Staff Writer

Pegged as the poor man's disease, tuberculosis long has been ignored by researchers who believed there was no niche market for an infection that already has treatments.

But Carol Nacy and her team at Sequella Inc., of Rockville, Md., are looking in the other direction - toward potential new therapies, vaccines and diagnostics for tuberculosis.

"There is no country free of tuberculosis, including the U.S.," said Nacy, who is Sequella's CEO and co-founder.

"There's over $1 billion spent every year for tuberculosis diagnosis and control in the U.S.," she added.

Nacy, who helped found Entremed Inc. in 1993, left her chief scientific officer position at that Rockville-based company following its initial public offering in 1996. She worked on a National Institutes of Health tuberculosis program before deciding in 1997 to co-found Sequella with Entremed colleague Leo Einck, who now serves as Sequella's president.

"We saw this as a unique opportunity to make new products for a disease that people were not paying attention to today," Nacy told BioWorld Today.

Until now, the company has kept a low profile. But with plans to move its first tuberculosis product, a therapeutic called SQ109, into the clinic in the first quarter of 2005, and with an agreement signed this week for tuberculosis inhibitors from Tokyo-based Sankyo Co. Ltd., it was time to share the story.

In the agreement with Sankyo, Sequella gained exclusive rights in all major markets and most of the rest of the world to novel anti-tuberculosis translocase inhibitors. In return, Sankyo would receive downstream milestone and royalty payments.

The inhibitors work on an enzyme required for cell-wall synthesis, known as mycobacterial translocase I. The lead compound could reach the clinic in 18 to 24 months.

"We have looked at the compound ourselves with Sankyo and it's actually quite a nice compound," Nacy said. "It attacks a different molecule than any of the other anti-TB drugs out there."

Sankyo was developing the drug as an aerosol-transmitted therapy, but the company decided to move away from infectious diseases and focus on its other programs. The company has completed several preclinical studies, including an in vivo demonstration of activity in an animal model of tuberculosis, as well as preliminary pharmacokinetic and toxicology studies.

Sequella plans to spend some time developing the lead compound as an oral therapy. All of the current drugs on the market are being delivered orally, Nacy said.

Aside from tuberculosis, Sequella has rights to the translocase inhibitors for all other potential applications.

"It actually has some activity with Gram-positive organisms," Nacy said. "Of course, it has not been optimized for treatment of other bacteria besides tuberculosis."

Two messages delivered by global health authorities in recent decades might have caused the pharmaceutical and biotech industries to overlook the need and potential for new products for tuberculosis. In the 1970s, physicians learned they could cure tuberculosis by treating the infected person with four different drugs over two years, suggesting there was no unmet medical need. And because tuberculosis flourishes where people live in close proximity, such as in developing nations, the World Health Organization talked publicly about tuberculosis being a disease of the poor, "as if no-one could pay for their therapy," Nacy said.

But the dubious Mycobacterium tuberculosis is creative. It knows how to move around the susceptibility to any one drug. More than 2 billion people - roughly one-third of the world's population - has been infected with M. tuberculosis, and 10 percent of them eventually will contract active disease. Every year, more than 2 million people die of the disease.

While 90 percent of all new cases of tuberculosis occur in sub-Saharan Africa, Southeast Asia, India and China, developing nations are not immune to the epidemic. It is estimated that 10 million to 15 million people in the U.S. are infected, and 20,000 go on to active tuberculosis each year.

Sequella also has programs developing diagnostics for tuberculosis. The most recent diagnostic products were developed between 50 and 100 years ago, and can take six weeks to six months to deliver an answer.

"Without a good diagnostic, it was going to be difficult to do a good clinical trial," Macy said.

Sequella has raised $20 million since inception and currently has 15 employees. In addition to its in-licensed translocase inhibitors, the company is working on second-generation antibiotics, a drug-compliance monitoring device, a therapeutic vaccine and diagnostic products.