BioVersys: First patients dosed in Phase 1 clinical trial on multidrug-resistant Tubercolosis infections

BioVersys AG, a privately owned, multi-asset Swiss pharmaceutical company focused on developing small molecules for multidrug-resistant bacterial infections with applications in Anti-Microbial Resistance (AMR) and targeted microbiome modulation, today announced that the first healthy volunteers have received BVL-GSK098 in a Phase 1 clinical trial designed to evaluate the safety, tolerability, and pharmacokinetics of BVL-GSK098 in healthy human volunteers through Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies.

• BVL-GSK098 is a novel compound potentiating and overcoming the resistance against ethionamide (Eto) or prothionamide (Pto) for the treatment of tuberculosis (TB). BVL-GSK098 targets bacterial transcriptional regulators, a groundbreaking approach that is being assessed globally for the first time in a clinical trial. BVL-GSK098 is developed in combination with Eto or Pto for the treatment of TB in collaboration with GSK. The program is supported by the IMI2 AMR Accelerator from the EU (TRIC-TB Project). The program originates from BioVersys and its partners at the University of Lille and Pasteur Institute Lille, France.
• BVL-GSK098 has completed GLP toxicology studies and shown excellent in vitro and in vivo efficacy in animal models against multidrug-resistant TB (MDR-TB), including overcoming pre-existing resistance mechanisms in Mycobacterium tuberculosis by employing novel bioactivation pathways for Eto. Furthermore, this combination has also proven to be effective against Isoniazid (INH) and Rifampicin (RIF) resistant strains. BVL-GSK098 in a fixed combination with Eto was granted QIDP Designation from the U.S. FDA in June 2019 for oral use in the treatment of pulmonary tuberculosis, making BVL-GSK098 eligible for FDA priority review, Fast Track designation, and a five-year extension of market exclusivity upon approval.

Dr. Sergio Lociuro, Chief Scientific Officer of BioVersys: “We are very excited to be testing BVL-GSK098 in a Phase 1 clinical trial, to evaluate its safety and pharmacokinetics in healthy volunteers. Although combinations for fighting resistance and/or potentiating the action of a drug are well known in the AMR field (e.g. beta-lactams/beta-lactamase inhibitors), thisis the first time that such an approach is applied in the TB field. Indeed, BVL-GSK098 combined with Eto or Pto offers the potential of increasing the potency of these drugs at significantly better tolerated low doses, while making them more bactericidal, faster-acting and active against Eto-Pto- and INH-resistant strains.”

Dr. David Barros-Aguirre, VP and Head of Global Health Pharma Research Unit, Global Health Pharma R&D, GSK: “GSK is committed to the discovery of novel treatments for tuberculosis including the drug-resistant forms of Mycobacterium tuberculosis. Entering clinical trials is an important milestone in our successful collaboration with BioVersys as we develop BVL-GSK098 within the IMI-2 TRIC-TB program, towards a potential treatment to optimize the beneficial effects of ethionamide.”

Dr. Marc Gitzinger, CEO and co-founder of BioVersys: “More than 1.5 million people die every year from Tuberculosis through a lack of efficacious treatments and access to medicines. In the midst of the current Covid-19 pandemic, this death toll is expected to rise significantly. At BioVersys we remain committed to developing innovative and life-saving treatments for patients suffering from drug-resistant infections, and the combination of BVL-GSK098 and Eto (or Pto) has the potential to improve patient outcomes, reduce treatment times, and even replace INH in first-line TB therapy.”

Dr. Seng Chin Mah, Chairman of BioVersys: “The BioVersys team has achieved yet another significant milestone by progressing a second program, BVL-GSK098, a novel treatment for highly resistant TB infections, into clinical development. This takes place within weeks of BV100 entering clinical development. We have now met all our immediate term goals for clinical development and look forward to executing on the next phase of our strategic plan as a significant innovator of urgently needed medicines in the AMR field.

TRIC-TB Project
The objective is to progress clinical candidates that potentiate the efficacy of and reverse the resistance to the anti-tubercular pro-drug ethionamide (Eto). The World Health Organization (WHO) considers Eto a crucial pillar of TB treatment, especially against MDR (multidrug-resistant) and XDR (extensively drug-resistant) strains. Our “booster” molecules act on novel bacterial transcription regulator targets, resulting in an increase of Eto efficacy by at least three-fold in vivo. This allows the use of lower efficacious doses of Eto in human anti-tuberculosis treatments and with a resultant reduction in dose dependent adverse effects in TB patients. Furthermore, data shows that the small molecules overcome pre-existing resistance mechanisms against Eto in Mycobacterium tuberculosis by employing novel bioactivation pathways for Eto, thus increasing the level of bioactivation. TRIC-TB has the potential to deliver a novel, fast acting TB agent potentially replacing Isoniazid as first line TB therapy.