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

Project Information

PREVAIL

Grant agreement ID: 101188094

DOI

10.3030/101188094

Project closed

EC signature date 27 August 2024

Start date 1 November 2024

End date 30 April 2026

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

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.)

Reporting period: 2024-11-01 to 2026-04-30

Summary of the context and overall objectives of the project

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).

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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.