THRD Third Harmonic Bio Inc

Third Harmonic Bio, Inc. (Nasdaq: THRD), a clinical-stage biopharmaceutical company focused on advancing the next wave of medicine for dermal, respiratory, and gastrointestinal inflammatory diseases, today announced results from its Phase 1 single and multiple ascending dose (SAD/MAD) clinical trial of THB335 in healthy volunteers. These data are expected to support the advancement of THB335 into a Phase 2 clinical trial in chronic spontaneous urticaria (CSU). The Company is initiating a strategic review process to run in parallel with Phase 2 readiness activities to identify opportunities to maximize shareholder value.

“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,” said Natalie Holles, Chief Executive Officer of Third Harmonic Bio. “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. With our strong balance sheet and disciplined operating strategy, we are well positioned to identify and capitalize on the best opportunities to accelerate that value creation.”

THB335 Phase 1 Clinical Results The Phase 1 SAD (n=48) and 14-day MAD (n=32) clinical trial in healthy volunteers evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics of THB335, a potent and selective oral small molecule inhibitor of KIT. SAD dose levels evaluated were 21 mg, 41 mg, 82 mg, 164 mg, and 205 mg. Food effect was evaluated at the 21mg dose level. MAD dose levels evaluated were once daily 21mg, 41 mg, 82 mg, and 205 mg.

THB335 has shown a half-life of approximately 40 hours, enabling once daily (QD) dosing. Dose-dependent increases in exposure were observed across all SAD and MAD cohorts, with trough plasma exposures exceeding the KIT IC90 at MAD dose levels of 41 mg QD and greater. A mild positive food effect was observed as well.

Pharmacodynamics Dose-dependent reductions in serum tryptase, a biomarker of mast cell activation, were observed in the MAD cohorts, with mean reductions from baseline ranging from 13% to 84% at Day 15. 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.

Safety THB335 was generally safe and well tolerated in the SAD cohorts. There were 3 subjects in the MAD cohorts with isolated, transient asymptomatic transaminase elevations. Two of the 3 subjects received placebo (1 subject in the 21 mg cohort, 1 subject in the 164 mg cohort), and 1 active subject received THB335 in the 164 mg cohort. Transaminase elevations in the 164 mg cohort were largely consistent in time course and magnitude for the placebo and active subjects. Based on review of the data with experts in drug-induced liver injury, management does not believe the single transaminase event in the active subject is drug-related. THB335 plasma metabolite identification data also confirm that the clinical metabolic profile is consistent with the nonclinical profile and lacks evidence for the presence of reactive intermediates.

Consistent with KIT biology, in the MAD cohorts, there were adverse events observed due to hair color change and reductions in hemoglobin and neutrophil counts. These events were largely dose-dependent and resolved in the follow-up period. Cross-study comparisons indicate a greater phlebotomy effect in this study versus the previously completed Phase 1 study for the Company’s first-generation KIT inhibitor, THB001, which may contribute to the greater incidence and severity of hemoglobin adverse events observed in this study.

The full Phase 1 clinical results will be presented as a poster presentation at the upcoming American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress on Sunday, March 2, 2025, at 9:45 a.m. PST.

THB335 Program Next StepsThe Company intends to continue THB335 development activities through the first half of 2025 to prepare for the initiation of a 12-week, placebo-controlled Phase 2 study in CSU by mid-year 2025. Key near-term activities include completion of ongoing subchronic toxicology studies and submission of regulatory filings to position THB335 for Phase 2 initiation.

Corporate Strategic Outlook In parallel with THB335 Phase 2 readiness activities, Third Harmonic Bio is initiating a process to identify opportunities to maximize shareholder value through a strategic transaction and/or business combination. The Company has engaged TD Cowen to advise on this process.

In conjunction with this announcement, the Company is halting all non-THB335 related research and discovery activities and undertaking a reduction in workforce of approximately 50%.

As of December 31, 2024, the Company had approximately $285 million in cash and cash equivalents (unaudited). After accounting for expenses related to THB335 Phase 2 readiness activities, continuing operations, and restructuring costs, the Company estimates it will have cash and cash equivalents in a range of approximately $262 million to $267 million on June 30, 2025.

Conference Call and WebcastThe conference call and webcast will take place today at 8:00 a.m. EST / 5:00 a.m. PST on February 11, 2025. Please click here to pre-register to participate in the conference call and obtain your dial in number and PIN.

A webcast of the live call will be available online under events and presentations within the investor relations section of the Third Harmonic Bio website. Access to the webcast replay will be available approximately two hours after completion of the call and will be archived on the Company’s website for approximately 90 days.

About Third Harmonic Bio, Inc.Third Harmonic Bio is a clinical-stage biopharmaceutical company focused on advancing the next wave of medicine for dermal, respiratory, and gastrointestinal inflammatory diseases through the development of novel, highly selective, small-molecule inhibitors of KIT, a cell surface receptor that serves as the master regulator of mast cell function and survival. Early clinical studies demonstrate that KIT inhibition has the potential to revolutionize the treatment of a broad range of mast-cell-mediated inflammatory diseases. Third Harmonic Bio’s lead product candidate, THB335, is a titratable, oral, small molecule inhibitor that the Company is preparing for potential initiation of a Phase 2 clinical trial for the treatment of chronic spontaneous urticaria. For more information, please visit the Third Harmonic Bio website: www.thirdharmonicbio.com.

Forward-Looking StatementThis press release contains “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the expected timing for clinical trials, progress of the clinical trials and the availability of clinical data from such trials, and regulatory submissions for THB335, planned clinical and development activities and timelines, and the sufficiency of Third Harmonic Bio’s estimated cash balance as of June 30, 2025, statements regarding Third Harmonic Bio’s plans to explore opportunities to maximize stockholder value, the Company’s ability to enter into any agreements or transactions in connection with the exploration of potential strategic transactions, or if entered into, that any such agreements or transactions will be successful or on attractive terms. Forward-looking statements can be identified by words such as: “anticipate,” “intend,” “plan,” “goal,” “seek,” “believe,” “project,” “estimate,” “expect,” “strategy,” “future,” “likely,” “may,” “should,” “will” and similar references to future periods. These statements are subject to numerous risks and uncertainties, including risks and uncertainties related to Third Harmonic Bio’s cash forecasts, ability to advance its product candidates, the receipt and timing of potential regulatory submissions, designations, approvals and commercialization of product candidates, our ability to protect our intellectual property, the timing and results of preclinical and clinical trials, changes to laws or regulations, market conditions, geopolitical events, and further impacts of pandemics or health epidemics, that could cause actual results to differ materially from what Third Harmonic Bio expects. Further information on potential risk factors that could affect Third Harmonic Bio’s business and its financial results are detailed under the heading “Risk Factors” included in Third Harmonic Bio’s Quarterly Report on Form 10-Q for the nine months ended September 30, 2024, filed with the U.S. Securities and Exchange Commission (SEC) on November 7, 2024, and in Third Harmonic Bio’s other filings filed from time to time with the SEC. Third Harmonic Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. 

Investor Contact:Chris Murphycmurphy@thirdharmonicbio.com

Media Contact: Lori Murraylori.murray@thirdharmonicbio.com