sorfequiline + pretomanid + linezolid

NC-009 (also known as the SPaL regimen) is an all-oral combination therapy under development by the TB Alliance for the treatment of both drug-sensitive and drug-resistant tuberculosis. The regimen consists of three small molecule drugs: sorfequiline (TBAJ-876), pretomanid, and linezolid. Sorfequiline is a next-generation diarylquinoline that inhibits mycobacterial ATP synthase with potentially higher potency and a better safety profile regarding hERG inhibition compared to bedaquiline. Pretomanid is a nitroimidazole that acts as a prodrug, activated by mycobacterial enzymes to inhibit cell wall synthesis and induce respiratory poisoning through nitric oxide release. Linezolid is an oxazolidinone antibiotic that inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit. The NC-009 Phase 2 trial is evaluating whether this combination can shorten the duration of TB treatment.