Third Harmonic Bio will lay off half of its workforce, the biotech has said as it prepares to take its chronic spontaneous urticaria (CSU) candidate into phase 2.
The company announced results for a phase 1 trial of various doses of the KIT inhibitor, dubbed THB335, in healthy volunteers this morning. Dose-dependent reductions in serum tryptase, a biomarker of mast cell activation, were seen in the multiple ascending dose (MAD) section of the trial, Third Harmonic said.
Specifically, mean reductions ranged from 13% to 84% at Day 15, Third Harmonic said in the Feb. 11 release. “The 41 mg, 82 mg and 164 mg dose cohorts all reached serum tryptase reduction levels believed to have the potential to provide clinical benefit in the treatment of chronic spontaneous urticaria,” the biotech explained.
The MAD cohort also saw adverse events such as hair loss and reductions in hemoglobin and neutrophil counts. These side effects were “consistent with KIT biology” and resolved in the study’s follow-up period, Third Harmonic said.
The company suggested that a greater phlebotomy effect—physical changes related to drawing blood—in this trial compared to a previous phase 1 study of the biotech’s first-generation KIT inhibitor THB001, may have “contribute[d] to the greater incidence and severity of hemoglobin adverse events observed in this study.”
That study of THB001 was marred by its own side effects, with Third Harmonic pulling the plug on the trial back in 2022 after observing raised liver enzymes in two patients who had received the 200 mg dose.
Despite side effects now casting a shadow over the THB335 trial as well, the company said it will complete subchronic toxicology studies and prepare for a 12-week, placebo-controlled phase 2 trial of THB335 in CSU, with kick-off expected by mid-year.
“From a drug development perspective, we expect the results of the phase 1 study will provide a basis for the advancement of THB335 into a phase 2 study in CSU,” Third Harmonic’s CEO Natalie Holles said in the release.
“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,” Holles added.
In practice, this means laying off 50% of the biotech’s workforce, as well as halting work on all R&D not tied to THB335. The company had 51 full-time employees at the end of September 2024, according to a Securities and Exchange Commission filing last year.
The company has also brought in TD Cowen to help it “identify opportunities to maximize shareholder value through a strategic transaction and/or business combination.”
Third Harmonic entered 2025 with around $285 million in cash. Taking into account the current trajectory for THB335 as well as the layoffs, the company said it expects to have retained between $262 million and $267 million by the middle of the year.