Slide 1: Virtual Investor Event: Pipeline Updates for Selective ARID1B, CBP and EP300 Degrader Programs
October 30, 2025 Virtual Investor Event Pipeline Updates for Selective ARID1B, Selective CBP and Selective EP300 Degrader Programs 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 Conference Call Agenda
| Foghorn Conference Call Agenda Opening Remarks Welcome Selective ARID1B Degrader Selective CBP Degrader Selective EP300 Degrader Karin Hellsvik Vice President Investor Relations Adrian Gottschalk President and CEO Alfonso Quintás-Cardama, MD Chief Medical Officer Steve Bellon, PhD Chief Scientific
Slide 4: Foghorn is a Leader in Chromatin Biology, Successfully Drugging Challenging Targets
| Foghorn is a Leader in Chromatin Biology, Successfully Drugging Challenging Targets 4 Targeting chromatin regulation Implicated in up to 50% of all tumors Multi-billion $ Opportunities Leading the way based on proprietary capabilities and new biology First-and-Best-in-Class Approaches Unlocking se
Slide 5: Foghorn's Platform Has Delivered Precision First-in-Class Therapeutics
| Foghorn’s Platform Has Delivered Precision First-in-Class Therapeutics, and is Poised to Unlock New Biology 5 1. Chromatin Biology 2. Chemistry, Biochemistry & Formulations 3. Degraders / Selective Targeting Deep mechanistic understanding of chromatin regulatory system Expertise in rules of degrad
Slide 6: 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 7: Foghorn: Precision Therapies With Potential for Multi-Billion Dollar Opportunities Across Oncology
| Foghorn: Precision Therapies With Potential for Multi-Billion Dollar Opportunities Across Oncology 7 Modality Program Phase 1 Enzyme Inhibitors Transcription Factor Disruptors Undisclosed Protein Degraders Partner FHD-909* (Selective SMARCA2) 3 Discovery Programs Undisclosed Partnered Undisclosed
Slide 8: Foghorn: Precision Therapies With Potential for Multi-Billion Dollar Opportunities Across Oncology
| Foghorn: Precision Therapies With Potential for Multi-Billion Dollar Opportunities Across Oncology 8 Modality Program Phase 1 Enzyme Inhibitors Transcription Factor Disruptors Undisclosed Partner FHD-909* (Selective SMARCA2) 3 Discovery Programs Undisclosed Partnered Undisclosed Disease SMARCA4 mu
Slide 9: Foghorn – A Pioneer in Novel Biology and Oncology Therapies
| Foghorn – A Pioneer in Novel Biology and Oncology Therapies 9 Selective ARID1B Degrader Selective CBP Degrader • Mutated in up to 5% of all solid tumors • First to demonstrate robust and selective degradation of the protein • Developing VHL and cereblon degraders, potential for oral delivery • Pro
Slide 10: Foghorn's Platform Demonstrates Significant Progress Across Degrader Portfolio
Foghorn’s Platform Demonstrates Significant Progress Across Degrader Portfolio • Selective ARID1B Degrader • Selective CBP Degrader • Selective EP300 Degrader Steve Bellon, PhD Chief Scientific Officer
Slide 11: Chromatin Regulatory System Orchestrates Gene Expression
| Chromatin Regulatory System Orchestrates Gene Expression: Multiple Opportunities for Targets and Therapeutics 11 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 Tra
Slide 12: Platform of Proprietary Tools and Unique Know-How Enables Best-in-Class Degraders
12 Platform of Proprietary Tools and Unique Know-How Enables Development of Best-in-Class Degraders and Expansion to Induced Proximity DEGRADERS INDUCED PROXIMITY Design Optimization Development BEST-IN-CLASS MOLECULES Proprietary E3 ligase binders • ~ 15 -17 in internal library • UBR5 • Well-develo
Slide 13: Platform of Proprietary Tools and Unique Know-How Enables Best-in-Class Degraders
13 Platform of Proprietary Tools and Unique Know-How Enables Development of Best-in-Class Degraders and Expansion to Induced Proximity DEGRADERS INDUCED PROXIMITY Design Optimization Development BEST-IN-CLASS MOLECULES Proprietary E3 ligase binders • ~ 15 -17 in internal library • UBR5 • Well-develo
Slide 14: Foghorn is Focused on Some of the Most Relevant Genes in Cancer
| Foghorn is Focused on Some of the Most Relevant Genes in Cancer 14 Mendiratta G, et al. Nature Communications (2021) Foghorn Focus Most Frequently Mutated Genes in Human Cancer Foghorn Focus
Slide 15: Selective ARID1B Degrader
Alfonso Quintás-Cardama, MD Chief Medical Officer Selective ARID1B Degrader • Selective degradation achieved • VHL and cereblon based degraders • Modulation of ARID target genes achieved • In vivo proof-of-concept in 2026 Steve Bellon, PhD Chief Scientific Officer
Slide 16: Targeting ARID1A Mutated Cancers Has Potential for Significant Impact to Patients
| Targeting ARID1A Mutated Cancers Has Potential for Significant Impact to Patients 16 TUMORS WITH ARID1A MUTATIONS NSCLCBladderGastric2 & GEJEndometrial 195K84K37K66KUS Incidence1 7%24%20%38%Mutation Frequency 14K20K7K25K US Incidence (2025) of ARID1A Mutated Tumors ARID1A mutations are prevalent a
Slide 17: Selective ARID1B Targeting Unlocks Synthetic Lethal Strategy for ARID1A Mutant Cancers
| Selective ARID1B Targeting Unlocks Synthetic Lethal Strategy for the Treatment of ARID1A Mutant Cancers 17 Synthetic Lethal Relationship Between ARID1A and ARID1B ARID1B Knockout Inhibits Cell Growth in ARID1A Mutant Cancer Cells EFE-184 (ARID1A Null) Non-targeting sgRNA ES2 (ARID1A WT) PCNA Knock
Slide 18: ARID1B: Drugging A Previously Undruggable Target
| 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 18 ARID1A/B BAF Nucleosome PDB ID: 6LTJ • Discover binders to ARID1B • Use binders to
Slide 19: Foghorn Platform Yields Several Selective ARID1B Binder Series
| Foghorn Platform Yields Several Selective ARID1B Binder Series 19 ARID1B ARID1A KD= 25.3 ± 3.4 µM N= 0.90 ± 0.02 ARID1B ARID1A >2x selectivity for ARID1B ARID1B Binding A R ID 1A B in di ng SERIES A SERIES B
Slide 20: Maximum Optionality Achieved Through Progression of Both Cereblon and VHL Based Degraders
| Maximum Optionality Achieved Through Progression of Both Cereblon and VHL Based Degraders in Parallel 20 C E R E B L O N V H L
Slide 21: Lead ARID1B Degrader Demonstrates Robust Degradation Across Multiple Cell Lines
| Lead ARID1B Degrader Demonstrates Robust Degradation Across Multiple Cell Lines 21 IMMUNOBLOT HiBiT - ENDPOINT HCT116 (Colorectal)HT-1376 (Bladder) HiBiT – KINETICS HCT116 (Colorectal) 24 hours 24 hours R e la ti v e L u m in es c e n c e U n it s (% C o n tr o l)
Slide 22: ARID1B Degradation is On-Mechanism Via Ubiquitin-Proteasome System
| ARID1B Degradation is On-Mechanism Via Ubiquitin-Proteasome System 22 Inhibitors of the UPS Pathway Rescue Degradation VHL-Inactive Degrader Does Not Affect ARID1B Levels Degradation Cell Viability Degradation + 750 nM MG132 (Proteosome inhibitor) + 250 nM Bortezomib (Velcade, Proteosome inhibitor
Slide 23: ARID1B Degrader Exhibits High Target Selectivity
| ARID1B Degrader Exhibits High Target Selectivity 23 ARID1B-HiBiT HCT116 ARID1A-HiBiT HCT116 SMARCA2-HiBiT HeLa SMARCA4-HiBiT HeLa
Slide 24: Selective ARID1B Degradation Demonstrated by Global Proteomics
| Selective ARID1B Degradation Demonstrated by Global Proteomics 24
Slide 25: First Ternary Complex X-ray Structure Reveals Unexpected Degrader Geometry
| First Ternary Complex X-ray Structure Reveals Unexpected Degrader Geometry Paving Way to Improved Degrader Molecules 25 Hypothesized exit vector Binary Ternary Determined to 2.1 Å resolution Experimentally determined exit vector VHL Degrader ARID1B
Slide 26: Selective ARID1B Degradation Has Demonstrated Effects on Downstream Target Genes
| 0.0 0.2 0.4 0.6 0.8 1.0 1 2 3 4 5 6 Selective ARID1B Degradation has Demonstrated Effects on Downstream Target Genes – Progressing Towards Proof of Concept 26 3 Day ARID1B shRNA Treatment ARID1B Degrader Treatment y = 0.6782x + 0.2591 R² = 0.7754 0.00 0.20 0.40 0.60 0.80 1.00 1.20 0.0 0.5 1.0 ARID
Slide 27: Selective CBP Degrader
Alfonso Quintás-Cardama, MD Chief Medical Officer Selective CBP Degrader • Application in EP300 mutant cancers – synthetic lethal • Potential application in ER+ breast cancer – Lineage dependency on CBP • Candidate molecule CBPd-171 advancing to DRF toxicology studies Q4 • IND-ready in 2026 Steve Be
Slide 28: EP300 and CBP are Critical Regulators of Cell Identity and Survival
| EP300 and CBP are Critical Regulators of Cell Identity and Survival 28 • EP300 and CREB Binding Protein (CBP) are histone acetyltransferases (HATs) which modify chromatin, marking it for active gene expression • EP300 and CBP predominantly function as enhancers, DNA regulatory sites controlling ke
Slide 29: Selectively Drugging CBP and EP300 is Difficult
| Selectively Drugging CBP and EP300 is Difficult 29 Historical development of specific drugs targeting EP300 has been hampered by the high degree of homology • CBP and EP300 are highly homologous ‒ 59% identity and 68% similarity • HAT domains are 88% identical • Bromodomains are 97% identical • Kn
Slide 30: Potential for Significant Impact to Patients with a Selective CBP Degrader
| Potential for Significant Impact to Patients with a Selective CBP Degrader 30 CBP Dependent CancersTUMORS WITH EP300 MUTATIONS ER+ Breast CancerOther (gastric2, CRC, NSCLC) Bladder Gynecological (endometrial, cervical, ovarian) 210K349K84K105KUS Incidence1 NA6%10%8% Mutation frequency NA21K8.4K8.4
Slide 31: Selective CBP Degradation Results in Significant Anti-Tumor Activity in EP300mut Models
| Selective CBP Degradation Results in Significant Anti-Tumor Activity in EP300mut Solid Tumor Models 31 EP300mut Bladder Cancer CDX (639V) EP300mut Gastric Cancer CDX (AGS) EP300mut Gastric Cancer PDX (ST020326) T u m o r V o lu m e (m m ³ + S E M ) B o d y W ei g h t C h an g e (% ) 20 30 40 50 60
Slide 32: Selective CBP Degradation Showed No Significant Impact on Platelet Counts
| Selective CBP Degradation Showed No Significant Impact on Platelet Counts and Spared Megakaryocytes 32 Platelet Counts Post Two Weeks of Dosing (In Vivo – Control Mice) Human Megakaryocyte Cell Viability Assay (In Vitro*) dCBP-59 CCS1477 (Inobrodib) Vehicle dCBP-59 (10 mg/kg, QD, SC) Vehicle CCS14
Slide 33: CBP Degradation Results in Down-Regulation of Genes Responsible for Cell Cycle and Proliferation
| CBP Degradation Results in Down-Regulation of Genes Responsible for Cell Cycle and Proliferation CBP RNAseq shows CBPd down-regulates gene sets responsible for cancer cell growth (24h treatment; RKO, CRC) Cells become arrested in G1 phase following CBPd treatment (RKO) Ultimately leading to potent
Slide 34: In Breast Cancer, CBP Degradation Disrupts ER Signaling and Inhibits Tumor Cell Growth
| In Breast Cancer, CBP Degradation Disrupts Estrogen Receptor (ER) Signaling and Inhibits Tumor Cell Growth CBP Robust & Potent CBP degradation …Resulting in cancer cell growth inhibition 34 0. 00 01 0. 00 1 0. 01 0. 1 1 10 10 0 10 00 10 00 0 10 00 00 10 00 00 0 % d e te c te d C B P p ro te in CBP
Slide 35: Selective CBP Degrader Shows Promise in Combination with Standard Therapies
| Foghorn Selective CBP Degrader Shows Promise in Combination with Standard Therapies in Preclinical ER+ Breast Cancer Models 35 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 36: Foghorn's Pre-DC CBP Degrader (CBPd-171) is Highly Selective
| Foghorn’s Pre-DC CBP Degrader (CBPd-171) is Highly Selective 36 CBPd-171 rapidly and potently degrades CBP, but not its paralog EP300 Dmax (%): 97% | Max Rate: 3.2 | DC50: 30pM Dmax (%): 5% | Max Rate: N/A F ra c ti o n a l L u m in e s c en ce (R L U ) 0 5 10 15 20 25 0.0 0.2 0.4 0.6 0.8 1.0 1.2
Slide 37: Foghorn's Pre-DC CBP Degrader (CBPd-171) is Highly Selective
| Foghorn’s Pre-DC CBP Degrader (CBPd-171) is Highly Selective 37 U2OS CBPd-171/DMSO 100 nM 3hr Log2FC Global proteomics confirms that CBPd-171 is selective
Slide 38: Long-Acting Injectable Formulation of CBPd-171 Enables Weekly Sub-Cutaneous Delivery
| Long-Acting Injectable Formulation of CBPd-171 Enables Weekly Sub-Cutaneous (SC) Delivery 38 Tumor Growth Inhibition Observed in EP300mut (AGS) Gastric Model (Daily Injections and SC weekly LAI Injection) • Weekly LAI injection of CBDd-171 results in efficacy comparable to daily SC injections in A
Slide 39: Selective EP300 Program
Alfonso Quintás-Cardama, MD Chief Medical Officer Selective EP300 Program • VHL based selective degrader shows impressive efficacy in multiple myeloma without thrombocytopenia • EP300 degraders show full efficacy in IMiD resistant cell lines • Collection of advanced leads evaluated for progression i
Slide 40: EP300 Degradation Shows Anti-Proliferative Activity in Broad Range of Hematological Malignancies
| EP300 Degradation Shows Anti-Proliferative Activity in Broad Range of Hematological Malignancies 40MM: Multiple Myeloma; DLBCL: Diffuse Large B-Cell Lymphoma; AML: Acute Myeloid Leukemia; BL: Burkitt’s Lymphoma; TCL: T-cell Lymphomas; T-ALL: T-cell Acute Lymphoblastic Leukemia; B-ALL: B-cell Acute
Slide 41: EP300 Degrader Applications Across Hematological Malignancies with High Unmet Need
| EP300 Degrader Applications Across Hematological Malignancies with High Unmet Need 41 Source: Clarivate Epidemiology 1. Includes de novo + transformed. EP300 Lineage Dependence AML+MDSDLBCLMultiple Myeloma 37K32K31KUS Incidence1 DLBCL: Diffuse Large B-Cell Lymphoma; AML: Acute Myeloid Leukemia; MD
Slide 42: Foghorn's Selective EP300 Degraders are Highly Potent and Selective
| Foghorn’s Selective EP300 Degraders (EP300d) are Highly Potent and Selective 42 Dmax (%): 95% | Max Rate: 2.5 | DC50: 3nM Dmax (%): 5% | Max Rate: N/A EP300 Cellular Kinetics CBP Cellular Kinetics EP300d-31 rapidly and potently degrades EP300, but not its paralog CBP
Slide 43: Foghorn's Selective EP300 Degraders are Highly Selective
| Foghorn’s Selective EP300 Degraders are Highly Selective 43U2OS EP300d/DMSO 300 nM 6hr Log2FC Global proteomics confirms that EP300d-79 is selective
Slide 44: Ternary Complex Structures Reveal Drastically Different Bromodomain Conformations
| Ternary Complex Structures Reveal Drastically Different Bromodomain Confirmations in Complex with VHL 44
Slide 45: EP300 Degradation Modulates the Transcription Factors That Multiple Myeloma Depends On
| EP300 Degradation Modulates the Transcription Factors That Multiple Myeloma Depends On 45 EP300 degradation downregulates the expression of several transcription factors H929 OPM2 Lineage-dependence on EP300-regulated transcription factors KMS11RPMI8226 OPM2 RPMI8226 KMS11 dEP300-9 treatment, cell
Slide 46: Selective EP300 Degradation Induces Apoptosis in MM
| Selective EP300 Degradation Induces Apoptosis in MM 46 Treatment with a selective EP300 degrader (dEP300-079) results in time- and concentration- dependent induction of apoptosis MM1S cell line
Slide 47: Selective EP300 Degradation Results in Significant Responses In Vivo, and Spares Platelets
| Selective EP300 Degradation Results in Significant Responses In Vivo, and Spares Platelets 47 • 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 degrader
Slide 48: Cereblon Based EP300 Degrader is Potent on Parental MM Cell Line, but Ineffective Against IMiD Resistant
| Cereblon Based EP300 Degrader is Potent on Parental MM Cell Line, but Ineffective Against IMiD Resistant Cell Lines 48 dEP300-9 VHL-based EP300 degrader dEP300-6 CRBN-based EP300 degrader MM1S parental MM1S mezigdomide resistant MM1S iberdomide resistant Iberdomide Mezigdomide
Slide 49: Selective EP300 Degrader Maintains Activity in IMiD Resistant Cell Lines
| Selective EP300 Degrader Maintains Activity in IMiD Resistant Cell Lines 49 Resistant MM1S cell lines were developed through 5–6 months of in vitro exposure to gradually increasing concentrations of lenalidomide, pomalidomide, iberdomide, or mezigdomide dEP300-9 dEP300-9 pomalidomide lenalidomide
Slide 50: Synergy Demonstrated in MM Between dEP300 and Pomalidomide
| Synergy Demonstrated in MM Between dEP300 and Pomalidomide 50 Extensive combination screen assessed the impact on growth following treatment with dEP300 and 33 approved agents across 6 different cell lines
Slide 51: Selective EP300 Degraders Approaching Pre-DC CBA
| Selective EP300 Degraders Approaching Pre-DC CBACompound 0.3 [104%]0.3 [99%]0.4 [95%]U2OS EP300 uDC50 (nM) [Dmax%] On- Target <0.15Actioned2.1MM1S EP300 uDC90 (24 hr, nM) 0.152.00.61MM1S (nM, uGI50) 31 / >10,000102 / >10,0004 / 3000CBP / BRD4 TR-FRET IC50 (nM) Off-Target 356x [63%]17497x [--]26x [
Slide 52: Closing Remarks
Closing Remarks Adrian Gottschalk President and CEO
Slide 53: Question & Answers
FOGHORN THERAPEUTICS Question & Answers