Emisphere's Oral Cromolyn Sodium Program
Emisphere has developed an oral formulation of cromolyn sodium for the treatments of asthma and allergy. Cromolyn sodium, a non-steroidal anti-allergy medication, has long been considered one of the safest and most effective drugs for mild to moderate asthma.

Although cromolyn sodium has been approved by the U.S. Food & Drug Administration as a prophylactic agent for the management of patients with mild to moderate bronchial asthma, as an inhalation aerosol and nebulized solution, the drug has shown poor absorption from the gastrointestinal tract. In the first human study, escalating single oral doses of cromolyn sodium combined with an EMISPHERE^® delivery agent demonstrated effective oral delivery and absorption.

Subsequently, a Phase I randomized, double-blind, placebo controlled multi-dose study in human allergy patients was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics for a duration of 10 days. This study revealed that oral delivery of cromolyn sodium, using an EMISPHERE^® carrier, was effectively delivered in allergic subjects. Absorption was rapid and no adverse events were reported during the study. Oral cromolyn sodium also had an excellent safety profile.

In addition to asthma and allergy testing, Emisphere is currently exploring alternative applications with cromolyn.

Market Opportunities
According to information from the American Lung Association, the Centers for Disease Control and Prevention (CDC), and the National Institute of Allergy and Infectious Diseases (NIAID) in 2002, approximately 24.7 million people in the United States have been diagnosed with asthma, with at least 7.7 million of them children under the age of 18. The annual economic cost of asthma has been estimated at $12.7 billion, with direct health care costs of $8.1 billion and indirect costs of $4.6 billion.

About Oral Cromolyn
Cromolyn is a potent mast cell stabilizer used for the treatment of allergy and asthma. Mast cells play an important role in the allergic response to allergens. Exposure to certain stimuli such as allergens (including pollen, aspirin, chemicals, cold air, or air pollutants) begins a process that destabilizes the mast cells and leads to the release of cytokines including histamine, prostaglandins and leukotrienes from mast cells granules. Cromolyn attenuates the release of these bio-chemicals, which, in susceptible individuals, cause allergic reactions or asthma attacks.

Cromolyn is known to be a safe drug with minimal side effects, even when given for long-term treatment. The main side effects of cromolyn are nasopharyngeal irritation and dry mouth.

About Asthma and Allergy
Asthma is a chronic and potentially life-threatening lung disease in which the bronchioles (collective term for the bronchial tubes and alveoli sacs in the lung) have an adverse reaction to ordinarily non-reactive elements, known as "triggers". Commonly identified triggers include allergens, food, exercise or respiratory infection. These triggers catalyze already sensitized bronchioles to become inflamed, constricted and to produce mucus, resulting in variable airflow obstruction. Asthmatics experience wheezing, coughing, shortness of breath and/or constriction within the chest cavity.

Therapy for all subgroups of asthma (except for mild, intermittent episodes) is long-term, and medication (i.e., anti-inflammatory agents) is typically administered daily. Cromolyn has been used both to prevent and treat asthma. It is a treatment prescribed for mild and moderate persistent asthmatics.

One of the most common forms of allergic reaction is allergic rhinitis, an allergy to airborne particles also known as hay fever. Hay fever can be seasonal or year-round. Common symptoms include sneezing, an itchy, runny or stuffy nose and itchy and irritated eyes, all of which include inflammation, and thus can be treated by cromolyn. The National Center for Health Statistics estimated that in 2002, 18.2 million adults and 7.5 million children were treated for hay fever.