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FOGHORN THERAPEUTICS Unique biology Precision therapeutics Broad impact August 2026 FHTX NASDAQ LISTED
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| Forward Looking Statements 2 This presentation contains forward-looking statements that are based on management's beliefs and assumptions and on informationcurrently available to management. 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,” “might,” “will,” “likely,”“anticipates,” “intends,” “plans,” “seeks,” “believes,” “estimates,” “expects,” “continues,” “projects” or the negative of these terms orother similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, butare not limited to, statements concerning: the potential outcomes from our collaboration agreement with Lilly; the initiation, timing,progress and results of our research and development programs and preclinical studies and clinical trials, including with respect to ourPhase 1 dose escalation trial of FHD-909 with Lilly; our ability to advance product candidates that we may develop and to successfullycomplete preclinical and clinical studies; our ability to leverage our initial programs to develop additional product candidates using ourGene Traffic Control Platform®; the impact of exogeneous factors, including macroeconomic and geopolitical circumstances, on ourand our collaborators’ business operations, including our research and development programs and preclinical studies; developmentsrelated to our competitors and our industry; our ability to expand the target populations of our programs and the availability of patientsfor clinical testing; our ability to obtain regulatory approval for FHD-909 and any future product candidates from the FDA and otherregulatory authorities; our ability to identify and enter into future license agreements and collaborations; our ability to continue to rely onour CDMOs and CROs for our manufacturing and research needs; regulatory developments in the United States and foreign countries;our ability to attract and retain key scientific and management personnel; the scope of protection we are able to establish, maintain andenforce for intellectual property rights covering FHD-909, our future products and our Gene Traffic Control Platform; and our use ofproceeds from capital-raising transactions, estimates of our expenses, capital requirements, and needs for additional financing. Youshould, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of thispresentation. Additional important factors to be considered in connection with forward-looking statements are described in theCompany's filings with the Securities and Exchange Commission, including withing the section entitled "Risk Factors" in the Company'sAnnual Report on Form 10-K for the fiscal year ended December 31, 2025. Any forward-looking statements represent the Company’sviews only as of the date of this presentation and should not be relied upon as representing its views as of any subsequent date. TheCompany explicitly disclaims any obligation to update any forward-looking statements. The Company’s business is subject tosubstantial risks and uncertainties.
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| Foghorn is a Leader in Chromatin Biology, Successfully Drugging Challenging Targets 3Targetingchromatin regulationImplicated in up to 50% of all tumorsTargetingchromatin regulationImplicated in up to 50% of all tumorsMulti-billion $ Opportunities Unlocking selectivity of previously undruggable targetsUnlocking selectivity of previously undruggable targetsFirst-and-Best-in-Class ApproachesInnovatingselective protein degradation with capabilities in induced proximityInnovatingselective protein degradation with capabilities in induced proximitySelective Target EngagementLeveraging a proven drug development platform with expansive potentialLeveraging a proven drug development platform with expansive potentialStrategic Partnership:Multiple Programs
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| Chromatin Regulatory System Orchestrates Gene Expression:Multiple Opportunities for Targets and Therapeutics 4 Chromatin –compacted form of DNA inside the nucleus of the cellChromatin Remodeling Complexes–specialized multiprotein machines that allow access to DNATargets: SMARCA2, ARID1B Transcription Factors – proteins that help turn specific genes "on" or "off" by working in concert with the chromatin remodeling complex to bind to DNATargets: Multiple TFsOther Chromatin Binding Proteins involved in gene expression / functionTargets: CBP, EP300 Chromatin Regulatory System genes are implicated across a wide range of cancers Leveraging synthetic lethality and lineage dependencies
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| Foghorn’s Platform Has Delivered Precision First-in-Class Therapeutics, and is Poised to Unlock New Biology 51. Chromatin Biology2. Chemistry, Biochemistry & Formulations 3. Degraders / Selective TargetingDeep mechanistic understanding of chromatin regulatory systemExpertise in rules of degrader optimizationTrack record with previously undruggable targetsExpansion into New TAs & Induced ProximityTrack record of delivering precision therapeutics
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| 3 Discovery ProgramsUndisclosed Inhibitor**Selective SMARCA2 Degrader Precision Therapies with Potential for Multi-billion Dollar Opportunities 6 Therapeutic AreaProgramPhase 1OncologySelective SMARCA2 Inhibitor FHD-909*Disease AreaSMARCA4-mutant cancers (e.g., NSCLC)Other Collaboration Programs Selective ARID1B DegraderARID1A-mutant cancers (e.g., endometrial, gastric, bladder, NSCLC) Selective CBP DegraderER+ breast cancerSelective EP300 DegraderHeme malignancies (MM and DLBCL) and prostate cancerPreclinicalNext Clinical Milestone *LY4050784, 50/50 U.S. economic split, ex-U.S. royalties. ** Pending Lilly decision to proceed, 50/50 U.S. economic split, ex-U.S. royalties. SMARCA2 = BRMDLBCL: Diffuse Large B-Cell Lymphoma; ER+: Estrogen Receptor-positive; I&I: Immunology and Inflammation; MM: Multiple Myeloma; NSCLC: Non-Small Cell Lung Cancer Phase 1a Monotherapy Data; Dose Expansion DecisionIND Targeted in 2027-I & I Novel Small Molecule Undisclosed IND Targeted in 2027-RIPTACsInduced ProximityOngoing InitiativesPlatformMolecular Glues
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| FHD-909 is Being Developed in Collaboration with Lilly; Landmark Agreement Signed in December 2021Significant Upfront and EconomicsStrong Momentum and Shared VisionOngoing Discovery Programs•$300 million cash •$80 million in Foghorn common stock at a price of $20 per share•50/50 U.S. economic split on SMARCA2-target and another undisclosed program•Tiered ex-U.S. royalties ranging from low double-digit into 20s•Lilly is a leading oncology company with a track record of innovation and execution• Lilly selected FHD-909 for developmentand initiated the first clinical trial in 2024•Thorough evaluation of FHD-909 in models of SMARCA2-dependent tumors•Three additional programs as part of collaboration (undisclosed)• Potential to earn royalties and up to $1.3 billion in potential milestones across these three programs7
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| Developing First-in-Class Precision Medicines Targeting Major Unmet Needs in Cancer 8Large Market PotentialChromatin biology is implicated in up to 50% of tumors, potentially impacting ~2.5 million patientsFoghorn’s current pipeline potentially addresses more than 500,000of these patientsBroad pipeline across a range of targets and small molecule modalitiesMajor Strategic CollaborationStrategic collaboration with Lilly; $380 million upfront; 50/50 U.S. economic split on two lead programsWell-Funded$167.6 millionin cash and equivalents(as of 06/30/2026)Cash runway into first half of 2028Shares outstanding: approximately 70.6M*(as of 06/30/2026)Value DriversSelective SMARCA2 Inhibitor, FHD-909, partnered with Lilly, in Phase 1 trialAdvancing Selective EP300 and Selective CBP degraders towards INDsAccelerating novel oral small molecule in Immunology & Inflammation towards INDProtein degrader platform with expansion into induced proximityLeader in Unique Area of Cancer BiologyFoghorn is a leader in targeting chromatin biology,which has the potential to address underlying dependencies of many genetically defined cancersPlatformwith initial focus in oncology, therapeutic area expansion potential *Includes pre-funded warrants.
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Selective SMARCA2 ProgramFor SMARCA4-mutant Cancers• FHD-909 (LY4050784) – Selective SMARCA2 Inhibitor9
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| SMARCA2: Clinical-stage FHD-909 Selective SMARCA2 Inhibitor and Preclinical Selective SMARCA2 Degrader 10 Selective SMARCA2 Inhibitor FHD-909*Selective SMARCA2 DegraderBiologyExploit the synthetic lethal relationship between SMARCA2 and mutated SMARCA4StatusPhase 1 monotherapy dose escalation trial ongoingAdvancing through late preclinical developmentOpportunitySMARCA4-mutated cancer including ~10% of NSCLC and up to 5% of all solid tumorsLilly Partnership50/50 global R&D cost share | 50/50 U.S. economics | tiered ex-U.S. royalties starting in the low double-digit range and escalating into the twenties*LY4050784
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| Selective SMARCA2 Inhibition: Promising Strategy to Exploit Synthetic Lethal Relationship Between SMARCA2 and Mutant SMARCA4 11No SMARCA4 MutationsNo SMARCA4 MutationsSMARCA4 MutationSMARCA4 MutationSMARCA4 Mutation and SMARCA2iSMARCA4 Mutation and SMARCA2iCell SurvivalCell SurvivalCell DeathCell DeathHealthy Cells Cancer CellsSMARCA4SMARCA2BAF Complex BAF Complex Mutant SMARCA4BAF Complex SMARCA2iPrecision medicine targeting synthetic lethal relationships is a proven clinical approach now used in multiple cancers (e.g., PARP inhibitors) SMARCA4 SMARCA2
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| SMARCA4 is Mutated in Up to 10% of NSCLC; Up to 5% of Solid Tumors 12 SMARCA4 mutated across a broad range of tumorsAccounts for ~5% of solid tumorsAACR GENIE via cBioPortal
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| FHD-909: Overall Goal is to Become a First-Line Treatment for SMARCA4-mutated NSCLC 13 1stLine NSCLC1stLine NSCLCPembrolizumab-based regimensOther immune checkpointinhibitor-based regimensChemotherapy-based regimens2ndLine NSCLC2ndLine NSCLCChemotherapy-based regimensRamucirumab (anti-VEGF) + chemotherapyCheckpoint inhibitor monotherapy3rdLine NSCLCChemotherapy-based regimensOther targeted agents + chemotherapyRelevant treatment regimens in each line of therapy for metastatic NSCLC*Agents evaluated preclinically in combination with FHD-909KRAS inhibitorsTargeted agentsNote:*Generalized across squamous and non-squamous metastatic NSCLC without driver mutation Source:CancerMPact 2024 US NSCLC TA report
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| 14 Significant Unmet Medical Need in NSCLC Metastatic Setting for SMARCA4 Patients~15 months~8 months1L (SMARCA4 WT) 1L (SMARCA4 Mut)39.1%21.9%2.7 monthsResponse Rate (%) PFS (months) OS (months)Significant Unmet NeedFrontline NSCLC Metastatic – PD1 + Chemo1 Source: 1. Alessi, J Thorac Oncol, 2023 2. Rittmeyer, Lancet, 2017; Fehrenbacher, J Thorac Oncol, 2018; Mazieres, J Thorac Oncol, 2021 Herbst, Lancet, 2016; Herbst, Abs OA03.07 3. S1800A – Lung-MAP Sub-study –ASCO 2022; Garon, Lancet, 2014 •Poor response to 1L chemo-immunotherapy for patients with SMARCA4 mutations1•2L outcomes with docetaxel are poor for allpatients (ORR 10-20% depending on agent/s2,3; PFS ~5-months)•SMARCA4-mutated patients are expected to fare even worse in the 2L setting•3L+ setting –experience suggests less than 10% ORR and 1 to 2 months PFSSignificant Unmet Need in SMARCA4-mutated NSCLC8.1 months6.1 months15.0 months
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| 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 w/ Other Mutations2Overall Survival for SMARCA4 wt vs SMARCA4 mut1;Frontline Metastatic NSCLC w/ ChemoimmunotherapySMARCA4 Mutations are Consequential – in NSCLC, Patients with Mutated SMARCA4 Have Significantly Worse Clinical Outcomes 15 SMARCA4 10%KRAS 29%EGFR 26%ALK 7%RET 4%MET 7%Source: 1. Alessi et al DOI: 10.1016/j.jtho.2023.01.091; 2. TCGA via cBioPortalOverall Survival(%)MonthsSupporting references: • Gandhi, et al, 2025; DOI: 10.1016/j.jtho.2025.01.016 • Alessi, et al, 2023; DOI: 10.1016/j.jtho.2023.01.091• Negrao, et al, 2023; DOI: 10.1158/2159-8290.Cd-22-1420 • Liu, et al, 2021; DOI: 10.1002/1878-0261.12831• Fernando, et al, 2020; DOI: 10.1038/s41467-020-19402-8• Schoenfeld, et al, 2020DOI: 10.1158/1078-0432.ccr-20-1825
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| 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 KRASmut16 Overall Response Rate (ORR) Source: Alessi et al DOI: 10.1016/j.jtho.2021.03.024 Progression-Free Survival (PFS)Overall Survival (OS) Median PFS, months (95% CI)Median OS, months (95% CI)KRAS mut + SMARCA4 wt (n:159): 15.1 (11.2–20.1)KRAS mut + SMARCA4 mut (n:17): 3.0 (1.0–9.3)HR = 0.25 [95% CI: 0.14–0.42]P < 0.001HR = 0.29 [95% CI: 0.17–0.50]P < 0.0010.0%(0/17)KRAS mut + SMARCA4 wt (n:159): 4.1 (2.8–6.0)KRAS mut + SMARCA4 mut (n:17): 1.4 (0.9–2.0)P = 0.0322.0%(35/159)
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| A First-in-Human Phase 1 Trial of FHD-909 in Advanced Solid Tumor Patients with SMARCA4 MutationsPhase 1a Dose EscalationAdvanced solid tumors with any SMARCA4 alteration(mTPI-2 method with backfillinga)Dose Level 1Dose Level 2Dose Level 3Dose Level nPhase 1b Dose ExpansionbPresence of a Known or Likely Loss of Function of SMARCA4Part A: 2L + NSCLCc(Optional Randomized Dose Optimization)Part B: Other Solid TumorsCohort A1Cohort A2 (optional)Cohort A3 (optional)RandomizedCohort B1•FHD-909 is administered orally BID, in 28-day cycles•Phase 1b may begin prior to completion of backfill in Phase 1a•In Phase 1b, no prior SMARCA2 (BRM) inhibitors/degraders are allowedNote:aEach dose level will enroll 3-6 DLT-evaluable patients; select dose levels may backfill up to 20 patients; N~80; b Phase 1b may open prior to completion of backfill; N~80; c prior platinum doublet, immunotherapy, and antibody-drug conjugate therapy allowed; sponsor may initiate a randomized dose optimization cohort within Phase 1b across 2 or more dose levels17
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| FHD-909 in Combination with Anti-PD1 Demonstrates Complete and Durable Regression 18 Double Combo Efficacy (LY4050784, anti-PD1, chemo) Body weight percentage change (%) •FHD-909 monotherapy demonstrates better efficacy (tumor regression) than chemo or anti-PD1 (progressive disease)•FHD-909 + anti-PD1 combo causes durable complete response (CR) that is maintained for at least 70 days after dosing stopped•In contrast, chemo + anti-PD1 combo results in stable disease suggesting SMARCA2 inhibition as the key driver of combination benefit with checkpoint blockade % body weight change Hai Hu, Philip Califati, Franny Hough, Wei Zheng, Shuang Chen MB49 SMARCA4 KO Syngeneic Model
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| Lack of Tumor Formation in CR Mice After Re-inoculation Suggests Immune Memory Formation 19 Re-challenge of Mice After CR with FHD-909 + Anti-PD1 Combos •Complete response (CR) mice were re-challenged with MB49 SMARCA4-KO cells alongside age-matched naïve controls •0% tumor take in CR mice vs. 100% in naïve controls demonstrates durable anti-tumor immune memory following FHD-909 + anti-PD-1 treatment Tumor volume (mm3) Hai Hu, Robert Stephen Flack, Andrew Capen, Shuang Chen(~70 days after dosing stopped)
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Degrader Programs• Selective EP300 Degrader • Selective CBP Degrader• Selective ARID1B Degrader20
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| Multi-billion Dollar Opportunities for Each Program Developing a Portfolio of Novel and Selective Degraders with Blockbuster Potential 21 Selective ARID1B DegraderSelective CBPDegrader• Mutated in up to 5% of all solid tumors• First to demonstrate robust and selective degradation of the protein• Developing cereblon degraders, potential for oral delivery• Mutated in up to 5% of all solid tumors• First to demonstrate robust and selective degradation of the protein• Developing cereblon degraders, potential for oral delivery• ER+ breast cancer• Highly selective and potent• Long-Acting Injectable (LAI) formulation• No significant preclinical heme toxicity• ER+ breast cancer• Highly selective and potent• Long-Acting Injectable (LAI) formulation• No significant preclinical heme toxicity• Heme malignancies (including MM and DLBCL) and prostate cancer• Highly selective and potent• No significant preclinical heme toxicity • IND targeted in 2027• Heme malignancies (including MM and DLBCL) and prostate cancer• Highly selective and potent• No significant preclinical heme toxicity • IND targeted in 2027Selective EP300 Degrader
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| CBP and EP300 Proteins – A Decades-long Challenge in Selectivity 22 CBP and EP300 Biology•CBP and EP300 are highly homologous, paralog histone acetyltransferases regulating enhancer-mediated transcription and protein stability•Dysregulation of CBP and EP300 has been implicated in multiple cancers•Dual targeting has revealed tolerability and safety issuesFoghorn’s Solution... Highly Selective Degradation•Achieved selective targeting which results in improved tolerability and efficacy •Advancing two separate programs with defined dependencies and patient populations CoA TFTFTFRNAPolymeraseAcAc CoAAc Ac AcCBP/ EP300MYCCell growthCell survivalAcEP300 Degrader Approach Focus on EP300 Lineage-dependent Cancers CBP Degrader Approach Focus on EP300-mutant Cancers via Synthetic Lethality
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Selective EP300 DegraderFor CBP-mutant and EP300-dependent Cancers 23
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| Summary: Selective EP300 Degrader for Heme Malignancies and Prostate Cancer 24 •E1A binding protein p300 (EP300)•Targeted protein degraderMMAML + MDSDLBCLTarget / Approach•IND targeted in 2027Next Clinical Milestone•Deeper efficacy response vs non-selective molecules•Improved tolerability profile vs non-selective molecules•Patient selection biomarker for DLBCL Asset DescriptionInitial Opportunity (U.S.)Incidence*31K32K38K*Per year incidence in the U.S. Source: Clarivate DRG Mature Markets Data EP300-dependent Hematological MalignanciesKey Differentiation•Broad range of heme malignancies focused on MM and DLBCL•AR+ prostateIndications
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| EP300 Degradation Shows Anti-Proliferative Activity in Broad Range of Hematological Malignancies 25MM: Multiple Myeloma; DLBCL: Diffuse Large B-Cell Lymphoma; AML: Acute Myeloid Leukemia; BL: Burkitt’s Lymphoma; PTCL: Peripheral T-cell Lymphomas; T-ALL: T-cell Acute Lymphoblastic Leukemia; B-ALL: B-cell Acute Lymphoblastic Leukemia; CML: Chronic Myeloid Leukemia; HL: Hodgkin Lymphoma; MCL: Mantle Cell Lymphoma, FL: Follicular Lymphoma Anti-Tumor Activity Across Full Range of Heme Sub-Lineages (~ 70% of All Tested Cell Lines are Sensitive)
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| Multiple Myeloma (MM1S) CDX DLBCL (KARPAS422) CDX AR+ Prostate (VCaP) CDX EP300 Degradation Results in Significant Tumor Growth Inhibition in MM, DLBCL and Prostate Models 26 Body Weight Change (%)510 15 20 25 30 35 40 4505001,0001,5002,000VehicleFHT-EP300d - 32, SC, 50mg/kg (BID)Days After Tumor InoculationFHT-EP300d - 32, SC, 20mg/kg (BID)FHT-EP300d - 32, SC, 10mg/kg (BID) Body Weight Change (%)10 15 20 25 3005001,0001,5002,0002,5003,000Days After Tumor Inoculation VehicleFHT-EP300d - 53, SC, 30mg/kg (QD)FHT-EP300d - 53, SC, 10mg/kg (QD)CCS1477 (Inobrodib), PO, 20mg/kg (QD)Fold Selectivity>1000xEP3000.7 nMCBP>1 uMDegrader SelectivityFHT-EP300d-53 DC50 @24hFold Selectivity>40xEP30023 nMCBP>1 uMDegrader SelectivityFHT-EP300d-32 DC50 @24h
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| •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 degraders can achieve deeper responses at tolerated doses with no thrombocytopenia Selective EP300 Degrader FHT-273 Shows Superior Efficacy and Tolerability Compared to Clinical Benchmark Inobrodib 27 FHT-101273 Demonstrates Dose-responsive Efficacy, Including Complete Responses, in MM1S CDX ModelSelective Degrader Spares Platelets PLT (x109cells/L)0500100015002000VehicleFHT-273, 30mpk, QD, s.cFHT-273, 10mpk, QD, s.cFHT-273, 3mpk, QD, s.cFHT-273, 1mpk, QD, s.cCCS1477(Inobrodib), 20mpk, QD, p.oVehicleFHT-273, 30mpk, QD, s.cFHT-273, 10mpk, QD, s.cFHT-273, 3mpk, QD, s.cFHT-273, 1mpk, QD, s.cCCS1477(Inobrodib), 20mpk, QD, p.o
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| VHL-based Selective EP300 Degrader Maintains Activity in IMiD Resistant Cell Lines 28 Resistant MM1S cell lines were developed through 5–6 months of in vitro exposure to gradually increasing concentrations of lenalidomide, pomalidomide, iberdomide, or mezigdomide dEP300-9dEP300-9pomalidomidelenalidomidemezigdomideiberdomide
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| 20 25 30 35 4001002003004001000200030004000Days After Tumor Inoculation VehicleFHT-EP300d-007, 30mpk, BID, s.c.CCS1477 (Inobrodib), 10mpk, BID (4d on / 3d off), p.oCCS1477 (Inobrodib), 20mpk, QD, p.o.Pomalidomide, 10mpk, QD, p.o.Selective EP300 Degrader Shows Superior Efficacy Compared to Pomalidomide and Inobrodib in an IMiD Resistant Multiple Myeloma ModelPomalidomide-resistant Multiple Myeloma CDX (MM1S-PomR) Treated with EP300d-007 29•Selective EP300 degrader achieves deeper responses (regressions) in a pomalidomide-resistant multiple myeloma model•Selective EP300 degrader with improved therapeutic window enables sustained target coverage and improved efficacy.
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| FHT-273: Potent and Selective EP300 DegraderFHT-273 Rapidly and Potently Degrades EP300, but Not Its Paralog CBPGlobal Proteomics Confirms that FHT-273 is Selective 30333nM FHT-273/DMSO 8hr Log2FC FHT-2730.3nMDC5096%Dmax1.8 hr-1RateFHT-273 EP300 KineticsFHT-273 CBP Kinetics
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| 31 Development Vision: EP300 in Hematological MalignanciesePatients with r/r hematological malignanciesDose Level 1Dose Level 2Dose Level 3Dose Level nRegister in specific hematological malignancies single agent or as part of combination regimen AML/MDST-Cell Malignancies Expand into earlier lines of therapyMMDLBCLEP300Explore combinations with SoCPhase 1a Dose EscalationDose Expansion/Explore CombinationsRegistration
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Selective CBP Degrader, FHT-171For EP300-mutant and CBP-dependent Cancers32
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| Summary: Selective CBP Degrader for CBP-dependent & EP300-mutant Cancers 33 •CREB binding protein (CBP) •Targeted protein degrader Gynecological cancers1Othercancers2Bladder cancerER+ breast cancerTarget / Approach•Preclinical Stage•Highly selective and potent •Increased tolerability relative to non-selective compounds•Long-acting formulation•Compelling combination potential Asset DescriptionInitial Opportunity (U.S.)Incidence*EP300 mut. FrequencyEP300 mut. Incidence105K 8%8.4K84K 10%8.4K349K 6%21K210K NA NA*Per year incidence in the U.S.. Source: Clarivate DRG Mature Markets Data; 1Endometrial, Cervical, and Ovarian Cancers; 2Gastric, CRC, NSCLC**CBP-dependent cancers do not exploit synthetic lethal relationships in paralogs EP300 mut.CancersCBP-dependent Cancers**Incidence*Key Differentiation
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| FHT-171 Reduces ER Levels in Wildtype ESR1 Breast Cancer Cell Lines T47D and CAMA1 FHT-171 degradation of CBP disrupts and suppresses ER signaling in a potentially ESR1 mutation agnostic manner FHT-171 Disrupts Estrogen Receptor (ER) Signaling in Breast Cancer 340.00.51.01.5Day 7Day 14Day 210.00.51.01.5Day 7Day 14Day 21ER levels normalized to DMSO control HALLMARK_ESTROGEN_RESPONSE_LATEHALLMARK_ESTROGEN_RESPONSE_EARLYHALLMARK_ESTROGEN_RESPONSE_LATEHALLMARK_ESTROGEN_RESPONSE_EARLYFHT-171FulvestrantFHT-171 Suppresses ER Target Genes, Comparable to FulvestrantNES = Normalized Enrichment ScoreA negative NES score means genes are suppressedSet of Estrogen Controlled GenesSet of Estrogen Controlled GenesT47DCAMA1
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| FHT-171 Demonstrates Anti-tumor Efficacy as a Monotherapy in Standard-of-care Resistant ER+ Breast Cancer ModelsER+ Metastatic Breast Cancer CDX (ST941C; ESR1m) ER+ Metastatic Breast Cancer PDX (ST4887B, ESR1 wt)ER+ Metastatic Breast Cancer PDX (ST4680D, ESR1m) 35 Tumor Volume (mm3) +/- SEM *Data were generated as part of a Mouse Clinical Trial executed by Xenostart. PDX models are from patients who have progressed from endocrine and CDK4/6 inhibitor therapies.020 4002004006008001000Days on treatment Untreated controlFHT-171, 10mg/kg QD, s.c.0 510 1502505007501000Days on treatmentTumor Volume (mm3) +/- SEMUntreated controlFHT-171, 10mg/kg QD, s.c.%TGI with 10mpk FHT-171Patient SegmentAdditional PDX Models60%ER fusionST3164B47%ESR1 WTST540039%ESR1 WTST3932
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| FHT-171 Shows No Impact on Platelet Counts and Spared Megakaryocytes• CBPPlatelet Counts Post Two Weeks of Dosing (In Vivo – Control Mice)Human Megakaryocyte Cell Viability Assay (In Vitro**) *CCS1477 (Inobrodib) inhibition study used 3 weeks of dosingPlatelet counts are unaffected by selective CBP degrader in in vivomodels**Human megakaryocytes derivedfrom primary human hematopoietic stem cells 36PLT (x109cells/L)05001,0001,5002,0002,500Study Day 14Platelets (X103 cells/uL)VehicleFHT-171, 10mg/kg, SC, QDDual BD inhibitor, (GNE-781), 30mg/kg, PO, BIDFHT-171Dual CBP/EP300Bromodomain InhibitorsVehicleDual BD inhibitor (CCS1477, Inobrodib), 20mg/kg, PO, QDGNE-781Inobrodib *
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| FHT-171: Potent and Selective CBP Degrader• CBPGlobal Proteomics Confirms that FHT-171 is Selective 37 FHT-171 Rapidly and Potently Degrades CBP, but not its Paralog EP300Dmax: 97%Max Rate: 3.2 hr-1DC50: 30pMDmax: 5%Max Rate: N/A 100nM CBPd-171/DMSO 3hr Log2FC FHT-171 CBP Kinetics FHT-171 EP300 Kinetics
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| Selective CBP Degradation Results in Significant Anti-Tumor Activity in EP300-mutant Solid Tumor ModelsEP300mut Bladder Cancer CDX (639V)EP300mut Gastric Cancer CDX (AGS)EP300mut Gastric Cancer PDX (ST020326) Tumor Volume (mm³+ SEM) Body Weight Change (%) 20 30 40 50 6005001,0001,500VehicleFHT-CBPd-59, 10mg/kg (QD)FHT-CBPd-59, 3mg/kg (QD)FHT-CBPd-59, 1mg/kg (QD)FHT-CBPd-59, 0.3mg/kg (QD)FHT-CBPd-59, 0.1mg/kg (QD) Tumor Volume (mm3± SEM) Body weight change (%)Fold Selectivity>20x>10000xEP3000.15 uM30uMCBP0.005 uM0.0024uMDegrader SelectivityFHT-CBPd-59 DC50 @24hFHT-CBPd-41 DC50@24h38
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| Long-Acting Injectable Formulation of CBPd-171 Enables Weekly Sub-cutaneous (SC) Delivery 39 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 AGS (gastric) model•We observe robust, dose-dependent CBP degradation across tumor models in PK/PD studies•LAI characterization in additional pharmacology studies planned to refine human dose predictions Tumor Volume (mm³+ SEM)
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| 40 Development Vision: CBP Degrader has the Potential to be an Attractive Combination Partner in ER+ Breast Cancer and BeyondPhase 1b Dose Expansion / CombinationER+ BC patients who failed at least 2L in advanced / metastatic settingIn parallel, explore combosDose Level 1Dose Level 2Dose Level 3Dose Level nExpansion cohorts based on Ph1aAdvance selected combinations into registrational studiesExpanding to earlier lines of therapy Additional combinations to enable future label expansion Endocrine Therapy:FulvestrantElacestrantTamoxifenCDK4/6: AbemaciclibPalbociclibRibociclibCBPdPhase 1a Dose EscalationRegistration
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Selective ARID1B DegraderFor ARID1A-mutant Cancers41
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| ARID1B is a Major Synthetic Lethal Target with Potential in Up To 5% of All Solid Tumors 42 •ARID1B•Targeted protein degrader Endometrial cancersGastric cancersBladder cancerNon-small cell lung cancer•Preclinical•Multiple ARID1B binders with nMaffinity and selectivity•Selective ARID1B degradationAsset DescriptionInitial Opportunity (U.S.)Incidence*ARID1A mut. FrequencyARID1A mut. Incidence66K 38%25K37K 20%7K84K 24%20K195K 7%14K*Per year incidence in the U.S.. Source: Clarivate DRG Mature Markets Data. Target / ApproachStageKey Differentiation
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| 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 ARID1A43 ARID1A/BBAFNucleosomePDB ID: 6LTJ•Discover binders to ARID1B•Use binders to develop bifunctional degradersDrug Targeting ConsiderationsApproach
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| Maximum Optionality Achieved Through Progression of Both Cereblon and VHL-based Degraders in Parallel 44 CEREBLON VHL FHT-654: DC50: 0.35 uMDC50: 3.7 uMARID1B-HiBiT HCT116 Colorectal Cell Line
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| Selective ARID1B Degradation Demonstrated by Global Proteomics 45 FHT-654 Cereblon-based Degrader ARID1A Log2FC ARID1B degrader 2.5uM/DMSO 24 hrARID1B-HiBiT HCT116
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| FHT-654 Modulates ARID1B Target Gene Expression in HCT-116 Colorectal ARID1A-/-CellsDMSO63 nM125 nM250 nM500 nM1000 nM63 nM125 nM250 nM500 nM1000 nM Relative expressionDMSO63 nM125 nM250 nM500 nM1000 nM63 nM125 nM250 nM500 nM1000 nM Relative expressionDMSO63 nM125 nM250 nM500 nM1000 nM63 nM125 nM250 nM500 nM1000 nM Relative expressionARID1B 48hProtein expressionDownregulatedGene 48h UpregulatedGene 48h FHT-654Ligase DeadFHT-654Ligase DeadFHT-654Ligase DeadLigase dead control has no effect on protein levels and no effect on either of these two genes demonstrating the on-target nature of ARID1B target gene expression46
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| Developing First-in-Class Precision Medicines Targeting Major Unmet Needs in Cancer 47Large Market PotentialChromatin biology is implicated in up to 50% of tumors, potentially impacting ~2.5 million patientsFoghorn’s current pipeline potentially addresses more than 500,000of these patientsBroad pipeline across a range of targets and small molecule modalitiesMajor Strategic CollaborationStrategic collaboration with Lilly; $380 million upfront; 50/50 U.S. economic split on two lead programsWell-Funded$167.6 millionin cash and equivalents(as of 06/30/2026)Cash runway into first half of 2028Shares outstanding: approximately 70.6M*(as of 06/30/2026)Value DriversSelective SMARCA2 Inhibitor, FHD-909, partnered with Lilly, in Phase 1 trialAdvancing Selective EP300 and Selective CBP degraders towards INDsAccelerating novel oral small molecule in Immunology & Inflammation towards INDProtein degrader platform with expansion into induced proximityLeader in Unique Area of Cancer BiologyFoghorn is a leader in targeting chromatin biology,which has the potential to address underlying dependencies of many genetically defined cancersPlatformwith initial focus in oncology, therapeutic area expansion potential *Includes pre-funded warrants.
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Unique biologyPrecision therapeuticsBroad impact48 August 2026
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Appendix49
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SMARCA2 Program50
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| FHD-909 Monotherapy Demonstrated Regression In Vivo in NCI-H2126 SMARCA4-mutant NSCLC Model at Tolerated Doses 51 NCI-H2126 Reduction in Tumor VolumeNCI-H2126 Body Weight Genetic Background: SMARCA4 W764R, TP53 E62*, STK11-/-, CDKN2A-/-, KEAP1 R272CNote: All doses were well tolerated. Dosing holidays were applied at the high dose, as appropriate. Tumor volume (mm3) Tumor Volume (mm3)
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| FHD-909 Monotherapy Demonstrated Strong In VivoActivity Across SMARCA4-mutant NSCLC Models at Tolerated Doses 52 0 714 21 28100200300400500Days of Dosing (Dose Start Day1) Vehicle ControlFHD-909, 20mg/kg, BID, POFHD-909, 40mg/kg, BID, POFHD-909, 60mg/kg, BID, POA549 ModelRERF-LC-AI ModelNCI-H1793 ModelGenetic Background: SMARCA4, Q729fs / H736Y, KRAS G12S, STK11-/-, CDKN2A-/-, KEAP1 G333CGenetic Background: SMARCA4 mut p.E1496*, TP53 p.Q104*, NF1 p.E1699*Genetic Background: SMARCA4, E514*, TP53 R209* R273H, ARID1A C884* Note: All doses were well tolerated. Dosing holidays were applied to the 60 mg/kg dose groups, as appropriate.
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| FHD-909 in Combination with Standard Therapies Demonstrates Significant Activity in the A549 (SMARCA4-mutant, KRAS G12S) Xenograft NSCLC Model 53 0 714 21 2820040060080010001200 Days of Dosing (Dose Start Day 1)Tumor volume (mm3) ******##Note: *p≤0.05 for pairwise comparisons for combination group vs vehicle and single agent groups and all treatment groups vs vehicle control,# additive by Bliss Independence analysis. Dosing holidays were applied to the 60mg/kg FHD-909 dose groups as appropriate. FHD-909 + cisplatin + pemetrexedA549 (SMARCA4mt, KRAS G12S)In vivo, combining FHD-909 with cisplatin and pemetrexed increased antitumor effect, resulting in tumor regressionAdditivity and synergy were also observed in vitro when FHD-909 was combined with cisplatin or pemetrexed
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| FHD-909 in Combination with Standard Therapies Demonstrates Significant Activity in the RERF-LC-AI (SMARCA4-mutant) Xenograft NSCLC Model 540 714 21 28200400600800100012001400 Days of Dosing (Dose Start Day 1)Tumor Volume (mm3) ******##Note:*p≤0.05 for pairwise comparisons for combination group vs vehicle and single agent groups and all treatment groups vs vehicle control, # additive by Bliss Independence analysis. In vivo, combining FHD-909 with cisplatin and paclitaxel increased antitumor effect, resulting in tumor regressionAdditivity and synergy were also observed in vitro when FHD-909 was combined with cisplatin or paclitaxel FHD-909 + cisplatin + paclitaxelRERF-LC-AI (SMARCA4mt)
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| Synergistic Activity Observed for FHD-909 in Combination with KRAS Inhibitors In Vitro 55 Inhibition (%) Inhibition (%) FHD-909+ olomorasib(KRAS G12C inhibitor)FHD-909+ pan-KRAS inhibitor Inhibition (%) Inhibition (%) 110 100 1000 10000-20020406080100120FHD-909 concentration (nM) DMSO7142856113225450900[LY4066434](nM) Inhibition (%) NCI-H2030, Lung, NSCLCSMARCA4-/- KRAS(G12C) PATU-8988T, Pancreas, PDACSMARCA4 - / fusion, KRAS(G12D)*SNU-407, Colon, CRCSMARCA4 P109fs194, R466C, Y507H, M1109V, KRAS(G12D) A549, Lung, NSCLCSMARCA4 Q729fs/H736Y, KRAS(G12S)PATU-8988T, Pancreas, PDACSMARCA4 - / fusion, KRAS(G12V)Note: FHD-909 is reported in unbound concentrations in the assays; *CRISPR KI, fs frameshiftFHD-909+ LY3962673(KRAS G12D inhibitor)FHD-909+ LY4066434(pan-KRAS inhibitor)FHD-909+ LY3962673(KRAS G12D inhibitor)FHD-909+ LY4066434(pan-KRAS inhibitor)NCI-H2030, Lung, NSCLCSMARCA4-/- KRAS(G12C)
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| Combination of FHD-909 with KRAS Inhibitors Demonstrates Synergistic Activity in SMARCA4, KRAS Co-mutated Human NSCLC Xenograft Models In VivoFHD-909 + olomorasib (KRAS G12C inh)NCI-H2030 (SMARCA4mt, KRAS G12C) 56 0 714 21 28050010001500200025003000 Days of Dosing (Dose Start Day1)Tumor Volume (mm3)##synergistic (p<0.05)***##Combination of FHD-909 with olomorasibdemonstrated synergistic antitumor activity and sustained tumor regression in vivo Note: Olomorasib – LY3537982; * p≤0.05 for pairwise comparisons for combination group vs vehicle and single agent groups and all treatment groups vs vehicle control, ## synergistic by Bliss Independence analysis.
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| Combination of FHD-909 with KRAS Inhibitors Demonstrates Synergistic Activity in SMARCA4, KRAS Co-mutated Human NSCLC Xenograft Models In VivoFHD-909 + pan-KRAS inhA549 (SMARCA4mt, KRAS G12S) 57Combination of FHD-909 with pan-KRAS inhibitor resulted in synergistic antitumor activity and sustained tumor regression in vivoNote: pan-KRAS inhibitor - LY4066434; * p≤0.05 for pairwise comparisons for combination group vs vehicle and single agent groups and all treatment groups vs vehicle control, ## synergistic by Bliss Independence analysis.
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| FHD-909 in Combination with Pembrolizumab Shows Significantly Enhanced Anti-Tumor Activity in A549 CD34+ HSC Humanized Xenograft NSCLC Model 58 FHD-909 sensitized the tumor cells to pembrolizumab treatment resulting in enhanced combination activityPembrolizumab alone had no effect on tumor growth compared to vehicle controlNote:HSC, hematopoietic stem cells; * p≤0.05 for pairwise comparisons for combination group vs vehicle and single agents; # additive, ## synergistic by Bliss Independence analysis. FHD-909 (20 mg/kg) + pembrolizumabA549 (SMARCA4mt, KRAS G12S)FHD-909 (40 mg/kg) + pembrolizumabA549 (SMARCA4mt, KRAS G12S)
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| Selective SMARCA2 Degrader Achieved Complete SMARCA2 Degradation and Cell Growth Inhibition In Vitro 59Degraders Caused Time- and Dose-dependent SMARCA2 Degradation Antiproliferative Effects in A549-mutant NSCLC Model A549 Ten-Day Proliferation AssaySMARCA2 / SMARCA4 HIBIT Data SMARCA2SMARCA4 % DegradationConcentration (uM)02550751001E-3 0.01 0.1 1 10Note: Data as of Q4 2021.
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Protein DegradationImportance of Rate Analysis FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex60
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| Degradation Rates and Their Relationship to Dmax 61•Slower rates lead to partial degradation, faster rates to complete loss•Rate is an indicator of degrader efficiency. If rate is slow, the process is inefficient and reflective of a degrader which does not have a high turnover rate of targetNative Deg RateTarget LevelTimeDmax10Dmax25Dmax50Dmax80Dmax95 ExperimentalRate vs. Dmax ExperimentalKinetic ProfileTheoreticalKinetic ProfileFractional Loss
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| Degradation Rate Dictates Dmax – Program Independent 62 Foghorn CBP ProgramFoghorn BRD9 ProgramFoghorn EP300 Program Large scale experimental kinetic analysis for a program reveals the relationship between rate and Dmax
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| Prelude VHL and CRBN Compounds Have Incomplete Dmax and also Have a Hook Effect 63•Prelude’s SMARCA2 (VHL) degrader was faster and achieved improved Dmax across concentrations as compared to SMARCA2 (CRBN)•The SMARCA2 (CRBN) degrader is considerably slower and therefore even at high concentration will be incomplete•Both degraders show a bifunctional hook effect which slows rate and impedes Dmax at high concentrations Prelude SMARCA2 (CRBN) DegraderPrelude SMARCA2 (VHL) Degrader Fractional Luminescence(RLU) Concentration Fractional Luminescence(RLU) ConcentrationHook EffectHook EffectRate max (ƛ) hr-1: 0.4Rate max (ƛ) hr-1: 1.5Fractional Loss Fractional Loss
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| Foghorn Analysis and Dmax Results Match Published Prelude Data 64 Prelude Published Data Prelude PRT3789 (VHL) 1Prelude PRT7732 (CRBN) 2 % Protein Prelude (CRBN) DegraderPrelude (VHL) DegraderFoghorn Replicated Data from Prelude Patents 1. AACR-NCI-EORTC 2023 Poster B113 – Ito et al.2. AACR 2024 Poster 4503 -Shvartsbart et al. % Degradation % Degradation