Third Harmonic Bio discontinues Phase 1b study of THB001

Third Harmonic Bio announced that the company has made the decision to discontinue the ongoing Phase 1b study of its investigational drug candidate, THB001, after observing asymptomatic liver transaminitis in two subjects enrolled in the first dose cohort of 200mg BID. The Company is initiating nonclinical studies to elucidate the mechanism for the observed transaminitis, which was not predicted by extensive GLP toxicology studies of THB001 nor observed in the Company’s Phase 1a study. In parallel with the early clinical development of THB001, the Company has conducted an extensive medicinal chemistry effort to identify chemically distinct next-generation oral wild-type KIT inhibitors and has advanced multiple candidate molecules into exploratory toxicology studies. The Company intends to nominate a development candidate from this program in 2023. The Phase 1b clinical trial in chronic inducible urticaria was designed to evaluate the safety and tolerability, efficacy and pharmacokinetics of three dose levels of THB001 over 12 weeks of treatment. Five subjects were enrolled in the first dose cohort of 200mg BID. The first subject completed the full 12-week dosing period with no signs or symptoms of liver toxicity. The second and third subjects presented with elevations in alanine transaminase and aspartate transaminase at their week 8 study visits, and dosing was halted for both subjects. All other laboratory and diagnostic measures have indicated no change in liver function in either subject and both subjects remain clinically asymptomatic. No alternate causes for the transaminitis have been identified, and the subjects continue to be closely monitored. Dosing of the fourth and fifth subjects enrolled has been stopped by the Company at weeks 4 and 2 of dosing, respectively, and neither of these subjects has any signs or symptoms of liver toxicity to date. Clinical follow-up of the five enrolled subjects will continue per protocol, but no additional subjects will be enrolled in the trial. Preliminary analyses show evidence of pharmacodynamic and clinical activity at the 200mg BID dose. The Company plans to present the full data set from the five enrolled subjects at an upcoming scientific conference, and to provide an update on overall corporate strategy and outlook in early 2023.