Our respiratory franchise has three development programs directed toward asthma and COPD: our GlaxoSmithKline (GSK) Long-Acting Beta2 Agonist (LABA) collaboration, known as the Horizon program; our Bifunctional Muscarinic Antagonist-Beta2 Agonist (MABA) program, which GSK has licensed under the terms of our strategic alliance; and our Long-Acting Muscarinic Antagonist (LAMA) program, which GSK also has licensed under the terms of our strategic alliance. In 2009, GSK returned the LAMA program to us because the current formulation of the LAMA compound is incompatible with GSK's proprietary inhaler device.

Long-Acting Beta2 Agonist (LABA)

Beta2 agonists are medicines that work by relaxing the muscles that line the bronchial airways, allowing the airways to expand (known as bronchodilation) and leading to relief and/or prevention of many of the symptoms of asthma and COPD.

Horizon Program

In our Horizon program, we plan to develop with GSK a long-acting beta2 agonist that can be taken as an inhaled medicine once a day and can be combined with a once-a-day inhaled corticosteroid so the combination medicine would also be taken once a day. We believe once-a-day dosing would be a significant convenience and compliance-enhancing advantage leading to improved overall clinical outcomes in patients with asthma or COPD.

Bifunctional Muscarinic Antagonist-Beta2 Agonist (MABA)

When inhaled into the lungs, both muscarinic antagonists and beta2 agonists cause bronchodilation, but by different mechanisms of action. Moreover, both classes of drugs have non-bronchodilator effects that can be complementary and beneficial in patients with COPD and perhaps in patients with severe asthma. Currently many patients are using both inhaled muscarinic antagonists and inhaled beta2 agonists (either in two separate inhalers or via the product, Combivent^®, which combines short-acting agents from the two drug classes).

Under our strategic alliance, we are developing with GSK a long-acting inhaled bronchodilator that is bifunctional, meaning that one small molecule functions as both a muscarinic antagonist and a beta2 receptor agonist. By combining bifunctional activity and high lung selectivity, we intend to develop a medicine with greater efficacy than single mechanism bronchodilators (such as tiotropium or salmeterol) and with equal or better tolerability. This bifunctional bronchodilator could potentially then serve as a basis for improved combination therapy through co-formulation with an inhaled corticosteroid that could potentially deliver three complementary therapeutic effects in a single product for patients with respiratory disease.

Inhaled Long-Acting Muscarinic Antagonist (LAMA)

Among the most frequently used bronchodilators for COPD are the inhaled muscarinic antagonists. Inhaled muscarinic antagonists work by inhibiting muscarinic receptors in the bronchial airways which leads to muscle relaxation and improved lung function.

We are developing an inhaled LAMA that is designed to produce a prolonged blockade of the relevant receptor sub-types while also being highly lung-selective, which means that lower concentrations of drug should get into the systemic circulation. We believe this approach should result in improved tolerability. The goal of the LAMA program is to develop an effective once-daily medicine that offers improved efficacy and tolerability relative to the market leaders.