Third Harmonic Bio (THRD) Morgan Stanley 22nd Annual Global Healthcare Conference summary

KIT inhibition and disease targeting

• KIT is a well-understood target essential for mast cell function, making it attractive for treating mast cell-mediated diseases like urticaria, atopic dermatitis, chronic rhinosinusitis, asthma, and certain GI disorders.

• KIT inhibition offers broad utility by blocking all mast cell activation pathways, potentially providing best-in-disease efficacy for conditions with high unmet need.

• Expansion beyond urticaria is planned, with severe asthma highlighted as a key future indication due to commercial opportunity and lack of new oral therapies.

• Indication expansion strategy will be refined after phase 1 data, with a focus on diseases where proof of concept can be achieved in 12-week studies.

Competitive landscape and differentiation

• Current urticaria treatments have limited efficacy; only about half of patients respond to antihistamines, and Xolair has low penetration due to safety and monitoring requirements.

• Oral KIT inhibitors may offer advantages over biologics, including lower anaphylaxis risk, flexible dosing, and patient convenience.

• Early data suggest KIT inhibition provides superior efficacy compared to other mechanisms in development, such as BTK, Syk, and Siglec inhibitors.

• Differentiation between small molecule and antibody approaches centers on safety and dosing flexibility.

Clinical development and learnings

• First-generation KIT inhibitor showed strong efficacy but was discontinued due to drug-induced liver injury; mechanistic studies identified and addressed the metabolic liability in the next-generation compound.

• Next-generation molecule (THB335) retains potency and selectivity, with improved metabolic profile, solubility, and peripheral restriction, and is expected to be a once-daily drug.

• Extensive preclinical work, including long-term metabolic and hepatotoxicity studies, supports the safety of the new compound.

• Patent protection for the new molecule extends into the early 2040s.