Drugs in Development
Sequella demonstrated the success of public-private partnerships when it received clearance from the FDA to enter Phase I trials in 2006 with its TB drug candidate SQ109—a diamine antibiotic that could replace one or more of the current first-line anti-TB drugs to shorten or simplify therapy.
SQ109 was discovered in NIAID’s intramural laboratories in 1999, and developed with extensive support from NIAID, as well as the NCI/NIAID Inter-Institute Program for the Development of AIDS-Related Therapeutics. SQ109 was granted FDA Fast Track status, as well as FDA and European Medicines Agency Orphan Drug Designation in 2007.
An orally active tablet, SQ109 has shown in vivo activity against pulmonary TB alone and with other TB drugs, according to Dr. Nacy. With a mechanism of action distinct from other antibiotics used in TB therapy, SQ109 inhibits cell wall synthesis in a select group of microorganisms with in vitro activity against both drug-susceptible and drug-resistant TB bacteria, including XDR-TB. “SQ109 apparently makes other TB drugs work better,” she insists, “enhancing both in vitro and in vivo their activity, thereby shortening the time required to cure mice of experimental TB by 30 percent.”
SQ109 is beginning Phase Ib clinical trials in the U.S. and Phase II studies will be initiated in Africa in 2009. The drug also has in vitro activity against common nosocomial fungal infections including Candida sp. and Aspergillus sp., Dr. Nacy notes.
Another Sequella offering, SQ641, is the lead drug candidate from a 7,000-compound library of semisynthetic TL-1 inhibitors developed as potential treatments for TB or bacterial pneumonia (Streptococcus pneumoniae). TL-1 is an enzyme required for cell wall synthesis in all bacteria, including TB-causing Mycobacteria. Sequella licensed the compound library from Daiichi-Sankyo, which identified the compound class and performed extensive research and preliminary preclinical development on several drug leads. Sequella has exclusive rights to the series of TL-1 inhibitors for the treatment of TB and all other indications for nearly every worldwide market.
In September, Sequella received a $2.3 million, three-year SBIR grant from NIAID for the development of SQ641. The Phase II SBIR grant will fund the conduct of several IND-related critical path studies, including delivery optimization in vivo. According to Dr. Nacy, the drug may be both orally and parenterally active, and the company is seeking to develop it for use in the hospital and elsewhere.
“Both of these promising drug candidates would enable control of drug-sensitive and drug-resistant TB, both are active and synergistic, both would shorten the treatment time from six months to much less, and both would improve efficacy,” Dr. Nacy concludes. “These compounds have the potential to provide early and prolonged bacterial clearance during the intensive phase of TB therapy and could shorten and improve TB treatment.”