Project: New Antifungals in preparation for clinical development against fungal infections
The long term and final goal of the Consortium is to provide New Chemical Entities (NCEs) with efficacy against fungal infections in humans. The current 3-year Meds4Fungs project will be the continuation of a previous Euro Trans Bio project (ETB-2010-42, Acronym: ArgiFun, Ended 07/2012) conducted by the same Ps, which has laid a solid foundation to accomplish subsequent goals. NCEs discovered and characterized in the ArgiFun project showed Minimum Inhibitory Concentrations (MICs) of Candida albicans growth below 1 µg/mL. Administration of these compounds in animal models of infection lead to plasma maximum concentrations over MIC values with no detectable toxic effects (see Annex). Based on these encouraging results, the current 3-year project aims to provide an antifungal candidate and backup molecules for subsequent Preclinical Development within 2 years after the completion of Meds4Fungs. At that point, the Investigational Medicinal Product Dossier on the selected NCE will be ready for application to the European Medicines Agency in order to start clinical trials in humans._x000D_Big pharmaceutical companies are swiftly changing their basic research policy. Both Preclinical and early Clinical phase assets have become of in-licensing interest for them, therefore shortening the period that SMEs need to monetize their investment. This is specifically true for the anti-infective arena, where outcomes associated to preclinical models generally extrapolate to humans. In this regard, Sanofi (Big Pharma leader at anti-infectives) has already shown interest in future collaboration by co-development and/or licensing agreement. The Letter of intent in support of this application stands the optimal scientific quality & feasibility from business development perspective (see Annex)._x000D_The need for antifungals from unexplored chemical spaces is urgent. First, multidrug fungal resistance is a growing threat despite the introduction of new agents (Pfaller, 2012). Second, newly introduced antifungal therapies are limited by their poor spectrum of activity, pharmacokinetics and risk for drug interactions (Lewis, 2011). The antifungal arsenal very much relies on azole compounds, showing high risk of drug interaction which is especially concerning for hospitalized patients under multiple therapies. Others such as echinocandins and amphotericin B are limited to intravenous use. Toxicity is a huge concern for immunosuppressed patients receiving antifungals for long periods. Actually, antifungals are usually associated with rash and with high renal, hepatic, cardiac and gastrointestinal toxicities among others. All this, together with patent expiring, makes again antifungal market global scale and interesting for Big Pharmas (see section 2.3)._x000D_Meds4Fungs Consortium has an optimal position and expertise to provide novel antifungals at Preclinical Development stage. Omnia is a drug discovery company focused in the anti-infective field. Omnia has developed a proprietary technology based on Aminoacyl-tRNA Synthetases (ARS) that delivers de-risked hit compounds for further optimization. Specs is one of the world's leading suppliers of chemistry solutions for drug discovery. Specs is focused on the supply of high-quality screening compounds, compound handling, cheminformatics and contract research for lead discovery and optimization. Innoprot is one of the CO Spanish cell-based assay providers. Innoprot provides high throughput screening, high content analysis and hit-to-lead optimization services and offers customized assay development, with a special focus on toxicity. The previous experience with the Argifun project puts into relevance the existence of synergies and a proper collaboration between the 3 Ps. The project execution is detailed in point 2.5._x000D_The mechanism of action of the antifungals will be based on Omnia´s expertise: ARS enzyme inhibition. ARS are essential enzymes present in every cellular organism (Ribas de Pouplana and Schimmel, 2001). ARS belong to a highly conserved protein family with low mutating ability and lower likelihood for resistance appearance. The target is validated by the ARS inhibitor mupirocin which is marketed for the treatment of bacterial skin infections (Yanagisawa et al, 1994). In the antifungals arena, Anacor is conducting a Clinical Trial Phase III targeting leucyl-tRNA synthetase (LRS). In the present case, and among the fungal ARS, Meds4Fungs will provide inhibitors of Candida albicans and Aspergillus fumigatus arginyl-tRNA synthetase (RRS). Actually, fungal RRS is an optimum target since it is the ARS showing the greatest difference from the human equivalent thereby minimizing compound risks.
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Acronym
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Meds4Fungs
(Reference Number: 7725)
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Duration
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01/12/2013 - 30/11/2016
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Project Topic
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The goal is to deliver a preclinical candidate and back-ups for clinical development against fungal infections. Proprietary, differential & patented technologies will be used. Clinical Trials will start two years after finishing the project.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 9
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Project partner
