An inhalation peptide drug candidate (NF1001) for Rx of MDR/XDR TB: We have a natural product derived peptide antibiotic with excellent in vitro and in vivo activity in mouse and guinea pig TB infection models. Peptide candidate kills TB through a novel mode of action by inhibiting ribosome associated GTPase activity blocking protein translation. Several in vivo, inhalation combination studies with Isoniazid and Rifampicin or second line drugs revealed superiority of peptide containing combinations. It reduced bacterial load in mouse lung tissue infected with drug resistant Mtb to below LOD in 1 month in combination with amikacin, moxifloxacin, ethambutol and pyrazinamide as compared to 3 months required for this combination without peptide antibiotic. Thus, this peptide has significant potential for treatment of MDR TB, shortening duration of therapy and sterilization. The drug candidate is at a stage of GLP toxicology preceding to filling IND.
A novel anti TB drug candidate (TBA3731) that targets mycobacterial DprE1cell wall target required for Arabinan synthesis. A series of azaindoles is at the stage of preclinical toxicology.
Inhibitors of Enoyl ACP reductase (InhA) of M.tuberculosis: InhA/ACP reductase is a clinically validated target of Isoniazid and Ethambutol. FNDR has well-characterised series of compounds with strong in vitro target inhibition profile and pharmacokinetics. This asset offers opportunity to develop direct inhibitors of InhA/ACP reductase, with a different mechanism of action. These compounds are expected to work on mycobacterial strains resistant due to catG mutations that account for majority of INH resistance. The asset is ready for lead optimization.