CINDY SANDERS

Asthma is a global problem crossing gender, ethnic, racial and socioeconomic lines. It is estimated that nearly 10 percent of the population is affected by asthma, which has serious morbidity, mortality and economic consequences.

In Tennessee, natural and manmade irritants exacerbate the problem. In their annual ranking of "Asthma Capitals," the Asthma and Allergy Foundation of America lists three Tennessee cities in the top 10 most challenging places to live with asthma. Among the nation's 100 largest metropolitan areas, Chattanooga ranked fourth, followed by Memphis and Knoxville in sixth and seventh places respectively. Nashville checked in at 32 on the list.

In an effort to give a promising new asthma technology the opportunity to move from the lab to the prescription pad, Nashville-based Cumberland Emerging Technologies, Inc. (CET) has entered into a licensing agreement with the University of Tennessee Research Foundation (UTRF) in Knoxville. From her Memphis lab at the University of Tennessee Health Science Center (UTHS), primary investigator D. Betty Lew, MD, is conducting non-clinical studies on a patented discovery tied to Mannan, a novel carbohydrate-based compound that is believed to prevent airway remodeling.

Lew, professor of pediatrics and director of training for the Allergy and Immunology Program at UTHS, said current treatment options including corticosteroids and adrenergic bronchodilators often require toxic doses with multiple side effects and simply don't work for a percentage of the population.

"We need another agent that works taken alone or in combination," she said. Mannan, she continued, is a mannose receptor blocker. "Airway smooth muscle cells express mannose receptors," Lew explained. "Activation of these receptors by lysosomal hydrolases causes hypertrophy and hyperplasia of smooth muscle… namely remodeling." Lew said Mannan appears to have both a great anti-inflammatory and anti-remodeling effect.

A.J. Kazimi, CEO of Cumberland Pharmaceuticals and CET, said this latest collaborative project furthers CET's mission to address "clinical, manufacturing, regulatory and funding challenges that often impede biopharmaceutical development."

When CET was formed, he continued, "We recognized that research institutions like the University of Tennessee have promising ideas that, if fostered with a development infrastructure, could result in products and technologies that would not only potentially improve patient care but also bolster our state's economy."

The new asthma technology was specifically of interest to CET because of the potential to bridge the current therapy gap.

"We look for products and technologies that will either fill an unmet medical need or improve upon existing treatment options," Kazimi said. "We then evaluate whether a product is technically and commercially viable. We believe this particular UT product candidate holds promise on both scientific and commercial fronts."

Under the new agreement, CET is providing formulation, grant funding, and regulatory and product development assistance in exchange for the rights to commercialize the technology should the requisite step-wise testing prove its safety and efficacy.

Richard Magid, PhD, licensing associate for UTRF, said his organization is the technology transfer agency for the University of Tennessee. As such, he is continually looking for the commercial potential in the many discoveries made by university researchers. While UT has the scientific and technological capabilities to come up with novel solutions, Magid said mass production and commercialization must happen in the private sector.

"We meet with CET every year and probably pitch six-to-10 technologies," he explained of the process. Like other potential partners, Magid said CET has strategic areas on which they focus. "If they're interested (in a technology), then we'll proceed with more information."

Magid continued, "CET really understands the University of Tennessee and how to work within the state and with the university. It's a very collaborative process… it's a win/win." He added that CET tries to keep the original researcher involved and engaged in the project as it moves forward.

The asthma project was recently awarded a Phase I NIH grant under the Small Business Technology Transfer program. Although the project has already received more than $190,000 in funding, Kazimi said development could easily wind up costing several million dollars.

After completion of preclinical trials, CET will put forth an investigational new drug application to the FDA followed by a series of clinical trials and ultimately the submission of a new drug application for official product approval.

"Even after product approval, the FDA could require certain post-marketing (phase IV) activities," noted Kazimi. "As with product development costs, the timeframe associated with a particular program varies based on necessary clinical and manufacturing work, ability to secure funding, and FDA requirements, among other things. Generally speaking, it may take six-10 years or more to develop a product like this and secure marketing approval."

Lew, a pediatric allergist, envisions the day when this treatment option might be available. She regularly sees children in the ICU who arrive in serious respiratory distress, as well as in her high-risk clinic at Le Bonheur Children's Medical Center where many of her asthma patients are fatality prone.

"That was the driving force… something that gives quick relief in an acute setting, as well as the controlling of asthma inflammation and remodeling," she said of her work. "I think it would be my pride and joy as an MD to write the first prescription for my own patient."