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Antibiotic resistance breakers could restore the efficacy of antibiotics

The threat of growing antimicrobial resistance has focused the attention of big pharma companies which have spent billions of euros trying to find new antibiotics. A novel approach by the QTB4AMR project may offer some hope.

Health

Antibiotic resistance is a major public health concern. The World Health Organization (WHO) has estimated that, annually around 700 000 people worldwide die due to infections caused by drug-resistant bacteria. Without effective antibiotics, the success of major surgery and cancer chemotherapy would be at risk. And yet, due to the costs involved in developing new antibiotics, many pharmaceutical companies have actually ceased clinical development of new antibiotics. Some have downsized their antibacterial and antiviral in-house R&D activities, while others, such as Novartis, have shut them down entirely. “Current opinion is that while development of a completely new stand-alone antibiotic is important, it won’t meet the urgent need. The field has turned to combinatory treatments, which could reach the market faster,” explains Fredrik Almqvist, CEO of QureTech Bio, the project host. The EU-supported project QTB4AMR has developed novel compounds that can restore antibiotic susceptibility in antibiotic-resistant Gram-positive bacteria, thereby boosting the efficacy of standard-of-care antibiotics. Gram-positive bacteria, such as Vancomycin-resistant Enterococci (VRE) and Methicillin-resistant Staphylococcus aureus (MRSA), account for about 60 % of respiratory, intra-abdominal and urinary tract infections. EU funding enabled QureTech to develop a business plan including analysis of epidemiological and market data. It allowed the team to assess user needs, establish intellectual property rights and create a commercialisation strategy. They were also able to conduct a clinical feasibility study, as a step towards clinical trials and to identify potential partners for preclinical development.

The ‘antibiotic resistance breakers’

The new chemical entities (NCEs) which form QureTech’s ‘antibiotic resistance breakers’ are called GmPcides. They descend from a well-established chemical platform developed by QureTech, with the lead compounds killing Gram-positive bacteria at very low concentrations. “The versatility of the chemistry platform allowed us to rapidly alter the nature of the compounds, so we could quickly develop new generations of compounds with better properties,” says Almqvist. The NCEs were tested in both cell cultures and animal models. The results showed that some of the compounds did restore antibiotic susceptibility of standard-of-care antibiotics in VRE and MRSA bacteria. “To the best of our knowledge, our approach is completely novel. Our tests showed that bacterial resistance to GmPcides is very low. Our vision is that the lead compound will be used in combination with standard-of-care antibiotics as first-line treatment for bacterial infections,” notes Almqvist.

Helping patients fight infections

The European Centre for Disease Control (ECDC) estimates that 33 000 patients in the EU die annually as a result of infections caused by resistant bacteria. A newly released report also shows that 39 % of the burden is caused by infections with bacteria resistant to last-line antibiotics. The costs related to healthcare expenditure incurred by antimicrobial resistance are estimated to be as high as EUR 1.5 billion annually. Over recent years, the challenge of fighting antibiotic resistance has been taken up by smaller biotech companies. As these nimbler players develop innovative solutions, so the interest of the bigger pharmaceutical companies is steadily renewed. QureTech’s chemical platform is scalable for the design and synthesis of active pharmaceutical ingredients, to be used alone or in combination with standard-of-care antibiotics, against antibiotic-resistant pathogens. The team will next conduct more animal experiments, along with analysis of the properties of different compounds, to identify a candidate drug. Once determined, the preclinical development will start. Ultimately, QureTech intends to out-license ongoing projects or identify strategic partners to take the GmPcides to the market.

Keywords

QTB4AMR, antimicrobial resistance, antibiotics, bacteria, drugs, compounds, GmPcides, Enterococci, VRE, Staphylococcus aureus, MRSA, respiratory, intra-abdominal, urinary tract infection

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