A Q&A with MedImmune’s Roland Kolbeck, VP, R&D, Respiratory, Inflammation, and Autoimmunity (RIA)
Einstein once said that “If you always do what you always did, you will always get what you always got.” A MedImmune scientist is likely to tell you: That’s a plain fact. And if ever there were proof, our investigational respiratory biologics portfolio would be it.
Asthma affects 315 million individuals worldwide1, yet no two patients are ever exactly alike. In addressing this heterogeneous disease—with complex biology and various immunological disease drivers2,3—MedImmune researchers have stepped out of the box to address an important unmet need. We are innovating to target specific biologic treatments to patient types, so that we might optimise individual responses to treatment.
As we prepare for this year’s American Thoracic Society (ATS) conference, held in Washington, DC, May 19-24, we thought we’d shift the focus from talking data, endpoints, and outcomes to digging back into the early science behind this portfolio — and how following the science has opened the door for new discovery.
In this Q&A, Roland Kolbeck, PhD, MedImmune’s VP, R&D, Respiratory, Inflammation, and Autoimmunity (RIA) shares his thoughts on the development of these important investigational biologics.
Q: Why is the early science important in biologics development?
A: Within the larger context of our RIA research and development, our focus is on the biological pathways that characterise conditions—whether asthma or chronic obstructive pulmonary disease (COPD), in the case of respiratory, or other inflammatory and autoimmune illnesses. Investigating these pathways and their molecular originations enables a better understanding of disease; this is our highest priority. Without this early work and the knowledge that it reveals—particularly in this era of personalized medicine—drug development today would continue along a path of “one size fits all” medicine. Early science moves us toward disruptive breakthroughs in treatment.
Q: How has the early science “personalized” respiratory biologics?
A: Inflammatory diseases—asthma and COPD, for example—encompass several distinct patient phenotypes, and these are characterised by the shared presence of cellular and molecular biomarkers.3 When we are able to link these biomarkers with clinical phenotypes, this significantly shifts and advances our understanding of pathophysiology; in turn, facilitating the clinical development of biologics. For example, today we know that eosinophils are a feature in the exacerbations of some patients with asthma, and particularly those with severe, uncontrolled asthma. We also know that interleukin (IL)-5 induces eosinophilic airway inflammation.4 We use this knowledge to drive our investigations into potential therapeutic options.
Q: What are you learning about other respiratory disease pathways, and how is this informing future drug development?
A: We are learning more about the IL-13 pathway and, more recently, the role of thymic stromal lymphopoietin (TSLP). What we know about IL-13 is that it plays a role in mediating the features of chronic, severe asthma.5
As such, our investigations seek to understand how targeting these pathways may play a role in helping patients with severe asthma.
Q: What do you hope most for in your early science efforts?
A: When we look at respiratory conditions like asthma and COPD, we see remarkable heterogeneity. In severe patients, we also see suboptimal control of symptoms through existing therapies that include inhaled corticosteroids (ICS).6 This means that there remains a substantial unmet need for treatments that improve symptom control and slow disease progression. The goal of early science is to understand the subtleties and diversity of disease, and identify specific biomarkers and pathways that will enable the development of highly targeted and potent biologics, most particularly for patients who may not have other options. We still have much to learn, but by scrutinising and following the early science at the cellular and molecular level, we are several steps closer in our efforts.
1. To T et al. Global asthma prevalence in adults: findings from cross-sectional world health survey. BioMed Central Public Health. 2012: 12(204).
2. Murdoch J.R et al. Chronic inflammation and asthma. Mutation Research. 2010; 690: 24–39.
3. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008;8(3):183-192.
4. Garcia G et al. Anti-interleukin-5 therapy in severe asthma. Eur Respir Rev. 2013;39:109-114.
5. Saha SK et al. Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol. 2008; 121(3):685-691
6. Sweeney J et al. Comborbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry. Thorax 2016;71:339-346