Therapies

Targeting Inflammatory Disease of Smooth Muscle:
Lead Clinical Development Opportunities for PI-301

Asthma

Overactive Bladder

Inflammatory Bowel Disease

Asthma

Asthma is characterized by chronic airway inflammation resulting in airway obstruction and hyperactivity to external stimuli. Common clinical features include episodes and recurrence of cough, chest tightness, shortness of breath, and wheezing.

Asthma is a major global health concern. 334 million people are estimated to be affected worldwide, with 27 million people in the United States alone. Global asthma prevalence is estimated to reach more than 400 million in year 2025. Despite the growing challenge of asthma, currently approved therapeutic options are limited. The preferred therapy for chronic persistent asthma includes inhaled corticosteroids and inhaled long acting β₂ adrenergic receptor agonists (LABAs). Nevertheless, asthma morbidity and mortality continue to rise. One important factor is the failure of patients to properly use inhaled medications leading to non-compliance and loss of asthma control. Alternatives for patients whose symptoms are poorly controlled are oral leukotriene receptor antagonists, however, genetic variations in leukotriene signaling genes may preclude their widespread efficacy. Injectable biologics can reduce asthma lung inflammation, but patient costs for these drugs of up to $30,000 per year limits their use to more severe disease. Importantly, these biologics are unable to protect against acute bronchospasm and present anaphylaxis risks. As an improved and affordable asthma therapy, Pantherics is developing an oral drug formulated with a single active compound (PI-301) to treat multiple symptoms of asthma.

Asthma exacerbations consist of acute or subacute episodes of progressively worsening shortness of breath, coughing, wheezing, and chest tightness and differ from poor asthma control. Most asthma exacerbations are medical emergencies that require immediate care, observation of lung function worsening, pharmacological treatment, and repeated treatment and symptom reassessment. In general, primary treatment consists of oxygen administration and administration of inhaled β₂ agonists and systemic corticosteroids with dosing adjusted depending on the severity of the exacerbation. In addition to these primary treatments, therapy with inhaled ipratropium bromide, magnesium sulfate, or other agents might also be necessary in severe exacerbations. Each year acute attacks account for 1.8 million emergency department visits and 439,000 hospital stays. Many patients discharged from ER return (“bounce back”) within 24-48 hours representing a substantial unreimbursed hospital cost. MIDD0301 formulated for nebulizer delivery offers a compelling new approach for asthma exacerbation treatment.

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease characterized by progressive airflow limitation that is not fully reversible. It is believed that a chronic inflammatory state leads to narrowing of the small airways and deterioration of the lung parenchyma. In many patients, exacerbations and comorbidities contribute to the disease severity. It is estimated that COPD affects 210 million people worldwide, resulting in more than 4 million deaths annually and is projected to be the 3^rd leading global cause of death by 2030. In the US, COPD affects about 16 million patients and many more millions are undiagnosed. Higher relative COPD prevalence is observed in women, American Indian and Alaska Native populations, and rural residents. In 2010, the cost of COPD in the US was projected to be approximately $50 billion, which includes $20 billion in indirect costs and $30 billion in direct health care expenditures. These costs can be expected to rise with an aging population and disease progressivity. Bronchodilators and corticosteroids are the mainstays of COPD management. Initial treatment for patients with few symptoms and low exacerbation risk consists of a short-acting inhaled bronchodilator, either short-acting β₂ agonist or muscarinic antagonist Corticosteroids are usually taken by inhaler, often in combination with a bronchodilator and may be given in a pill form to provide larger doses. PI-301 (in either oral or nebulized form) offers a new mechanism of action for COPD patients to reduce inflammation and improve airway function.

Overactive bladder

Overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS) are common conditions that cause urinary urgency and frequency, as well as frequent nightly wakening with the urge to urinate. OAB and IC/PBS are believed to affect as many at 16% of Western populations. OAB affects >38 million Americans, and approximately one in three elderly adults. Patients with OAB have an average of 84% more yearly physician visits and 21% more urinary tract infections. Together OAB and IC/PBS are estimated to incur yearly societal and economic costs of greater than $70 billion in the US. Chronic inflammation of the bladder is closely associated with the OAB symptoms. Overexpression of pro-inflammatory genes and increased macrophages, chemokines, cytokines, and eosinophils have been identified in IC/PBS patients. Although treatment options exist, no single treatment has been proven to be most effective. Often a combination of therapy is required to successfully manage OAB symptoms. Antimuscarinics are the primary class of pharmaceutical agents used to treat OAB. However, side effects of these agents (such as dry mouth, dry eyes, constipation, and heart palpitations) are common because muscarinic receptors are found throughout the body. A β₃ adrenoceptor agonist can be used as an alternative therapy or in those who poorly tolerate antimuscarinic agents. PI-301 offers a new strategy to control inflammation and smooth muscle contractility in OAB.

Inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic incurable condition characterized by relapsing inflammation of the gut. In Crohn’s disease strictures, there is thickening of smooth muscle layers and cell proliferation. Research has shown that growth and contractile properties of intestinal smooth muscle are substantially altered during mucosal inflammation, which can result in intestinal dysmotility and pain. The global prevalence of IBD is estimated at 5 million persons; with US prevalence of 1.2 million resulting in direct healthcare costs estimated to be between $11-28 billion. Conventional therapies include anti-inflammatory drugs (e.g., aminosalicylates) and corticosteroids, which are considered first-line therapies for most patients and often associated with substantial adverse effects and poor symptom control. Treating intestinal inflammation and smooth muscle dysmotility with MIDD0301 offers a novel strategy for improved symptom control in IBD.

According to the “Real-World Evaluation of Asthma Control and Treatment” (REACT) study, more than half of  (55 percent) of Americans with moderate-to-severe asthma self reported they do not have their asthma symptoms under control despite the fact that most had health insurance and regular doctor visits.