DESCRIPTION (provided by applicant): Asthma is a chronic, debilitating disease characterized by intermittent attacks of wheezing, shortness of breath, chest tightness, cough and excess sputum/mucus production. As many as 300 million people worldwide may have some form of asthma and the prevalence has steadily increased at an alarming rate over the past two decades. Today in the United States alone, more than 24 million people (~ 10 million children) have asthma resulting in more than 500,000 hospital admissions annually due to asthmatic symptoms and more than 5000 deaths each year. Most asthmatics have a mild form of the disease, which is well controlled by inhaled bronchodilators; however, up to 5% have severe asthma for which there is no effective treatment. These are the patients who show up at the emergency room during an acute, life threatening attack and can remain in the hospital for up to one week or longer. The cost of asthma is great and asthma-related hospitalizations accounts for almost 80% of the healthcare expenditures for this disease representing a huge financial burden on both families and governments. The cost of asthma in the United States is estimated to be more than $14 billion per year. The Heat Biologics R&D team is developing a novel treatment that deals directly with the underlying causes of asthma, rather than just symptom relief, and if successful, will revolutionize the way asthma is treated. Controlling inflammation is now a central objective of asthma therapy and is essential for better control of the disease. Asthma is an immune-mediate disease and, therefore, new, more effective treatments will modulate the immune system to block the onset and progression of asthma. Heat Biologic's novel approach is focused on modulating T cell activity and pro-inflammatory cytokine production and secretion such that the immune system, which is overactive in diseases like asthma, is 'dialed down' to a level where there is no longer chronic inflammation present in the lungs and the airways are allowed to repair and return to normal function. The specific aims for this grant are to 1) generate and characterize a humanized form of the current molecule that would be appropriate for eventual testing in human asthmatics and 2) to continue to evaluate the effectiveness of this molecule as a novel treatment for the 'causal events of asthma' in well characterized animal models. The work conducted in Phase 1 of this grant will enable Heat Biologics to be in a position to initiate production of high quality material for use in preclinical safety studies in depth analysis if the mechanism of action and to demonstrate the potential therapeutic benefits to human asthmatics. PUBLIC HEALTH RELEVANCE: As many as 300 million people worldwide may have some form of asthma and both the incidence and prevalence are increasing at an alarming rate. Today in the United States alone, more than 24 million people (~ 10 million children) have asthma resulting in more than 500,000 hospitalizations annually due to asthmatic symptoms, a huge drain on healthcare system and more than 5000 deaths each year (approximately 450 deaths per month, 100 per week and 15 each day!). The overall goal of this project is to develop and validate a novel therapeutic for the treatment of asthma that addresses the underlying causal factors of the disease, not just treating symptoms, providing a means for improving the quality of life for the millions who suffer from asthma.

Project Narrative As many as 300 million people worldwide may have some form of asthma and both the incidence and prevalence are increasing at an alarming rate. Today in the United States alone, more than 24 million people (~ 10 million children) have asthma resulting in more than 500,000 hospitalizations annually due to asthmatic symptoms, a huge drain on healthcare system and more than 5000 deaths each year (approximately 450 deaths per month, 100 per week and 15 each day!). The overall goal of this project is to develop and validate a novel therapeutic for the treatment of asthma that addresses the underlying causal factors of the disease, not just treating symptoms, providing a means for improving the quality of life for the millions who suffer from asthma.