Project Portfolio

The AMR Accelerator Project Portfolio is the consolidated overview of therapeutic assets being advanced across the Innovative Medicines Initiative (IMI) AMR Accelerator programme — a coordinated, public-private effort to rebuild the antibiotic and antimycobacterial pipeline in Europe. The portfolio comprises assets contributed by seven of the nine AMR Accelerator projects: AB-Direct, ERA4TB, GNA NOW, RespiriNTM, RespiriTB, TRIC-TB, and UNITE4TB. Together these assets span three therapeutic priority areas: tuberculosis (including multi-drug-resistant and non-tuberculous mycobacterial disease), Gram-negative bacterial infections of WHO priority-pathogen concern, and host-directed therapies that complement direct antibacterial action. For each asset, the portfolio lists its mechanism of action (MoA), its current development stage, an assessment of novelty (whether it represents a new chemical class, a new MoA, or both), and the asset owner — typically a partner pharmaceutical company, biotech SME, or academic institution. Development stages follow the standard preclinical-to-clinical progression used across the AMR Accelerator: Discovery and (Pre-)Hit-to-Lead at the earliest research end, followed by Lead-to-Candidate, Candidate-to-Phase I, and the clinical phases (Phase I, Phase IIa, Phase IIb), with the most advanced compounds currently in Phase IIb regimen-selection studies for tuberculosis. The portfolio is intended both as a public reference and as a coordination tool for the AMR Accelerator partnership, and is updated as assets progress, are added, or are deprioritised.

All Projects Discovery & Hit‑to‑Lead Lead to Candidate Candidate to Phase I Phase I Phase II

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Alpibectir

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

MoA: Bacterial transcriptional regulation.

Development stage: Phase 2a – alone or in combination

Novelty: New class, new MoA

Asset owner: BioVersys and GSK

Alpibectir/Ethionamide

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

MoA: Bacterial transcriptional regulation.

Development stage: Phase 2a – alone or in combination

Novelty: New class, new MoA

Asset owner: Leibniz-HKI/LMU

BV500

Description: BV500 program results from BioVersys’ proprietary Ansamycin Chemistry platform. The compounds are designed to circumvent intrinsic resistance mechanisms in M. abscessus, while maintaining a broad anti-NTM spectrum of activity.

MoA: Inhibition of bacterial RNA polymerase.

Development stage: Lead to Candidate

Novelty: –

Asset owner: BioVersys AG

BTZ-043

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

MoA: Inhibits an essential enzyme for cell wall synthesis in Mycobacteria tuberculosis.

Development stage: Phase 2b – Regimen selection

Novelty: New class, new MoA

Asset owner: LMU/Leibniz HKI

Delpazolid

Description: Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis.

MoA: Inhibits protein synthesis and mRNA translation.

Development stage: Phase 2b – Regimen selection

Novelty: New class, new MoA

Asset owner: LegoChem Biosciences, Inc.

ERA4TB-03

Description: Compounds targeting energy metabolism.

MoA: Electron chain transport.

Development stage: Phase I

Novelty: –

Asset owner: –

ERA4TB-04

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

MoA: Lysine transfer RNA synthase

Development stage: Lead to Candidate

Novelty: New class, new MoA

Asset owner: –

ERA4TB-05

Description: A new chemical series displaying excellent in vivo efficacy. Mode of action is currently unknown

MoA: Unknown

Development stage: Lead to Candidate

Novelty: New class, new MoA

Asset owner: –

ERA4TB-06

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

MoA: Mycobacterial membrane protein Large 3 (Mmpl3)

Development stage: Lead to Candidate

Novelty: New class, new MoA

Asset owner: –

ERA4TB-09

Description: Natural product analogs active against Mycobacterium tuberculosis.

MoA: Unknown

Development stage: Lead to Candidate

Novelty: New class, new MoA

Asset owner: –

ERA4TB-10

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

MoA: Targets and covalently inhibits the enzyme Decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1).

Development stage: Phase I

Novelty: New class, new MoA

Asset owner: –

ERA4TB-11

Description: Small molecule oxaborole.

MoA: Inhibits leucyl tRNA synthetase (LeuRS)

Development stage: Phase I

Novelty: New class, new MoA

Asset owner: –

ERA4TB-13

Description: Targets cholesterol cycle in Mycobacterium tuberculosis.

MoA: Cholesterol catabolism.

Development stage: Candidate to Phase I

Novelty: New class, new MoA

Asset owner: –

ERA4TB-14

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

MoA: Inhibits the mycobacterial cytochrome bc1 complex in the cellular respiration pathway.

Development stage: Phase I

Novelty: New class, new MoA

Asset owner: –

ERA4TB-17

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

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.

Development stage: Lead to Candidate

Novelty: New class, new MoA

Asset owner: –

ERA4TB-18

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

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.

Development stage: Lead to Candidate

Novelty: New class, new MoA

Asset owner: –

Ganfeborole

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

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

Development stage: Phase 2b – Regimen selection

Novelty: New class, new MoA

Asset owner: GSK

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 inhibition of two different Type II topoisomerase enzymes. Thanks to positive PhIII results for other indications (uUTI & gonorrhoea) is investigated by GNA NOW for its suitability to treat severe enteric infections in low- and middle income countries.

MoA: Topoisomerase type II inhibitor

Development stage: Candidate to Phase I

Novelty: New class, new MoA

Asset owner: GSK

Gepotidacin tissue distribution

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

MoA: Topoisomerase type II inhibitor.

Development stage: Phase I

Novelty: New class, new MoA

Asset owner: GSK

HDT

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

MoA: Various

Development stage: Discovery

Novelty: New class, new MoA

Asset owner: Janssen

MenG

Description: H2L medChem for novel menaquinone biosynthesis inhibitors.

MoA: Inhibits menG, a product of which catalyses methylation of demethylmenaquinone.

Development stage: (Pre)-Hit to Lead

Novelty: New class, new MoA

Asset owner: Janssen

Mtr

Description: Target exploration of Mycobacterium transcription regulator (Mtr) complex.

MoA: Mycobacterium transcription regulator (Mtr)

Development stage: Discovery

Novelty: New class, new MoA

Asset owner: Janssen

PASA

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

MoA: Dihydrofolate reductase (DHFR)

Development stage: (Pre)-Hit to Lead

Novelty: New class

Asset owner: Janssen

Quabodepistat

Description: A newly discovered molecule with a new mechanism of action that has potent antituberculosis activity and a favourable safety profile.

MoA: Inhibits an essential enzyme for Mycobacterium tuberculosis to synthesize key components of its cell wall.

Development stage: Phase 2b – Dose ranging/Regimen selection

Novelty: New class, new MoA

Asset owner: OTSUKA

HDT

Description:: Exploring known host-directed therapies for TB treatment.
MoA:: Various
Development stage:: Discovery
Novelty:: New class, new MoA
Asset owner:: Janssen

Mtr

Description:: Target exploration of M. tuberculosis transcription regulator (Mtr) complex.
MoA:: Mycobacterium transcription regulator (Mtr)
Development stage:: Discovery
Novelty:: New class, new MoA
Asset owner:: Janssen

MenG

Description:: H2L medChem for novel menaquinone biosynthesis inhibitors.
MoA:: Inhibits menG, a product of which catalyses methylation of demethylmenaquinone.
Development stage:: (Pre)-Hit to Lead
Novelty:: New class, new MoA
Asset owner:: Janssen

PASA

Description:: Novel PAS analogues.
MoA:: DHFR
Development stage:: (Pre)-Hit to Lead
Novelty:: New class
Asset owner:: Janssen

BV500

Description:: BV500 program results from BioVersys’ proprietary Ansamycin Chemistry platform. The compounds are designed to circumvent intrinsic resistance mechanisms in M. abscessus, while maintaining a broad anti-NTM spectrum of activity.
MoA:: Inhibition of bacterial RNA polymerase.
Development stage:: Lead to Candidate
Asset owner:: BioVersys AG

ERA4TB-04

Description:: Compound targeting lysine transfer RNA synthase (Rv3598c), which is an essential gene as assessed by transposon mutagenesis.
MoA:: Lysine transfer RNA synthase
Development stage:: Lead to Candidate
Novelty:: New class, new MoA
Asset owner:: –

ERA4TB-05

Description:: A new chemical series displaying excellent in vivo efficacy. Mode of action is currently unknown.
MoA:: Unknown
Development stage:: Lead to Candidate
Novelty:: New class, new MoA
Asset owner:: –

ERA4TB-06

Description:: Potent in vitro inhibitory and bactericidal activity against Mycobacterium tuberculosis.
MoA:: Mycobacterial membrane protein Large 3 (Mmpl3)
Development stage:: Lead to Candidate
Novelty:: New class, new MoA

ERA4TB-09

Description:: Natural product analogs active against Mycobacterium tuberculosis.
MoA:: Unknown
Development stage:: Lead to Candidate
Novelty:: New class, new MoA

ERA4TB-17

Description:: A novel class of small-molecule antibiotics that targets several Mtb biosynthesis pathways.
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.
Development stage:: Lead to Candidate
Novelty:: New class, new MoA

ERA4TB-18

Description:: A novel class of small-molecule antibiotics that targets several Mtb biosynthesis pathways.
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.
Development stage:: Lead to Candidate
Novelty:: New class, new MoA

ERA4TB-13

Description:: Targets cholesterol cycle in M. tuberculosis.
MoA:: Cholesterol catabolism.
Development stage:: Candidate to Phase I
Novelty:: New class, new MoA

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 inhibition of two different Type II topoisomerase enzymes. Thanks to positive Phase III results for other indications (uUTI & gonorrhoea) is investigated by GNA NOW for its suitability to treat severe enteric infections in low- and middle income countries.
MoA:: Topoisomerase type II inhibitor
Development stage:: Candidate to Phase I
Novelty:: New class, new MoA
Asset owner:: GSK

ERA4TB-03

Description:: Compounds targeting energy metabolism.
MoA:: Electron chain transport.
Development stage:: Phase I

ERA4TB-10

Description:: Derivative of piperazinobenzothiazinone that acts as an anti-mycobacterial compound.
MoA:: Targets and covalently inhibits the enzyme Decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1).
Development stage:: Phase I
Novelty:: New class, new MoA

ERA4TB-11

Description:: Small molecule oxaborole.
MoA:: Inhibits leucyl tRNA synthetase (LeuRS)
Development stage:: Phase I
Novelty:: New class, new MoA
Asset owner:: –

ERA4TB-14

Description:: Small molecule compound that leads to the depletion of ATP in three mycobacterial species, M. tuberculosis, M. leprae, and M. ulcerans.
MoA:: Inhibits the mycobacterial cytochrome bc1 complex in the cellular respiration pathway.
Development stage:: Phase I
Novelty:: New class, new MoA

Gepotidacin tissue distribution

Description:: Demonstrating penetration of gepotidacin in tonsillar and prostate tissues.
MoA:: Topoisomerase type II inhibitor.
Development stage:: Phase I
Novelty:: New class, new MoA
Asset owner:: GSK

Alpibectir

Description:: Boosts ethionamide efficacy and lowers the dose with small molecule transcriptional modulators to overcome multi-drug resistant TB infections.
MoA:: Bacterial transcriptional regulation.
Development stage:: Phase IIa – alone or in combination
Novelty:: New class, new MoA
Asset owner:: BioVersys and GSK

Alpibectir/Ethionamide

Description:: Boosts ethionamide efficacy and lowers the dose with small molecule transcriptional modulators to overcome multi-drug resistant TB infections.
MoA:: Bacterial transcriptional regulation.
Development stage:: Phase IIa – alone or in combination
Novelty:: New class, new MoA
Asset owner:: Leibniz-HKI/LMU

BTZ-043

Description:: A first-in-class investigational antitubercular agent is being developed to treat TB as part of a future combination regimen.
MoA:: Inhibits an essential enzyme for cell wall synthesis in M. tuberculosis.
Development stage:: Phase IIb – Regimen selection
Novelty:: New class, new MoA
Asset owner:: LMU/Leibniz HKI

Delpazolid

Description:: Delpazolid has in vitro activity against Gram-positive bacteria, including M. tuberculosis.
MoA:: Inhibits protein synthesis and mRNA translation.
Development stage:: Phase IIb – Regimen selection
Novelty:: New class, new MoA
Asset owner:: LegoChem Biosciences, Inc.

Ganfeborole

Description:: A first-in-class investigational antitubercular agent is being developed to treat TB as part of a future combination regimen.
MoA:: Suppresses protein synthesis in M. tuberculosis by inhibiting the enzyme leucyl tRNA synthetase (LeuRS).
Development stage:: Phase IIb – Regimen selection
Novelty:: New class, new MoA
Asset owner:: GSK

Quabodepistat

Description:: A newly discovered molecule with a new mechanism of action that has potent anti-TB activity and a favourable safety profile.
MoA:: Inhibits an essential enzyme for M. tuberculosis to synthesize key components of its cell wall.
Development stage:: Phase IIb – Dose ranging/Regimen selection
Novelty:: New class, new MoA
Asset owner:: OTSUKA