EPFL-based non-profit iM4TB has received a two-year grant of USD 769’000 from the Bill & Melinda Gates Foundation to improve the formulation of their innovative anti-tuberculosis drug PBTZ169.
EPFL-based non-profit iM4TB has received a two-year grant of USD 769’000 from the Bill & Melinda Gates Foundation to improve the formulation of their innovative anti-tuberculosis drug PBTZ169.
The iM4TB team and board members proudly congratulate the President of the board, Professor Sir Stewart Cole on his investiture as Knight Commander of the Order of Saint Michael and Saint George by Prince William at Buckingham Palace, London, on June 24th. Sir Stewart was decorated in the 2022 New Year’s Honours list for his “service to science” and this, of course, includes TB.
New publication in the Journal of Antimicrobial Agents and Chemotherapy: Pharmacodynamic analysis of PBTZ169 in Kramnik mouse model for tuberculosis shows promising results.
“Multiple drug discovery initiatives for tuberculosis are currently ongoing to identify and develop new potent drugs with novel targets in order to shorten treatment duration. One of the drug classes with a new mode of action is DprE1 inhibitors targeting an essential process in cell wall synthesis of Mycobacterium tuberculosis.
Read MoreOn March 24th 2021, World TB Day, Stewart Cole, President of the Institut Pasteur, stated that “Before the COVID-19 pandemic, TB control was making progress towards the sustainable development goals but, according to WHO, COVID-19 has set back TB control by 8 years!”. In 2020, COVID-19 overtook TB as the leading cause of human death due to a single infectious agent. Cole also said that “Governments have learned that Emerging Infectious Diseases like COVID-19 must no longer be neglected but policy makers must not forget that TB is a greater long-term threat than COVID-19 and need to plan accordingly. ERA4TB is an important part of the plan.” Since it first appeared, TB has claimed an estimated 1 billion lives around the world and, as recently as 70 years ago, was a leading cause of death in Europe. Today, TB remains highly prevalent in developing countries.
Professor Stewart Cole was invited as a speaker to the renowned Jenner Lecture at St George’s University of London in October 2020. Prof. Cole’s presentation emphasized the need to accelerate tuberculosis drug development, considering that over 10 million active cases were reported only in 2018. Prof. Cole also talked about the Covid-19 pandemic and how the lessons learned from TB research could be used in managing this global issue.
Watch the recording of the lecture by Professor Stewart Cole at the Jenner Day 2020:
Accelerating Tuberculosis Drug Development
The third panel of the Phase Ib trial has started, aiming at evaluating the safety and tolerability of PBTZ169 at a dose of 600 mg, once a day for 14 days, in healthy volunteers.
Our colleagues from the Laboratory & Service of Clinical Pharmacology at the CHUV validated an innovative methodology using multiplex UHPLC-MS/MS for the analysis and quantification of PBTZ169, as well as five of its metabolites, in the plasma of the healthy volunteers who participated in the phase Ia clinical study.
Read MoreThe Trial Safety Board assessed the safety and tolerability parameters for panels A and B, and authorized dose escalation as no salient adverse events were observed with PBTZ169 300 mg administered b.i.d. for 2 weeks. The trial will continue with panel C (600 mg q.d.) scheduled for June 2019.
The phase Ib clinical trial with PBTZ169 (multiple ascending doses) officially started, dose escalation will be performed through four panels A, B, C and D.
To evaluate the efficacy of PBTZ169 in combination with a range of other anti-tuberculosis (TB) drugs, our collaborators from the Cole lab, at the Global Health Institute of the EPFL, used in vitroassays and mouse models in order to design a new regimen against active TB. Notably, synergism could be observed when PBTZ169 was applied in combination with bedaquiline, clofazimine, delamanid and sutezolid.
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