ABAC Therapeutics embarks on research for antibiotics to combat drug resistant gram-negative bacteria
ABAC Therapeutics, together with the artificial intelligence (AI) company Peptris and the Foundation for Neglected Disease Research (FNDR), with scientific support from Medicines for Malaria Venture (MMV), has collaborated to optimize a new chemical structure that has shown effectiveness against gram-negative bacteria, the current threat to public health.
There has been a significant increase in infections caused by the gram-negative bacteria namely Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae known as the four killers.
The two-year project, in four stages will see researchers to identify and optimise molecules that could be progressed to clinical studies for antimicrobial resistance (AMR) and multi-resistant bacteria.
Artificial intelligence and in silico methods will be used to analyse the screening data, and propose new chemical series, which will then be optimised for both their antibacterial activity and their safety and tolerability, said the researchers.
The key effort is to go all out to identify new therapies against gram-negative bacteria. Specifically, species, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, are of particular concern. These microorganisms cause serious infections, such as pneumonia, bloodstream infections, and urinary tract infections, which affecting high-risk patients such as those recovering from surgery or undergoing cancer treatment.
“Due to the severity of infection these bacteria cause high resistance to available antibiotics. Our focus is to discover new antibiotics,” stated Dr. Domingo Gargallo-Viola, CEO, ABAC Therapeutics, a leading company in the research of new antibiotics.
The company has initially screened 145,000 compounds from MMV’s compound collection against a range of bacteria. Chemical series with a narrow spectrum of activity against bacterial pathogens of interest were identified, and these include a new chemotype with demonstrated activity against Gram-negative bacteria, he added.
Highlighting the global nature of the project, Dr. Venkatasubramanian Narayanan, CEO, Peptris said that those dedicated to combating infectious diseases, operate in a global environment, because of the geographical dimension of the problem .
This global vision for fighting infections aligns with the concept of ‘One Health’, making sure that there is interdisciplinary collaboration at different levels to optimize the health of people, animal and the environment. There is a huge unmet medical need for developing new antibiotics,” noted Dr. Shridhar Narayanan, CEO, FNDR.
“Targeting novel mechanisms especially for gram negative bacterial infections, require solutions Being a global problem, it is essential for partners from around the world. This consortium brings together synergistic global expertise in the field of antibiotic drug discovery, including use of AI/ML to achieve a faster timeline to deliver a clinical candidate.” Dr. Jeremy Burrows, Vice President, Head of Drug Discovery, MMV.
Noting that MMV provided compounds for screening, Dr Burrows said, “We will contribute our experience in the discovery and development of anti-infective agents, as well as its management capacity and knowledge in international projects.”
ABAC Therapeutics will participate in carrying out antibacterial activity and safety in vitro testing, in vivo toxicity studies, and will contribute its experience in microbiology, cell biology, pharmacology, DMPK and safety for in vitro and in vivo.
The Bengaluru-based Peptris experience is in the management and development of computer tools, in computational chemistry, drug discovery, medicinal chemistry, biology and bioinformatics.
FNDR is responsible for the synthesis and delivery of the new compounds. It will determine the physicochemical properties, assess the performance of stability studies of the new compounds under different experimental conditions, and study the therapeutic efficacy in experimental models of infection.
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