CIO Bulletin

EpiEndo Pharmaceuticals – Developing novel drugs to address the huge global burden of chronic respiratory diseases

"EpiEndo is developing first-in-class, orally-available disease-modifying drugs to address the global burden of COPD and viral airway diseases."

Despite enormous unmet medical needs in respiratory medicine, very few new classes of safe and effective therapy have been introduced over the past 40 years. In spite of its enormous burden, respiratory medicine appears to have fewer new approved therapies than other common disease areas, such as cardiovascular, metabolic and neurological diseases, with fewer drug candidates and a higher failure rate. Furthermore, as in other areas of drug discovery, the time for drug development is getting longer and the risk of failure ever higher, leading to enormous and growing development costs. Greater collaboration in recent years between academia and the pharmaceutical industry has produced major scientific breakthroughs in the mechanistic, cellular and molecular understanding of respiratory diseases. This has resulted in new translational options for developing innovative therapies for patients with unmet medical needs, but not innovation in the respiratory drug area. Clear efforts are being made to understand and address the limitations in the current disease modeling approaches, with greater willingness to move away from the standard “off-the-shelf” historical models to those that directly measure what the candidate molecule is targeting.

With over a decade of experience EpiEndo Pharmaceuticals is at the forefront in discovering novel approaches to treat chronic respiratory diseases. Its research into the disease etiology of chronic obstructive pulmonary disease (COPD) has led to unique insights in inflammatory processes. EpiEndo Pharmaceuticals is an Icelandic clinical stage pharmaceutical company with a unique focus on impairment of epithelial barriers as a common mechanism of many inflammatory conditions such as the airway, gastrointestinal tract and skin. Its new class of orally-available macrolide candidate NCEs show promise as first-in-class disease-modifying therapeutics for COPD. EpiEndo's lead compound is a non-antibiotic analogue of azithromycin which modulates inflammation through strengthening the lung epithelium. The company is actively exploring additional potential applications for post COVID-19 treatment, where the established anti-inflammatory properties of its technology may be of value. The company operates an agile business with an experienced core team based across Iceland, Sweden, Germany and the UK, supported by global key opinion leaders and pulmonary specialists, with contractors and consultants filling other key functions.

The Global Burden of COPD

COPD is a slow progressing chronic respiratory disorder characterised by an obstructive ventilatory pattern which is not fully reversible. The primary causes of COPD in the developed world are tobacco smoking and pollution, while in developing countries, cooking over open fires is a major cause. Cigarettes are smoked by more than 1.1 billion people, nearly 20% of the world's population, while according to the WHO more than 3 billion people around the world cook their food and heat their homes with open or barely contained fires. A typical cooking fire produces about 400 cigarettes’ worth of smoke an hour. COPD is currently incurable. Today, management of COPD currently relies primarily on inhaled drugs, including long-acting adrenoceptor agonists (LABA), long-acting muscarinic receptor antagonists (LAMA), and corticosteroids (ICS), however these treatments address symptoms only. Despite 50 years of active research in this pharmacotherapeutic area, there are still no clinical trials showing that any existing medications for COPD modify the long-term decline in lung function that characterizes this disease.

EpiEndo Pharmaceuticals to the Rescue: Addressing the Growing Burden of Airway Diseases

EpiEndo is developing first-in-class, disease-modifying drugs to address the global burden and high unmet need of chronic obstructive pulmonary disease (COPD) and viral airway diseases. COPD (chronic bronchitis and emphysema), asthma and cystic fibrosis are chronic lung diseases associated with chronic airway inflammation and epithelial dysfunction. Airway diseases represent some of the most important public health challenges because of their high prevalence, estimated at more than a quarter of a billion cases worldwide in 2019, increasing incidence and related disability and mortality.

EpiEndo's proprietary macrolide compounds exhibit a novel mechanism that enhances the integrity of the epithelial cell layer in the lung, which the company and its team believe may slow progression through reduction of underlying disease pathology. Exacerbations are attacks of restricted breathing, characterized by breathlessness, that become worse as the disease progresses, ultimately leading to death. Early intervention and avoidance of disease progression is therefore critical and EpiEndo's clinical treatment goal is to reduce the frequency, duration and severity of exacerbations.

A Unique Macrolide Portfolio

EpiEndo is developing first-in-class, orally-available disease-modifying drugs to address the global burden of COPD and viral airway diseases. The 15-membered ring macrolide antibiotic azithromycin has established efficacy against COPD, however concern for the potential development of antimicrobial resistance continues to suppress widespread use of azithromycin for prevention of COPD exacerbations. Accumulating evidence suggests that the known clinical efficacy of these macrolides for COPD stems from novel mechanisms that strengthen epithelial barriers and anti-inflammatory effects, independent of anti-bacterial effects. EpiEndo’s lead compounds are analogues of azithromycin, specifically designed to have no antibacterial activity. IMPD-enabling studies for the lead compound EP395 are underway, with first-in-man trials planned to commence in late 2020. By enhancing the epithelial integrity, the compounds reduce leakage across and exert an anti-inflammatory effect. The company is supported by favorable class safety and long-term data for macrolides.

The New Paradigm

Almost all drug development efforts for COPD continue to focus on an anti-inflammatory approach to treatment. EpiEndo has strong support from world-leading KOLs for a new paradigm: that epithelial barrier insufficiency is a key driver of inflammation in chronic respiratory diseases. It has been shown that patients with COPD exhibit increased leakage across the lung epithelium. EpiEndo's compounds enhance the epithelial barrier, appearing to strengthen the junctions between cells and reducing leakage across the epithelium. Importantly EpiEndo's compounds are devoid of antibiotic activity which eliminates concerns about possible antibiotic resistance effects that might limit wider use of azithromycin. Azithromycin has been demonstrated to reduce exacerbations of COPD that are caused by bacterial and/or viral infections and air pollution, but when used chronically can lead to anti-microbial resistance. EpiEndo’s compounds are azithromycin analogues lacking anti-microbial activity, that have shown promising results for inhibiting airway inflammation and restoring epithelial integrity in preclinical models.

EpiEndo has strong support from world-leading KOLs for a new paradigm: that epithelial barrier insufficiency is a key driver of inflammation in chronic respiratory diseases. In human studies, it has been shown (unpublished data) that patients with COPD exhibit increased leakage across the lung epithelium. Pre-clinical studies of EpiEndo’s compounds in tests that represent insults from stimuli such as smoke, air pollution, endotoxins and viruses have shown very promising results, with better efficacy than the macrolide antibiotic azithromycin, currently shown to reduce exacerbations in COPD patients¹. Importantly EpiEndo's compounds are devoid of antibiotic activity which eliminates concerns about possible antibiotic resistance effects that might limit wider use of azithromycin. Their compounds display anti-inflammatory effects that may prevent the complications associated with viral lung infections, such as influenza, RSV and possibly SARS-CoV-2, independent of and without any direct antiviral effect. The firm is accumulating pre-clinical data that move forward with trials to explore a potential role for the lead compounds to substitute for azithromycin, where indicated for viral lung infections.

About the Leader

Maria Bech, MSc is the Chief Executive Officer of EpiEndo Pharmaceuticals. She has an in-depth knowledge of development strategies, clinical programs and study design, gained from more than 25 years’ experience working across the pharmaceutical industry from global project management to line management of a clinical/R&D dept. She also serves on the Board of Directors of four companies, of which three are listed: EQL Pharma, Iconovo, Paxman and Neuronano. Maria holds an MSc Molecular Biology from the University of Lund.