Building oral-small-molecule programs against validated targets

ArrePath selects opportunities where target biology is validated, oral-small-molecule options are limited, and a differentiated candidate profile can be defined.

Target-specific AI/ML workflows and indication-first, multi-parameter design allow new programs to start rapidly.

Our pipeline

ArrePath pipeline: Project 1 outpatient UTI oral LpxH inhibitor in late lead optimization; Project 2 mycobacterial lung disease programs targeting M. abscessus, broad-spectrum NTM, and tuberculosis; Project 3 first oral small molecule against a validated immunology target; Project 4 first oral small molecule against a validated inflammation target.

Project 1: Outpatient UTI

A novel oral LpxH inhibitor for drug-resistant Enterobacterales

Opportunity

Drug-resistant UTI is rising in the community while existing oral options have limited or no CRE coverage, creating a clear need for a differentiated outpatient therapy.

Differentiation

Project 1 inhibits LpxH through a clinically novel mechanism distinct from existing antibiotic classes, including LpxC. The target has no human homolog, is highly conserved across Enterobacterales, and has been validated in vitro and in vivo.

  • Bactericidal activity
  • Low resistance frequency (~1 × 10−9)
  • MIC90 ≤ 4 µg/mL across MDR, MBL, and CRE isolates
X-ray crystal structure of the lead compound bound in the active-site pocket of its bacterial target, shown as a cartoon ribbon protein with the ligand rendered as a space-filling surface.
Crystal structure of the lead compound bound to LpxH

Status

Late lead optimization, with favorable in vivo efficacy, solubility, metabolic stability, oral bioavailability, and minimal cytotoxicity. ArrePath is seeking a partner to advance this differentiated outpatient UTI program.

Project 2: Mycobacterial Lung Disease

Novel oral classes for diseases with limited treatment options

Need. Mycobacterial lung diseases still rely on long, difficult-to-tolerate regimens, and M. abscessus has no approved therapy. New oral classes are needed.

Coverage. Project 2 includes target-specific programs for M. abscessus, broad-spectrum NTM, and tuberculosis.

Status. Hit-to-Lead for M. abscessus; Hit Expansion for broad-spectrum NTM; early hits identified for tuberculosis.

Project 3

First oral small molecule against a validated immunology target.

Project 4

First oral small molecule against a validated inflammation target.

Supported by leading antimicrobial-funding organizations

CARB-X — Combating Antibiotic-Resistant Bacteria PACE — Pathways to Antimicrobial Clinical Efficacy

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Interested in learning more about our strategy, or in discussing a
partnership? Contact us to get the conversation started.

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