In conversation with Bing Yao

As an SVP of AstraZeneca’s (NYSE:AZN) MedImmune unit, Bing Yao heads the Respiratory, Inflammation & Autoimmunity (RIA) Innovative Medicines unit at MedImmune, leading a team dedicated to the strategy, prioritization, and advancement of MedImmune and AstraZeneca’s RIA portfolio. Dr. Yao has worked in the biotech and pharmaceutical industries for almost 20 years. Before joining MedImmune, he worked with Genentech, Aventis and Amgen. In this interview with, Dr. Yao discusses how biologics are influencing the asthma treatment landscape, the size of the asthma market, and the company’s pipeline.

What sparked your personal interest in biologics research, specifically in the respiratory area?

I earned my doctorate in microbiology and immunology and have always had an interest in the development and treatment of immune-mediated inflammatory diseases. So many conditions – including asthma and chronic obstructive pulmonary disease – are rooted in inflammatory diseases, and I have always been interested in helping the diverse and large group of patients with these conditions.

How will biologics and the use of biomarkers change the asthma treatment landscape?

Many patients’ severe asthma is not controlled with currently available treatments, and these patients face limited effective treatments that can reduce the frequency or severity of their asthma attacks. With high specificity to target inflammatory molecules or cells that contribute to asthma, biologics have the potential to improve the landscape of asthma treatment options and potentially provide alternative medicines, especially among patients with severe forms of diseases who are not responding to existing therapy. Currently, there is only one approved biologic for asthma in the U.S. – a monoclonal antibody – and it’s approved for a subset of severe asthmatics with elevated levels of immunoglobulin E antibody in their bodies.

At MedImmune, we’re specifically focusing on creating monoclonal antibodies that may treat patients with different subtypes of severe form of asthma. One such subgroup of patients is characterized by airway inflammation due to eosinophils – white blood cells whose natural role is to defend the body against parasites. These blood cells accumulate wherever allergic reactions take place. Therefore, the more eosinophils in a person, the more severe their asthma is. Eosinophil levels can be measured through simple blood and sputum tests. Using this biomarker, scientists can pinpoint patients with higher eosinophil levels who are most likely to benefit from specific treatments. Ultimately, this helps us get the right medicine to the right patients sooner.

What is the market opportunity in severe asthma?

Almost 11% of Americans have been diagnosed with asthma, and the rate is expected to increase because of environmental and childhood risk factors. Approximately 1.4 million [Americans] have been diagnosed with severe asthma and of that, 40% to 60% are thought to have elevated eosinophils. Although the marketing options for asthma are currently shrinking as patents expire on many of the leading inhaled asthma drugs, the industry is poised to see moderate growth as the number of patients with asthma increases and more biotech and pharmaceutical companies enter the market.

How is MedImmune looking at asthma?

Asthma is a heterogeneous disease, and therefore, we are focusing our efforts on personalized therapeutics rather than on broad agents. By understanding the molecular phenotype of asthma, we can target specific patient groups to hopefully optimize the effectiveness of treatment options and improve outcomes for severe asthmatics. This approach isn’t going to cure asthma today or tomorrow, but it’s helping us make serious progress toward controlling the disease.

In our pipeline, we have several biologics for asthma, of which we’re exploring the diagnostic potential for a personalized approach. We’re focused on the development of large molecules, instead of small, oral molecules. One molecule in particular – benralizumab – entered Phase 3 clinical development this past fall as a treatment to decrease exacerbations among asthma patients with elevated eosinophils.

How does benralizumab work? Is it unique?

Benralizumab is a monoclonal antibody that binds to the receptor for the cytokine interleukin-5 (IL-5) and is engineered to have enhanced antibody-dependent cellular cytotoxicity. This cytokine controls the growth, activation, and survival of eosinophils. Upon binding to this receptor (IL-5Rα), benralizumab leads to depletion of eosinophils in patients with asthma, potentially reducing the frequency of asthma exacerbations. Benralizumab is different from other IL-5 inhibitors in development, because it targets the receptor for IL-5 and because of its depleting property.

What’s the potential for benralizumab?

Benralizumab is the first in a series of respiratory biologic therapies at MedImmune driven by our focus on personalized healthcare, and we believe it has the potential to be best in class. Its current Phase 3 clinical trials are testing whether benralizumab will reduce the number of asthma attacks in patients with severe, uncontrolled asthma, despite their use of inhaled corticosteroids and a second treatment option, such as a long-acting beta agonist.

What else is in store for MedImmune and its respiratory pipeline?

MedImmune is committed to advancing innovative research for respiratory diseases. Our vision is to become an industry leader in targeted therapies for asthma, complementing our company’s broader efforts in inhaled and small molecule development. In pursuit of that goal, we have many drugs in development, including:

 • Tralokinumab which is a human monoclonal antibody that targets IL-13 and blocks multiple effects in the lung, such as inflammation and airway hyper-responsiveness, and which is being evaluated for advancement into Phase 3 trials in early 2014;

• Brodalumab, a monoclonal antibody that targets the IL-17 receptor and may be beneficial for patients with neutrophilic asthma, that is being developed in conjunction with Amgen and is in a Phase 2b clinical study;

• MedI9929/AMG157, an upstream cytokine that blocks the interaction of thymic stromal lymphopoietin (TSLP) with the TSLP receptor, that is also in development with Amgen and has completed a Phase 1b study.  This molecule has the potential to target a broader population than other asthma compounds.

We know that regulators are extremely cautious about new biologics that affect the immune system, since the target patients for these drugs are already chronic users of medication. We also recognize that due to the chronic nature of severe asthma, patients and insurers demand drugs that demonstrate clear value in the face of potentially less expensive inhaled and oral drugs. Therefore, we’re working hard to show that our new biologics can reduce asthma attacks – and potentially even expensive hospitalizations due to attacks – ultimately driving down healthcare costs in the long run and improving patient care.

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