Two pre-clinical candidates, BVL-GSK038 and BVL-GSK098, both with adequate properties for candidate selection, resulted from an extensive Lead Optimization program that was completed before the start of the project.
The more advanced molecule, BVL-GSK098, successfully achieved the first TRIC-TB objective, the delivery of a Phase 2 ready drug candidate. The backup compound, BVL-GSK038, was produced in sufficient quantities to be ready for CTA-enabling studies, achieving the second project objective.
In the first project year, the synthetic route for the backup compound was optimized and BVL-GSK038 was produced in sufficient quantity and purity, achieving milestone 1 (MS1).
In the second project year, BVL-GSK098 completed the 28-day toxicology and safety pharmacology studies, so called CTA-enabling studies. Due to the favourable profile, the compound was endorsed to enter the first-in-human (FIH) studies. For the FIH study, the oral formulation was optimized and BVL-GSK098 was filled in capsules. The CTA was filed in 2020, achieving MS2.
In 2022, TRIC-TB successfully completed Phase 1 clinical trials. BVL-GSK098 was generally safe and well tolerated and showed a linear pharmacokinetic (PK) profile at therapeutically effective doses in healthy volunteers, achieving MS3 (Phase 2a ready).
Finally, a regulatory acceptable sub-chronic toxicology package has been generated for BVL-GSK098. The safety-margin to the anticipated therapeutic human dose is more than 10-fold. With the successful completion and reporting of the toxicology studies, MS4 was achieved, allowing BVL-GSK098 to enter Phase 2b trials.
There were some deviations from the original workplan, partially the result of the COVID-19 pandemic and the subsequent inflation of the costs of the planned studies. The team appropriately applied contingency measures to prioritize the continued development of BVL-GSK098 while removing deliverables associated with development of the backup compound BVL-GSK038 through GA amendment procedures.
The project results have been extensively disseminated. Twenty-eight presentations and posters were presented at international conferences within the project duration.
BioVersys received U.S. FDA Qualified Infectious Disease Product (QIDP) designation and Orphan Drug Designation (ODD) for BVL-GSK098 and ETH fixed-dose combination for treatment of TB. These qualifications reflect the the potential for bETH to improve treatment options for patients who have TB.
BVL-GSK098 seamlessly transitioned into Phase 2a study (funded by EDCTP), studying the early bactericidal activity (EBA), safety, tolerability and PK of ETH alone and in combination with BVL-GSK098 in TB patients. The consortium members from TRIC-TB are also involved in the EBA study. This is rewarding for the team that has worked together for many years on the development of BVL-GSK098 and a prime example of the project’s sustainability.
In summary, TRIC-TB has met and even exceeded all the objectives as described in the grant agreement, and the development of the BVL-GSK098 continues beyond the IMI funding.
