Two New TB Drugs Show Synergy In Vitro

Sequella, Inc., a clinical-stage biopharmaceutical company developing drugs for treatment of infectious diseases, announces the publication of studies in the journal Antimicrobial Agents and Chemotherapy on synergy between SQ109, its lead drug candidate for the treatment of TB, and TMC207, Tibotec lead TB drug candidate.

The results of the studies, a research collaboration between Sequella and Tibotec, demonstrated that the combination of SQ109 with TMC207 decreased the TMC207 minimal inhibitory concentration (MIC) by four- to eight-fold for the etiologic agent of TB, Mycobacterium tuberculosis. SQ109 also improved the rate of killing of TB bacteria over the rate of killing by each single drug, and it extended the drug post antibiotic effect of TMC207 by four hours, with no observable antagonistic activities. The presence of rifampin (RIF) in three-drug combinations did not affect the synergistic activities of SQ109 and TMC207, and SQ109 also significantly decreased the MIC of RIF. SQ109 was active by itself, its activity was improved by TMC207, and it improved the in vitro activities of both RIF and TMC207.

"These results are very encouraging," says Dr. Carol Nacy, CEO of Sequella. "TMC207 and SQ109 are two of the first new TB drugs in 40 years with the potential to form the foundation for a better treatment regimen for TB and MDR-TB patients everywhere. We look forward to the further substantiation of these results during the in vivo phase of our partnership with Tibotec. "

SQ-109 is a new diamine antibiotic intended to replace one or more of the current first-line anti-TB drugs to improve and simplify patient therapy. SQ109 was granted U.S. FDA Fast Track designation and FDA/EMEA Orphan Drug Designation in 2007. SQ109 shows activity against drug sensitive and multi-drug resistant (MDR and XDR) Mycobacterium tuberculosis, the causative agent of TB. SQ109 has successfully completed its Phase I safety studies and will begin its Phase II clinical efficacy program 2H 2010 in a number of sites in Africa.

Reference: Reddy, V.M., L. Einck, K. Andries, and C.A. Nacy. In Vitro Interactions between New Antitubercular Drug Candidates SQ109 and TMC207. Antimicrob. Agents Chemother. 54:2840-2846, Vol. 7, July 2010.