Third Harmonic Bio (THRD) Jefferies London Healthcare Conference 2024 summary

Company overview and lead program

• Focused on therapies for mast cell-mediated inflammatory diseases, with lead compound THB335 targeting chronic spontaneous urticaria (CSU).

• THB335 is a first-in-class, once-daily oral KIT inhibitor currently in phase I trials in healthy volunteers.

• Phase I data expected in Q1 2025 will inform phase II trial design and potential expansion to other indications.

• Strong financial position with $296 million in cash as of September 30, supporting operations through phase II data and beyond.

Clinical development and differentiation

• Phase I data will focus on safety, pharmacokinetics, and tryptase reduction as a biomarker for efficacy.

• Targeting tryptase reduction similar to or slightly below the 83% seen with the first-generation molecule.

• Extensive preclinical work addressed prior liver toxicity by modifying metabolic liabilities, resulting in a distinct and safer profile for THB335.

• Additional efforts to limit blood-brain barrier penetration and testicular toxicity, with ongoing reproductive toxicity studies.

• Oral administration offers patient convenience and physician preference, with potential to differentiate from antibody therapies by reducing anaphylaxis risk.

Market positioning and future plans

• Belief that oral KIT inhibitors can capture significant market share due to convenience and safety profile, despite being later to market.

• Too early to compare directly with other next-generation oral KIT inhibitors; focus remains on generating robust clinical data.

• Post-phase I, the next catalyst is the initiation of a robust phase II dose-ranging trial in CSU, with potential expansion to other mast cell-mediated diseases.

• Severe asthma identified as a promising next indication, with plans to monitor other diseases like EoE, PN, and atopic dermatitis.

• Chronic toxicity studies for asthma will run in parallel with phase II in CSU, enabling future expansion.