Foghorn Therapeutics Inc. · NASDAQ:FHTX
Foghorn Therapeutics — AACR 2026
14 slides from Foghorn Therapeutics's conference presentation, April 2026
Slide 1: Targeting chromatin regulatory proteins in hematologic malignancies
Targeting chromatin regulatory proteins in hematologic malignancies Gromek Smolen, PhD VP, Biology Company Confidential & Proprietary Information 1
Slide 2: Lineage dependence
Lineage dependence Tumor cells remain addicted to Lineage dependencies are dominated Clinical agents targeting the lineage specifying genes by TFs with selective expression lineage vulnerabilities DepMap vulnerabilities Hormone receptor modulators Progenitor cell Gene type: Transcription Factor (TF)
Slide 3: Lineage dependence
Lineage dependence Tumor cells remain addicted to Ample opportunities for targeting lineage vulnerabilities the lineage specifying genes DepMap lineage vulnerabilities Progenitor (heme vs solid tumors) cell Differentiation Oncogenesis Gene type: Transcription Factor (TF) Chromatin Regulatory Other C
Slide 4: EP300 – a critical regulator of gene expression
EP300 – a critical regulator of gene expression Role in gene regulation Target dependence in oncology EP300 DepMap sensitivity (by lineage) AT PROMOTERS AT ENHANCERS Company Confidential & Proprietary Information 4
Slide 5: Historical development of EP300 drugs hampered by homology with CBP
Historical development of specific drugs targeting EP300 has been hampered by the high degree of homology with CBP • CBP and EP300 are highly homologous • 59% identity and 68% similarity • HAT domains are 88% identical • Bromodomains are 97% identical • Vast majority of known binders/inhibitors are
Slide 6: Development of selective EP300 degraders
Development of selective EP300 degraders Kinetic experiments reveal remarkably efficient Selectivity of EP300 degraders and selective degradation EP300-HiBiT dEP300-9 U2OS (CBP/EP300 WT) MM1.S (CBP/EP300 WT) Dmax: 96% 6hrs – 300nM 6hrs – 200nM Rate: 2.5 λ/hr DC50: 3 nM EP300 EP300 CBP-HiBiT U2OS cel
Slide 7: All multiple myeloma cell lines tested are sensitive to dEP300-9
All multiple myeloma cell lines tested are sensitive to dEP300-9 Cell sensitivity data Selective EP300 degradation OPM2 dEP300-9 (nM) EP300 CBP vinculin GI50 (nM) RPMI8226 dEP300-9 (nM) EP300 CBP N3 K 1 1S K B K Z K M M 3 26 2 A 1 S1 M6 PM 27 K 26 0 8 S1 1 M S26 O 4 K E 1 M 9 K MM 92 6 LP S3 S2 O S1
Slide 8: EP300 degradation effects on MM cell lines
EP300 degradation effects on MM cell lines EP300 degradation downregulates the Lineage dependence of EP300-regulated expression of several transcription factors transcription factors OPM2 RPMI8226 H929 OPM2 KMS11 RPMI8226 KMS11 Company Confidential & Proprietary Information dEP300-9 treatment, cell
Slide 9: Selective EP300d shows robust efficacy and tolerability in MM1S model
Selective EP300d shows robust efficacy and tolerability in MM1S model EP300d-73 demonstrates dose-responsive efficacy, Selective EP300 degrader spares platelets including complete responses Vehicle CCS1477, 20mpk, QD, p.o EP300d-73, 1mpk, QD, s.c EP300d-73, 3mpk, QD, s.c EP300d-73, 10mpk, QD, s.c EP
Slide 10: Selective EP300d shows robust efficacy in an IMiD-resistant MM model
Selective EP300d shows robust efficacy an IMiD-resistant MM model Pomalidomide-resistant MM model (MM1S-PomR) treated with dEP300-7 • Selective EP300 degrader achieves deeper responses (regressions) in a pomalidomide-resistant MM model • Selective EP300 degrader with improved therapeutic window enab
Slide 11: dEP300 combinations converge on key lineage transcription factors
dEP300 combinations converge on key lineage transcription factors Combination therapy dEP300 combinations regulate EP300 regulates specific opportunities for EP300d multiple key TFs chromatin sites Motifs enriched in closing ATAC-seq IRF4 MYC sites after EP300d treatment Synergy Score 0 15 30 dEP300
Slide 12: Conclusions and ongoing efforts
Conclusions and ongoing efforts • Selective EP300 degradation has the potential to be a well-tolerated and effective treatment strategy in multiple indications, including multiple myeloma • Robust activity in the context of IMiD-resistant MM cell lines • EP300 controls the expression of critical tra
Slide 13: Expanding the induced proximity toolbox to target lineage dependence
Expanding the induced proximity toolbox to target lineage dependence Induced proximity in controlling biological Rapidly growing array of therapeutic processes approaches Company Confidential & Proprietary Information 13 Stanton BZ, et al., Science (2018) Liu X, et al., ACS Cent Sci (2023)
Slide 14: Acknowledgements
Acknowledgements Biology Pharmacology/DMPK Computational Biology Chemistry Laura La Bonte Mei Yun Lin Dave Lahr Kevin Wilson Qianhe Zhou Brandon Antonakos David Mayhew Wesley Austin Claudia Dominici Brian Ethell Shawn Schiller Mark Zimmerman Protein Degradation Solymar Negretti Hafiz Ahmad Drug Disc