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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


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In human studies, it has been shown (unpublished data) that patients with COPD exhibit increased leakage across the lung epithelium. 


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.


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. 



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.


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.


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.

Parnham 2014, JPT, Azi rev.png

Pharmacology & Therapeutics 143 (2014) 225–245

Michael J. Parnham, Vesna Erakovic Haber, Evangelos J. Giamarellos-Bourboulis, Gianpaolo Perletti, Geert M. Verleden, Robin Vos


Hung. Mucosal Immunol 2019. Macrophages

Macrophages promote epithelial proliferation following infectious and non-infectious lung injury through a Trefoil factor 2-dependent mechanism

Mucosal Immunology (2019) 12:64–76;

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

Erakovic Haber Future Med Chem 2014. Des

The design of novel classes of macrolides for neutrophil-dominated inflammatory diseases

Future Med. Chem. (2014) 6(6), 657–674

Vesna Eraković Haber, Martina Bosnar & Goran Kragol

2018_Pomares et al - Clinical and Safety

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, 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

Parnham 2005, EJP, azi in COPD.png

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 

Hodge Respirology 2012. Azithromycin enh

Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophages in chronic obstructive pulmonary disease subjects

Respirology. 2012 Jul;17(5):802-7. doi: 10.1111/j.1440-1843.2012.02135.x.

Hodge S, Reynolds PN.

Arason et al Resp Res 2019. Azi and TEER

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).

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

2014_Uzun et al - Azithormycin maintenan

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

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

Nujic Cellular Immunology 2012. AZM, HCQ

Impairment of lysosomal functions by azithromycin and chloroquine contributes to anti-inflammatory phenotype

Cellular Immunology
Volume 279, Issue 1, September 2012, Pages 78-86

Krunoslav Nujic ́, Mihailo Banjanac, Vesna Munic ́, Denis Polancec, Vesna Erakovic ́ Haber

Halldorsson ajrcmb 2010. AZM maintains e

Azithromycin Maintains Airway Epithelial Integrity during Pseudomonas aeruginosa Infection

Am J Respir Cell Mol Biol Vol 42. pp 62–68, 2010

Skarphedinn Halldorsson, Thorarinn Gudjonsson, Magnus Gottfredsson, Pradeep K. Singh, Gudmundur Hrafn Gudmundsson, and Olafur Baldursson

Asgrimsson AAC 2006. Azi enhances tight-

Novel Effects of Azithromycin on Tight Junction Proteins in Human Airway Epithelia

Antimicrob Agents Chemother. 2006 May; 50(5): 1805–1812.
doi: 10.1128/AAC.50.5.1805-1812.2006

Valthor Asgrimsson, Thorarinn Gudjonsson, Gudmundur Hrafn Gudmundsson, and Olafur Baldursson

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