Third Harmonic Bio (THRD) TD Cowen Chronic Urticaria Summit summary

Company strategy and clinical development

• Focused on developing oral wild-type KIT inhibitors for mast cell-mediated diseases with significant unmet need.

• Lead candidate THB335 is in phase I, with data expected in Q1 next year and rapid transition planned to phase II in chronic spontaneous urticaria (CSU).

• Phase II will be a multi-dose, efficacy-powered study aiming for direct progression to registration studies.

• Operational efforts and parallel activities are underway to expedite the phase I to II transition.

• Strong cash position ($255M) ensures funding through phase II CSU readout and continued execution.

Scientific rationale and differentiation

• KIT is a validated target for mast cell diseases, offering broad utility due to its upstream regulatory role.

• Oral small molecule approach offers patient and physician preference, dose titration flexibility, and avoids antibody-related anaphylaxis risk.

• Oral KIT inhibitors may provide best-in-disease efficacy and durability, with potential commercial advantages over injectables.

• Biomarker serum tryptase is used as a powerful efficacy correlate in early studies.

Clinical experience and molecule evolution

• Initial candidate THB001 showed strong efficacy (4/5 responders at suboptimal dose) but was halted due to hepatotoxicity from a metabolic liability.

• Structural modifications in THB335 eliminated the problematic metabolic pathway, improved PK, solubility, and selectivity, and extended IP protection to 2043.

• Safety and selectivity profiles of THB335 are robust, with no off-target kinase activity and reversible on-target effects.