Guggenheim 3rd Annual Healthcare Innovation Conference - FOGHORN THERAPEUTICS INC

Financial Performance:

• Post-restructuring in October, the company maintains a cash runway extending into the second half of 2029.
• Capital is allocated to fund the EP300 program up to IND approval, the INI program through First-in-Human (FIH) initiation, the CBP program's in vivo pharmacology, and the induced proximity program's chemical matter validation.
• Specific revenue, profit margins, or debt figures were not disclosed as the company remains in the pre-revenue clinical development stage.
• Deferred revenue and cash flow metrics are not applicable given the absence of commercial products.

Guidance and Future Outlook:

• EP300 Program: IND expected by end of 2027; potential for strategic partnership or financing prior to clinical entry.
• INI Program: Non-GLP toxicology studies slated for December; First-in-Human (FIH) studies targeted before end of 2027.
• CBP Program: Go/No-Go decision expected in the first half of 2027 following human dose projection completion and combination studies with CDK4-6 inhibitors.
• Induced Proximity Platform: Goal to demonstrate in vitro proof of concept and initiate partnership discussions by the first half of 2027.
• Long-term Goal: Generation of Safety and Dose Assignment Maximum Adverse Drug (SADMAD) package and initial patient data for the INI program by Q3 2028.

Business Segments and Product Lines:

• Strategic Pivot: Discontinued the SMARCA2 (FHD-909) program and moved away from chromatin remodeling and synthetic lethality approaches due to lack of clinical translation despite robust preclinical data.
• EP300 Program: Targeting hematological malignancies (multiple myeloma, DLBCL); focuses on a once-weekly subcutaneous formulation with high selectivity (>100x to 10,000x) over CBP to mitigate thrombocytopenia; parallel development with Cellcentric's dual-targeting molecule.
• CBP Program: Targeting ER-positive breast cancer; currently delayed due to a CRO facility loss in May requiring relocation of in vivo models; formulation is a once-weekly long-acting injectable.
• INI Program: Novel program targeting ulcerative colitis and Crohn's disease (IBD); highly selective inhibitor with preclinical efficacy comparable to an IL-12/23P40 antibody; no public competition identified for this specific target.
• Induced Proximity Platform: New capability harnessing the endoplasmic reticulum to degrade secreted cytokines (IL-12, IL-23, TNF-alpha) and transmembrane proteins (PD-L1, EGFR); transitioning toward molecular glues.

Market and Competitive Landscape:

• Multiple Myeloma: Recognized as a chronic disease landscape where patients eventually relapse; opportunity identified for orthogonal mechanisms in later lines of therapy (2nd, 3rd, 4th) in combination with BCMA, CD38, IMiDs, or proteasome inhibitors.
• Selectivity Advantage: The EP300 program aims to outperform dual CBP/EP300 degraders by eliminating CBP inhibition, addressing the rate-limiting toxicities (cytopenia) seen in current peer programs.
• Partnership Strategy: Open to strategic partnerships for oncology indications (myeloma, breast, prostate, lung) to manage combination complexity and capital requirements; multiple pharma conversations ongoing regarding the induced proximity platform.

Risks and Challenges:

• Clinical Failure: The SMARCA2 program failure highlights the risk of preclinical biology not translating to clinical efficacy in the oncology space.
• Operational Delays: The CBP program faced delays due to a CRO losing its animal facility, necessitating a restart of in vivo studies.
• Toxicity Management: Potential for cytopenic side effects if selectivity between CBP and EP300 is not sufficiently optimized.
• Early Stage Uncertainty: The induced proximity and INI programs are in very early stages (pre-GLP tox), carrying high technical and timeline risks.

Management Commentary and Tone:

• Management expressed a pragmatic and transparent tone, acknowledging the "flawed understanding of biology" in the SMARCA2 program rather than attributing failure to molecule quality.
• CEO Adrian Gottschalk demonstrated strategic confidence in the company's ability to evolve its platform from chromatin targets to broader protein degradation and induced proximity, emphasizing "novel biology" in the ER.
• The tone regarding the SMARCA2 target was skeptical but not absolute, advising caution on capital allocation for similar programs while acknowledging "hope springs eternal" in the industry.
• Management conveyed strong commitment to the new pipeline, highlighting the unique selectivity and first-in-class potential of the INI and EP300 programs.

Analyst Questions and Answers:

• SMARCA2 Validation: Clarified that the target itself is likely not the issue, but the synthetic lethality concept or specific biology approach failed; management remains skeptical of other industry programs on this target.
• EP300 Selectivity: Explained that 100x selectivity may be sufficient; selectivity is achieved through a combination of binding chemistry and degrader geometry engineering.
• Myeloma Market Fit: Discussed that the EP300 mechanism offers an orthogonal approach to existing CD38, BCMA, IMiD, and proteasome inhibitor classes, fitting well in later-line combination therapies.
• Partnering Plans: Confirmed openness to partnering the EP300 program, potentially even pre-clinically, to navigate the complex combination therapy requirements in competitive oncology spaces.
• Timeline Specifics: Provided detailed milestones for non-GLP tox (INI) in December, IND (EP300) by end of 2027, and Go/No-Go (CBP) in H1 2027.

Other Key Points:

• The company has successfully pivoted its platform capabilities to include "induced proximity" to target proteins previously considered undruggable.
• Preclinical data for the INI program shows disease activity control equivalent to IL-12/23P40 antibodies in murine colitis models.
• The EP300 program benefits from a backup oral delivery effort, though the primary candidate is subcutaneous.
• Management plans to withhold detailed cytokine impact data until the first half of the following year.