Third Harmonic Bio Announces Phase 1 Clinical Results for THB335 and Provides Corporate Strategic Update
Third Harmonic Bio (THRD) has announced positive Phase 1 clinical results for THB335, supporting advancement to Phase 2 trials in chronic spontaneous urticaria (CSU). The trial demonstrated that THB335, a KIT inhibitor, achieved dose-dependent reductions in serum tryptase ranging from 13% to 84%, with multiple dose levels showing potential clinical benefit.
The company reported the drug was generally safe and well-tolerated, with a 40-hour half-life enabling once-daily dosing. While some adverse events were observed, including hair color changes and blood count reductions, these were largely dose-dependent and resolved during follow-up.
THRD is initiating a strategic review process while preparing for Phase 2 trials, including a workforce reduction of 50%. The company maintains a strong financial position with approximately $285 million in cash as of December 2024, projecting $262-267 million by June 2025 after accounting for Phase 2 preparations and restructuring costs.
Third Harmonic Bio (THRD) ha annunciato risultati positivi dalla fase 1 degli studi clinici per THB335, supportando il passaggio alla fase 2 delle prove cliniche per l'orticaria spontanea cronica (CSU). La sperimentazione ha dimostrato che THB335, un inibitore del KIT, ha raggiunto riduzioni dose-dipendenti della triptasi sierica che vanno dal 13% all'84%, con diversi livelli di dosaggio che mostrano un potenziale beneficio clinico.
L'azienda ha riferito che il farmaco era generalmente sicuro e ben tollerato, con una emivita di 40 ore che consente un dosaggio giornaliero. Sebbene siano stati osservati alcuni eventi avversi, inclusi cambiamenti nel colore dei capelli e riduzioni della conta ematica, quest'ultimi erano per lo più dose-dipendenti e si sono risolti durante il follow-up.
THRD sta avviando un processo di revisione strategica mentre si prepara per la fase 2 degli studi, inclusa una riduzione della forza lavoro del 50%. L'azienda mantiene una solida posizione finanziaria con circa 285 milioni di dollari in contanti entro dicembre 2024, prevedendo tra 262 e 267 milioni di dollari entro giugno 2025, dopo aver considerato le preparazioni e i costi di ristrutturazione per la fase 2.
Third Harmonic Bio (THRD) ha anunciado resultados positivos de la fase 1 de ensayos clínicos para THB335, lo que apoya su avance a ensayos de fase 2 en urticaria espontánea crónica (CSU). El ensayo demostró que THB335, un inhibidor de KIT, logró reducciones dependientes de la dosis en la triptasa sérica que varían del 13% al 84%, con múltiples niveles de dosis mostrando un posible beneficio clínico.
La empresa informó que el medicamento fue generalmente seguro y bien tolerado, con una vida media de 40 horas que permite la dosis una vez al día. Si bien se observaron algunos eventos adversos, incluidos cambios en el color del cabello y reducciones en el recuento sanguíneo, estos fueron en gran medida dependientes de la dosis y se resolvieron durante el seguimiento.
THRD está iniciando un proceso de revisión estratégica mientras se prepara para los ensayos de fase 2, incluyendo una reducción del 50% en la fuerza laboral. La empresa mantiene una sólida posición financiera con aproximadamente 285 millones de dólares en efectivo a partir de diciembre de 2024, proyectando entre 262 y 267 millones de dólares para junio de 2025 después de tener en cuenta los costos de preparación y reestructuración de la fase 2.
Third Harmonic Bio (THRD)는 만성 자발적 두드러기(CSU)에 대한 THB335의 1상 임상 결과가 긍정적이었다고 발표하며 2상 시험으로 나아갈 것을 지원하고 있습니다. 이 시험은 KIT 억제제인 THB335가 혈청 트립타제에서 13%에서 84%까지 용량 의존적인 감소를 달성했으며, 여러 용량 수준이 잠재적인 임상 효과를 보였다는 것을 보여주었습니다.
회사는 이 약물이 일반적으로 안전하고 잘 견딜 수 있으며 40시간의 반감기로 인해 하루에 한 번 복용할 수 있다고 보고했습니다. 모발 색 변화와 혈액 수 감소를 포함한 일부 부작용이 관찰되었지만, 이러한 부작용은 주로 용량 의존적이며 추적 조사 중에 해결되었습니다.
THRD는 2상 시험을 준비하는 동안 전략 검토 프로세스를 시작하고 있으며, 인력의 50%를 감축할 계획입니다. 회사는 2024년 12월 기준으로 약 2억 8500만 달러의 현금을 보유하고 있으며, 2상 준비 및 재구성 비용을 고려하여 2025년 6월까지 2억 6200만에서 2억 6700만 달러를 예측하고 있습니다.
Third Harmonic Bio (THRD) a annoncé des résultats positifs de la phase 1 des essais cliniques pour THB335, soutenant ainsi son avancement vers des essais de phase 2 pour l'urticaire spontanée chronique (CSU). L'essai a démontré que THB335, un inhibiteur du KIT, a atteint des réductions dose-dépendantes de la tryptase sérique allant de 13% à 84%, avec plusieurs niveaux de dose montrant un bénéfice clinique potentiel.
L'entreprise a rapporté que le médicament était généralement sûr et bien toléré, avec une demi-vie de 40 heures permettant une posologie quotidienne. Bien que certains événements indésirables aient été observés, y compris des changements de couleur des cheveux et des réductions des comptes sanguins, ceux-ci étaient largement dépendants de la dose et se sont résolus lors du suivi.
THRD est en train d'initier un processus de révision stratégique tout en se préparant pour les essais de phase 2, y compris une réduction de la main-d'œuvre de 50%. L'entreprise maintient une solide position financière avec environ 285 millions de dollars en liquidités à partir de décembre 2024, prévoyant entre 262 et 267 millions de dollars d'ici juin 2025 après avoir tenu compte des préparations et des coûts de restructuration pour la phase 2.
Third Harmonic Bio (THRD) hat positive Ergebnisse aus der Phase-1-Studie für THB335 bekannt gegeben, die den Schritt zu Phase-2-Studien bei chronischer spontaner Urtikaria (CSU) unterstützen. Die Studie zeigte, dass THB335, ein KIT-Inhibitor, dosisabhängige Reduktionen der Serumtriptase von 13% bis 84% erzielte, wobei mehrere Dosislevels potenzielle klinische Vorteile aufwiesen.
Das Unternehmen berichtete, dass das Medikament im Allgemeinen sicher und gut verträglich war, mit einer Halbwertszeit von 40 Stunden, die eine einmal tägliche Einnahme ermöglicht. Obwohl einige Nebenwirkungen beobachtet wurden, einschließlich Farbveränderungen der Haare und Reduzierungen der Blutzahlen, waren diese größtenteils dosisabhängig und klärten sich während der Nachverfolgung.
THRD leitet einen strategischen Überprüfungsprozess ein und bereitet sich gleichzeitig auf die Phase-2-Studien vor, einschließlich einer Reduzierung der Belegschaft um 50%. Das Unternehmen hat eine starke finanzielle Position mit etwa 285 Millionen Dollar in bar zum Dezember 2024 und prognostiziert zwischen 262 und 267 Millionen Dollar bis Juni 2025, nachdem die Kosten für Vorbereitung der Phase 2 und Umstrukturierungen berücksichtigt wurden.
- Phase 1 trial results support advancement to Phase 2 in CSU
- Strong cash position of $285 million as of December 2024
- Significant tryptase reduction (13-84%) at multiple dose levels
- 40-hour half-life enabling once-daily dosing
- 50% workforce reduction implemented
- Halting all non-THB335 research and discovery activities
- Adverse events observed including hair color changes and blood count reductions
- Strategic review process indicates possible sale or merger consideration
Insights
The Phase 1 results for THB335 demonstrate several compelling attributes that position it well for Phase 2 development in chronic spontaneous urticaria (CSU). The 40-hour half-life enabling once-daily dosing represents a significant advantage for patient compliance compared to multiple daily dosing regimens. The dose-dependent serum tryptase reductions of up to 84% at therapeutic doses (41-164mg) strongly support target engagement and potential clinical efficacy.
The safety profile appears manageable, with transaminase elevations occurring in both placebo and treatment groups, suggesting these may not be drug-related. The observed KIT-related effects on hair color and blood counts are mechanism-based and reversible, indicating a predictable safety profile that should be monitorable in Phase 2.
However, the parallel announcement of a 50% workforce reduction and strategic review process signals a significant shift in corporate strategy. With
The engagement of TD Cowen for strategic review while maintaining Phase 2 readiness activities represents a dual-track strategy that could accelerate value creation. This approach allows the company to maintain program momentum while exploring strategic options, potentially creating competitive tension among interested parties.
THB335 Phase 1 data support advancement into Phase 2 clinical trial in chronic spontaneous urticaria (CSU)
Company initiating process to leverage balance sheet strength to maximize shareholder value
Cash and cash equivalents of approximately
Management to hold conference call/webcast today Tuesday, February 11, 2025, at 8:00 a.m. EST to discuss clinical results and corporate next steps
SAN FRANCISCO, Feb. 11, 2025 (GLOBE NEWSWIRE) -- 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
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 Steps
The 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
As of December 31, 2024, the Company had approximately
Conference Call and Webcast
The 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 Statement
This 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 Murphy
cmurphy@thirdharmonicbio.com
Media Contact:
Lori Murray
lori.murray@thirdharmonicbio.com
FAQ
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