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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Bronchomycn (First in class epithelial Barrier-enhancing medicine for respiratory diseases)

Teaser

Summary

EpiEndo is a biotech company that leads innovative compound design and preclinical research for drug development. We have established an in-house platform focusing on the discovery and development of novel compounds that restore the physiological integrity of epithelial tissues.

Epithelial barrier failure is a recognised factor in the clinical pathophysiology of diseases involving epithelial inflammation or epithelitis. Loss of barrier integrity is involved in a wide range of chronic conditions that affect millions of people and cost health systems billions of euros yearly, including COPD, Cystic Fibrosis and asthma in the airway, psoriasis and eczema in the skin and ulcerative colitis and Crohn\'s disease in the intestinal tract.

According to clinical guidelines there are no therapies available targeting barrier failure directly and the mainstay pharmaceutical investment strategies rely on therapies with immunosuppressive or anti-inflammatory mechanisms.

Our discovery platform can be applied to a pan-epithelial model and allows selection of compounds targeting specific epithelial tissues in airways, skin, gastrointestinal, urinary and glandular tracts. Our agenda is to develop novel barrier enhancing compounds and techniques to evaluate their therapeutic potential and ability to restore epithelial integrity.

Initially focusing on airway epithelia diseases, we have designed a development rationale that validates the novel pharmaceutical concept of barrier integrity enhancement for every stage of the lead compound testing phases.

We have completed in vitro testing with over 30 novel compounds with airway disease indications. We have recently initiated In vivo pharmacology studies, followed by proof-of-concept efficacy trials.

The large number of people with chronic conditions related to barrier failure means that successful development of EpiEndoÂ´s compounds and technologies will have significant health, social and financial impacts worldwide within the next 7-10 years.

Work performed

TECHNICAL FEASIBILITY

Objective 1: To prepare for the in-vivo pre-clinical studies. Main results: We have developed a specification for the work required to deliver the pre-clinical studies. We have identified commercial research partners who can undertake this work and have received quotations from 3 different companies.

Objective 2: To prepare the Phase 1 clinical trial protocol. Main results: We have created a Phase 1 clinical trial protocol and identified a centre that we wish to engage to deliver this work. The clinical trial plan can be provided as a separate document If required.

Objective 3: To confirm pending regulatory steps. Main results: We have identified the required regulatory pathway and this support will be provided at each stage by our commercial research partners. Our initial target is classified as an Orphan Condition under the Orphan Drug Act and we will file the necessary paperwork with the EMA and FDA in the next 12 months to apply for Orphan Designation.

Objective 4: To conduct a thorough risk assessment & update our contingency measures. Main results: We have identified a range of risks in relation to the technical development of the project. We have put in place mitigation and contingency measures where possible. As a result of this project we have modified our first clinical target as this reduces the cost and time to market as well as the number of competitors and opens up additional funding opportunities.

COMMERCIAL FEASIBILITY

Objective 5: To assess the pharmaceutical market for respiratory conditions. Main results: We have updated our market information to assess the current state of the market and to evaluate the market size and opportunities relating to CF.

Objective 6: To undertake qualitative research to assess the opinion of doctors, advocacy groups and patients. Main Results: We have interviewed 30 stakeholders including doctors, advocacy groups and patients in order to assess the market opportunity. This has provided some positive response although these have been tempered by the current stage of the product and the remaining time to market.

Objective 7: To confirm our IPR Freedom-To-Operate. Main Results: We have commissioned an International Patent Report as well as undertaking our own FTO research using Patent Inspiration. We have identified a number of prior art patents and we are currently modifying our claims with our patent attorneys in order to ensure we have novelty.

Objective 8: To update our current IPR strategy and prepare an IPR protection plan. Main results: We have assessed different forms of IPR in order to assess the most appropriate forms for protection. We have created a formal reporting and review structure to assess new IPR and decide on the format and timing or protection. Our primary strategy is to take individual patent protection for each molecule and application while putting in place overarching patents to protect the platform concept.

Objective 9: To review and update our investment plan. Main results: We are in the process of seeking additional funding for further development. We have updated our investment case and we are sharing this with a range of venture capital companies in the EU and North America in order to raise out next round.

Objective 10: To obtain quotations for pre-clinical and clinical research and evaluate partner organisations. Main results: We have quotations for both pre-clinical and clinical research from three companies for each stage, which can be provided on request. We are currently seeking quotations for GMP production of the lead molecule.

FINANCIAL FEASIBILITY

Objective 11: To assess the total investment required to complete this project. Main results: The full estimation of the budget required to complete this project, â‚¬3,4M, is shown on page 20, distributed in different items.

Objective 12: To build our financial projections and estimate the expected profitability in a 5-year period. Main results: Our financial pr

Final results

Chronic Airways Diseases (CAD) are a group of diseases affecting the airways of the respiratory system.
CADs include chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, Cystic Fibrosis (CF), diffuse panbronchiolitis (DPB) and bronchiectasis. They are considered inflammatory diseases, yet treatments targeting this aspect of the disease, such as steroids, do not improve health nor prognosis.
This is due to:
- A poor understanding of the underlying inflammatory mechanisms
- A lack of \'gold standard\' anti-inflammatory drugs
- A lack of biomarkers to predict therapeutic response
- A heterogeneity between patients with the same disease

EpiEndo is investigating whether the enhancement of the epithelial barrier is a superior strategy to prevent inflammation in airway epithelium. We are developing a novel family of pharmaceutical compounds for the treatment of Chronic Airways Diseases: BARRIOLIDES.
The epithelial barrier enhancing effect of the Barriolides is unique, since although the epithelial inflammation is clinically diminished, it is not due to a direct anti-inflammatory or immunomodulatory effect of the drugs.

ïƒ¾ Barriolides have the potential to cause a revolutionary paradigm shift in research and treatment of many epithelial inflammatory diseases of the human body.
ïƒ¾ The barrier integrity paradigm offers a novel approach to measuring and monitoring airway barrier integrity as an efficacy endpoint, both in preclinical and clinical trials for drug development.
ïƒ¾ It may lay the foundation for a new predictive biomarker and physiologic monitoring methods in respiratory disease research and clinical care.
ïƒ¾ Barriolides are non-antibiotic compounds

Non-bacterial airway diseases are one of the most common causes of anti-biotic over prescription. By developing non-antibiotic novel drugs, EpiEndo intends to diminish the antibiotic over prescription, which is responsible of the current global threat of bacterial resistance.
Bacterial resistance is particularly problematic in the case of Cystic Fibrosis patients. CF is an orphan condition, which affects approximately 90,000 people worldwide â€“ primarily in North America and the EU. Our lead compound, Bronchomycin, which is non-antibiotic, has been designed for the treatment of CF. Bronchomycin is the first in class tissue specific epithelial barrier-enhancing medicine.

In addition, Barriolides have the potential to be applied to several Chronic Airway Diseases (CAD, e.g. COPD, asthma, etc.). There are over 401,000 yearly deaths in the EU-28 resulting from diseases of the respiratory system, equivalent to 8.0 % of all deaths. The World Health Organization states that over 3 million people die per annum from chronic obstructive pulmonary disease (COPD), which is equivalent to 6% of all deaths worldwide. COPD is the fourth leading cause of deaths worldwide and the 7th most common cause of DALYs (disability-adjusted life years). Respiratory diseases are a huge burden on our health and social care systems as well as quality of life of the patients. Acute exacerbation of COPD is the most common cause of hospital admission in western health care.

Our long-term objective is to gain approval in a spectrum of respiratory diseases that currently present unsolved concerns for Drs. and patients and contribute to tackle the social and economical burden of Chronic Airways Diseases globally.