Third Harmonic Bio Announces Phase 1 Results and Strategic Restructuring

Third Harmonic Bio, a biotechnology company focusing on chronic spontaneous urticaria (CSU) treatments, has revealed promising phase 1 trial results for its KIT inhibitor THB335, while simultaneously announcing a significant restructuring of its operations.

Phase 1 Trial Results Show Promise and Challenges

The phase 1 trial of THB335 in healthy volunteers demonstrated dose-dependent reductions in serum tryptase, a key biomarker of mast cell activation. Mean reductions ranged from 13% to 84% at Day 15, with the 41 mg, 82 mg, and 164 mg dose cohorts reaching levels believed to have potential clinical benefit in CSU treatment.

However, the trial also revealed notable adverse events, including hair loss and reductions in hemoglobin and neutrophil counts. Third Harmonic stated these side effects were "consistent with KIT biology" and resolved during the study's follow-up period. The company suggested that a greater phlebotomy effect in this trial compared to a previous study of their first-generation KIT inhibitor, THB001, may have contributed to the increased incidence and severity of hemoglobin-related adverse events.

Strategic Restructuring and Future Plans

Despite the side effects observed in the THB335 trial, Third Harmonic has decided to proceed with a 12-week, placebo-controlled phase 2 trial in CSU patients, expected to commence by mid-2025. To support this decision, the company has announced a strategic restructuring, including:

1. A 50% reduction in workforce, affecting approximately 25 employees based on the company's reported 51 full-time staff as of September 2024.
2. Halting all R&D activities not directly related to THB335.
3. Engaging TD Cowen to explore strategic transactions and/or business combinations to maximize shareholder value.

CEO Natalie Holles commented on the restructuring, stating, "As we evaluate the competitive landscape and current market dynamics, we believe the right thing for our stakeholders is to evaluate a full range of strategic transactions and/or business combinations to maximize value creation across all assets in the company."

Financial Outlook

Third Harmonic entered 2025 with approximately $285 million in cash. Following the announced restructuring and continued development of THB335, the company projects a cash position between $262 million and $267 million by mid-2025.

This strategic shift comes in the wake of Third Harmonic's previous setback in 2022, when the company halted a trial of its first-generation KIT inhibitor, THB001, due to elevated liver enzymes observed in two patients receiving the 200 mg dose.

As Third Harmonic Bio navigates these challenges, the pharmaceutical industry will be closely watching the progress of THB335 and the company's efforts to maximize value for its stakeholders.