THB001 / Third Harmonic Bio - LARVOL DELTA

Emerging IgE and non-IgE targeted therapies for chronic urticaria. (PubMed, Ann Allergy Asthma Immunol) - "Dupilumab received FDA approval for antihistamine refractory chronic spontaneous urticaria (CSU) supporting the targeting of type-2 cytokines, IL-4 and IL-13, in this disease. Bruton's tyrosine kinase (BTK) inhibitors show promise, with remibrutinib receiving FDA approval and demonstrating significant reductions in UAS7 in Phase 3 trials. c-Kit (c-Kit or KIT) inhibition with barzolvolimab shows robust efficacy with sustained effects post-treatment...Although some programs have been discontinued due to safety concerns or lack of efficacy such as fenebrutinib (BTK inhibitor), THB001 (c-Kit inhibitor), EP262 (MRGPRX2 antagonist), tezepelumab (anti- TSLP), as well as lirentelimab and AK006 (Siglec-targeting agents), these studies have informed many of the other positive studies. In summary, over the last year, we have seen the CU pipeline mature with multiple Phase 3 programs and new approvals representing diverse mechanisms of action. Nevertheless, significant..."

Journal • Review • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • IL13 • IL4 • TSLP

Late Breaking Abstract - Reducing mast cells mitigates development of allergic asthma features (ERS 2025) - "THB001 effectively reduced mast cell numbers and suppressed HDM-induced contractions ex vivo and in vivo, while also mitigating airway inflammation, hyperresponsiveness, and remodeling. These findings support targeting the mast cell signaling pathways as a potential allergic asthma treatment."

Late-breaking abstract • Asthma • Immunology • Inflammation • Respiratory Diseases

Effectiveness of THB001, A Selective KIT Inhibitor, in Uncovering Mast Cell Function in Asthma (ATS 2025) - "In vitro, THB001 effectively suppressed the contractions in guinea pig trachea to HDM. In vivo, THB001 markedly inhibited the HDM-induced asthmatic features such as early allergic reaction, airway inflammation, airway hyperresponsiveness, and remodeling. These results indicate that allergic asthma is caused by activation of mast cells and that inhibiting this action is a promising treatment of asthma."

Asthma • Immunology • Inflammation • Respiratory Diseases • IL4 • IL5

Third Harmonic Bio Announces Third Quarter 2024 Financial Results (GlobeNewswire) - "The Phase 1 SAD/MAD clinical trial of THB335 is being conducted in healthy volunteers to assess safety and tolerability, characterize pharmacokinetics, and to measure the pharmacodynamic effect by reductions in serum tryptase, a biomarker associated with mast cell activation and correlated with clinical response in urticaria studies. Results are expected in the first quarter of 2025....Research and development (R&D) expenses increased to $11.3 million for the three months ended September 30, 2024, from $6.0 million for the same period in 2023. R&D expenses for the nine months ended September 30, 2024, increased to $26.0 million, from $18.1 million for the same period in 2023. The increases were primarily due to increased spend related to the THB335 program and increased personnel-related expenses, partially offset by decreases in development costs relating to the termination of the THB001 program."

Commercial • P1 data • Chronic Spontaneous Urticaria • Immunology • Urticaria

A Study to Evaluate THB001 in Adult Patients With Chronic Cold Urticaria (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Third Harmonic Bio, Inc. | Trial completion date: Sep 2023 ➔ Apr 2023 | Suspended ➔ Terminated; The decision to discontinue the study was made after observing moderate drug induced liver injury in two subjects enrolled in the first dose cohort.

Trial completion date • Trial termination • Dermatology • Immunology • Urticaria

An Open-label, Sequential Dose-Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamic Effects of THB001 in Adult Patients With Chronic Cold Urticaria. (EADV 2023) - "While therapies exist, such as antihistamines and the approved anti-IgE antibody omalizumab, many patients have inadequate responses, and there remains a high unmet medical need for more effective therapies. The study was halted early due to transaminase elevations in two participants enrolled in the first dose cohort (200mg BID THB001). The underlying cause is being investigated. These data, along with the PK, PD and clinical data to be presented from this study, will inform our next generation oral kit inhibitor program currently under development."

Clinical • PK/PD data • Cardiovascular • Dermatology • Hepatology • Immunology • Liver Failure • Urticaria

Third Harmonic Bio Announces Second Quarter 2023 Financial Results (GlobeNewswire) - P1b | N=5 | NCT05510843 | Sponsor: Third Harmonic Bio | "Third Harmonic Bio, Inc...today announced financial results for the second quarter ended June 30, 2023...the company announced its next-generation product candidate, THB335, and disclosed topline results of the Phase 1b clinical trial of THB001 for the treatment of chronic inducible urticaria, which was discontinued in December 2022 due to observed liver transaminitis in two of five patients enrolled. The results demonstrated evidence of clinical benefit in four of the five patients, achieving partial or complete responses despite early termination of the trial...The company plans to file a U.S. IND and initiate clinical trials of THB335 in the first half of 2024....Cash and cash equivalents totaled $278.1 million as of June 30, 2023."

Commercial • IND • P1 data • Dermatology • Immunology • Urticaria

First-in-human Safety, Pharmacokinetics and Pharmacodynamics of THB001: An Orally Available, Potent and Highly Selective Small Molecule Inhibitor of Wild Type KIT Receptor Tyrosine Kinase (AAAAI 2023) - "THB001 administered orally up 400 mg BID for 14 days in healthy participants demonstrates a favorable safety, tolerability, PK and PD profile. THB001 represents a promising drug candidate for patients suffering from mast cell driven allergic diseases."

Clinical • P1 data • PK/PD data • Allergy • Hematological Disorders

Efficacy of THB001, a Potent and Selective Oral Small Molecule Inhibitor of Wild Type KIT Receptor Tyrosine Kinase, in a Rat Passive Cutaneous Anaphylaxis Model (AAAAI 2023) - "THB001, a potent and selective inhibitor of wild type KIT, demonstrated efficacy in a rat PCA model at clinically relevant exposures."

Preclinical • Immunology • Inflammation • CSF1R • PDGFRA

A Study to Evaluate THB001 in Adult Patients With Chronic Cold Urticaria (clinicaltrials.gov) - P1 | N=5 | Suspended | Sponsor: Third Harmonic Bio, Inc. | N=30 ➔ 5 | Recruiting ➔ Suspended | Trial primary completion date: Jun 2023 ➔ Mar 2023

Enrollment change • Trial primary completion date • Trial suspension • Dermatology • Immunology • Urticaria

A Study to Evaluate THB001 in Adult Patients With Chronic Cold Urticaria (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Third Harmonic Bio, Inc.

New P1 trial • Dermatology • Immunology • Urticaria