SQ109
Product: SQ109 is a 1,2-ethylene diamine compound, some of which family are used in the first-line treatment of tuberculosis (ethambutol).
The therapeutic focus: pulmonary tuberculosis, including MDR forms; perspective focus – extrapulmonary and generalized tuberculosis, including genitourinary and nervous system tuberculosis, osseous-articular system, as well as tuberculosis of the lymph glands.
Status: Phase 2b-3 clinical trial, preparation of registration dossier
Partner: Sequella, Inc.
Description:
SQ109, basically developed by the biotechnology company Sequella, is a low-molecular ethylene diamine compound.
The drug has a unique multicomponent triple mechanism of action, including:
- inhibition of mMpl3 – membrane transporter of Tregalose Monomycolate involved in cell wall synthesis of mycobacteria.
- inhibition of enzymes involved in quinone biosynthesis MenA and MenG
- affects respiration/electron transfer: acts as an uncoupler, collapsing Proton Motive Force (PMF): pH gradient (ΔpH) and membrane potential (ΔΨ) in bacterial systems, thereby reducing ATP synthesis
The results of preclinical studies and a series of early phase clinical studies, including in patients with pulmonary tuberculosis, have showed that the drug has a good safety and tolerability, which is important in the case of long-term combined treatment.
The preclinical studies have showed:
- High efficiency against all forms tuberculosis (both sensitive and drug-resistant)
- Activity against slowly vegetative forms (can be considered as latent tuberculosis)
- Good pharmacokinetic parameters allowing to achieve target concentration during the treatment course
- Reach maximal concentration in lung and lien cells in peroral administration
- Shorten treatment time by 25% in in vivo experimental models
- Synergistic effect with other anti-tuberculosis drugs (isoniazid, rifampin, bedakvilin).
Development:
At the present time the company is due to complete a phase 3 clinical study of the drug SQ109 and evaluate the efficacy of chemotherapy in patients with MDR pulmonary tuberculosis.