
OUR THERAPEUTIC PIPELINE
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 our lead compound EP395 are underway, with first-in-man trials planned to commence in late 2020. We are supported by favourable class safety and long-term data for macrolides.
Source: (1) Azithromycin for Prevention of Exacerbations of COPD, Albert, R.K. et al., N Engl J Med 2011; 365:689-698; DOI: 10.1056/NEJMoa1104623
OUR NEW PARADIGM
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In human studies, it has been shown (unpublished data) that patients with COPD exhibit increased leakage across the lung epithelium.
ENHANCING EPITHELIAL BARRIER FUNCTION
EpiEndo's compounds enhance the epithelial barrier, appearing to strengthen the junctions between cells and reducing leakage across the epithelium. Our proposed mechanism is that our 15-membered macrolide compounds influences epithelial biology through targeting the epidermal differentiation complex such that basal cells transition from unattached state to attached. This enhances epithelial integrity and improves the barrier function of epithelial tissues to better protect the lung against disruptive pathological forces. EpiEndo’s lead compounds are also powerful anti-inflammatory drugs.
IMPROVEMENT OVER AZITHROMYCIN
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 eliminate concerns about possible antibiotic resistance effects that might limit wider use of azithromycin.
INTELLECTUAL PROPERTY
We have strong intellectual property around our compounds, with a portfolio of patents based on composition of matter, providing protection out to at least 2036.
ADDRESSING VIRAL INFLAMMATORY COMPLICATIONS
Our 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.
We are accumulating pre-clinical data that move forward with trials to explore a potential role for our lead compounds to substitute for azithromycin, where indicated for viral lung infections.


Putative Mechanism of Action
Within the lung, terminal bronchioles are lined with a simple columnar epithelium, one cell layer deep. Our data suggests that loss of epithelial integrity plays a role in the inflammatory condition associated with COPD and other lung diseases.
By enhancing the epithelial integrity, our compounds reduce leakage across and exert an anti-inflammatory effect.

An effective orally available therapeutic for COPD can have significant climate change benefit
About 50 million inhalers are prescribed annually in the UK. The majority of which use hydrofluoroalkane propellants, potent greenhouse gases. Every metered-dose inhaler replaced mitigates the equivalent of 150kg - 400kg of carbon dioxide emissions annually - similar to the carbon footprint reduction of cutting meat from diet.
OUR RESEARCH | KEY PUBLICATIONS
We are continually engaged in medical science research and clinical studies at the forefront of our field of interest. Find out more about the findings and underlying data that supports the basis for our clinical and mechanistic viewpoints.
Pharmacology & Therapeutics 143 (2014) 225–245
Michael J. Parnham, Vesna Erakovic Haber, Evangelos J. Giamarellos-Bourboulis, Gianpaolo Perletti, Geert M. Verleden, Robin Vos
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Macrophages promote epithelial proliferation following infectious and non-infectious lung injury through a Trefoil factor 2-dependent mechanism
Mucosal Immunology (2019) 12:64–76; https://doi.org/10.1038/s41385-018-0096-2
Li-Yin Hung, Debasish Sen, Taylor K. Oniskey, Jeremey Katzen, Noam A. Cohen, Andrew E. Vaughan, Wildaliz Nieves, Anatoly Urisman, Michael F. Beers, Matthew F. Krummel and De’Broski R. Herbert
Clinical and Safety Outcomes of Long-Term Azithromycin Therapy in Severe COPD Beyond the First Year of Treatment
Chest, Volume 153, Issue 5,
2018, Pages 1125-1133, ISSN 0012-3692, https://doi.org/10.1016/j.chest.2018.01.044.doi: 10.1128/AAC.50.5.1805-1812.2006
Xavier Pomares, MD; Concepción Montón, MD, PhD; Miriam Bullich, MD; Oscar Cuevas, PhD; Joan Carles Oliva, MStat; Miguel Gallego, MD, PhD; and Eduard Monsó, MD, PhD
Modulation of neutrophil and inflammation markers in chronic obstructive pulmonary disease by short-term azithromycin treatment
European Journal of Pharmacology 517 (2005) 132 – 143
Michael J. Parnham, Ognjen Culic ́, Vesna Erakovic ́, Vesna Munic ́, Sanja Popovic ́-Grle, Karmela Barixic ́, Martina Bosnar, Karmen Brajxa, Ivana Cepelak, Snjezana Cuzic ́, Ines Glojnaric ́, Zoran Manojlovic ́, Renata Novak-Mircetic ́, Katarina Oreskovic ́, Verica Pavicic ́-Beljake, Senka Radoxevic ́, Mirna Sucic
Azithromycin induces epidermal differentiation and multivesicular bodies in
airway epithelia
Arason, A.J., Joelsson, J.P., Valdimarsdottir, B. et al. Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia. Respir Res 20, 129 (2019). https://doi.org/10.1186/s12931-019-1101-3
Ari Jon Arason, Jon Petur Joelsson, Bryndis Valdimarsdottir, Snaevar Sigurdsson, Alexander Gudjonsson ,
Skarphedinn Halldorsson, Freyr Johannsson , Ottar Rolfsson, Fredrik Lehmann, Saevar Ingthorsson ,
Paulina Cherek , Gudmundur H. Gudmundsson, Fridrik R. Gardarsson , Clive P. Page, Olafur Baldursson ,
Thorarinn Gudjonsson and Jennifer A. Kricker
Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial
Lancet Respir Med 2014; 2: 361–68 PublishedOnline
April 16, 2014 http://dx.doi.org/10.1016/
Sevim Uzun, Remco S Djamin, Jan A J W Kluytmans, Paul G H Mulder, Nils E van’t Veer, Anton A M Ermens, Aline J Pelle, Henk C Hoogsteden, Joachim G J V Aerts, Menno M van der Eerden