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Challenges and shortcomings of antibacterial discovery projects

OBJECTIVES: Antibacterial drug discovery activities are essential for filling clinical pipelines with promising clinical candidates. Little information is available about the challenges and shortcomings of small companies and academic institutions in performing these important discovery tasks. METHO...

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Autores principales: Theuretzbacher, Ursula, Baraldi, Enrico, Ciabuschi, Francesco, Callegari, Simone
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10160915/
https://www.ncbi.nlm.nih.gov/pubmed/36503116
http://dx.doi.org/10.1016/j.cmi.2022.11.027
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author Theuretzbacher, Ursula
Baraldi, Enrico
Ciabuschi, Francesco
Callegari, Simone
author_facet Theuretzbacher, Ursula
Baraldi, Enrico
Ciabuschi, Francesco
Callegari, Simone
author_sort Theuretzbacher, Ursula
collection PubMed
description OBJECTIVES: Antibacterial drug discovery activities are essential for filling clinical pipelines with promising clinical candidates. Little information is available about the challenges and shortcomings of small companies and academic institutions in performing these important discovery tasks. METHODS: We performed a content analysis of 463 reviewer comments on 91 funding applications of antibacterial drug discovery projects submitted to two major global funders between 2016 and 2020 that had not proceeded further in the selection process. This quality assessment was complemented with the inputs (via e-mail) from a panel involving six antibiotic research and development (R&D) experts with long-standing expertise and experience in antibiotic drug discovery. RESULTS: Common critical comments of reviewers are grouped into three main categories: scientific and technical shortcomings, unclear potential societal impact, and insufficient capability and expertise of the project team regarding the R&D process. Insufficient characterization of in vitro activity and/or testing of the hits/leads and insufficient antibacterial activity were the most common critical comments. Other areas of concern were insufficient or lack of differentiation from available drugs or projects with a long R&D history, and the research team's insufficient knowledge of a structured streamlined R&D process as reflected in severe gaps in the expertise of the R&D team. Little appreciation for the problem of the emergence of target-based resistance, especially in single-target approaches, and little awareness of toxicological issues, including approaches with historical liabilities were also commonly mentioned. The shortcomings identified through the analysis of funding applications are echoed by the results of the expert panel. DISCUSSION: Our analysis identified an urgent need of strengthening the support for antibacterial drug discovery teams to help more projects reach such a quality to be eligible for global funders and private investors.
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spelling pubmed-101609152023-05-06 Challenges and shortcomings of antibacterial discovery projects Theuretzbacher, Ursula Baraldi, Enrico Ciabuschi, Francesco Callegari, Simone Clin Microbiol Infect Original Article OBJECTIVES: Antibacterial drug discovery activities are essential for filling clinical pipelines with promising clinical candidates. Little information is available about the challenges and shortcomings of small companies and academic institutions in performing these important discovery tasks. METHODS: We performed a content analysis of 463 reviewer comments on 91 funding applications of antibacterial drug discovery projects submitted to two major global funders between 2016 and 2020 that had not proceeded further in the selection process. This quality assessment was complemented with the inputs (via e-mail) from a panel involving six antibiotic research and development (R&D) experts with long-standing expertise and experience in antibiotic drug discovery. RESULTS: Common critical comments of reviewers are grouped into three main categories: scientific and technical shortcomings, unclear potential societal impact, and insufficient capability and expertise of the project team regarding the R&D process. Insufficient characterization of in vitro activity and/or testing of the hits/leads and insufficient antibacterial activity were the most common critical comments. Other areas of concern were insufficient or lack of differentiation from available drugs or projects with a long R&D history, and the research team's insufficient knowledge of a structured streamlined R&D process as reflected in severe gaps in the expertise of the R&D team. Little appreciation for the problem of the emergence of target-based resistance, especially in single-target approaches, and little awareness of toxicological issues, including approaches with historical liabilities were also commonly mentioned. The shortcomings identified through the analysis of funding applications are echoed by the results of the expert panel. DISCUSSION: Our analysis identified an urgent need of strengthening the support for antibacterial drug discovery teams to help more projects reach such a quality to be eligible for global funders and private investors. Elsevier 2023-05 /pmc/articles/PMC10160915/ /pubmed/36503116 http://dx.doi.org/10.1016/j.cmi.2022.11.027 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Theuretzbacher, Ursula
Baraldi, Enrico
Ciabuschi, Francesco
Callegari, Simone
Challenges and shortcomings of antibacterial discovery projects
title Challenges and shortcomings of antibacterial discovery projects
title_full Challenges and shortcomings of antibacterial discovery projects
title_fullStr Challenges and shortcomings of antibacterial discovery projects
title_full_unstemmed Challenges and shortcomings of antibacterial discovery projects
title_short Challenges and shortcomings of antibacterial discovery projects
title_sort challenges and shortcomings of antibacterial discovery projects
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10160915/
https://www.ncbi.nlm.nih.gov/pubmed/36503116
http://dx.doi.org/10.1016/j.cmi.2022.11.027
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