Leibniz active agent of the year 2023 is a tuberculosis antibiotic candidate
The molecular structure of the active agent BTZ-043, a new drug candidate against tuberculosis.
The drug candidate BTZ-043 has a novel mechanism of action and belongs to a new class of substances. Discovered at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), the active agent has been under development since 2014 in collaboration with the Tropical Institute at LMU University Hospital Munich and Hapila GmbH in Gera in the framework of the German Center for Infection Research (DZIF) and the InfectControl 2020 consortium, among others. BTZ-043 has now been named Leibniz Drug of the Year 2023 at the Leibniz Wirkstofftage in Braunschweig.
While tuberculosis has become relatively rare in Germany and other industrialised nations, around ten million people contract the bacterial infection every year, especially in poorer countries. This makes tuberculosis the most common bacterial cause of death worldwide. According to the World Health Organisation (WHO), around 1.6 million people die from it every year, mainly in Southeast Asia, Africa and the Western Pacific region. The infection is particularly dangerous for people with weakened immune systems; HIV-infected people are frequently affected.
In addition to the lack of medical care in poorer countries, the increasing number of resistances to common tuberculosis therapies is problematic. At the same time, hardly any new antibiotics are being developed. The nitrobenzothiazinones (BTZ) discovered and developed at Leibniz-HKI are a very effective class of antibiotic candidates against the tuberculosis pathogen Mycobacterium tuberculosis, including resistant strains. BTZ-043 was the first member of this compound family to obtain worldwide patent protection for its activity against the tuberculosis pathogen. "The active agent irreversibly binds to an enzyme that mycobacteria need to build the bacterial cell wall," explains Florian Kloß. As head of the Transfer Group Anti-infectives at Leibniz-HKI, he played a key role in the development of the active substance.
First clinical studies successful
The substance, which has now been named “active agent of the year”, has already successfully undergone initial clinical trials. A Phase I study conducted in Germany in healthy volunteers showed that BTZ-043 was well tolerated. The subsequent Phase IIa clinical trial was conducted in tuberculosis patients in Cape Town, South Africa. It confirmed BTZ-043 as safe and effective—an important step in the development of a new drug. Further Phase II clinical trials are currently being planned within the PanACEA II consortium as well as within the Academia and Industry United Innovation and Treatment for Tuberculosis (UNITE4TB) research consortium to investigate BTZ-043 in combination with various standard antituberculotics. Therefore, it is now within reach that BTZ-043 could replace one of the conventional antibiotics, which are often susceptible to resistance, in a combination therapy and shorten the duration of tuberculosis treatment.
For the preclinical and clinical studies, Leibniz-HKI has been cooperating closely with the Tropical Institute at LMU University Hospital Munich since 2014. The studies are designed, commissioned and supervised by the Director of the Tropical Institute—DZIF-Professor Michael Hoelscher and his team. The drug development, which cost several million euros, is only possible thanks to joint funding from the public and private sectors: In particular, the two research networks InfectControl and the German Center for Infection Research (DZIF), which are funded by the BMBF with public money, are involved in the drug development. A complete overview of the funding partners is available on the BMBF website (in German): https://www.gesundheitsforschung-bmbf.de/de/btz-043-moglicher-gamechanger-im-kampf-gegen-tuberkulose-16225.php
In addition to Florian Kloß, Sina Gerbach and Freddy Bernal were honoured with the award. While Kloß mainly led the chemical aspects of the preclinical and clinical development of BTZ-043 and was involved in several patent applications and publications, Gerbach commissioned the research on drug safety and for the in vitro studies required by the regulatory authority on possible drug-drug interactions to contractors. Bernal developed computer models to study the relationship between the structure of benzothiazinones, their physical properties, and their effectiveness.
Source: Press release of Leibniz-HKI
