Degradation is On-Mechanism Via Ubiquitin-Proteasome System Inhibitors of the UPS Pathway VHL-inactive Degrader Does Not Affect ARID1B Levels Rescue Degradation Degradation Cell Viability Degradation ARID1B degrader + 750 nM MG132 (Proteosome inhibitor) + 250 nM Bortezomib (Velcade, Proteosom
Slide 44: Selective ARID1B Degradation Demonstrated by Global Proteomics
44 | Selective ARID1B Degradation Demonstrated by Global Proteomics
Slide 45: ARID1B Degradation Affects Downstream Target Genes
Selective ARID1B Degradation has Demonstrated Effects on Downstream Target Genes – Progressing Towards In Vivo Proof-of-concept 3 Day ARID1B shRNA Treatment ARID1B Degrader Treatment Down Gene A Expression Up Gene B Expression ARID1B Gene Expression 1.20 Down Gene A Expression Up Gene B Expression 3
Slide 46: Developing First-in-Class Precision Medicines Targeting Major Unmet Needs in Cancer
Developing First-in-Class Precision Medicines Targeting Major Unmet Needs in Cancer Leader in Unique Area of Cancer Biology Foghorn is a leader in targeting chromatin biology, which has the potential to address underlying dependencies of many genetically defined cancers Platform with initial focus i
Slide 47: Unique biology, Precision therapeutics, Broad impact
Unique biology Precision therapeutics Broad impact January 2026 47
Slide 48: Appendix
Appendix 48
Slide 49: SMARCA2 Program
SMARCA2 Program 49
Slide 50: FHD-909 Monotherapy Regression in SMARCA4-mutant NSCLC Model
FHD-909 Monotherapy Demonstrated Regression In Vivo in NCI-H2126 SMARCA4-mutant NSCLC Model at Tolerated Doses NCI-H2126 Reduction in Tumor Volume NCI-H2126 Body Weight 350 120 Vehicle Control FHD-909, 20mg/kg, PO, BID 300 FHD-909, 40mg/kg, PO, BID ) FHD-909, 60mg/kg, PO, BID Weight) 110 3 (mm 250 S
Slide 51: FHD-909 Strong In Vivo Activity Across NSCLC Models
A549 Model RERF-LC-AI Model NCI-H1793 Model 1500 1200 500 Vehicle Control Vehicle Control 1250 FHD-909 20mg/kg, BID, PO 1000 FHD-909, 20mg/kg, BID, PO FHD-909, 40mg/kg, BID, PO ) 400 FHD-909, 40mg/kg, BID, PO 3 ) 3 FHD-909, 60mg/kg, BID, PO ) 3 FHD-909, 60mg/kg, BID, PO 1000 (mm 800 (mm (mm 300 750
Slide 52: FHD-909 with Cisplatin and Pemetrexed in A549 Model
FHD-909 + cisplatin + pemetrexed A549 (SMARCA4mt, KRAS G12S) 1200 ) 1000 3 (mm 800 volume 600 * * Tumor 400 * * 200 *# *# 0 7 14 21 28 FHD-909 in Combination with Standard Therapies Demonstrates Significant Activity in the A549 (SMARCA4-mutant, KRAS G12S) Xenograft NSCLC Model In vivo, combining FHD
Slide 53: FHD-909 with Cisplatin and Paclitaxel in RERF-LC-AI Model
1400 1200 3 ) In vivo, combining FHD-909 with cisplatin and paclitaxel increased antitumor effect, (mm 1000 resulting in tumor regression 800 Additivity and synergy were also observed in vitro when FHD-909 was Volume * combined with cisplatin or paclitaxel 600 * Tumor 400 Vehicle Control * 40mg/kg F
Slide 54: Synergy of FHD-909 with KRAS Inhibitors In Vitro
Synergistic Activity Observed for FHD-909 in Combination with KRAS Inhibitors In Vitro NCI-H2030, Lung, NSCLC PATU-8988T, Pancreas, PDAC A549, Lung, NSCLC SMARCA4-/- KRAS(G12C) SMARCA4—/ fusion, KRAS(G12D)* SMARCA4 Q729fs/H736Y, KRAS(G12S) 120 [olomorasib] (nM) 120 [LY3962673] (nM) 120 [LY4066434](n
Slide 55: FHD-909 with Olomorasib Shows Synergistic Activity In Vivo
3000 FHD-909 + olomorasib (KRAS G12C inh) NCI-H2030 (SMARCA4mt, KRAS G12C) ## synergistic (p<0.05) 2500 3 ) (mm 2000 Combination of FHD-909 with olomorasib demonstrated synergistic antitumor activity 1500 and sustained tumor regression in vivo Volume * Tumor 1000 Vehicle Control 500 40mg/kg FHD-909,
Slide 56: FHD-909 with Pan-KRAS Inhibitor Shows Synergistic Activity
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) Combination of FHD-909 with pan-KRAS inhibitor resulted in synergistic antitumor activity and sustained tu
Slide 57: FHD-909 with Pembrolizumab in Humanized Xenograft Model
FHD-909 in Combination with Pembrolizumab Shows Significantly Enhanced Anti-Tumor Activity in A549 CD34+ HSC Humanized Xenograft NSCLC Model FHD-909 (20 mg/kg) + pembrolizumab FHD-909 (40 mg/kg) + pembrolizumab A549 (SMARCA4mt, KRAS G12S) A549 (SMARCA4mt, KRAS G12S) FHD-909 sensitized the tumor cell
Slide 58: Selective SMARCA2 Degrader Achieved Complete Degradation In Vitro
Selective SMARCA2 Degrader Achieved Complete SMARCA2 Degradation and Cell Growth Inhibition In Vitro SMARCA2 / SMARCA4 HIBIT Data A549 Ten-Day Proliferation Assay 100 SMARCA2 75 50 Degradation 25 % 0 SMARCA4 1E-3 0.01 0.1 1 10 Concentration (uM) Degraders Caused Time- and Dose-dependent SMARCA2 Degr
Slide 59: Protein Degradation Importance of Rate Analysis
Protein Degradation Importance of Rate Analysis FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex 59
Slide 60: Degradation Rates and Their Relationship to Dmax
Theoretical Experimental Experimental Kinetic Profile Kinetic Profile Rate vs. Dmax Native Deg Rate Level Dmax10 Loss Dmax25 Dmax50 Target Dmax80 Fractional Dmax95 Time Degradation Rates and Their Relationship to Dmax Slower rates lead to partial degradation, faster rates to complete loss Rate is an
Slide 61: Degradation Rate Dictates Dmax
Foghorn BRD9 Program Foghorn CBP Program Foghorn EP300 Program Degradation Rate Dictates Dmax – Program Independent Large scale experimental kinetic analysis for a program reveals the relationship between rate and Dmax 61 |
Slide 62: Prelude VHL and CRBN Compounds Have Incomplete Dmax and Hook Effect
Prelude SMARCA2 (VHL) Degrader Prelude SMARCA2 (CRBN) Degrader Concentration Concentration 3000 nM 3000 nM 1.5 Rate max hr-1: 1.5 750 nM 1.5 Rate max hr-1: 0.4 750 nM 188 nM 188 nM Hook Effect 46 nM 46 nM 1.0 1.0 Loss Hook Effect 12 nM Loss 12 nM Luminescence 3 nM Luminescence 3 nM (RLU) 0.7 nM (RLU
Slide 63: Foghorn Analysis and Dmax Results Match Published Prelude Data
Foghorn Analysis and Dmax Results Match Published Prelude Data Prelude Published Data Foghorn Replicated Data from Prelude Patents Prelude PRT3789 (VHL) 1 Prelude (VHL) Degrader VHL degrader (2 hours) 100 VHL degrader (24 hours) 100 SMARCA2 80 80 60 60 Degradation 40 Degradation 40 % % 20 20 0 0 0.0
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