telacebec (Q203) / Qurient - LARVOL DELTA

PrrAB is a Selective Therapeutic Target and Regulator of Respiration in Mycobacterium tuberculosis. (PubMed, ACS Infect Dis) - "DAT-48 displayed potent, sterilizing effects against laboratory and clinical M. tuberculosis strains (H37Rv 4 μg/mL; Mt103 16 μg/mL) but lacked efficacy against M. abscessus ATCC19977 Smooth morphotype (MIC > 128 μg/mL), further highlighting species-specific PrrAB dependency. Molecular docking predicted DAT-48 binding to the ATP pocket of the PrrB sensor kinase, and DAT-48 synergized with bedaquiline (FICI = 0.42) and telacebec (FICI = 0.33), reinforcing PrrAB's central role in mycobacterial respiration. These findings establish PrrAB as a central regulator of energy metabolism in M. tuberculosis but dispensable in M. abscessus, defining it as a highly selective and promising target for next-generation TB therapeutics."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Discovery of novel Cytochrome bd oxidase inhibitors against Mycobacterium tuberculosis. (PubMed, Eur J Med Chem) - "Importantly, co-treatment with Q203, a cytochrome bcc oxidase (Cyt-bcc) inhibitor, resulted in pronounced synergistic bactericidal effects. These findings highlight the potential of dual Cyt-bd/Cyt-bcc inhibition as a new strategy for treating drug-resistant and latent TB, and validate the effectiveness of our virtual screening pipeline for discovering new anti-TB agents."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Mycobacterium Ulcerans Ulcer: Current Trends in Antimicrobial Management and Reconstructive Surgical Strategies. (PubMed, Life (Basel)) - "The paper advocates for RCTs to refine treatment protocols, surgical guidelines, and explore emerging antibiotic therapies such as telacebec. BU remains a global health challenge, requiring early diagnosis, timely antimicrobial therapy, and surgery in selected cases. Future research will refine treatment and reduce long-term impacts."

Journal • Review • Dermatology • Infectious Disease • Pediatrics

Inhibition of cytochrome bd oxidase in Mycobacterium tuberculosis by benzothiazole amides. (PubMed, Bioorg Med Chem) - "This study explores benzothiazole amides as potential inhibitors of Cyt-bd oxidase for their ability to deplete ATP in the presence of the Cyt-bc1:aa3 inhibitor Q203...These results highlight the potential of benzothiazole amides as promising candidates for anti-TB drug development, specifically targeting the Cyt-bd oxidase. Future research will focus on further optimising these compounds and conducting preclinical evaluations to realize their clinical potential as adjuncts in TB therapy."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

TREAT-BU: Telacebec (T) Treatment in Adults With Buruli Ulcer (BU). (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Barwon Health | Active, not recruiting ➔ Recruiting | N=40 ➔ 120 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date

Targeting Metabolic Vulnerabilities: Valinomycin Augments the Potency of Bioenergetic Inhibitors in Combatting Drug-Resistant and Dormant Mycobacterium tuberculosis (ASM Microbe 2025) - "Hence, there is a pressing need to develop a combinational strategy to increase efficacy with reduced frequency of resistance for bedaquiline (BDQ) and other bioenergetic inhibitors like telacebec (Q203) and clofazimine (CFZ). Valinomycin combined with bioenergetic inhibitors presents a robust strategy against both replicating and non-replicating Mtb, offering a promising approach to enhance TB treatment efficacy. These findings underscore the potential of targeting metabolic vulnerabilities in Mtb for creating a novel therapeutic regimen."

Infectious Disease • Respiratory Diseases • Tuberculosis

Mycobacteriophage-mediated gene transfer enables in vitro drug screening and in vivo tracking of Mycobacterium leprae. (PubMed, Proc Natl Acad Sci U S A) - "Mycobacteriophage infection of M. leprae was shown using TM4 expressing the highly sensitive BRET-nanoluciferase-based reporter, GeNL (TM4::GeNL), which enables luminescence measurement for over 72 h. When M. leprae was exposed to rifampicin, dapsone, and Q203 for 24 and 48 h, followed by TM4::GeNL infection, the luminescence output decreased in a dose-dependent manner, establishing an in vitro two-day screening assay for drugs. We have also electroporated M. leprae with a ColE1-integration proficient plasmid expressing GeNL and shown that the transformed leprosy bacilli could be propagated in mice footpads and detected using an in vivo imaging system (IVIS). These findings introduce powerful genetic tools for M. leprae research enabling in vivo tracking and in vitro viability testing."

Journal • Preclinical • Gene Therapies • Infectious Disease

A Telacebec-shaped Puzzle Piece in the Treatment of Mycobacterial Diseases. (PubMed, Am J Respir Crit Care Med) - No abstract available

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Unprecedented in vivo activity of telacebec against Mycobacterium leprae. (PubMed, PLoS Negl Trop Dis) - "We demonstrated that monotherapy of TCB exhibited bactericidal activity against M. leprae comparable to that of MDT and that all combination therapies were as effective as MDT, except the combination TCB + CFZ, possibly due to an antagonism between these two drugs."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Efficacy of novel regimens targeting oxidative phosphorylation in Mycobacterium tuberculosis. (PubMed, Antimicrob Agents Chemother) - "The combination of bedaquiline, clofazimine, pyrazinamide, alongside telacebec, and SQ109 was investigated against both wild-type M. tuberculosis H37Rv and an Rv0678 mutant with cross-resistance between bedaquiline and clofazimine. The addition of T to BCZ prevented the amplification of bedaquiline-resistant mutants and reduced the number of mice relapsing. Our finding underscores the potential of targeting the OxPhos pathway to combat M. tuberculosis, paving the way for innovative approaches in tuberculosis therapy."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Structural and mechanistic study of a novel inhibitor analogue of M. tuberculosis cytochrome bc1:aa3. (PubMed, NPJ Drug Discov) - "The mycobacterial respiratory complex cytochrome bc1:aa3 has emerged as a promising target, exemplified by the success of first-in-class inhibitor Q203 in phase 2 clinical trials...Validation of the binding site is further achieved by generating and isolating the JNJ-2901 resistant mutations in M. tuberculosis, followed by purification and resistance analysis of the resistant cytochrome bc1:aa3 complex. Our comprehensive work lays the foundation for further clinical validations of JNJ-2901."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Repurposing drugs to advance the treatment of Buruli ulcer. (PubMed, Antimicrob Agents Chemother) - "Using a virulent reporter strain of M. ulcerans with intrinsic bioluminescence (MuAL), we compared the minimum inhibitory concentration (MIC) of moxifloxacin, bedaquiline, telacebec, tebipenem, omadacycline, and epetraborole with standard-of-care drugs-rifampin and clarithromycin. The MuAL strain is useful in the rapid screening of drugs' efficacy and potency against M. ulcerans. We should leverage the progress made in the tuberculosis drug development pipeline to repurpose the drugs for the rapid development of new therapeutic modalities for Buruli ulcer."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Telacebec, A Potent Agent in the Fight Against Tuberculosis: Findings from A Randomized, Phase 2 Clinical Trial and Beyond. (PubMed, Am J Respir Crit Care Med) - "The results confirm telacebec's clinical activity against M. tuberculosis. Longer trials, in combination with other agents, are required to validate these results and to investigate telacebec's full potential. These results encourage exploring telacebec for more effective, shorter treatment regimens for leprosy and Buruli ulcer. A clinical trial for Buruli ulcer is underway."

Journal • P2 data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

TREAT-BU: Telacebec (T) Treatment in Adults With Buruli Ulcer (BU). (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Barwon Health | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2024 ➔ Dec 2025

Enrollment closed • Trial primary completion date

Contribution of telacebec to novel drug regimens in a murine tuberculosis model. (PubMed, Antimicrob Agents Chemother) - P1, P2 | "The clinical efficacy of combination drug regimens containing the first-generation diarylquinoline (DARQ) bedaquiline in the treatment of multidrug-resistant tuberculosis has validated ATP synthesis as a vulnerable pathway in Mycobacterium tuberculosis...Against both strains, combinations of a DARQ, clofazimine, and T were highly bactericidal. However, only against HN878 did T contribute synergistically, whereas an antagonistic effect was observed against H37Rv. These results demonstrate the therapeutic potential of T and highlight how differences in the susceptibility of M. tuberculosis strains could lead to different conclusions about a drug's potential contribution to novel drug regimens.CLINICAL TRIALSThis study is registered with Clinicaltrials.gov as NCT04890535 and NCT06058299."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Dongkoo Bio acquires exclusive domestic rights to Curient's 'Telacebec' [Google translation] (Biospectator) - "DongKoo Bio announced on the 18th that it signed a letter of intent with Qurient, a new drug development biotech company and its largest shareholder, for the domestic supply, distribution, and sales of 'Telacebec'...According to this letter of intent, Dongkoo Biopharmaceutical will be in charge of domestic distribution and sales of Telacebec. In addition, Dongkoo Biopharmaceutical will be granted priority negotiation rights in the Korean and Southeast Asian markets for the CDK7 inhibitor 'Q901' and the Axl/Mer/CSF1R triple inhibitor 'Q702', which are being developed by Qurient as anticancer drugs."

Commercial • Hematological Malignancies • Infectious Disease • Oncology • Solid Tumor

Mycobacterium tuberculosis inhibitors: an updated patent review (2021-present). (PubMed, Expert Opin Ther Pat) - "Additionally, Q203 analogues, demonstrate strong antitubercular activity, good microsomal stability, and favorable safety profiles. Finally, LysRS inhibitors also show significant promise in vivo models. These advancements underscore the importance of novel targets and innovative strategies in developing effective, resistance-resistant TB treatments."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Antibiotics Trigger Host Innate Immune Response via Microbiota-Brain Communication in C. elegans. (PubMed, Int J Mol Sci) - "Mechanistically, the innate immune response triggered by both the cyoB mutation and Q203 is found to depend on the host brain response, as evidenced by their reliance on the host neural gene unc-13, which is required for neurotransmitter release in head neurons. Therefore, our findings elucidate the critical involvement of the microbiota-brain axis in modulating the host immune response, providing mechanistic insights into the role of antibiotics in triggering the host immune response and, thus, facilitating host defense against pathogens."

Journal

TREAT-BU: Telacebec (T) Treatment in Adults With Buruli Ulcer (BU). (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Barwon Health | Not yet recruiting ➔ Recruiting

Enrollment open

TREAT-BU: Telacebec (T) Treatment in Adults With Buruli Ulcer (BU). (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Barwon Health

New P2 trial

Telacebec's Contribution to Combination Drug Regimens Is Strain-Dependent in a Mouse Model of Tuberculosis (ATS 2024) - "In H37Rv-infected mice, addition of pyrazinamide or clofazimine significantly increased the bactericidal activity of the next-generation diarylquinoline TBAJ-587, while telacebec did not; nor did telacebec increase the activity of either diarylquinoline TBAJ-587 or TBAJ-876 combined with clofazimine. However, in HN878-infected mice, addition of telacebec significantly increased the activity of bedaquiline+clofazimine ± pretomanid. Likewise, adding telacebec to the pretomanid+linezolid combination was antagonistic in H37Rv-infected mice but additive in HN878-infected mice; and addition of telacebec significantly increased the activity of rifapentine+moxifloxacin+pyrazinamide in HN878-infected, but not H37Rv-infected, mice...These experiments clearly highlight differences in the vulnerability of two commonly used M. tuberculosis strains to telacebec, which impact on its contribution to combination therapy. Recent work suggests that the H37Rv laboratory strain more..."

Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Exploring Scaffold Hopping for Novel 2-(Quinolin-4-yloxy)acetamides with Enhanced Antimycobacterial Activity. (PubMed, ACS Med Chem Lett) - "Utilizing a scaffold-hopping strategy from the drug candidate telacebec, a novel series of 2-(quinolin-4-yloxy)acetamides was synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (Mtb) growth...Finally, a selected compound prevented Mtb growth by more than 1.7 log10 colony forming units in a macrophage model of tuberculosis (TB) infection. These findings validate the proposed design and introduce new 2-(quinolin-4-yloxy)acetamides with potential for development in TB drug discovery campaigns."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Real-world diagnostic landscape and incidence of pulmonary hypertension in adult congenital heart disease patients using administrative claims data in Japan. (PubMed, Curr Med Res Opin) - "Therefore, we sought to clarify the frequency of diagnostic tests and incidence of PH/ES in patients with ACHD using the Medical Data Vision (MDV) database, the largest anonymized database of diagnosis procedure combination hospitals in Japan. We conducted a retrospective cohort study using the MDV database (April 2008 to December 2021) of patients with ACHD (International Classificaiton of Diseases, 10th revision codes: Q203-204, Q210-213, Q250) aged ≥15 years...The incidence rate of PH/ES was 32.8 per 1000 person-years. The incidence rate of PH/ES increased from 24.6 to 46.7 per 1000 person-years from 2008-2015 to 2016-2021. We have clarified the frequency of diagnostic tests related to PH/ES and the incidence of PH/ES in patients with ACHD in clinical practice in Japan, including non-specialist institutions for PH."

Journal • Real-world • Real-world evidence • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Unlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans. (PubMed, ACS Infect Dis) - "Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions...Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs."

Journal • Review • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Deciphering insights into the binding mechanism and plasticity of Telacebec with M. tuberculosis cytochrome bcc-aa3 supercomplex through an unbiased molecular dynamics simulation, free-energy analysis, and DFT study. (PubMed, J Biomol Struct Dyn) - "Meanwhile, DFT calculations were utilized to elucidate Q203's molecular properties. Overall, this study deciphers key insights into the cytochrome bcc-aa3 supercomplex with Q203 on the ground of molecular mechanics and quantum mechanics that may facilitate structure-based drug design and optimization for the discovery of the next-generation antitubercular drug(s).Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis