According to the World Health Organization, tuberculosis (TB) causes approximately 1.5 million deaths worldwide each year. More than one-third of the world’s population has tested positive for Mycobacterium tuberculosis (Mtb), the bacterium that causes TB, but are not yet ill (latent infection). Of these, approximately ten percent are expected to progress to active TB infection. Treatment is lengthy, and the drugs often come with serious side effects. This has led to poor treatment compliance and allowed the rise of drug-resistant TB strains. 

The National Institute of Allergy and Infectious Diseases (NIAID) and Sequella, Inc. began collaborating in 1999 to identify and develop new drugs against TB based on a current TB drug ethambutol (EMB), an ethylenediamine compound. Under a Cooperative Research and Development Agreement (CRADA), they synthesized and screened more than 100,000 second-generation ethambutol molecules, which led to the selection and early development of SQ109. 

Sequella is conducting clinical trials with SQ109 as a drug for the treatment of TB, Helicobacter pylori (H. pylori) infections, and gastric carcinomas. The knowledge gained by NIAID during this collaboration contributes to the laboratory’s understanding of the mechanism of action of EMB, and may lead to the discovery and development of future therapeutics. 

Sequella continues to advance the development of SQ109 as a therapeutic, and has filed two Investigational New Drug applications for its use against TB and H. pylori-related duodenal ulcers. The FDA and the European Medicines Agencies granted the company Orphan Drug status for SQ109 for use against drug-susceptible and drug-resistant TB. Sequella also commenced Phase II trials using SQ109 to treat H. pylori-associated duodenal ulcers. In addition, NIAID and Sequella continue to collaborate to study the potential of SQ109 as a tracer to identify TB lesions. These technology transfer activities have resulted in the development of an exciting new drug that exceeds both parties’ expectations at the start of the collaboration. 

Awardees

NIH - National Institute of Allergy and Infectious Diseases

• Dr. Clifton Barry III
• Meghan Van Horn
• Tristan Mahyera
• Dr. Mukul Ranjan

NIH - Office of Technology Transfer

• Edward Fenn