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Antibacterial innovation in European SMEs

Nature Reviews Drug Discovery volume 15, pages 812–813 (2016)Cite this article

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There is a severe innovation gap in antibiotic R&D, and the field faces two daunting challenges. First, the discovery of novel antibiotics with no pre-existing cross- and co-resistance, and with a very low potential for emergence of resistance, presents considerable scientific obstacles, especially for Gram-negative bacteria. Second, large pharmaceutical companies, discouraged by years of unsuccessful discovery efforts and business model concerns, have mostly turned to other therapeutic areas.

These SMEs are pursuing a wide variety of approaches, ranging from discovery of directly acting small molecules to investigation of adjuvants or preventive strategies (Fig. 1c). Twenty SMEs are focusing on developing a new class of agents that are active against multidrug-resistant (MDR) Gram-negative or Gram-positive pathogens. Projects in the Gram-negative field include antimicrobial peptides and lipopeptides. Most of these projects are in the hit-to-lead or lead optimization stages, with few having advanced to the drug candidate stage. Indeed, only the Pseudomonas-specific macrocycle murepavadin has completed phase I trials. Activity specific to a single pathogen or, at best, a very limited spectrum of activity, is a common characteristic of this group. Projects in the Gram-positive field include a pleuromutilin, an aminoacyl-tRNA inhibitor, topoisomerase inhibitors and various structurally diverse lipid II inhibitors targeting distinct domains of this essential membrane-bound cell wall precursor, for example, lantibiotics and defensins.

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Figure 1: Landscape for European small and medium-sized enterprises in the antibacterial area.

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  1. Ursula Theuretzbacher is at the Center for Anti-Infective Agents, Eckpergasse 13, 1180 Vienna, Austria.,

    Ursula Theuretzbacher

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  1. Ursula Theuretzbacher
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Correspondence to Ursula Theuretzbacher.

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European SMEs* with antibacterial products in clinical trials (PDF 142 kb)

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Theuretzbacher, U. Antibacterial innovation in European SMEs. Nat Rev Drug Discov 15, 812–813 (2016). https://doi.org/10.1038/nrd.2016.229

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