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BIA-Brukerstyrt innovasjonsarena

CRITical - preclinical testing of novel antibiotic resistance breaker

Alternative title: CRITical - preklinisk testing av nytt legemiddel mot antibiotika resistens

Awarded: NOK 16.0 mill.

Project Manager:

Project Number:

321442

Project Period:

2021 - 2024

Funding received from:

Partner countries:

Antimicrobial resistance (AMR) is an emerging and devastating global health problem caused in large by misuse of antibiotics both in humans and animals. Antibiotics are needed to prevent infections e.g. when performing operations and cancer therapy. In additon, antibiotics are crucial to fight serious bacterial infections. The CRITical project addresses this global health problem by developing a novel product (APC148) that will be combined with an approved antibiotic, meropenem. This combination will secure the effect of meropenem if the bacteria develops resistant enzymes against meropenem. This project consists of three important research activities to completet the preclinical program and prepare for a later clinical program: Activity 1 - The synthesis procedure of APC148 needs to be optimized with respect to substance yield, purity and scale-up production. Analytical methods to quantify APC148 and degradation products are important to secure quality and stability of the product. These actvities will secure supply of APC148 for the preclinical program and later for production for clinical trials. Activity 2 - The mechanism-of-action of APC148 combined with meropenem needs to be investigated to better understand mechanisms of actions and predict potential side-effects when tested in animals and later in patients. APC148 and meropenem will be investigated for their their potential of developing bacterial resistance. Activity 3 - The preclinical testing in animals will test APC148 doses alone and in combination with meropenem to predict their distribution and elimination in the human body, and disclose potential interactions. This information will decide how to administer the two substances to animals and humans, and is crucial for the design of both the preclinical and clinical program.

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Antimicrobial resistance (AMR) is an emerging and devastating global health problem caused directly by use and over-use of antibiotics. AMR jeopardizes our ability to perform many life-saving procedures such as surgery and cancer chemotherapy. CRITical addresses this global problem by developing our adjuvant technology which inhibits a key bacterial resistance mechanism, restoring antibiotic efficacy against life-threatening, multidrug resistant bacterial infections. The project consist of three main activities; H1 - The product consist of a new molecule (APC148) that will be combined with an approved antibiotic, probably meropenem. The synthesis pathway of APC148 needs to be decided and optimized. The synthesis procedure needs to be improved with respect of intermediates, reactants, APC148 yield, purity, stability and ease of scale-up production. The work includes development of analytical methods for APC148 and degradation products. The activities will enable the company to supply APC148 for the preclinical program and prepare for GMP scale-up needed for clinical trials. H2 - The mechanism-of-action (MoA) of APC148 combined with meropenem (antibiotic) needs to be investigated including importing knowledge about the potential of APC148 and meropenem to develop bacterial resistance. The MoA is important to understand to predict potential toxicity in the preclinical and clinical program. This knowledge will reduce project and regulatory risks and make APC148 more attractive to private investors. H3 - The preclinical program will test APC148 alone and combined with meropenem to disclose potential toxicity and efficacy including pharmacokinetios and pharmacodynamics. This information is crucial for the design of the clinical program.

Funding scheme:

BIA-Brukerstyrt innovasjonsarena