Compounds directed against a novel aminoacyl-tRNA Synthetase target site represent a new approach that reduces the chances that bacteria can develop drug resistance to it.
CARB-X is awarding Oxford Drug Design Ltd. of Oxford, UK, up to $2.55 million in non-dilutive funding with the possibility of $4.24 million more if certain project milestones are met, to develop a new class of antibiotics for the treatment of Gram-negative bacterial infections using an approach designed to reduce the likelihood that resistance will emerge.
“We need new antibiotics and other products to combat the global rise of drug resistance and to prevent, diagnose and treat bacterial infections that are killing thousands of people each year,” said Kevin Outterson, executive director of CARB-X and professor of law at Boston University. “CARB-X partners are making solid progress supporting innovative antibacterial R&D like the Oxford Drug Design project to treat drug-resistant bacterial infections. But we know that much more is needed—more investment and global leadership to establish incentives that will ensure that life-saving products reach the market and patients who need them.”
Oxford Drug Design CEO, Paul Finn, said: “We are delighted to be working with CARB-X to develop our series of aminoacyl tRNA synthetase inhibitors, which have been identified with the aid of our innovative cheminformatics and machine learning technologies. The compounds represent a new class of antibiotics with activity against Gram-negative organisms, an area of critical unmet medical need, which the CARB-X funding will enable us to accelerate towards clinical evaluation.”
Oxford Drug Design is working to develop inhibitors of aminoacyl-tRNA synthetases (aaRSs), enzymes that are essential for bacterial viability. The aaRSs are a clinically validated target family, but to date, no inhibitors with systemic activity have reached the market. Oxford Drug Design has discovered a novel class of small-molecule aaRS inhibitors with activity against Gram-negative ESKAPE pathogens. The compounds are directed against a novel aminoacyl-tRNA Synthetase target site with a design strategy of targeting more than one synthetase, decreasing the probability of resistance emerging to the new compounds compared to aaRS inhibitors pursued in the past. Oxford Drug Design intends to progress these compounds as quickly as possible through hit-to-lead and optimization towards clinical development.
In addition to the CARB-X award, the company has received £2 million in funding from Innovate UK, on behalf of the UK government’s Department for Health and Social Care (DHSC), which will provide synergistic resources to accelerate other aspects of Oxford Drug Design’s novel tRNA synthetase inhibitor research portfolio.
New antibiotics urgently needed to fight superbug crisis
Drug-resistant superbugs are on the rise worldwide and represent a threat to global public health and health security. According to the World Health Organization, an estimated 700,000 people die each year worldwide from bacterial infections. In the United States, an estimated 23,000 people die each year from drug-resistant bacterial infections. In Europe, the number of deaths yearly is estimated at 33,000.
Partnership driving antibacterial innovation globally
The CARB-X portfolio is the world’s largest antibacterial development portfolio with 29 projects in five countries. Since its inception in 2016, CARB-X has announced awards for 44 projects in seven countries exceeding $126.15 million, with the possibility of additional funds if project milestones are met, to accelerate the development of antibacterial products. These funds are in addition to investments made by the companies themselves. As well as funding, CARB-X provides business and scientific support for projects through the CARB-X Global Accelerator Network, a network of 10 expert organizations around the world. The CARB-X pipeline will continuously evolve, as projects progress or fail.
CARB-X, led by Boston University, is investing more than $500 million in antibacterial R&D between 2016 and 2021 to support the development of new antibiotics, vaccines, diagnostics and other products. The goal is to support projects through the early phases of development through Phase 1, so that they will attract additional support for further clinical development and approval for use in patients. The scope of CARB-X funding is restricted to projects that target drug-resistant bacteria highlighted on the Centres for Disease Control and Prevention (CDC)’s 2013 Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the WHO in 2017—with a priority on those pathogens deemed Serious or Urgent on the CDC list or Critical or High on the WHO list.
CARB-X recently announced four new funding rounds for 2019, each with a specific scope and application period. Product developers from around the world are invited to apply.
This news release is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by an award from Wellcome Trust. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the HHS Office of the Assistant Secretary for Preparedness and Response, Wellcome Trust, or other CARB-X funders.