Guggenheim 3rd Annual Healthcare Innovation Conference - FOGHORN THERAPEUTICS INC

Explicit Guidance:

• Cash Runway: Current cash position extends into the second half of 2029, covering the EP300 IND, INI non-GLP/GLP toxicology, CBP in vivo studies, and induced proximity partnership discussions; includes a full year of cash post-SADMAD (Single Ascending Dose Maximum Attempted Dose) for the INI program.
• EP300 Clinical Milestones: IND submission expected by end of 2027; potential strategic partnership sought prior to clinic entry or concurrently with dose escalation; combination with Cellcentric's dual CBP/EP300 degrader (Obradib) anticipated to be presented at ASH.
• INI Program Clinical Milestones: Non-GLP toxicology studies (rat and dog) scheduled to begin in December; GLP toxicology and First-in-Human (FIH) study initiation targeted before end of 2027; goal to generate Single Ascending Dose Maximum (SADMAD) data and initial disease patient information by Q3 2028.
• CBP Program Milestones: Go/No-Go decision expected in the first half of the next year following in vivo pharmacology and human dose projections; program currently paused due to CRO facility loss, requiring re-evaluation of in vivo models.
• Induced Proximity Program: Expected to present in vitro proof-of-concept data demonstrating degradation of targets (IL-12, IL-23, IL-17, TNF-alpha, PD-L1, EGFR) and combination with machinery by the first half of the next year; potential business development activities anticipated in 2027.
• Data Disclosures: Additional preclinical data regarding the INI program (cytokine impact) expected in the first half of the upcoming year.

Business-Segment Outlook:

• Therapeutic Area Shift: Strategic pivot from chromatin remodeling (BAF complex) and synthetic lethality to novel INI programs for Inflammatory Bowel Disease (Ulcerative Colitis, Crohn's) and targeting secreted/transmembrane proteins via endoplasmic reticulum (ER) induction.
• EP300 Program: Focused on hematological malignancies, specifically multiple myeloma (potentially second-line and beyond) and diffuse large B-cell lymphoma; aims to eliminate thrombocytopenia by selectively targeting EP300 over CBP, offering an orthogonal mechanism to BCMA, CD38, IMiDs, and proteasome inhibitors.
• INI Program: Initial focus on IBD with preclinical data showing efficacy comparable to IL-12/23p40 antibodies in murine models; potential expansion into psoriasis.
• CBP Program: Targeting ER-positive breast cancer; program timeline delayed due to CRO facility loss; formulation is a once-weekly long-acting injectable, with future potential for oral delivery.
• Platform Evolution: Leveraging capabilities in difficult-to-produce proteins and degraders to expand into induced proximity, specifically targeting ER-resident machinery to degrade secreted cytokines and transmembrane proteins.

Market and Competitive Outlook:

• Multiple Myeloma Landscape: Acknowledges market saturation with four primary mechanisms (CD38, BCMA, IMiD, proteasome inhibitors) but identifies significant unmet need due to relapse rates and chronic disease nature; positions EP300 selective targeting as a solution to reduce cytopenia in combination therapies.
• Competitive Differentiation: Claims superior selectivity for EP300 over CBP (100-fold to 10,000-fold) compared to dual-targeting competitors; suggests the "right threshold" for selectivity may be lower than 100-fold.
• Target Validation: Notes industry validation for dual CBP/EP300 targeting by competitors (e.g., Cellcentric, Prelude) but expresses skepticism regarding the SMARCA2 target given lack of clinical translation despite robust molecule engineering.
• Novelty Claim: Asserts the INI target is unique in the public domain for IBD, with no other entities currently working on this specific target.

Macro / Industry Outlook:

• Biotech Capital Environment: Management notes "hope springs eternal" despite skepticism in allocating capital to targets with failed clinical translation; emphasizes the necessity of clinical trials to validate biology.
• Partnership Feasibility: Open to strategic partnerships for oncology indications (lung, prostate, breast, multiple myeloma) due to the complexity of running numerous combination trials; views the INI and induced proximity platforms as "very much open for partnering."
• Structural Changes: Moving away from "first chapter" chromatin strategies to broader protein degradation and induced proximity, driven by the realization that the initial synthetic lethality hypothesis was flawed.

Strategic Initiatives:

• Restructuring: Completed restructuring in October to optimize cash usage and extend runway to late 2029.
• Partnership Strategy: Proactively seeking strategic partners for EP300 and the induced proximity platform; open to financing INI clinical entry if economics dictate.
• Technology Development: Investing in engineering selectivity within degrader molecules and validating the endoplasmic reticulum-induced proximity platform for broad cytokine degradation.
• Pipeline Diversification: Shifting resources entirely to the INI (IBD) and EP300 (Oncology) programs while halting the FHD909 (SMARCA2) and CBP (Breast Cancer) programs in their prior configurations.

Risks and Headwinds to Outlook:

• Clinical Failure Risk: High risk associated with the underlying biology of the SMARCA2/BAF complex, leading to a strategic withdrawal from that approach based on clinical non-translation.
• Operational Delays: CBP program delayed significantly due to a CRO losing its entire animal facility, requiring a restart of in vivo modeling.
• Biology Validation: Uncertainty remains regarding whether the INI target will successfully translate to human efficacy despite robust murine data; skepticism expressed regarding the viability of SMARCA2 as a target for the broader industry.
• Regulatory/Timing: All clinical timelines (IND, FIH, SADMAD) are contingent on successful toxicology studies (non-GLP/GLP) planned for December and early 2027.

Management Tone on the Future:

• Confidence: High confidence in the evolution of the platform to address "clear and frank dependency" in oncology and complex protein targets in IBD; optimistic about the selectivity advantages of the EP300 program.
• Caution: Skeptical regarding SMARCA2 and synthetic lethality broadly; explicitly states they would be "skeptical" allocating capital to that target if on a board.
• Pragmatism: Willing to pivot quickly if data does not support the hypothesis; emphasizes that the company has "turned the page" on chromatin/synthetic lethality without regret, viewing it as a learning phase.
• Transparency: Open about delays (CBP) and the specific reasons for program termination (biology flaw), reinforcing credibility.

Miscellaneous:

• Collaboration Status: Collaboration with Lilly on FHD909 has concluded; collaboration with Cellcentric on the dual CBP/EP300 program is active with shared interest in ASH data.
• Formulation Specifics: EP300 program utilizes a once-a-week subcutaneous formulation; backup efforts may yield an oral option.