FOGHORN THERAPEUTICS INC. (FHTX) - GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - FOGHORN THERAPEUTICS INC

Financial Performance:

• Cash runway extends into the second half of 2029, following a restructuring and capital raise completed in early October.
• Funding is sufficient to support the EP300 program to IND, advance the induced proximity platform to chemical matter and partnership discussions, and sustain CBP in vivo pharmacology studies.
• The company has approximately one year of cash runway remaining post-SADMAD (Single Ascending Dose) package generation for the INI program.
• No specific revenue or earnings figures were provided as the company remains in the pre-commercial development stage.

Guidance and Future Outlook:

• EP300 Program: IND filing targeted by the end of 2027; potential strategic partnership or clinical financing expected prior to clinic initiation.
• INI Program: Non-GLP toxicology studies (rat and dog, 2-week) scheduled for December; GLP toxicology to follow; First-in-Human (FIH) studies targeted before the end of 2027.
• INI Program Data: Expected to release SADMAD package and potential disease activity data by Q3 2028.
• CBP Program: "Go/No-Go" decision expected in the first half of 2028 following completion of in vivo pharmacology and human dose projections.
• Induced Proximity: Aiming to demonstrate in vitro proof-of-concept in H1 2027, with potential Business Development (BD) activity in 2027.

Business Segments and Product Lines:

• SMARCA2 (FHD 909): Program discontinued; decision made not to proceed forward despite a safe, well-tolerated clinical profile due to a lack of biological translation in oncology.
• EP300: Focus on hematological malignancies (multiple myeloma, DLBCL); parallel efforts include a subcutaneous once-weekly formulation and potential oral backup. Data from partner Cellcentric's dual CBP-EP300 degrader shows compelling efficacy, supporting the selectivity strategy of Foghorn's monoselective EP300 approach to reduce thrombocytopenia.
• CBP: Targeting ER-positive breast cancer; delayed due to a CRO losing its animal facility in August, necessitating re-evaluation with new models. Program is a once-weekly long-acting injectable currently in dose range-finding studies, pending combination work with CDK4-6 and SERDs.
• INI Program: Novel target for Inflammatory Bowel Disease (Ulcerative Colitis, Crohn's); data shows efficacy comparable to anti-IL-12/23P40 antibodies in murine models. No other public programs target this specific INI setting.
• Induced Proximity/ER Platform: Leveraging endoplasmic reticulum biology to degrade secreted cytokines (IL-12, IL-23, IL-17, TNF-alpha) and transmembrane proteins (PD-L1, EGFR). Platform includes molecular glue and binder screening.

Market and Competitive Landscape:

• Multiple Myeloma: Addressed as a chronic disease with a expanding patient population; opportunity exists in 2nd-4th line settings for orthogonal mechanisms that avoid cumulative cytopenia when combined with existing standard-of-care therapies (CD38, BCMA, IMiDs, proteasome inhibitors).
• Selectivity Advantage: Foghorn's EP300 degraders demonstrate 100x to 10,000x selectivity over CBP, contrasting with dual-targeting approaches that may limit tolerability in combination regimens.
• Differentiation: The INI program targets a "blue ocean" opportunity in IBD with no known public competitors for this specific target in the INI space.

Risks and Challenges:

• Target Validation Risk: The FHD 909 program highlighted that preclinical synthetic lethality data did not translate clinically, suggesting flaws in biological understanding rather than molecule quality.
• Development Delays: The CBP program faced a delay due to a third-party CRO losing its animal facility, requiring a restart of in vivo modeling.
• Clinical Translation: Skepticism expressed regarding other industry programs targeting SMARCA2, though the company acknowledges the inherent uncertainty of clinical trials.
• Combination Complexity: Future programs in oncology will require extensive combination testing, potentially necessitating partnership to manage the resource intensity.

Management Commentary and Tone:

• CEO Adrian Gottschalk maintained a pragmatic and confident tone, framing the SMARCA2 discontinuation as a strategic pivot away from chromatin complexes toward "clear and frank dependency" and challenging targets using their platform.
• Management emphasized a shift from synthetic lethality to induced proximity and degradation of difficult-to-drug proteins (cytokines, transmembrane proteins).
• Tone regarding the INI program was highly positive, citing "striking effects" in IBD models.
• Management indicated an open-minded approach to partnering, particularly for competitive oncology indications like multiple myeloma and breast cancer, while retaining flexibility for internal development of the INI program.

Analyst Questions and Answers:

• SMARCA2 Validation: Analyst asked if the FHD 909 failure invalidates the target; Management stated the biology is likely flawed for their specific approach and they would be skeptical of allocating capital to similar programs, though they did not rule out all future possibilities.
• EP300 Selectivity: Analyst queried the selectivity threshold; Management confirmed 100x-10,000x selectivity and noted that geometry engineering in degraders enhances this.
• Partnership Strategy: Management clarified that for large, competitive oncology indications, a strategic partner is likely needed to manage combination studies, potentially before IND.
• Timeline Updates: Management provided specific milestones for IND filings (EP300 end of 2027, INI before end of 2027) and toxicology schedules (INI non-GLP in December).

Other Key Points:

• The company is moving away from the "first chapter" of chromatin remodeling/BAF complex targeting to a broader platform application.
• Cellcentric's data on dual CBP-EP300 degraders (presenting at ASH) is viewed as validating the space while reinforcing Foghorn's advantage in monoselectivity.
• The company holds a "laundry list" of targets degraded via the ER-induced proximity platform, including cytokines and immune checkpoints.
• No revenue is currently generated; the focus is entirely on de-risking the pipeline and positioning for partnerships.