UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): April 9, 2024
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(Exact name of registrant as specified in its charter)
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(Registrant’s telephone number, including area code): (617 ) 586-3100
Not Applicable
(Former name or former address, if changed since last report)
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |||||
| Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |||||
| Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |||||
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) | |||||
Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01 Regulation FD Disclosure.
On April 9, 2024, Foghorn Therapeutics Inc. (the “Company”) is hosting a conference call and webcast to review pipeline updates presented at the 2024 American Association for Cancer Research (“AACR”) Annual Meeting. A copy of the presentation from the conference call and webcast is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
Additionally, the Company is furnishing as Exhibit 99.2 to this Current Report on Form 8-K a presentation, dated April 2024, which the Company intends to use in meetings with or presentations to investors.
The information in this Item 7.01 (including Exhibits 99.1 and 99.2 attached hereto) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any filing by the Company under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
On April 9, 2024, the Company issued a press release announcing preclinical data for multiple programs from various poster presentations at the AACR 2024 Annual Meeting, including BRM selective inhibitor FHD-909, selective CBP degrader and selective EP300 degrader programs.
A copy of the Company’s press release is attached hereto as Exhibit 99.3 and is incorporated herein by reference.
Forward-Looking Statements
This Current Report on Form 8-K contains “forward-looking statements.” Forward-looking statements include statements regarding the Company’s clinical trials, product candidates and research efforts and other statements identified by words such as “could,” “may,” “might,” “will,” “likely,” “anticipates,” “intends,” “plans,” “seeks,” “believes,” “estimates,” “expects,” “continues,” “projects” and similar references to future periods. Forward-looking statements are based on our current expectations and assumptions regarding capital market conditions, our business, the economy and other future conditions. Because forward-looking statements relate to the future, by their nature, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. As a result, actual results may differ materially from those contemplated by the forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include regional, national or global political, economic, business, competitive, market and regulatory conditions, including risks relating to our clinical trials and other factors set forth under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission. Any forward-looking statement made in this Current Report speaks only as of the date on which it is made.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. | Description | ||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
FOGHORN THERAPEUTICS INC. | |||||||||||
| By: | /s/ Michael LaCascia | ||||||||||
| Michael J. LaCascia | |||||||||||
| Chief Legal Officer | |||||||||||
April 9, 2024 Unique biology Precision therapeutics Broad impact 2024 AACR and Pipeline Update Exhibit 99.1
| 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,” “might,” “will,” “likely,” “anticipates,” “intends,” “plans,” “seeks,” “believes,” “estimates,” “expects,” “continues,” “projects” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning: the potential outcomes from our collaboration agreements with Lilly; the initiation, timing, progress and results of our research and development programs and pre-clinical studies and clinical trials, including with respect to our Phase 1 study of FHD-286 in combination with decitabine or cytarabine in relapsed and/or refractory AML patients and anticipated timing of release of clinical data, the planned Phase 1 dose escalation study of FHD-909 with Loxo@Lilly and the status of our selective CBP and EP 300 degrader programs; our ability to advance product candidates that we may develop and to successfully complete preclinical and clinical studies; our ability to leverage our initial programs to develop additional product candidates using our Gene Traffic Control Platform; the impact of exogeneous factors, including macroeconomic and geopolitical circumstances, on our and our collaborators’ business operations, including our research and development programs and pre-clinical studies; developments related to our competitors and our industry; our ability to expand the target populations of our programs and the availability of patients for clinical testing; our ability to obtain regulatory approval for FHD-286 and any future product candidates from the FDA and other regulatory authorities; our ability to identify and enter into future license agreements and collaborations; our ability to continue to rely on our 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 and enforce for intellectual property rights covering FHD-286, our future products and our Gene Traffic Control Platform; and our use of proceeds from capital-raising transactions, estimates of our expenses, capital requirements, and needs for additional financing. Any forward-looking statements represent the Company’s views only as of today and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements. The Company’s business is subject to substantial risks and uncertainties.
| 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
| 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 help turn specific genes "on" or "off" by working in concert with the chromatin remodeling complex to bind to DNA Helicases & Other Chromatin Binding Proteins involved in gene expression / function Gene expression in the right cells at the right time is critical for normal growth, development, and homeostasis
| 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 impacting ~2.5 million patients Historically difficult to target chromatin regulatory system with drug discovery efforts • BAF complex offers limited options to disrupt enzymatic activity • Similarity among various proteins makes selective inhibition and/or degradation challenging
| 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 Partnered Program Undisclosed Disease BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Relapsed/Refractory AML Selective BRM BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Selective ARID1B ARID1A mutant cancers (~5% of all solid tumors) Selective CBP EP300 mutant cancers (e.g., ~5-10% of bladder, gastric, breast, NSCLC, colorectal) Selective EP300 EP300 dependent cancers (e.g., prostate, DLBCL), CBP mutant cancers (e.g., ~9-10% of NSCLC, bladder, melanoma) Undisclosed Undisclosed Undisclosed
| 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 BRM BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Selective ARID1B ARID1A mutant cancers (~5% of all solid tumors) Undisclosed Undisclosed Undisclosed Key Updates and Upcoming Milestones for These Programs are the Focus for Today’s Call FHD-286 (BRG1/BRM) FHD-909 (Selective BRM) BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Relapsed/Refractory AML Selective CBP EP300 mutant cancers (e.g., ~5-10% of bladder, gastric, breast, NSCLC, colorectal) Selective EP300 EP300 dependent cancers (e.g., prostate, DLBCL), CBP mutant cancers (e.g., ~9-10% of NSCLC, bladder, melanoma)
| 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 Dr. Alfonso Quintás-Cardama Chief Medical Officer • FHD-909 preclinical data demonstrates strong efficacy, with promising safety profile, across multiple xenograft models • Selective CBP and Selective EP300 degrader programs active against multiple tumor cell lines and in xenograft models Dr. Steve Bellon, PhD Chief Scientific Officer
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
| 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 maintenance of a leukemic phenotype
| 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 21.4x 85 (90%) 7.5mg RUNX1, KRAS, ASXL, JAK2, TET2, EZH2, ETNK 5 15x 95 (81%) 7.5mg N/A 8 6.3x 94 (65%) 7.5mg ASXL1, TP53, U2AF1 19 3.3x 92 (45%) 5mg RUNX1, NRAS, KRAS, SF3B1, ASXL2, CSF3R, GATA2 3 29x 94 (80%) 5mg RUNX1, NRAS, ASLX1 4 22.8x 98 (93%) 5mg N/A 6 13x 93 (88%) 5mg TET2, WT1 GATA2 PLCG2 ARHGEF28, BRD4, CDK12, DDX41, KMT20, PARP1, ZRSR2 3 8.1x 86 (27%) 5mg N/A 4 6.5x 93 (29%) 5mg DNMT3a, TET2 21 4.1x 30 (88%) 2.5mg NRAS, WT1 3 4.8x 93 (4%) CD11b (marker of differentiation) increases CD34 (leukemic stem cell marker) decreases FHD 286 significantly reduced leukemic burden, and promoted recovery of normal blood cell counts Activity observed irrespective of cytogenetic and mutational background profiles
| 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) 1 mg/kg decitabine (n=7) 1.5 mg/kg FHD-286 (n=7) Vehicle (n=7)6 weeks Rx ✱ ✱ ✱ ✱ ✱ FHD 286 used in combination significantly prolonged survival compared to decitabine and a menin inhibitor alone • The combination of FHD-286 with standard AML therapeutic provided greater reduction in leukemic burden than FHD-286 alone • These results, coupled with clinical results with FHD- 286 as monotherapy, provide a basis for clinical evaluation of FHD-286 with multiple combinations in R/R AML • Combinations with experimental agents (e.g., menin, BET inhibitors) were tested with similar results, suggesting FHD-286’s broad combination potential 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 QD + Decitabine Potential Next Steps: FHD-286 + Decitabine Expansion FHD-286 + Other Agent Escalation Subjects on an antifungal agent classified as a strong CYP3A4 inhibitor Subjects NOT on an antifungal agent classified as a strong CYP3A4 inhibitor Parallel Dose Escalations Potential additional escalations Potential additional escalations Escalation ongoing and enrolling well Data anticipated in H2’24
| 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 have no actionable mutations • No meaningful developments for the broad AML patient population since the approval of Venetoclax • Recent development has focused predominantly on AML subsets harboring actionable mutations – FLT3, IDH1/2, and MLL** ̽ Source: Decision Resources Group 2025 Forecast: **Menin inhibitors not yet approved; R/R: relapsed/refractory; CRc: composite complete response • Post Ven/Aza, treatment options are limited – CRc rates 15-17% • Mortality remains high for this population, mOS ~3mo • Patients with actionable mutations who relapse post targeted therapy have high unmet need Initial FHD-286 Opportunity ~17,000 Drug Treatable R/R Patients* FHD-286 could provide a meaningful opportunity to improve outcomes in the R/R setting. We believe there is an additional opportunity in the newly diagnosed setting.
| 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
| 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 BRMiBRG1 Precision medicine targeting synthetic lethal relationships is a proven clinical approach now used in multiple cancers (e.g., PARP inhibitors)
| 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
| 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% RET 4% MET 7% 1. Alessi JV, et al., 2021; 2. TCGA via cBioPortal
AACR Data • FHD-909 – Selective BRM Inhibitor • Selective CBP Degrader • Selective EP300 Degrader Research Update Dr. Steve Bellon, PhD Chief Scientific Officer
| 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 Across 17 BRG1 (SMARCA4) Mutant and Wild-Type Cell Lines 20 Spread in potency for wild type versus mutant cell lines indicates 33-fold selectivity Selectivity = 33x Median IC50 (µM) BRG1 WT 0.0932 BRG1 MUT 0.0028
| 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 appropriate 0 7 14 21 28 100 150 200 250 300 350 Days of Dosing (Dose Start Day1) Tu m or v ol um e (m m 3 ) Vehicle Control FHD-909, 20mg/kg, PO, BID FHD-909, 40mg/kg, PO, BID FHD-909, 60mg/kg, PO, BID 0 7 14 21 28 80 90 100 110 120 Days of Dosing (Dose Start Day1) B od y W ei gh t ( % o f S ta rt in g W ei gh t)
| 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 Start Day1) Tu m or V ol um e (m m 3 ) Vehicle Control FHD-909 20mg/kg, BID, PO FHD-909, 40mg/kg, BID, PO FHD-909, 60mg/kg, BID, PO 0 7 14 21 28 0 250 500 750 1000 1250 1500 Days of Dosing (Dose Start Day1) Tu m or V ol um e (m m 3 ) Vehicle Control 20mg/kg LY4050784, PO, BID 40mg/kg LY4050784, PO, BID BRG1 Q729fs / H736Y, KRAS G12S, STK11-/-, CDKN2A-/-, KEAP1 G333C BRG1 mut p.E1496*, TP53 p.Q104*, NF1 p.E1699* Genetic Background Genetic Background
| 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: All doses were well tolerated. Dosing holidays were applied at the high dose, as appropriate 0 7 14 21 28 100 200 300 400 500 Days of Dosing (Dose Start Day1) Tu m or V ol um e (m m 3 ) Vehicle Control FHD-909, 20mg/kg, BID, PO FHD-909, 40mg/kg, BID, PO FHD-909, 60mg/kg, BID, PO BRG1 E514*, TP53 R209* R273H, ARID1A C884*Genetic Background:
| 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 Foghorn is working on two separate programs, each with their own defined dependencies and patient populations
| 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 Inoculation Tu m or V ol um e (m m ³+ S EM ) Vehicle (BID) FHT-CBPd - 9, 3 mg/kg (BID) FHT-CBPd - 9, 10 mg/kg (QD) 5 10 15 20 25 30 0 500 1,000 1,500 2,000 2,500 Days After Tumor Inoculation Tu m or V ol um e (m m ³ + S EM ) Vehicle Control FHT-CBPd - 8, 50mg/kg (BID) FHT-CBPd - 8, 20mg/kg, (BID) 20 30 40 50 60 0 500 1,000 1,500 Days After Tumor Inoculation Tu m or V ol um e (m m ³ + S EM ) Vehicle (BID) FHT-CBPd - 9, 10mg/kg (QD) FHT-CBPd - 9, 3mg/kg (QD) FHT-CBPd - 9, 1mg/kg (QD) FHT-CBPd - 9, 0.3mg/kg (QD) FHT-CBPd - 9, 0.1mg/kg (QD) Efficacy was observed at doses that had no significant impact on weight; IND-enabling studies are planned to start by the end of 2024
| 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, sc, QD Dual BD inhibitor, 30mg/kg, p.o, BID FHT-CBPd Dual CBP/EP300 Inhibitor Vehicle Dual CBP / EP300 InhibitorControl Rat Control dCBP-9 10mg/kg QD Mouse Hypocellularity Megakaryocyte Sparing
| 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 Post Dose C BP L ev el s / % Ve hi cl e Plasm a PK (ng/m L) CBP Levels - PDPlasma PK (ng/ml) 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 Post Dose C B P Le ve ls / % Ve hi cl e Plasm a PK (ng/m L) CBP Levels - PDPlasma PK (ng/ml) 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 Post Dose C B P Le ve ls / % Ve hi cl e Plasm a PK (ng/m L) CBP Levels - PDPlasma PK (ng/ml)
| 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 FHT-EP300d, 50mg/kg, BID 5 10 15 20 25 30 35 40 45 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 FHT-EP300d, 50mg/kg (BID) FHT-EP300d, 20mg/kg, (BID) FHT-EP300d, 10mg/kg, (BID) In vivo efficacy in both EP300 dependent and CBP null models (e.g., synthetic lethality) suggests potential broad applicability across cancers DLBCL KARPAS422 (CBP Null) Model
| 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-EP300d Dual CBP/EP300 Inhibitor Vehicle
Closing Remarks Adrian Gottschalk President and CEO
| 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 Strategic Collaboration Strategic collaboration with Loxo@Lilly; $380 million upfront; 50/50 U.S. economic split on two lead programs Well- Funded $234.1 million in cash and equivalents (as of 12/31/2023) Provides runway into H1’26 Value Drivers Anticipate data from the Phase 1 study of FHD-286 in combination with decitabine in H2’24 BRM Selective Inhibitor (FHD-909), partnered with Loxo@Lilly, anticipating IND filing in Q2’24 Advancement of preclinical assets (BRM Selective Degrader, CBP, EP300, ARID1B) towards INDs 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 Broad pipeline across a range of targets and modalities
Question & Answers
April 2024 Unique biology Precision therapeutics Broad impact Exhibit 99.2
| 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,” “might,” “will,” “likely,” “anticipates,” “intends,” “plans,” “seeks,” “believes,” “estimates,” “expects,” “continues,” “projects” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning: the potential outcomes from our collaboration agreements with Lilly; the initiation, timing, progress and results of our research and development programs and pre-clinical studies and clinical trials, including with respect to our Phase 1 study of FHD-286 in combination with decitabine or cytarabine in relapsed and/or refractory AML patients and anticipated timing of release of clinical data, and the planned Phase 1 dose escalation study of FHD-909 with Loxo@Lilly; our ability to advance product candidates that we may develop and to successfully complete preclinical and clinical studies; our ability to leverage our initial programs to develop additional product candidates using our Gene Traffic Control Platform; the impact of exogeneous factors, including macroeconomic and geopolitical circumstances, on our and our collaborators’ business operations, including our research and development programs and pre-clinical studies; developments related to our competitors and our industry; our ability to expand the target populations of our programs and the availability of patients for clinical testing; our ability to obtain regulatory approval for FHD-286 and any future product candidates from the FDA and other regulatory authorities; our ability to identify and enter into future license agreements and collaborations; our ability to continue to rely on our 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 and enforce for intellectual property rights covering FHD-286, our future products and our Gene Traffic Control Platform; and our use of proceeds from capital-raising transactions, estimates of our expenses, capital requirements, and needs for additional financing. Any forward-looking statements represent the Company’s views only as of today and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements. The Company’s business is subject to substantial risks and uncertainties.
| First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer 3 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 Strategic Collaboration Strategic collaboration with Loxo@Lilly; $380 million upfront; 50/50 U.S. economic split on two lead programs Well- Funded $234.1 million in cash and equivalents (as of 12/31/2023) Provides runway into H1’26 Value Drivers Anticipate data from the Phase 1 study of FHD-286 in combination with decitabine in H2’24 BRM Selective Inhibitor (FHD-909), partnered with Loxo@Lilly, anticipating IND filing in Q2’24 Advancement of preclinical assets (BRM Selective Degrader, CBP, EP300, ARID1B) towards INDs 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 Broad pipeline across a range of targets and modalities
| Unique Insights into Chromatin Biology to Prosecute Untapped Area for Novel Targets and Therapeutics 4 Novel Targets Guided by Genetic Dependencies Tailored Drugging Approaches Transcription Factor Mutations / Overexpression Chromatin Remodeling Complex Mutations / Overexpression Helicases & Other Chromatin Binding Proteins involved in gene expression / function Enzymatic Inhibitors Highly selective and allosteric small molecule inhibitors Transcription Factor Disruptors Disrupt interactions between chromatin remodeling complexes and transcription factors Potential druggable sites ATP ADP Chromatin Regulatory System Critical for Gene Expression Targeted Protein Degradation Molecular glue and bi-functional protein degraders 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 help turn specific genes "on" or "off" by working in concert with the chromatin remodeling complex to bind to DNA
| Foghorn’s Validated Gene Traffic Control© Platform Enables an Integrated, Scalable, Efficient and Repeatable Paradigm 5 Deep mechanistic understanding of the chromatin regulatory system Biology first, small molecule modality agnostic Targeting Disease Selective Therapeutics What to Drug: Identify disease dependencies with novel targets How to Drug: Small molecules, degrader and delivery platform Biochemistry, biophysics and assays of large complexes and proteins Specialized Approach Where to Drug: Engineer selectivity via unique assays and protein capabilities Transcription Factor Disruptors Enzymatic Inhibitors Targeted Protein Degraders
| 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 Partnered Program Undisclosed Disease BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Relapsed/Refractory AML Selective BRM BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Selective ARID1B ARID1A mutant cancers (~5% of all solid tumors) Selective CBP EP300 mutant cancers (e.g., ~5-10% of bladder, gastric, breast, NSCLC, colorectal) Selective EP300 EP300 dependent cancers (e.g., prostate, DLBCL), CBP mutant cancers (e.g., ~9-10% of NSCLC, bladder, melanoma) Undisclosed Undisclosed Undisclosed
FHD-286: Dual BRM/BRG1 Inhibition Targeting BAF Dependency in Cancer FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex
| Exploring BAF Dependency in Cancer with FHD-286 – Potent, Small Molecule Inhibitor Targeting BRM and BRG1 8 Clinical and pre-clinical data demonstrate broad- based differentiation across AML and multiple solid tumors BAF ATPase: BRG1/BRM FHD-286: • Allosteric modulation inhibiting the activity of both BRM and BRG1 • Oral, daily, potent small molecule inhibitor FHD-286 Differentiation Pre-clinical data support ability to overcome drug resistance (i.e., EGFR NSCLC, enzalutamide- resistant CRPC, PD-1 refractory) Overcoming Drug Resistance Clinical data demonstrate an increase of CD8+ T- cells and a reduction of T-regulatory cells Immune Modulation Current and Potential Future Opportunity Pre-clinical data support ability to address BAF mutated cancers (e.g., BRG1 mutant)Mutations
| First-in-Class Broad-Based Differentiation Agent With Significant Combination Potential in AML 9 Completed Phase I Monotherapy Safety and Efficacy Results Ongoing Phase I Combination Study Efficacy • Differentiation observed in heavily pre-treated patients, regardless of mutational status • Multiple patients with bone marrow and peripheral blast improvements and associated ANC recovery Safety • Adverse event profile consistent with late-line AML population • Most frequent ≥ grade 3 TRAEs: increased blood bilirubin, hypocalcemia, differentiation syndrome (DS), stomatitis, increased ALT • Adjudicated Differentiation Syndrome rate of 15% • Phase I dose escalation study evaluating oral daily dosing of FHD-286 with fixed dose decitabine or cytarabine • Standard 3+3 dose escalation design • Data anticipated in H2’2024
| Significant Opportunity for Novel, Effective Therapy in Patients with R/R AML 10 • 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 have no actionable mutations • No meaningful developments for the broad AML patient population since the approval of Venetoclax • Recent development has focused predominantly on AML subsets harboring actionable mutations – FLT3, IDH1/2, and MLL** ̽ Source: Decision Resources Group 2025 Forecast: **Menin inhibitors not yet approved; R/R: relapsed/refractory; CRc: composite complete response • Post Ven/Aza, treatment options are limited – CRc rates 15-17% • Mortality remains high for this population, mOS ~3mo • Patients with actionable mutations who relapse post targeted therapy have high unmet need Initial FHD-286 Opportunity ~17,000 Drug Treatable R/R Patients* FHD-286 could provide a meaningful opportunity to improve outcomes in the R/R setting. We believe there is an additional opportunity in the newly diagnosed setting.
| Study Design for FHD-286 Phase 1 Multicenter Dose-Escalation in Combination with Decitabine in AML 11 Target Indication: • R/R AML Treatment Plan & Dose Escalation: • 3+3 escalation design • Oral FHD-286, QD, 28-day cycles • Standard decitabine dose schedule Key Objectives Primary • Safety/Tolerability • Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) determinations Secondary • Preliminary clinical activity • PK parameters of FHD-286 in combination with Decitabine in subjects on/off triazole antifungal agents classified as strong CYP3A4 inhibitors Exploratory • PD effects of FHD-286 in combination with Decitabine • MRD 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 QD + Decitabine Potential Next Steps: FHD-286 + Decitabine Expansion FHD-286 + Other Agent Escalation Subjects on a triazole antifungal agent classified as a strong CYP3A4 inhibitor Subjects NOT on a triazole antifungal agent classified as a strong CYP3A4 inhibitor Parallel Dose Escalations Potential additional escalations Potential additional escalations
| FHD-286 Demonstrated Differentiation Across a Broad Range of Genetic Backgrounds 12 Dose Level Mutations Cytogenetics Risk Starting CD11b% Max CD11b% CD11b+ Fold Change Starting CD34% Min CD34% CD34+ % Decrease 10mg N/A Adverse 7 62 9.2x 94 27 (71%) 7.5mg CBFB (locus at 16q22) 2 94 59.4x 70 2 (97%) 7.5mg KMT2A rearrangement Adverse 3 58 21.4x 85 9 (90%) 7.5mg RUNX1, KRAS, ASXL1, JAK2, TET2, EZH2, ETNK Adverse 5 73 15x 95 18 (81%) 7.5mg N/A Adverse 8 52 6.3x 94 33 (65%) 7.5mg ASXL1, TP53, U2AF1 Adverse 19 63 3.3x 92 51 (45%) 5mg RUNX1, NRAS, KRAS, SF3B1, ASXL2, CSF3R, GATA2 Adverse 3 74 29x 94 19 (80%) 5mg RUNX1, NRAS, ASLX1 Adverse 4 97 22.8x 98 7 (93%) 5mg N/A Adverse 6 79 13x 93 11 (88%) 5mg TET2, WT1 GATA2 PLCG2 ARHGEF28, BRD4, CDK12, DDX41, KMT20, PARP1, ZRSR2 3 24 8.1x 86 62 (27%) 5mg N/A Adverse 4 28 6.5x 93 66 (29%) 5mg DNMT3a, TET2 21 88 4.1x 30 4 (88%) 2.5mg NRAS, WT1 Adverse 3 13 4.8x 93 89 (4%) CD11b (marker of differentiation) increases CD34 (leukemic stem cell marker) decreases
| Bone Marrow Aspirate: Clear Evidence of Differentiation Bone Marrow Blast Reduction from 40% to 6% Clear Signs of Differentiation in Heavily Pre-Treated, Secondary AML Patient with Abnormal Karyotype 13 Patient Background: • 47-year-old male, secondary AML • Abnormal karyotype: Del (7Q), Inv (3), Der (7;12), -8, ADD(1) Prior AML Treatment: • Progressive disease: 4 lines prior treatment and 2 bone marrow transplants Prior non-AML treatment: • MDS with inv(3) and der(7;12) and ASXL1 mut. Received AZA x 4. Initiation of FHD-286 at 10 MG Dose: • Bone marrow blast from 40% to 6% with clear evidence of differentiation with persistence of cytogenetics abnormalities. ANC recovery.
| Absolute Neutrophil Count (ANC) Peripheral Blast Count Meaningful Clinical Benefit in Heavily Pre-Treated Patient 14 100% 0% 50% 10 5 10/13/21 10/24/21 11/4/21 11/14/21 11/25/21 12/6/21 0 Initiation of FHD 286 1st SCT 2nd SCT Patient Background: • 25-year-old male, treatment-related AML • KMT2A rearrangement Prior AML Treatment: • Progressive disease with CNS Leukemia: 7 lines prior treatment and 2 bone marrow transplants Prior non-AML treatment: • Ewing’s sarcoma: Treated with Chemo/RT/Surgery (VCR, doxo, cyclophos, ifos, etoposide) Initiation of FHD-286 at 10 MG Dose: • Drop in peripheral blast, 97% to 5% • Bone marrow reduction from 89% to 48%, with ANC recovery 5/23/19 11/22/19 5/22/20 5/23/2111/21/20 11/22/21 Initiation of FHD 286
| FHD-286 + decitabine (MLL-AFP + FLT3 TKD Luc/GFP PDX) Pre-Clinical Data Demonstrate Significant Combination Potential with Multiple Agents in AML 15 FHD-286 + BET inhibitor (mtNPM1 + FLT3 ITD Luc/GFP AML PDX) FHD-286 + menin inhibitor (mtNPM1 + FLT3 ITD Luc/GFP AML PDX) FHD-286 + cytarabine (MV4, 11 FLT3 ITD CDX) SNDX-5613: Menin inhibitor 0 20 40 60 0 25 50 75 100 Days, post-infusion % S ur vi va l FHD-286 + decitabine (n=8) 1 mg/kg decitabine (n=7) 1.5 mg/kg FHD-286 (n=7) Vehicle (n=7)6 weeks Rx ✱ ✱ ✱ ✱ ✱
Selective BRM Modulators For BRG1 Mutated Cancers FHD-286 is a Potent, Selective, Allosteric, Small Molecule Inhibitor of the BRG1 and BRM subunits of the BAF complex
| BRM Selective Inhibitor FHD-909 IND Targeted in Q2’24, BRM Selective Degrader Continues Late-Stage Pre-Clinical Development 17 BRM Selective Inhibitor (FHD-909) BRM Selective Degrader Biology Exploit the synthetic lethal relationship between BRM (SMARCA2) and mutated BRG1 (SMARCA4) Stage IND submission planned in Q2’24 Advancing in parallel through late pre- clinical development Opportunity BRG1 mutated cancer including ~10% of NSCLC and up to 5% of all solid tumors Loxo@Lilly Partnership 50/50 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
| BRM Selective Inhibition is a Promising Strategy to Exploit the Synthetic Lethal Relationship Between BRM and Mutated BRG1 18 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 BRMiBRG1 Precision medicine targeting synthetic lethal relationships is a proven clinical approach now used in multiple cancers (e.g., PARP inhibitors)
| BRG1 is Mutated in Up to 10% of NSCLC; Up to 5% of Solid Tumors 19 BRG1 mutated across a broad range of tumors Accounts for ~5% of all tumors AACR GENIE via cBioPortal
| 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 20 BRG1 10% KRAS 29% EGFR 26% ALK 7% RET 4% MET 7% 1. Alessi JV, et al., 2021; 2. TCGA via cBioPortal
| 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 Across 17 BRG1 (SMARCA4) Mutant and Wild-Type Cell Lines 21 Spread in potency for wild type versus mutant cell lines indicates 33-fold selectivity Selectivity = 33x Median IC50 (µM) BRG1 WT 0.0932 BRG1 MUT 0.0028
| FHD-909 Monotherapy Demonstrated In Vivo Activity in H2126 BRG1 Mutant NSCLC Model; Well Tolerated 22 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 appropriate 0 7 14 21 28 100 150 200 250 300 350 Days of Dosing (Dose Start Day1) Tu m or v ol um e (m m 3 ) Vehicle Control FHD-909, 20mg/kg, PO, BID FHD-909, 40mg/kg, PO, BID FHD-909, 60mg/kg, PO, BID 0 7 14 21 28 80 90 100 110 120 Days of Dosing (Dose Start Day1) B od y W ei gh t ( % o f S ta rt in g W ei gh t)
| RERF-LC-AI Model FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across BRG1 Mutant NSCLC Models; Well Tolerated 23 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 Start Day1) Tu m or V ol um e (m m 3 ) Vehicle Control FHD-909 20mg/kg, BID, PO FHD-909, 40mg/kg, BID, PO FHD-909, 60mg/kg, BID, PO 0 7 14 21 28 0 250 500 750 1000 1250 1500 Days of Dosing (Dose Start Day1) Tu m or V ol um e (m m 3 ) Vehicle Control 20mg/kg LY4050784, PO, BID 40mg/kg LY4050784, PO, BID BRG1 Q729fs / H736Y, KRAS G12S, STK11-/-, CDKN2A-/-, KEAP1 G333C BRG1 mut p.E1496*, TP53 p.Q104*, NF1 p.E1699* Genetic Background Genetic Background
| FHD-909 Monotherapy Demonstrated Strong In Vivo Activity Across BRG1 Mutant NSCLC Models; Well Tolerated 24 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: All doses were well tolerated. Dosing holidays were applied at the high dose, as appropriate 0 7 14 21 28 100 200 300 400 500 Days of Dosing (Dose Start Day1) Tu m or V ol um e (m m 3 ) Vehicle Control FHD-909, 20mg/kg, BID, PO FHD-909, 40mg/kg, BID, PO FHD-909, 60mg/kg, BID, PO BRG1 E514*, TP53 R209* R273H, ARID1A C884*Genetic Background:
| BRM Selective Degrader Achieves Complete BRM Degradation and Cell Growth Inhibition 25 Degraders Cause Time- and Dose-Dependent BRM Degradation Antiproliferative Effects in A549 Mutant NSCLC Model A549 Ten-Day Proliferation AssayBRM/BRG1 HIBIT Data BRM BRG1 % D eg ra da tio n Concentration (uM) 0.01 0.1 1 10 100 -50 0 50 100 150 FHT-BRMd Concentration (uM) % In hi bi tio n % Inhibition of Cell Growth 0 25 50 75 100 1E-3 0.01 0.1 1 10 Data as of Q4 2021
Selective CBP Protein Degrader For EP300 Mutated Cancers
| Summary: Selective CBP Protein Degrader for EP300 Mutated Cancers 27* Per year incidence in the U.S., EU5, Japan Target / Approach • CREB binding protein (CBP) • Targeted protein degrader Initial Indication • EP300 mutated cancers (e.g., subsets of bladder, colorectal, breast, gastric and lung cancers) Mutation / Aberration • EP300 mutated cancers Stage • Pre-clinical New Patients Impacted / Year* • Over 100,000 10% 10% 8% 7% 6% 6% 5% 5% 3% 0% 5% 10% 15% Melanoma NSCLC Bladder Cancer Endometrial Gastric Breast Pancreatic Cancer Colorectal Cancer Commercial Opportunity SCCHN % of Patients with EP300 Mutation
| Colorectal RKO (EP300 Null) Model Selective CBP Protein Degrader Result in Significant Tumor Growth Inhibition in Colorectal and Bladder EP300 Null Models 28 Bladder 639V (EP300 Null) Model 30 40 50 -20 -10 0 10 20 Days after Tumor Inoculation B od y W ei gh t C ha ng e (% ) 30 40 50 0 500 1,000 1,500 2,000 2,500 3,000 Days after Tumor Inoculation Tu m or V ol um e (m m ³+ S EM ) Vehicle (BID) FHT-CBPd - 9, 3 mg/kg (BID) FHT-CBPd - 9, 10 mg/kg (QD) 5 10 15 20 25 30 0 500 1,000 1,500 2,000 2,500 Days After Tumor Inoculation Tu m or V ol um e (m m ³+ S EM ) Vehicle Control FHT-CBPd - 8, 50mg/kg (BID) FHT-CBPd - 8, 20mg/kg, (BID) 5 10 15 20 25 30 -20 -10 0 10 20 Days After Tumor Inoculation B od y W ei gh t C ha ng e (% )
| Selective CBP Protein Degrader Result in Tumor Regression in Gastric EP300 Null Models 29 Gastric AGS (EP300 Null) Model 20 30 40 50 60 -20 -10 0 10 20 B od y w ei gh t C ha ng e (% ) Days after Tumor Inoculation 20 30 40 50 60 0 500 1,000 1,500 Days After Tumor Inoculation Tu m or V ol um e (m m ³+ S EM ) Vehicle (BID) FHT-CBPd - 9, 10mg/kg (QD) FHT-CBPd - 9, 3mg/kg (QD) FHT-CBPd - 9, 1mg/kg (QD) FHT-CBPd - 9, 0.3mg/kg (QD) FHT-CBPd - 9, 0.1mg/kg (QD)
| 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 30 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, sc, QD Dual BD inhibitor, 30mg/kg, p.o, BID FHT-CBPd Dual CBP/EP300 Inhibitor Vehicle Dual CBP / EP300 InhibitorControl Rat Control dCBP-9 10mg/kg QD Mouse Hypocellularity Megakaryocyte Sparing
| Long-Acting Injectable Formulations of CBP Degrader Could Enable Once Every 2 Weeks, or Less Frequent, Dosing 31 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 Post Dose C BP L ev el s / % Ve hi cl e Plasm a PK (ng/m L) CBP Levels - PDPlasma PK (ng/ml) 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 Post Dose C B P Le ve ls / % Ve hi cl e Plasm a PK (ng/m L) CBP Levels - PDPlasma PK (ng/ml) 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 Post Dose C B P Le ve ls / % Ve hi cl e Plasm a PK (ng/m L) CBP Levels - PDPlasma PK (ng/ml)
Selective EP300 Protein Degrader For CBP Mutated and EP300 Dependent Cancers
| Summary: Selective EP300 Protein Degrader for CBP Mutant & EP300 Dependent Cancers 33 * Per year incidence in the U.S., EU5, Japan Target / Approach • E1A binding protein p300 (EP300) • Targeted protein degrader Initial Indications • AR+ Prostate • DLBCL • Bladder, melanoma, others Mutation / Aberration • EP300 dependent cancers • CBP mutant cancers Stage • Pre-clinical New Patients Impacted / Year* • Over 100,000 Commercial Opportunity EP300 Dependent Cancers • Solid Tumors • AR+ mCRPC • HR+ breast • Hematologic malignancies • DLBCL • Multiple Myeloma CBP Mutant Cancers 10% 10% 9% 8% 8% 8% 6% 0% 5% 10% 15% Melanoma Bladder NSCLC Endometrial Colorectal Gastric Breast % of Patients with CBP Mutation
| EP300 Degradation Results in Significant Tumor Growth Inhibition in AR+ VCAP Prostate and KARPAS422 DLBCL Models 34 Prostate AR+ VCAP Model DLBCL KARPAS422 (CBP Null) 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 FHT-EP300d, 50mg/kg, BID 10 20 30 40 50 -20 -15 -10 -5 0 5 10 15 20 Days After Tumor Inoculation B od y W ei gh t C ha ng e (% ) 5 10 15 20 25 30 35 40 45 -20 -10 0 10 20 B od y W ei gh t C ha ng e (% ) Days After Tumor Inoculation 5 10 15 20 25 30 35 40 45 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 FHT-EP300d, 50mg/kg (BID) FHT-EP300d, 20mg/kg, (BID) FHT-EP300d, 10mg/kg, (BID)
| Selective EP300 Degradation Does Not Show Thrombocytopenia In Vivo 35 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-EP300d Dual CBP/EP300 Inhibitor Vehicle
Selective ARID1B Protein Degrader For ARID1A Mutated Cancers
| ARID1B is a Major Synthetic Lethal Target Implicated in Up To 5% of All Solid Tumors 37* Per year incidence in the U.S., EU5, Japan Target / Approach • ARID1B • Targeted protein degrader Initial Indication • ARID1A mutated cancers Mutation / Aberration • ARID1A mutations (e.g., ovarian, endometrial, colorectal, bladder and other cancers) Stage • Pre-clinical New Patients Impacted / Year* • > 175,000 ARID1A ARID1B ~5% of all solid tumors harbor ARID1A mutations Uterine Bladder Stomach Cholangiocarcinoma Liver Esophageal Ovarian Colorectal Melanoma 0% 10% 20% 30% 40% Commercial Opportunity % of Patients with ARID1A Mutation
| Targeting ARID1B for ARID1A Mutated Cancers is Enabled by Foghorn’s Unique Biology and Discovery Capabilities 38 Gene Traffic Control Platform Protein Degrader Capabilities Program Status • Platform produces BAF complexes and subcomplexes containing either ARID1A or ARID1B at scale • Enables proprietary screens against ARID1B • Utilize protein degrader toolbox to create ARID1B hetero-bifunctional degraders PROGRAM STATUS • Validated selective chemical binders of ARID1B • In process of expanding binders into novel selective protein degraders • Assessing outcomes of ARID1B degradation and impact on BAF complex formation ARID1B Highly purified ARID1B / BAF complex
Transcription Factors A Novel Approach FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex
| Foghorn’s Novel Approach to Drugging Transcription Factors Enabled by Its Protein Production and Discovery Capabilities 40 • Highly involved in gene expression • Implicated in range of cancers and other diseases • Featureless surface: no druggable binding pocket • Tight interactions with DNA: undruggable affinities • Druggable binding pockets • Druggable affinities Transcription Factors are Compelling Drug Targets… …But Historically Difficult to Target… Foghorn Has a New Approach Focusing on Interaction with BAF HISTORICAL FOCUS POTENTIAL DRUGGABLE SITES FOGHORN’S FOCUS
| Transcription Factors Bind to BAF Directly with High Degree of Specificity; Unique Insights into Where and How Transcription Factors Bind 41 Mass spec. foot-printing Pull-down assays Foghorn’s collection of BAF sub-complexes and domains Biophysical Biochemical Structural AUC / SPR / ITC TR-FRET / FP Crystal / NMR SPI1 Mapping the TF-BAF Interaction Validating the TF-BAF Interaction SPI1 TF B TF C TF D
| Broad and Deep Pipeline Across a Range of Targets and Modalities 42 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 Partnered Program Undisclosed Disease BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Relapsed/Refractory AML Selective BRM BRG1 mutant cancers (e.g., ~8-10% of NSCLC, bladder, endometrial, colorectal) Selective ARID1B ARID1A mutant cancers (~5% of all solid tumors) Selective CBP EP300 mutant cancers (e.g., ~5-10% of bladder, gastric, breast, NSCLC, colorectal) Selective EP300 EP300 dependent cancers (e.g., prostate, DLBCL), CBP mutant cancers (e.g., ~9-10% of NSCLC, bladder, melanoma) Undisclosed Undisclosed Undisclosed
| First-In-Class Precision Medicines Targeting Major Unmet Needs in Cancer 43 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 Strategic Collaboration Strategic collaboration with Loxo@Lilly; $380 million upfront; 50/50 U.S. economic split on two lead programs Well- Funded $234.1 million in cash and equivalents (as of 12/31/2023) Provides runway into H1’26 Value Drivers Anticipate data from the Phase 1 study of FHD-286 in combination with decitabine in H2’24 BRM Selective Inhibitor (FHD-909), partnered with Loxo@Lilly, anticipating IND filing in Q2’24 Advancement of preclinical assets (BRM Selective Degrader, CBP, EP300, ARID1B) towards INDs 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 Broad pipeline across a range of targets and modalities
Exhibit 99.3
Foghorn Therapeutics Presents New Preclinical Data on Potential First-in-Class BRM Selective Inhibitor FHD-909 and Selective CBP and Selective EP300 Degrader Oncology Programs
First-in class BRM (SMARCA2) selective inhibitor FHD-909 demonstrated favorable tolerability and dose-dependent single agent activity in BRG1 mutated cancers preclinically; IND filing on track for Q2 2024
Robust preclinical monotherapy anti-tumor activity for both selective CBP and selective EP300 degrader programs
Progress with FHD-909, selective CBP, and selective EP300 degrader programs further validates Foghorn’s drug discovery engine
Conference call and webcast today at 5 pm ET / 2 pm PT
Conference call and webcast today at 5 pm ET / 2 pm PT
CAMBRIDGE, Mass. -- (GLOBE NEWSWIRE) – April 9, 2024 -- Foghorn® Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, today announced new preclinical data for potential first-in-class medicines including FHD-909, a BRM (SMARCA2) selective inhibitor, selective CBP degrader, and selective EP300 degrader programs at the 2024 American Association for Cancer Research (AACR) Annual Meeting. Foghorn management will hold a conference call and webcast today at 5 p.m. ET to review important pipeline updates.
“We are pleased with the encouraging data for our highly selective and potent drug candidates, which address historically very challenging cancer targets," said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. “Notably, our first-in-class BRM selective inhibitor FHD-909 has demonstrated favorable tolerability and encouraging dose-dependent single agent activity in preclinical models of BRG1 mutated tumors. We believe FHD-909 offers a potential new approach for the treatment of cancer. The primary target patient population is BRG1 mutated non-small cell lung cancer (NSCLC), which accounts for about 10% of NSCLC. We look forward to continued progress with Lilly with an IND filing for FHD-909 on track for the second quarter of the year.”
Steve Bellon Ph.D., Chief Scientific Officer of Foghorn Therapeutics added, “CBP and EP300 are nearly identical proteins which has made targeted specific approaches challenging. Our selective CBP program demonstrates significant tumor growth inhibition in solid tumors without thrombocytopenia or anemia, that have been observed with dual CBP/EP300 inhibition. Our selective EP300 program, which is earlier in development, also demonstrates promising
preclinical efficacy with no thrombocytopenia or negative effects on megakaryocyte viability, which are often seen in dual approaches. Additionally, we are applying our long-acting formulation capabilities to our degrader programs, which further enhances the clinical potential of these drug candidates. These are exciting achievements in the development of protein degraders for major cancer types, and we look forward to further progress across these important targets.”
Presentation Highlights
FHD-909 Program
FHD-909 Program
BRM and BRG1 are highly homologous and mutually exclusive subunits of the BAF complex. BRG1 mutations occur in a variety of tumor types, including approximately 10% of non-small cell lung cancers (NSCLC), and result in tumors being dependent on BRM activity for their survival. Selectively blocking BRM activity is a promising synthetic lethal strategy to induce tumor death while sparing healthy cells. However, the ATPase domains of BRM and BRG1are 92% identical which has made identifying a selective BRM inhibitor challenging.
Poster 3230 / 14: Discovery of selective BRM (SMARCA2) ATPase inhibitors for the treatment of BRG1 (SMARCA4) mutant cancers
Preclinical data presented at AACR support FHD-909 as an oral, novel, potent and selective BRM inhibitor with robust anti-tumor monotherapy activity:
•~ 30-fold selectivity for BRM inhibition over BRG1 in cell-based assays
•Dose dependent and robust tumor growth inhibition and regression as a monotherapy in multiple BRG1 mutant xenograft models
•Favorable tolerability with dose dependent modulation of BRM target genes in vivo
•Lilly plans to file an IND application for potential first-in-class orally bioavailable, selective BRM inhibitor, FHD-909, with initial focus in BRG1 mutated NSCLC in Q2 2024
Selective CBP and Selective EP300 Degrader Programs
CBP and EP300 are paralog histone acetyltransferases involved in many cellular processes. Dysregulation of one or both is implicated in various cancer types, and functional genomic screens have suggested a synthetic lethal relationship in tumor cells. Attempts to selectively inhibit CBP or EP300 individually have been challenging due to the high homology between the two proteins. Additionally, dual inhibition of CBP/EP300 has led to hematopoietic toxicity.
Selective CBP Program
Poster 6067 / 26: Identification of selective CBP degraders with robust preclinical PK, PD, efficacy, and safety across solid tumor indications
Preclinical pharmacodynamic and pharmacokinetic data presented at AACR support the identification of potent and selective CBP degraders with anti-tumor activity across various EP300 mutant cell lines from multiple indications:
•Deep and sustained CBP degradation leading to significant tumor growth inhibition in mouse xenograft solid tumor models
•Robust monotherapy anti-tumor activity that was not associated with significant body weight loss
•In vivo, no evidence of thrombocytopenia, which is attributed to the sparing of megakaryocytes, nor evidence of anemia
•Long-acting CBP-selective protein degrader formulations with first-in-class potential for patients with tumors harboring EP300 mutations
Selective EP300 Program
Poster 6064 / 23: Discovery of potent and selective EP300 degraders with anti-cancer activity
Preclinical pharmacodynamic and pharmacokinetic data presented at AACR support the identification of potent and selective EP300 degraders with anti-tumor activity in prostate and hematological malignancies:
•Reduced growth of androgen receptor positive prostate cells and attenuated androgen signaling
•Reduced the growth of prostate cancer xenograft tumors in mice
•Broad anti-tumor activity across a panel of multiple myeloma and DLBCL cell lines
•In vivo efficacy demonstrated in a DLBCL model
•Well tolerated in vivo with no observed decrease in platelet levels, additionally mechanistic studies ex vivo show no effects on megakaryocyte viability at pharmacologically relevant concentrations.
Conference Call and Webcast Information
Foghorn management will hold a conference call and webcast today at 5 p.m. ET to review pipeline updates. The dial-in number for the conference call is 1-877-704-4453 (U.S./Canada) or 1-201-389-0920 (international). The conference ID for all callers is 13745314. The live webcast and replay may be accessed under Events and Presentations in the Investors section of the Foghorn’s website, www.foghorntx.com, and will be available for up to 30 days.
About FHD-909
FHD-909 is a highly potent, allosteric and orally available small molecule that selectively inhibits the ATPase activity of BRM over its closely related paralog BRG1, two proteins that are the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, tumors with mutations in BRG1 rely on BRM for BAF function. FHD-909 has shown significant anti-tumor activity across multiple BRG1-mutant lung tumor models.
About Foghorn Therapeutics
Foghorn® Therapeutics is discovering and developing a novel class of medicines targeting genetically determined dependencies within the chromatin regulatory system. Through its proprietary scalable Gene Traffic Control® platform, Foghorn is systematically studying, identifying and validating potential drug targets within the chromatin regulatory system. The Company is developing multiple product candidates in oncology. Visit our website at www.foghorntx.com for more information on the Company, and follow us on X (formerly Twitter) and LinkedIn.
Forward-Looking Statements
This press release contains “forward-looking statements.” Forward-looking statements include statements regarding the Company’s clinical trials, product candidates and research efforts, including statements relating to FHD-286, FHD-909 and its selective CBP and selective EP300 degrader programs, and other statements identified by words such as “could,” “may,” “might,” “will,” “likely,” “anticipates,” “intends,” “plans,” “seeks,” “believes,” “estimates,” “expects,” “continues,” “projects” and similar references to future periods. Forward-looking statements are based on our current expectations and assumptions regarding capital market conditions, our business, the economy and other future conditions. Because forward-looking statements relate to the future, by their nature, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. As a result, actual results may differ materially from those contemplated by the forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include regional, national or global political, economic, business, competitive, market and regulatory conditions, including risks relating to our clinical trials and other factors set forth under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission. Any forward-looking statement made in this press release speaks only as of the date on which it is made.
Contacts:
Greg Dearborn, Foghorn Therapeutics Inc. (Investors)
gdearborn@foghorntx.com
gdearborn@foghorntx.com
Karin Hellsvik, Foghorn Therapeutics Inc. (Investors & Media)
khellsvik@foghorntx.com
khellsvik@foghorntx.com
Adam Silverstein, ScientPR (Media)
adam@scientpr.com
adam@scientpr.com
Peter Kelleher, LifeSci Advisors (Investors)
pkelleher@lifesciadvisors.com