PReclinical EVAluation and Investigation of Laterocidamide - A novel antibiotic from a new drug class to overcome polymyxin resistance.

Projektinformationen

PREVAIL

ID Finanzhilfevereinbarung: 101188094

DOI

10.3030/101188094

Projekt abgeschlossen

EK-Unterschriftsdatum 27 August 2024

Startdatum 1 November 2024

Enddatum 30 April 2026

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 150 000,00

Koordiniert durch

UNIVERSITEIT LEIDEN
Netherlands

Periodic Reporting for period 1 - PREVAIL (PReclinical EVAluation and Investigation of Laterocidamide - A novel antibiotic from a new drug class to overcome polymyxin resistance.)

Berichtszeitraum: 2024-11-01 bis 2026-04-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The primary objective of the PREVAIL ERC Proof of Concept project was to determine the technical and commercial feasibility of a novel class of lipopetide antibiotics. With widespread antibiotic resistance increasing rapidly and the rate of antibiotics development being alarmingly low, we are running out of effective antibiotics. This has led to increased use of so-called “last-resort” antibiotics like the polymyxins which are also known to have serious toxicities. In Europe and throughout the world, polymyxins are used for the treatment of bacterial infections caused by multi-drug resistant Gram-negative pathogens. However, their dose-limiting nephrotoxicity requires a careful balance between the dose required for efficacy while minimizing toxicity. The increasingly frequent use of polymyxin antibiotics, despite their serious side effects, results in unnecessary pressure on healthcare systems and underscores the urgent need for safe alternatives. In the ERC PoC project PREVAIL we set out to develop novel lipopeptide antibiotics, including next-generation polymyxins, with improved safety profiles and potent antibacterial activity. These proof-of-concept studies successfully demonstrated the potential of novel lipopeptide antibiotics developed in our group in the context of the recently completed ERC CoG project NO-ESKAPE (#725523).

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

In Project PREVAIL, the following activities were conducted: (i) optimization of the synthetic route used to prepare the next generation lipopeptide antibiotics, (ii) minimum inhibitory concentration (MIC) assays to assess antibacterial potency against diverse bacterial pathogens (iii) cell-based toxicity studies using HK-2 and CIPTEC kidney cell lines to assess nephrotoxicity, and (iv) perform an extensive analysis of the anti-Gram-negative antibiotics market including competitors and potential strategic partners.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The results obtained in the PoC project are encouraging and will serve to pave the way for key-follow up studies aimed a further demonstrating the therapeutic potential of the next generation lipopeptide antibiotics developed. Specifically, a number of pre-clinical studies will be needed to ensure both the efficacy and safety of these compounds for future 1st in human trials. Significant outside investment will be necessary to further support such development.