Bedaquiline Fumarate

Thuto Pulane, a TB survivor and participant in the NC-009 trial, at a follow-up appointment with Dr. William Brumskine, NC-009 principal investigator at the Aurum Institute Clinical Research Site COPENHAGEN (November 19, 2025)—New clinical trial results presented by TB Alliance at the Union World Conference on Lung Health show that the novel antibiotic candidate sorfequiline (TBAJ-876), a next-generation diarylquinoline, has the potential to improve tuberculosis (TB) treatment when combined with pretomanid and linezolid in a treatment regimen known as “SPaL.” The NC-009 trial (a pan-Phase 2 clinical trial) showed that, overall, sorfequiline had greater activity than bedaquiline. The 100 mg SPaL regimen had greater activity against TB than the standard of care HRZE (isoniazid, rifampin, pyrazinamide, and ethambutol), indicating the potential to shorten treatment time for active TB. In addition, the SPaL regimen had a comparable safety profile to the standard of care for people with drug-sensitive TB (DS-TB). TB Alliance conducted the trial in 22 sites in South Africa, the Philippines, Georgia, the United Republic of Tanzania, and Uganda. “Science continues to surge forward, to the benefit of health care systems, people with TB, their families, and their communities,” said Dr. Mel Spigelman, President and CEO of TB Alliance. “The development of the BPaL regimen allowed us to reduce treatment time for most drug-resistant TB to six months, a critical development for patients. Now, we have an opportunity to shorten treatment even further – representing an important milestone toward our goal of developing an ultra-short regimen capable of treating both drug-sensitive and drug-resistant TB.” Sorfequiline and bedaquiline both belong to the diarylquinoline class of antibiotics, which target a key enzyme of the tuberculosis bacteria involved in energy production. In 2012, bedaquiline was approved for drug-resistant TB treatment, making it the first new antibiotic to be approved in decades. However, recent years have seen a rise in strains of TB that are resistant to bedaquiline. TB Alliance has been developing sorfequiline all the way through the R&D process, from early discovery to, now, late-stage clinical trials. Trial results show that sorfequiline could have a potentially a better safety profile than bedaquiline along with the potential to treat many of the strains that are resistant to bedaquiline. “The research pipelines addressing a neglected disease like TB continue to deliver the promise of shorter and safer treatment for the millions affected around the world,” said Dr. Rod Dawson, Principal Investigator for NC-009 and Managing Director & Clinical Research Unit Head at the University of Cape Town Lung Institute. “Goals that once seemed wholly aspirational, like the eradication of TB, are made increasingly possible because of advancements like sorfequiline and, before that, pretomanid. But we have a lot of work ahead of us and cannot stop until TB is no longer a threat.” TB Alliance is strengthening partnerships with high-burden countries like India, China, Indonesia, South Africa and Brazil in advance of launching a Phase 3 clinical trial in 2026. This upcoming trial is an opportunity to earn approval for a new drug and regimen, as well as the first step in the process of developing an ultra-short regimen. These partnerships build from the work performed in the development and roll out of BPaL-based regimens, and seek to further streamline the process of developing new TB treatments and accelerating the pace at which those impacted by TB can access improved treatments. “The treatment was amazing. It was shorter and easier than I expected,” said Thuto Pulane, a participant in the NC-009 clinical trial. “I’d tell anyone not to be afraid. TB treatment has come a long way, and this new research gives us even more hope.” Sorfequiline has been developed in pill form and SPaL will also be an all-oral TB treatment. In addition to the upcoming SPaL Phase 3 trial, TB Alliance plans to explore delivering a sorfequiline-based regimen as a long-acting injectable (LAI), a formulation that could potentially help reduce treatment duration to as little as one month. “For decades, the standard treatment time for tuberculosis has been six months,” said Dr. Maria Beumont, Vice President and Chief Medical Officer at TB Alliance. “With BPaL, we proved that we can dramatically simplify and shorten drug-resistant TB treatment, but that was just the first step. With regimens currently in development, we believe we can shorten and simplify treatment even further – for all forms of TB. The results from this trial bring us closer to our goal and the eventual eradication of TB as a global health threat.” Background TB is a difficult infection to cure, requiring patients to take a combination of medicines for at least four to six months. Even after symptoms disappear, medicines still need to be taken so that all traces of the disease can be fully eradicated. The scope and intensity of TB globally is in large part fueled by antiquated and inadequate TB drugs. Novel drug regimens are urgently needed to bring the TB pandemic under control. The BPaL regimen—which combines the antibiotics bedaquiline (B), pretomanid (Pa), and linezolid (L)—was first clinically studied by TB Alliance. Pretomanid, as part of the BPaL regimen, received its first regulatory approval in August 2019 for use against highly drug-resistant strains of TB. This marked the first-ever regulatory approval of a TB drug developed by a non-profit. Previously, fewer than two-thirds of drug-resistant TB patients around the world had been successfully treated. Treatment options were limited, expensive, toxic, and lengthy – requiring patients to take more than 20 pills per day for 9 months to two years or longer. Since approval, more than 210,000 courses of pretomanid have been ordered globally, leading to an estimated 11,000 lives and $100 million USD saved globally. In past in vitro studies, sorfequiline demonstrated anti-mycobacterial activity approximately 10-fold greater than bedaquiline and, in preclinical studies, sorfequiline showed the potential to be safer than bedaquiline, including low potential for QT prolongation. In Phase 1 studies involving 165 healthy subjects, few, generally mild, adverse events were observed. About TB Alliance TB Alliance is a not-for-profit organization dedicated to finding faster-acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia’s Department of Foreign Affairs and Trade, Cystic Fibrosis Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Gates Foundation, Germany’s Federal Ministry of Research, Technology and Space (BMFTR) through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Korea International Cooperation Agency, MedAccess, Raoul Follerau Foundation, South Korea’s Ministry of Foreign Affairs, United States Department of Defense Congressionally Directed Medical Research Programs (CDMRP), United States Department of State, United States National Institutes for Health – National Center for Advancing Translational Sciences (NCATS), United States National Institutes for Health – National Institute of Allergy and Infectious Diseases (NIAID), and Unitaid. For more information, please visit: www.tballiance.org.

COPENHAGEN, Denmark (19 November 2025)—New interim data from the IMPAACT 2034 study presented today as a late-breaking oral abstract at the 2025 Union World Conference on Lung Health demonstrates that a single dose of pretomanid, in female children with rifampicin-resistant tuberculosis (RR-TB), was safe, well-tolerated, and achieved pharmacokinetic exposures comparable to adults. These findings are an important advance toward the goal of making pretomanid-containing regimens available to children. Pretomanid is a nitroimidazole antibiotic approved for use as part of BPaL-based regimens (comprised of bedaquiline, pretomanid, and linezolid) in adults with drug-resistant tuberculosis (DR-TB). To address the urgent need for child-friendly formulations, 10 mg and 50 mg dispersible tablets were developed and initially studied to confirm they achieved the same drug exposure levels as the existing adult formulation before being evaluated in pediatric populations. IMPAACT 2034 is the first clinical study to evaluate pretomanid pharmacokinetics (PK), safety, and acceptability in children with TB. The Phase 1 IMPAACT 2034 study enrolled 28 female children with RR-TB, including 7 children living with HIV, from South Africa (n=26) and Thailand (n=2). It is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). IMPAACT 2034 is being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, which receives support from NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health, all parts of NIH. Additional funding is provided by TB Alliance. Participants were divided into four weight-based cohorts and received a single dose of pretomanid (20-200 mg) using either the marketed adult tablet or pediatric dispersible formulations. Weights ranged from 6.9 to 56.8 kg and ages from 0.6 to 17.6 years. “As the first clinical study of pretomanid in children, these findings provide foundational data that will guide future development toward expanding access to pretomanid for children with drug-resistant TB,” said Dr. Eugene Sun, Senior Vice President of R&D at TB Alliance. “By demonstrating that pediatric formulations achieve the expected drug levels and are well tolerated, this research underscores the vital role of continued innovation in developing effective, child-friendly therapies for drug-resistant TB.” The primary objective was to confirm weight-based dosing strategies. Participants were followed for two weeks after dosing, and an interim PK and safety analysis was conducted. Key findings include: Comparable drug exposure: Pretomanid exposures in children were comparable to those observed in healthy adults and adults with TB, across all weight-based cohorts. Favorable safety profile: A single dose of pretomanid was well tolerated, with no unexpected safety signals reported in any cohort. The study successfully characterized the PK profile of pretomanid across age and weight groups, confirming modeled dosing predictions and supporting progression to the next phase of pediatric evaluation. The enrollment of male children in this study was not recommended by the U.S. Food and Drug Administration due to concerns of testicular toxicity in male rodents (but not primates) during pre-clinical studies. Data from a human semen study in adults with DR-TB were reassuring, and there is a plan to enroll male children in a subsequent, multidose study. “Developing MDR-TB specific therapies tailored to the needs of children is critical to closing the treatment gap for TB,” said Dr. Sharon Nachman, Principal Investigator and Chair at the IMPAACT Network. “Ensuring that children with TB have access to effective, tolerable, and child-friendly treatment options will significantly improve outcomes and quality of life.” ### About Pretomanid Pretomanid is a tuberculosis (TB) drug developed by TB Alliance that was first approved by the U.S. Food and Drug Administration in 2019 for the treatment of highly drug-resistant forms of TB for use in a combination regimen with bedaquiline and linezolid (known as the BPaL regimen). Pretomanid-based regimens are now included in WHO guidelines for drug-resistant TB and are being rapidly and widely adopted for use around the world. Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazole oxazines. Novel compounds are important in pursuing new TB treatments because resistance to drugs and drug classes currently used to treat TB is widespread. About IMPAACT The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network is a global collaboration of investigators, institutions, community representatives, and other partners with a mission to improve health outcomes in infancy, childhood, adolescence, pregnancy, and postpartum among those who are impacted by or living with HIV, tuberculosis, and other related complications through the conduct of high-quality clinical trials. IMPAACT’s vision and overall goal is to end the worldwide HIV epidemic among these populations. To achieve this goal, the IMPAACT Network evaluates novel and durable treatments for HIV, TB, and related diseases and conditions, strategies for antiretroviral treatment (ART)-free remission, and strategies to prevent and manage neuropsychological and mental health complications of HIV and its treatment. Overall support and funding for IMPAACT is provided by the National Institute of Allergy and Infectious Diseases (NIAID), with support and co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the United States National Institutes of Health (NIH). For more information, please visit: www.impaactnetwork.org. About the National Institutes of Health (NIH) NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit: www.nih.gov. About TB Alliance TB Alliance is a not-for-profit organization dedicated to finding faster acting and affordable drug regimens to fight TB. Through innovative science and with partners around the globe, we aim to ensure equitable access to faster, better TB cures that will advance global health and prosperity. TB Alliance operates with support from Australia’s Department of Foreign Affairs and Trade, Cystic Fibrosis Foundation, Foreign, Commonwealth and Development Office (United Kingdom), Gates Foundation, Germany’s Federal Ministry of Research, Technology and Space (BMFTR) through KfW, Global Disease Eradication Fund (South Korea), Global Health Innovative Technology Fund, Korea International Cooperation Agency, MedAccess, Raoul Follerau Foundation, South Korea’s Ministry of Foreign Affairs, United States Department of Defense Congressionally Directed Medical Research Programs (CDMRP), United States Department of State, United States National Institutes for Health – National Center for Advancing Translational Sciences (NCATS), United States National Institutes for Health – National Institute of Allergy and Infectious Diseases (NIAID), and Unitaid. For more information, please visit: www.tballiance.org.