telacebec (Q203) / Qurient - LARVOL DELTA

Activity of MMV Pandemic Response Box compounds against Mycobacterium ulcerans viability and mycolactone production. (PubMed, Microbiol Spectr) - "By combining this mycolactone-detecting assay with the routinely used resazurin microplate assay, we identified hits (such as pradigastat) that are potential starting points for further development of antivirulence drugs for BU...In addition, we reliably reidentified drugs known to be active against M. ulcerans (such as bedaquiline, Q203, clofazimine, sutezolid, and epetraborole), thus validating our screening approach.IMPORTANCEMycolactone is a key requirement in the pathogenesis of Buruli ulcer (BU)...Here, we used our screening platform, which comprises a simple mycolactone-detecting ELISA combined with a standard resazurin microplate assay, to identify a set of hits from the Medicines for Malaria Venture Pandemic Response Box that could reduce mycolactone expression even without affecting M. ulcerans viability. This screening methodology will contribute to further development of antivirulence drugs for BU."

Journal • Infectious Disease • Malaria

The Mycobacterial cyt-bc1:aac3 Oxidase as a Drug Target: Activities of Arylvinylpiperazine Amides and Aminoquinazolines against Mycobacterium ulcerans. (PubMed, J Med Chem) - "The recommended treatment regimen is the daily administration of rifampicin and clarithromycin for 8 weeks, and efforts are being made to develop new treatment regimens that are faster acting, easier to administer, and have fewer side effects. Repurposing new antitubercular drugs is an attractive strategy to reduce development costs of new BU treatments, and drugs targeting the mycobacterial ATP generation pathway are of special interest, given the success of bedaquiline and telacebec (Q203)...Several APA derivatives had low micromolar activity against M. ulcerans, while many AQ derivatives showed nanomolar activity with excellent selectivity indices. Thus, we propose the most promising derivatives for further development."

Journal

TREAT-BU: Telacebec (T) Treatment in Adults With Buruli Ulcer (BU). (TREAT BU) (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Barwon Health | N=140 ➔ 200 | Trial completion date: Dec 2026 ➔ Jan 2028 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date

Multidrug-resistant tuberculosis: a comprehensive review of pathogenesis, drug resistance, current treatment and future prospects. (PubMed, Arch Microbiol) - "New molecules that can potentially disarm MTB have been explored, including SQ109, GuaB2, Q203, Largazole, and Auranofin. In addition, natural compounds, bacteriophage therapy, antimicrobial peptides, and probiotics are also explored to help address the global threat posed by MTB."

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

QcrB inhibitor Q203 (Telacebec) can synergize with clofazimine and clarithromycin to control a Mycobacterium avium infection. (PubMed, PLoS One) - "To determine if Q203 can function as an antibiotic against the non-tuberculosis mycobacteria M. avium and M. intracellulare (MAC), MIC and bactericidal studies were performed, both against various laboratory and clinical strains of MAC as well as in vivo infection studies. These studies found that Q203 provides synergistic activity against all tested MAC isolates when combined with clarithromycin and provided significant added benefit in a acute M. avium mouse infection model when combined with clarithromycin and clofazimine."

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

6-methylflavone exerts selective antimycobacterial activity with membrane energetics disruption and demonstrates therapeutic potential against Mycobacterium abscessus infection. (PubMed, Microbiol Spectr) - "Checkerboard assays demonstrated strong synergy with clarithromycin, while the effect with amikacin was limited to weak synergy or indifference. Mycobacteria have unique energy metabolic systems distinct to other bacteria and have been reported to be particularly susceptible to energy metabolism disruptors, such as bedaquiline, clofazimine, and telacebec (Q203). We hope this research will inspire further studies aimed at developing novel antimycobacterial strategies based on energetics disruption."

Journal • Infectious Disease • Inflammation • Metabolic Disorders • Nontuberculous Mycobacterial Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

The Mycobacterium abscessus cytochrome bcc:aa3 oxidase structure paves the way for an agent targeting subunit QcrB. (PubMed, Nat Commun) - "The cytochrome bcc:aa3 oxidase is the target of telacebec, a clinically advanced drug developed for Mycobacterium tuberculosis. Leveraging these insights, we designed ND-011458, a QcrB inhibitor with potent activity against M. abscessus and being bactericidal in combination with Clofazimine. The 2.26 Å inhibitor-bound structure elucidates its binding mode and provides a framework for the design of next-generation inhibitors for M. abscessus pulmonary diseases."

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

Annual progress in chemotherapy for tuberculosis in 2025 (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "New agents such as Telacebec, Quabodepistat, Sutezolid, and Delpazolid exhibit potent bactericidal activity and lower toxicity, laying the foundation for regimen shortening and combination optimization...In addition, 9-month (Bedaquiline-Linezolid-Fluoroquinolone-based) and 6-9-month all-oral regimens with varied combinations have shown comparable efficacy across different resistance patterns and resource settings, providing feasible alternatives in regions where Pretomanid availability is limited...Future progress is expected to focus on four key directions: discovery of new mechanisms and innovative regimen combinations; precision pharmacological management guided by pharmacokinetic/pharmacodynamic principles and therapeutic drug monitoring; safety assessment and stratified strategies for special populations; and the generation of robust real-world evidence to support globally harmonized yet locally adapted implementation. This review systematically summarizes advances..."

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

A bactericidal tuberculosis drug regimen driven by inhibition of the terminal oxidases by pretomanid. (PubMed, EMBO Mol Med) - "This property leads to a pronounced synergy with telacebec (Q203), a clinical-stage drug targeting the cytochrome bcc:aa3, while concurrently curtailing the emergence of resistance to pretomanid. Furthermore, the incorporation of the cytochrome bd oxidase inhibitor ND-011992 resulted in a triple drug combination highly bactericidal against antibiotic-tolerant, non-replicating as well as replicating M. tuberculosis. The combination of pretomanid and drugs targeting the terminal oxidases holds the potential to serve as the cornerstone for an efficacious sterilizing drug regimen against tuberculosis."

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

Targeting InhA for Tuberculosis Therapy: A Review of Recent Advances in Enzyme Inhibition and Drug Development. (PubMed, Curr Drug Targets) - "Tiliacorinine, 2'-nortiliacorinine, and griselimycin, derived from natural sources, paved the way for the development of compounds and approved drugs, such as bedaquiline, delamanid, pyrifazimine, proteomandid, and telacebec, which are currently under review for use. This review provides a brief on the design, synthesis, protein, activity, and pharmacophore moieties and their substitutions that cause the inhibition of this versatile target. We verified publications from 2013 that explore the same topic and reviewed chemistry-related research from Elsevier and other publishers, including future directions and targets that have been available."

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

A Series of Pyrazolo-Quinazoline Amines Inhibits the Cytochrome bd Oxidase in Mycobacterium tuberculosis. (PubMed, J Med Chem) - "In addition to telacebec (Q203), a clinical-stage drug candidate, several preclinical cyt-bcc:aa3 inhibitors have been reported...Mode of action studies validated the cyt-bd target as the molecular target. While further chemical optimization is required, favorable microbiological, ADMET, and in vivo potency of ETX1975-3 makes it a promising preclinical candidate for tuberculosis and NTM infections."

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

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