END2AMR

Antimicrobial resistance (AMR) represents a major threat to health worldwide. It was responsible for just over 1 million deaths in 2021, and that figure could rise to 10 million a year by 2050 if nothing is done. We urgently need innovative treatments for these infections, but developing new antimicrobials is incredibly difficult; just 3 new classes of antibiotics were brought to the market in the last 30 years.

As its name suggests, END2AMR has set itself the ambitious goal of reinvigorating the antimicrobial drug development pipeline by delivering innovative approaches to treating resistant infections.

Part of the project will focus on advancing the development of new treatment modalities that could trigger a step change in the treatment of bacterial infections. For example, the team will explore how certain enzymes called lysins and proteins called PROTACs (proteolysis targeting chimeras) could be used to target bacteria that are currently very difficult to treat, such as slow-growing bacteria and bacteria that live inside human cells and so are hidden from the immune system. They will also use a technique called transposon sequencing to identify bacterial drug targets and characterise compounds that could target them.

New ways of delivering drugs are another focus of the project. New delivery technologies could help to boost the feasibility of the new treatment modalities the project will work on. Crucially, they could also improve the way we use existing antimicrobials, for example by making it possible to reduce doses (and side effects). One delivery technology the project will apply is nanofitin conjugates – these short, hyper-stable proteins can (among other things) reduce side effects associated with some medicines. The project also plans to work on long-acting therapeutics, applying the concept to existing antibiotics.

Finally, the project aims to deliver a versatile, scalable ‘toolkit’ that can be used to develop innovative antimicrobial treatments for a wide range of infections and covering diverse

When working on the treatment and delivery modalities, the END2AMR team will concentrate their efforts on the treatment of infections that remain particularly hard to treat. These include tuberculosis (TB); invasive and diarrhoeal bacterial diseases (a leading cause of death worldwide); and wound infections (which are a serious problem in disasters and conflicts).

Ultimately, END2AMR hopes to speed up the development of new ways of treating resistant infections; strengthen the European AMR research ecosystem; and boost Europe’s preparedness for disease outbreaks.