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): May 19, 2022
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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:
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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.
Foghorn Therapeutics Inc. (the “Company”) is furnishing as Exhibit 99.1 to this Current Report on Form 8-K (this “Current Report”) a presentation, dated May 2022, which the Company intends to use in meetings with or presentations to investors.
The information in this Item 7.01 (including Exhibit 99.1 attached hereto) is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
On May 19, 2022, the Company issued a press release announcing that the Food and Drug Administration (the “FDA”) has placed the Phase 1 dose escalation study of FHD-286 in relapsed and/or refractory acute myelogenous leukemia (“AML”) and myelodysplastic syndrome (“MDS”) on a partial clinical hold. The partial clinical hold was initiated by the FDA following the report of a recent death that occurred in a subject with potential differentiation syndrome. Differentiation syndrome is associated with AML/MDS therapeutics that induce differentiation, an effect that is believed to be on-target for the proposed mechanism of action for FHD-286. The FDA has requested a review of the safety database, risk mitigation strategies and a breakdown of clinical activity across dose levels. Until the Company has resolved the partial clinical hold for the AML/MDS study, it is suspending guidance on the timing of the data release for the dose escalation phase of the FHD-286 program.
A copy of the press release is attached to this Current Report as Exhibit 99.2 and is incorporated herein by reference.
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/ Allan Reine | ||||||||||
| Allan Reine, M.D. | |||||||||||
| Chief Financial Officer | |||||||||||
Targeting the Chromatin Regulatory System Broadening the Impact of Precision Medicines for Oncology and Other Diseases May 2022 Exhibit 99.1
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 the Collaboration Agreement with Lilly; the initiation, timing, progress and results of our research and development programs and preclinical and clinical trials, including the potential resolution of the partial clinical hold and anticipated timing of release of initial clinical data; our ability to advance product candidates that we may develop and 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 the COVID-19 pandemic on our and our collaborators’ business operations, including our research and development programs and preclinical 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, FHD-609 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 and FHD-609, 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. Forward-Looking Statements 2
Dysregulation of the Chromatin Regulatory System Has Been Implicated in up to 50% of All Cancers 3 Significant Market Opportunity 2.5M People 50% of All Cancers Based on exome sequencing, the chromatin regulatory system is implicated in ~50% of all cancers $400+ billion 2030 global oncology market opportunity Patients impacted by these cancers
Foghorn Well Positioned to Discover and Develop First in Class Precision Medicines Targeting Cancer and Other Diseases Significant Global Partnerships Strategic Collaboration with Loxo Oncology at Lilly Merck collaboration to drug single specified transcription factor target Expertise across drug discovery, clinical development and commercialization Experienced Leadership Team FHD-286: Data (TBD) - mUM study enrolling; AML/MDS study on partial clinical hold FHD-609: Initial clinical data expected in 2023 Upcoming Milestones Biology implicated in up to 50% of cancer potentially impacting ~2.5 million patients Potential applications in virology, autoimmune diseases and neurology Large Market Potential 4 $424.7 million in pro forma cash and equivalents (as of 03/31/2022) Well Funded
Advancing a Broad Pipeline Across a Range of Targets and Modalities 5 Precision Oncology / Breadth and Depth Program / Target Modality Discovery IND Enabling Phase 1 Phase 2 Commercial Rights FHD-286 (BRG1/BRM) Enzyme Inhibitor FHD 609 (BRD9) Protein Degrader Selective BRM I) Enzyme Inhibitor 50/50 U.S., Ex-U.S. RoyaltiesII) Protein Degrader Selective ARID1B Protein Degrader Partnered Program (Undisclosed) Undisclosed 50/50 U.S., Ex-U.S. Royalties Synthetic Lethal Targets (Multiple) I) Enzyme Inhibitors II) Protein Degraders Transcription Factors (Multiple) I) Transcription Factor Disruptors II) Protein Degraders Partnered Program (Undisclosed) Transcription Factor Disruptor WW Royalties Three Discovery Programs (Undisclosed) Undisclosed WW Royalties (Opt-in for U.S. Rights) AML & MDS Uveal melanoma Synovial Sarcoma BRG1 Mutated Cancers BRG1 Mutated Cancers ARID1A Mutated Cancers
Strategic Collaboration with Loxo Oncology at Lilly 6 Foghorn to Lead Discovery and Research Activities $380 Million Up-front $300 million cash $80 million in Foghorn common stock at a price of $20 per share Three Undisclosed Discovery Programs Option to participate in a percentage of the U.S. economics Tiered ex-U.S. royalties from the mid-single digit to low- double digit range $1.3 billion in potential milestones 50/50 U.S. Economics on Two Programs 50/50 U.S. economic split on BRM-Selective and another undisclosed program Tiered ex-U.S. royalties starting in the low double-digit range and escalating into the twenties based on revenue levels
The Chromatin Regulatory System Orchestrates Gene Expression
Normal gene expression The Chromatin Regulatory System Orchestrates Gene Expression 8 Two Major Components Work in Concert - Chromatin Remodeling Complexes and Transcription Factors Work together to orchestrate gene expression TF’s guide chromatin remodeling complexes to the right locations Once chromatin unpacked, gene expression can occur 1 2 3 Chromatin – compacted form of DNA inside the nucleus of the cell Chromatin Right genes Transcription FactorChromatin remodeling complex
Breakdowns in the Chromatin Regulatory System can Lead to Disease 9 Mutations or overexpression in chromatin remodeling complexes result in abnormal gene expression Mutated or overexpressed TF hijacks chromatin remodeling complex to wrong location DISEASE DISEASE
Chromatin Regulatory System – Abundance of Targets 10 28 Chromatin Remodeling Complexes and >1,000 TFs Estimate >100 Transcription Factors Associated with just the BAF Complex BAF Complex and Associated Transcription Factors + BAF Complex Subunits Mutated and Dysregulated in Cancer
Mutations Lead to Disease Specific Genetic Dependencies on the Chromatin Regulatory System 11 Transcription Factor Mutations / Overexpression Chromatin Remodeling Complexes Mutations / Overexpression Mutations that Impinge on the Chromatin Regulatory System Novel Targets / Dependencies Targeted Protein Degradation: Bi-functional protein degraders for targets with no enzymatic activity Enzymatic Inhibitors: Highly selective and allosteric small molecule inhibitors Transcription Factor Disruptors: Disrupt interactions between chromatin remodeling complexes and transcription factors Tailored Drugging Approaches ATP ADP Potential druggable sites
Foghorn’s Gene Traffic Control Platform Makes It Possible to Understand and Drug Genetic Dependencies within the Chromatin Regulatory System 12 Integrated, Scalable, Efficient – Repeatable Paradigm Target Identification & Validation Production of Chromatin Regulatory System Components at Scale & Proprietary Assays Discovery and Optimization of Chemical Matter Targeted Protein Degraders Enzymatic Inhibitors Transcription Factor Disruptors Translation to Clinic and Identification of Biomarkers Determine dependencies (e.g., synthetic lethal)
Production of Chromatin Regulatory System Components Platform is Powered by Ability to Produce Components at Scale Drives Drug Discovery Pipeline with Cutting Edge Technology Surface Mapping Assembly HTS Biophysics / SPR Affinity Screening and Validation Characterize TF / BAF Binding Sites Synthesize subcomplexes to enable drug discovery ASMS on full complex to yield novel degraders Multiple screening options with full complex Validation of novel small molecule binders BenefitsFeatures 13
Foghorn Pursuing >8 Targeted Protein Degraders Heterobifunctional Degrader Platform Bioinformatics • Optimal E3 ligase target pairing • Proteomics Chemical Toolbox Screening and Characterization Structural and Computational Approaches to Degrader Design Optimization of Degrader Drug Properties • Proprietary chromatin remodeling assays • Protein degradation kinetics • Proprietary library of drug-like linkers and E3 ligase binders • Chemistry to rapidly identify and optimize degraders • Structure based optimization of binders • Ternary complex crystal structures and modeling approaches for degrader optimization • Guidelines for both of oral and IV administered degraders • PKPD / efficacy and safety modeling to optimize dosing and scheduling 14
Advancing a Broad Pipeline Across a Range of Targets and Modalities 15 Precision Oncology / Breadth and Depth Program / Target Modality Discovery IND Enabling Phase 1 Phase 2 Commercial Rights FHD-286 (BRG1/BRM) Enzyme Inhibitor FHD 609 (BRD9) Protein Degrader Selective BRM I) Enzyme Inhibitor 50/50 U.S., Ex-U.S. RoyaltiesII) Protein Degrader Selective ARID1B Protein Degrader Partnered Program (Undisclosed) Undisclosed 50/50 U.S., Ex-U.S. Royalties Synthetic Lethal Targets (Multiple) I) Enzyme Inhibitors II) Protein Degraders Transcription Factors (Multiple) I) Transcription Factor Disruptors II) Protein Degraders Partnered Program (Undisclosed) Transcription Factor Disruptor WW Royalties Three Discovery Programs (Undisclosed) Undisclosed WW Royalties (Opt-in for U.S. Rights) AML & MDS Uveal melanoma Synovial Sarcoma BRG1 Mutated Cancers BRG1 Mutated Cancers ARID1A Mutated Cancers
FHD-286: Clinical Entry Point - AML and Uveal Melanoma FHD-286 is a Potent, Selective, Allosteric, Small Molecule Inhibitor of the BRG1 and BRM subunits of the BAF complex
FHD-286 Targets Abnormal Dependencies on BAF in Cancer • BRM / BRG1 is the engine (ATPase) of the BAF chromatin remodeling complex • BRG1 & BRM are highly similar proteins BRG and BRM Subunits BRMBRG1 Target / Approach • BRG1 / BRM ATPase • Small molecule, allosteric, oral enzymatic inhibitor Indications • Acute myelogenous leukemia (AML) • Uveal melanoma • Indication expansion work ongoing in multiple solid tumors Mutation / Aberration • AML: Elevated BRG1-BAF / TF activity in AML blast cells • Uveal melanoma: GNAQ / GNA11 mutated UM is driven by dependency on BAF / TF activity Program Status / Milestones • Phase 1 studies enrolling in mUM; partial clinical hold for AML/MDS study • Initial clinical data (TBD) New Patients Impacted / Year* • AML: Over 20,000 relapsed and / or refractory patients • Uveal melanoma: Over 5,000 patients BAF Chromatin Remodeling Complex * U.S., EU5, Japan 17
AML & Dependency on BRG1 / Lineage Dependent TF Interactions Disease State Treatment with FHD-286 Loss of blast phenotype / Apoptosis Differentiation AML blasts stuck in BAF / TF dependent proliferative phase HSC Cancerous blast cells rely on BRG1 containing BAF / TF activity BAF – TF Activity BAF – TF Activity 18
AML Dependent on BRG1 / Lineage TF Interaction 19 Subtype Sample ID TF #1 SPI1 (PU.1) TF #3 TF #4 SPI1 (PU.1) / BAF Dependency SPI1 ChIPseq TF Association with AML by FAB Classification: 70% BRG1 Inhibition Leads to Loss of SPI1 (PU.1) Occupancy on Chromatin
Preclinical FHD-286 Data Shows Broad Efficacy Across AML Patient Derived Samples 20 Notable Patient ID Deep Response Pathology Review Disease Status 1690AML1 Y AML Secondary 1695AML1 Y AML/MDS Secondary 1696AML1 Y AML Secondary 1701AML1 Y AML Secondary 1893AML1 Y AML R/R 1899AML1 Y AML R/R 1990pAML1 Y AML R/R 1991pAML1 Y AML de novo 2041AML1 Y N/A de novo 2043pAML1 Y AML R/R 2059AML1 Y AML R/R 1682AML1 ~ N/A N/A 1689AML1 ~ AML/MDS de novo 1684AML1 N CML R/R 1924AML1 N AML/MDS R/R • Response observed in a majority of primary AML samples, irrespective of prior treatment or disease stage • Additional data set from patient derived samples demonstrate mutation agnostic responses 1695AML1 – BM-secondary AML Aza + venetoclax 7+3 Pro-differentiation effect Y = Deep reduction in blast cells ~ = Partial reduction N = No response
FHD-286 Shows Effect Across a Range of Mutations in AML Patient-Derived Samples 21 IC 50 (n M ) Patient Samples DNMT3A FLT3 IDH1 IDH2 KIT NF1 NPM1 NRAS RUNX1 TET2 TP53
Dose-Dependent Tumor Growth Inhibition Observed with FHD-286 Treatment in AML CDX Models 22 Tumor Volume Body Weight 0 7 14 21 0 250 500 750 1000 1250 Days Post Treatment Tu m or V ol um e (m m 3 ) 0 7 14 21 0 800 1600 2400 3200 Days Post Treatment Tu m or V ol um e (m m 3 ) 0 7 14 21 80 90 100 110 120 Days Post Treatment Bo dy W ei gh t C ha ng e (% ) 0 7 14 21 80 90 100 110 120 Days Post Treatment B od y W ei gh t C ha ng e (% ) MV4-11 CDX Model (FLT3 ITD, MLL-AF4) OCI-AML2 CDX Model (MII-AF6, DNMT3a mut.) Tumor Volume Body Weight
Tumor Growth Inhibition with FHD-286 Treatment Observed by Bioluminescence Imaging in a Disseminated AML model FHD-286 1.5 mg / kg, BID (5on / 8off) x3 Sorafenib 15 mg / kg, QDx14 Vehicle FHD-286 1.5 mg / kg QDx28 FHD-286 Survival Advantage in Disseminated AML Model 23
Therapeutic Rationale for Uveal Melanoma: Dependency on Overexpression of the MITF / SOX10 Transcription Factors and the BAF Complex 24 Inhibiting BRG1 / BRM to Shut Down the Abnormal TF Interaction with the BAF Complex SOX10 MITF MITF ChIPseq SOX10 ChIPseq Biology Over 85% of uveal melanoma cancers have GNAQ or GNA11 mutations Validation of Dependency and Approach
FHD-286 was Associated with Dose-Dependent Tumor Regression in Uveal Melanoma CDX Models at Tolerated Doses 25 0 7 14 21 28 0 300 600 900 1200 Days Post Treatment Tu m or V ol um e (m m 3 ) Tumor Volume 0 7 14 21 28 80 90 100 110 120 Days Post Treatment Bo dy W ei gh t C ha ng e (% ) Body Weight 0 5 10 15 20 0 150 300 450 600 750 900 Days Post Treatment Tu m or V ol um e (m m 3 ) 0 5 10 15 20 80 90 100 110 120 Days Post Treatment Bo dy W ei gh t C ha ng e (% ) Tumor Volume Body Weight MP-46 uveal melanoma CDX model • Dose-dependent tumor growth inhibition • Well tolerated 92-1 uveal melanoma CDX model • Dose-dependent tumor growth inhibition • Tumor regression at 1.5 mg / kg, PO, QD • Well tolerated
FHD-286 Clinical Development Plan 26 Two Parallel Phase 1 Studies Activated Initial Clinical Data: Timing Dependent on Resolution of AML/MDS Study Partial Clinical Hold Trial Designs • Single patient accelerated titration (n=1) • Convert to 3+3 once relevant PK / PD, safety or clinical activity observed • Retrospective biomarker analysis to further evaluate safety and efficacy • Assess safety, PK, biomarkers and efficacy CLINICAL PLAN AML & Uveal Melanoma FIH Phase 1 Studies Expansion cohorts in AML, UM and potentially other indications Potential for entry into definitive efficacy trials in AML Potential for entry into definitive efficacy trials in metastatic uveal melanoma Potential for indication expansion beyond AML and UM Metastatic Uveal Melanoma Relapsed / Refractory AML & MDS
FHD-609: Clinical Entry Point – Synovial Sarcoma FHD-609 is a Selective, Potent, Protein Degrader of the BRD9 component of the BAF complex
BRD9 is required for the survival of synovial sarcoma cells FHD-609 Targets and Degrades the BRD9 subunit of BAF which is Required for Synovial Sarcoma Cells to Survive Selective, Potent BRD9 Targeted Protein Degrader SS18-SSX1 / SSX2 / SSX4 mutated subunit Target / Approach • BRD9 • Intravenous protein degrader Initial Indication • Synovial sarcoma Mutation / Aberration • SS18-SSX1 / SSX2 / SSX4 protein fusions Program Status / Milestones • Initial clinical data expected 2023 New Patients Impacted / Year* • Synovial sarcoma: Over 1,800 patients / year B R D 9 D ep en de nc y Sc or e BRD9 subunit * U.S., EU5, Japan 28
Robust in vivo Activity Observed in Synovial Sarcoma Model and BRD9 Degradation Associated with FHD-609 Treatment Weekly Dosing of FHD-609 Achieved Sustained BRD9 Degradation SY01 Synovial Sarcoma CDX Model • Mutation: SS18-SSX2 • Inhibited tumor growth • Dose dependent BRD9 degradation correlated with anti-tumor activity Sustained BRD9 Degradation 29
ASKA CDX Model Superior Tumor Growth Inhibition of FHD-609 in a Synovial Sarcoma Model as Compared to Ifosfamide and Pazopanib 30 Tumor Volume Body Weight • Mutation: SS18-SSX1 • Superior tumor growth inhibition compared to ifosfamide and pazopanib • Complete suppression observed over 30 days at 2 mg / kg of FHD-609 0 7 14 21 28 80 90 100 110 120 Days Post Treatment % Bo d y W ei gh t C ha ng e 0 10 20 30 40 0 700 1400 2100 2800 Days Post Treatment Tu m or Vo lu m e (m m 3 )
FHD-609 Clinical Development Plan Metastatic Synovial Sarcoma Synovial sarcoma expansion cohorts Synovial Sarcoma FIH Phase 1 Potential for entry into definitive efficacy trials in synovial sarcoma CLINICAL PLAN Initial clinical data in 2023 SMARCB-1 deleted tumors and potentially other indications Trial Designs • Single patient accelerated titration (n=1) • Convert to 3+3 once relevant PK / PD, safety or clinical activity observed • Assess safety, PK, clinical activity and biomarkers Biomarkers: • SS18-SSX1, SS18-SSX2 or SS18-SSX4 translocation 31
Selective BRM Modulators for BRG1 Mutated Cancers Enzymatic Inhibitor and Protein Degrader Programs
BRG1 Mutations Create a Genetic Dependency on BRM Selective BRM Modulators Overview BRM BRG1 Target / Approach • BRM • Enzymatic inhibitor • Targeted protein degrader Indication • BRG1 mutated cancers (e.g., NSCLC), 30+ cancers with BRG1 mutations Mutation / Aberration • BRG1 Stage • Pre-clinical New Patients Impacted / year* • > 100,000 B R M D ep en de nc y Sc or e * U.S., EU5, Japan 33 Economics of Lilly Collaboration • 50/50 U.S. economics • Tiered ex-U.S. royalties starting in the low double digit range and escalating into the twenties
BRG1 Mutated in ~5% of All Tumors Broad Addressable Patient Population BRG1 mutated across range of tumors Accounts for ~5% of all tumors BRG1 mutated in up to 10% of NSCLC tumors, minimal overlap with other mutations 34
BRM Selective Inhibitor in vivo Efficacy Demonstrates PK / PD and In vivo Efficacy in a BRG1 Mutant Lung CDX Model BRG1 cellular IC50 BRM cellular IC50 A549-BRG1 Mutant NSCLC Model Body Weight Plasma Exposure Vehicle Control (BID) Cisplatin 4 mg / kg (IP) FHT-BRMi 15 mg / kg (BID) FHT-BRMi 30 mg / kg (BID) 35
Enzymatic Selectivity Approaching 200x Achieved 36
Advancing BRM Selective Degraders Achieving Complete BRM Degradation Degraders cause time- and dose-dependent BRM degradation, antiproliferative effects in A549 BRG1 mutant NSCLC lung model 0.01 0.1 1 10 100 -50 0 50 100 150 FHX-NSXLX Conc (uM) % in hi bi tio n F T-BRMd BRM / BRG1 HiBit Data A549 Ten-Day Proliferation Assay 37
Selective ARID1B Protein Degrader for ARID1A Mutated Cancers
ARID1A: Most Mutated Subunit in BAF Complex – Creates Dependency on ARID1B 39 Selective ARID1B Protein Degrader Overview ARID1A ARID1B Target / Approach • ARID1B • Targeted protein degrader 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 AR ID 1B D ep en de nc y Sc or e * U.S., EU5, Japan
Targeting ARID1A Mutated Cancers: ARID1B Protein Degrader Advantaged by Gene Traffic Control Platform and Protein Degrader Capabilities Gene Traffic Control Platform Protein Degrader Capabilities • 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 Biology & Opportunity • ARID1A is the most highly mutated subunit of the BAF complex in cancer • ~5% of all tumors harbor ARID1A mutations including; endometrial cancer (~40%), bladder cancer (~25%) and ovarian (~15%) • Synthetic lethal relationship with ARID1B ARID1B Highly purified ARID1B / BAF complex 40
Novel Approach to Targeting Transcription Factors Disrupting Transcription Factor – Chromatin Remodeling Complex Interactions
A New Approach to Drugging Transcription Factors Enabled by Proprietary Ability to Purify and Synthesize Chromatin Regulatory System Components 42 • Highly involved in gene expression • Implicated in range of cancers and other diseases TFs are compelling drug targets… • Featureless surface: no druggable binding pocket • Tight interactions with DNA: undruggable affinities …but historically difficult to target Historical Focus Potential druggable sites Foghorn’s Focus Foghorn has a new approach focusing on interaction with BAF Druggable binding pockets Druggable affinities
Transcription Factor-Chromatin Remodeling Complex Interactions 43 Unique Insights in Where and How Transcription Factors Bind TF #2TF #1 TF #3 Transcription Factors (TF): TF #4 0.01 0.1 1 10 100 1000 0 100 200 300 400 SPI1 (nM) RU KD = 21 nM 0.1 1 10 100 1000 10000 0 50 100 150 200 250 MYOD1 (nM) RU KD = 125 nM KD = 351 nM 0.1 1 10 100 1000 10000 0 50 100 150 200 250 300 350 MITF (nM) RU KD = 94 nM TF #1 (nM) TF #2 (nM) TF #3 (nM) TF #4 (nM)
• Merck collaboration to drug single specified transcription factor target • $425 million in up-front, research, development and sales-based milestones • Up to low double-digit royalties on product sales Highly Scalable Approach and Significant Unmet Medical Need 44 Potential to Drug > 100 TFs Associated with BAF • >100 TFs estimated associated with BAF • Foghorn pursuing multiple TFs in parallel • Approach highly scalable and potential broad application – other chromatin remodeling complexes and other diseases
Foghorn Well Positioned to Discover and Develop First in Class Precision Medicines Targeting Cancer and Other Diseases Significant Global Partnerships Strategic Collaboration with Loxo Oncology at Lilly Merck collaboration to drug single specified transcription factor target Expertise across drug discovery, clinical development and commercialization Experienced Leadership Team FHD-286: Data (TBD) - mUM study enrolling; AML/MDS study on partial clinical hold FHD-609: Initial clinical data expected 2023 Upcoming Milestones Biology implicated in up to 50% of cancer potentially impacting ~2.5 million patients Potential applications in virology, autoimmune diseases and neurology Large Market Potential 45 $424.7 million in pro forma cash and equivalents (as of 03/31/2022) Well Funded
Appendix
Proven Leadership Team 47 Steve Bellon, Ph.D., SVP, Drug Discovery Adrian Gottschalk, President & CEO Carlos Costa, SVP, Human Resources Sam Agresta, M.D., M.P.H., Chief Medical Officer Jacqueline Cinicola, VP Regulatory Affairs Murphy Hentemann, Ph.D., VP Program Leadership Chong-Hui Gu, Ph.D., VP, CMC and QARyan Kruger, Ph.D., VP, Biology Fanny Cavalie, Chief Strategy and Business &Operations Officer Michael LaCascia, Chief Legal Officer Nicola Majchrzak, VP, Clinical DevelopmentAllan Reine, M.D., Chief Financial Officer Scott Innis, VP, Program Leadership Ben Strain, VP, Investor Relations & Corporate Communications Marina Nelen, Ph.D., VP, Drug Discovery Kevin Wilson, VP, ChemistryDanette Daniels, Ph.D., VP, Protein Degradation Platform Karin Hellsvik, VP Corporate Affairs
Charles Sawyers, M.D. MSKCC, HHMI – SAB Chair David Schenkein, M.D. General Partner, GV Craig Peterson, Ph.D. Professor UMass Medical School Tony Kouzarides, Ph.D. Gurdon Institute – University of Cambridge Gerald Crabtree, M.D. Stanford, HHMI; Founder Doug Cole, M.D. Flagship Pioneering – Board Chair; Founder Cigall Kadoch, Ph.D. Dana-Farber, Broad, HMS; Founder Scott Biller, Ph.D. Former CSO and Strategic Advisor, Agios Adam Koppel, M.D., Ph.D. Bain Capital Life Sciences Simba Gill, Ph.D. Evelo Biosciences, Partner at Flagship Pioneering Michael Mendelsohn, M.D. Cardurion Pharmaceuticals Adrian Gottschalk Foghorn President & CEO Ian Smith Exec. Chair of Solid Bio., Chair of ViaCyte, Former COO of Vertex Industry Leading Board of Directors and Advisors 48 BOARD OF DIRECTORS SCIENTIFIC AND OTHER ADVISORS
Exhibit 99.2
Foghorn Therapeutics Provides Update on Phase 1 Study of FHD-286 in Relapsed and/or Refractory AML and MDS
CAMBRIDGE, Mass. -- (GLOBE NEWSWIRE) -- May 19, 2022 -- Foghorn® Therapeutics Inc. (Nasdaq: FHTX), a clinical stage biotechnology company pioneering a new class of medicines that modulate gene expression through selectively targeting the chromatin regulatory system, today announced the Food and Drug Administration (FDA) has placed the Phase 1 dose escalation study of FHD-286 in relapsed and/or refractory acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) on a partial clinical hold. The partial clinical hold was initiated by the FDA following the report of a recent death that occurred in a subject with potential differentiation syndrome. Differentiation syndrome is associated with AML/MDS therapeutics that induce differentiation, an effect that is believed to be on-target for the proposed mechanism of action for FHD-286. The FDA has requested a review of the safety database, risk mitigation strategies and a breakdown of clinical activity across dose levels.
Patients currently enrolled in the dose escalation Phase 1 study of FHD-286 in AML/MDS and benefitting from treatment may continue to receive treatment, although no new patients can be enrolled until the partial clinical hold is resolved. The partial clinical hold does not apply to the FHD-286 dose escalation Phase 1 study in metastatic uveal melanoma (mUM), with enrollment in that study continuing per protocol.
“Patient safety remains our top priority. We appreciate the dialogue with the FDA and will work diligently with the Agency to resolve the partial clinical hold in AML/MDS as soon as possible,” said Foghorn CEO Adrian Gottschalk.
Until Foghorn has resolved the partial clinical hold for the AML/MDS study, the Company is suspending guidance on the timing of the data release for the dose escalation phase of the FHD-286 program.
About FHD-286
FHD-286 is a highly potent, selective, allosteric and orally available, small-molecule, enzymatic inhibitor of BRG1 and BRM, two highly similar proteins that are the ATPases, or the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors. To learn more about these studies please visit ClinicalTrials.gov. (Link here for metastatic uveal melanoma and here for AML and MDS).
About AML
Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.
About Uveal Melanoma
Uveal (intraocular) melanoma (UM) is a rare eye cancer that forms from cells that make melanin in the iris, ciliary body, and choroid. It is the most common eye cancer in adults. It is diagnosed in about 2,000 adults every year in the United States and occurs most often in lightly pigmented individuals with a median age of 55 years. However, it can occur in all races and at any age. UM metastasizes in approximately 50% of cases, leading to very poor prognosis.
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.
Forward-Looking Statements
This press release contains “forward-looking statements.” Forward-looking statements include, but are not limited to, statements concerning the Company’s clinical programs for FHD-286, including potential resolution of the partial clinical hold and anticipated timing of release of initial clinical data. 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, 2021 and subsequent Quarterly Reports on Form 10-Q, 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.
Contact:
Ben Strain, Foghorn Therapeutics Inc. (Media and Investors)
bstrain@foghorntx.com
bstrain@foghorntx.com
Michael Lampe, ScientPR (Media)
michael@scientpr.com
michael@scientpr.com
Hans Vitzthum, LifeSci Advisors (Investors)
hans@lifesciadvisors.com
hans@lifesciadvisors.com