Next Generation Polymyxin Antibiotics: Optimization and Validation

ended

In the NOVA ERC PoC project, we present a novel class of semi-synthetic polymyxins as an innovative solution to address the inherent toxicity of the polymyxins family of antibiotics. We here disclose the first candidate compounds of this novel family of antibiotics with potential for use as front-line treatment for multi-drug-resistant Gram-negative bacterial infections. Due to antimicrobial resistance (AMR), a resurgence in the use of polymyxin antibiotics has occurred over the last decade, despite the well characterised and dose-limiting nephrotoxicity associated with these compounds. Though designated as last-resort antibiotics due to these side effects, the ongoing rise of AMR is forcing clinicians to rely on unsafe antibiotics such as the polymyxins. Increased polymyxin use results in risks for patients and pressure on healthcare systems. Our novel semi-synthetic polymyxins have best-in-class potential given their significantly improved safety profile and offer a superior alternative to current last-resort anti-Gram-negative antibiotics. Succinctly, the next generation polymyxins we have developed offer key advantages over current last-resort antibiotics: (i) reduced nephrotoxic side effects, (ii) effectiveness against multi-resistant strains with negligible resistance induction, and (iii) ability to be produced at low cost. Moreover, our robust semisynthetic approach will allow us to generate additional analogues in the future. In NOVA, we will explore the technical and commercial potential of our next generation polymyxins. Specifically, we will validate the first candidate compounds and perform preliminary preclinical toxicity studies in vivo. In parallel, we will evaluate the commercial feasibility of the next generation polymyxins. This entails analysing the market and (existing and emerging) competitors, as well as the IP position and strategy. By the end of the project, we will consolidate the project outcomes in an investor-ready business plan.