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Progress novel assets (one FIH start) for non-tubercular mycobacteria that may act synergistically with bedaquiline and cytochrome bc drugs

Objective

Non-tuberculous mycobacteria, such as Mycobacterium avium complex (MAC) and Mycobacterium abscessus, cause lung diseases resembling TB, mainly in immune-compromised patients or patients suffering from other lung diseases (e.g. cystic fibrosis). The incidence and prevalence of lung diseases caused by NTM are increasing worldwide. Importantly, in the US and Japan, as well as in other areas of the world where TB has declined, NTM disease is already at least three times more prevalent than TB. Treatment of NTM diseases relies on antibiotic combinations, however the drugs active against NTM are rather few and mainly different than those active against TB. These NTM treatments for the most common species (MAC and M. abscessus) are much less active than the current anti-TB regimen is for TB treatment. It is often necessary to administer antibiotic combinations for at least 12-24 months. The long and complex drug regimen that is currently recommended as a treatment against NTM-caused diseases carries the risk of inducing resistance in NTM. Several studies have already shown the existence and emergence of multidrug resistant NTM. The overall objective of RESPIRI-NTM is to find new drug candidates as potential components of a new, more efficient combination drug regimen against NTM that is less prone to resistance and allows shortening of treatment duration for NTM and multidrug-resistant NTM. Such a drug combination will synergistically target the energy metabolism of NTM or complementary targets. To achieve this, we will advance recently discovered inhibitors of the mycobacterial respiratory pathway. In addition, we will perform a novel, phenotypic screen in order to identify novel targets in NTM. Finally, we will also target host-factors that are essential for the intracellular survival of NTM. Together, we present a comprehensive plan to find novel strategies to combat non-tuberculous mycobacteria, shorten treatment time and reduce chances of drug resistance.

Coordinator

ACADEMISCH ZIEKENHUIS LEIDEN
Net EU contribution
€ 1 570 226,25
Address
Albinusdreef 2
2333 ZA Leiden
Netherlands

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Region
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 15 000,00

Participants (8)

UNIVERSITEIT LEIDEN
Netherlands
Net EU contribution
€ 766 250,00
Address
Rapenburg 70
2311 EZ Leiden

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Region
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITEIT ANTWERPEN
Belgium
Net EU contribution
€ 1 191 325,00
Address
Prinsstraat 13
2000 Antwerpen

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Region
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
SORBONNE UNIVERSITE
France
Net EU contribution
€ 726 750,00
Address
21 Rue De L'ecole De Medecine
75006 Paris

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Region
Ile-de-France Ile-de-France Paris
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
MEDIZINISCHE UNIVERSITAET WIEN
Austria
Net EU contribution
€ 848 750,00
Address
Spitalgasse 23
1090 Wien

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Region
Wien Wien
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 395 776,00
KOBENHAVNS UNIVERSITET
Denmark
Net EU contribution
€ 260 067,50
Address
Norregade 10
1165 Kobenhavn

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
JANSSEN PHARMACEUTICA NV
Belgium
Net EU contribution
€ 0,00
Address
Turnhoutseweg 30
2340 Beerse

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Region
Vlaams Gewest Prov. Antwerpen Arr. Turnhout
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 1 961 881,00
MITOLOGICS
France
Net EU contribution
€ 153 060,00
Address
Avenue Gaston Roussel 102
93230 Romainville

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Ile-de-France Ile-de-France Seine-Saint-Denis
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
FFUND BV
Netherlands
Net EU contribution
€ 171 555,00
Address
Hollandse Kade 32
1391 JM Abcoude

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
West-Nederland Utrecht Utrecht
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00