Project portfolio-4
Gepotidacin tissue distribution ERA4TB-01 ERA4TB-02 ERA4TB-03 ERA4TB-04 ERA4TB-06 ERA4TB-09 ERA4TB-10 ERA4TB-11 ERA4TB-13 ERA4TB-14 ERA4TB-15 ERA4TB-16 ERA4TB-17 ERA4TB-18 Gepotidacin BC1 back up MenG BDQ LAI PASA HDT Mtr TBA Alpibectir GSK656 BTZ-043

Gepotidacin tissue distribution

Description: Demonstrating penetration of gepotidacin in tonsillar and prostate tissues.

Mode of Action (MoA): Topoisomerase type II inhibitor.

ERA4TB-01

Description: Molecule targeting mycobacterial cholesterol cycle.

Mode of Action (MoA): Cholesterol catabolism.

ERA4TB-02

Description: Compound targeting Mycobacterium tuberculosis tryptophan synthase, an enzyme that catalyses the final two steps in tryptophan biosynthesis.

Mode of Action (MoA): M. tuberculosis tryptophan synthase.

ERA4TB-03

Description: Compounds targeting energy metabolism.

Mode of Action (MoA): Electron chain transport.

ERA4TB-04

Description: Compound targeting lysine transfer RNA synthase (Rv3598c), which is an essential gene as assessed by transposon mutagenesis.

Mode of Action (MoA): Lysine transfer RNA synthase.

ERA4TB-06

Description: Potent in vitro inhibitory and bactericidal activity against Mycobacterium tuberculosis.

Mode of Action (MoA): Mycobacterial membrane protein Large 3 (Mmpl3)

ERA4TB-09

Description: Natural product analogs active against Mycobacterium tuberculosis.

Mode of Action: Unknown.

ERA4TB-10

Description: Derivative of piperazinobenzothiazinone that acts as an anti-mycobacterial compound.

Mode of Action: Targets and covalently inhibits the enzyme Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1).

ERA4TB-11

Description: Small molecule oxaborole.

Mode of Action (MoA): Inhibits leucyl tRNA synthetase (LeuRS)

ERA4TB-13

Description: Targets cholesterol cycle in Mycobacterium tuberculosis.

Mode of Action (MoA): Cholesterol catabolism.

ERA4TB-14

Description: Small molecule compound that leads to the depletion of ATP in three mycobacterial species, M. tuberculosis, M. leprae, and M. ulcerans.

Mode of Action (MoA): Inhibits the mycobacterial cytochrome bc1 complex in the cellular respiration pathway.

ERA4TB-15

Description: A novel class of small-molecule antibiotics shown to inhibit new targets within the M. tuberculosis mycolic acid biosynthesis pathway.

Mode of Action (MoA): Covalently inhibits the acyl transferase domain of Mtb Pks13, a polyketide synthase involved in mycolic acid biosynthesis via a novel mode of inhibition.

ERA4TB-16

Description: A novel class of small-molecule antibiotics shown to inhibit new targets within the M. tuberculosis mycolic acid biosynthesis pathway.

Mode of Action (MoA): Covalently inhibits the acyl transferase domain of Mtb Pks13, a polyketide synthase involved in mycolic acid biosynthesis via a novel mode of inhibition.

ERA4TB-17

Description: A novel class of small-molecule antibiotics that targets several Mtb biosynthesis pathways.

Mode of Action (MoA): Inhibits FadD32, a key enzyme at the interface between the fatty acid synthase and polyketide synthase biosynthetic pathways and is involved in mycolic acid biosynthesis.

ERA4TB-18

Description: A novel class of small-molecule antibiotics that targets several Mtb biosynthesis pathways.

Mode of Action (MoA): Inhibits FadD32, a key enzyme at the interface between the fatty acid synthase and polyketide synthase biosynthetic pathways and is involved in mycolic acid biosynthesis.

Gepotidacin

Description: Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a novel mechanism of action and binding site by inhibiting two different Type II topoisomerase enzymes. Thanks to positive PhIII results for other indications (uUTI & gonorrhoea), gepotidacin is investigated by GNA NOW for its suitability to treat severe enteric infections in low- and middle-income countries.

Mode of Action (MoA): Topoisomerase type II inhibitor

BC1 back up

Description: Lead optimisation program on BC1 inhibitors.

Mode of Action (MoA): Cytochrome bc1 complex in the cellular respiration pathway.

MenG

Description: H2L medChem for novel menaquinone biosynthesis inhibitors.

Mode of Action (MoA): Inhibits menG, a product of which catalyses methylation of demethylmenaquinone.

BDQ LAI

Description: Novel long-acting injectable formulation of bedaquiline for Tb preventive therapy.

Mode of Action (MoA): ATPase.

PASA

Description: Novel para-Aminosalicylic acid (PAS) analogues.

Mode of Action (MoA): Dihydrofolate reductase (DHFR).

HDT

Description: Exploring known host-directed therapies for TB treatment.

Mode of Action(MoA): Various.

Mtr

Description: Exploring known host-directed therapies for TB treatment.

Mode of Action (MoA): Various.

TBA

Description: Novel assets (one first-in-human start) that may synergise with bedaquiline and cytochrome bc1 drugs.

Mode of Action (MoA): Unknown.

Alpibectir

Description: Boosts ethionamide efficacy and lowers the dose with small molecule transcriptional modulators to overcome multi-drug resistant tuberculosis infections.

Mode of Action (MoA): Bacterial transcriptional regulation.

GSK656

Description: A first-in-class investigational antitubercular agent is being developed to treat tuberculosis as part of a future combination regimen.

Mode of Action (MoA):  Suppresses protein synthesis in Mycobacterium tuberculosis by inhibiting the enzyme leucyl t-RNA synthetase (LeuRS).

BTZ-043

Description: A first-in-class investigational antitubercular agent is being developed to treat tuberculosis as part of a future combination regimen.

Mode of Action (MoA): Inhibits an essential enzyme for cell wall synthesis in Mycobacteria tuberculosis.