DNL.L Regulatory News (DNL)

14 October 2021

Diurnal Group plc

("Diurnal" or the "Company")

Distribution agreement signed with ExCEEd Orphan for Central and Eastern Europe

Agreement extends the Company's commercial footprint to over two-thirds of the European Economic Area population

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that it has signed a distribution agreement with ExCEEd Orphan, a company providing full business solutions for the treatment of rare diseases, for the distribution and marketing of Alkindi® (hydrocortisone granules in capsules for opening) and Efmody® (hydrocortisone modified-release hard capsules) in Central and Eastern European (CEE) countries.

Under the terms of the agreement, ExCEEd Orphan will receive the exclusive rights to distribute and market Alkindi® and Efmody® in the CEE countries including; Albania, Bosnia and Herzegovina, Croatia, Czechia, Hungary, Kosovo, Montenegro, North Macedonia, Poland, Serbia, Slovakia, and Slovenia. Based on the Company's estimates and market research conducted by ExCEEd Orphan, there are estimated to be in total around 9,500 patients in the CEE region suffering from paediatric adrenal insufficiency (AI) and adult congenital adrenal hyperplasia (CAH).

Alkindi® already has marketing authorisation in the European Union and is the first preparation of hydrocortisone (synthetic cortisol) specifically designed for use in children suffering from AI, including the related condition CAH. Efmody® is a modified-release preparation of hydrocortisone for the treatment of patients with CAH, a rare condition caused by a genetic deficiency of adrenal enzymes. In May 2021, Efmody® was granted marketing authorisation in the European Union and was subsequently launched by the Company in Germany, Austria and the UK in September 2021.

In line with the Company's other global distribution agreements, Diurnal will provide Alkindi® and Efmody® from its established European supply chain for sale by ExCEEd Orphan. This agreement adds to the Company's ongoing strategy for commercialisation of its lead products by optimising market access outside of the larger European markets, where Diurnal directly markets its products, through entering marketing and distribution agreements with companies focused on niche and orphan conditions. With the execution of this agreement, the Company's two lead products will be available to over two-thirds of the European Economic Area (EEA) population, and ExCEEd Orphan will work to make these products available in territories beyond this region in Central and Eastern Europe.

Martin Whitaker, Chief Executive Officer of Diurnal, commented:

"We are pleased to announce this distribution agreement with ExCEEd Orphan to make Alkindi® and Efmody® available to patients with diseases of cortisol deficiency across Central and Eastern Europe. Following this agreement, Diurnal's products are now available to over two-thirds of the EEA population and we are looking forward to working with ExCEEd Orphan who have a strong track record of launching orphan medicines within this region. As Efmody® has now launched for patients in Europe, this agreement is in line with our commercialisation strategy in order to optimise global market access for our products outside of large European markets."

Jiri Hermanek, Chief Executive Officer and Founding Partner of ExCEEd Orphan, commented:

"We are very pleased to announce this collaboration to make Alkindi® and Efmody® available to patients with diseases of cortisol deficiency across Central and Eastern European countries. Both products will represent an important addition to the continuously growing portfolio of rare disease medications marketed and distributed by ExCEEd Orphan and we are fully committed to bringing these unique medications to all patients in needs in all respective countries."

This is a business press release containing financial information and/or data for the benefit of shareholders and potential investors. Data are included to allow informed investment decisions.

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014 (MAR).

Notes to Editors

About paediatric adrenal insufficiency

Paediatric AI, including the genetic condition CAH is a condition characterised by deficiency in cortisol, an essential hormone in regulating metabolism and the response to stress. The primary symptoms of AI are chronic fatigue and patients are at risk of adrenal crisis and death if they do not have adequate cortisol replacement. AI is either primary or secondary, with primary AI resulting from diseases intrinsic to the adrenal gland and secondary AI resulting from pituitary diseases where there is a failure of stimulation of the adrenal by the pituitary of the signalling hormone ACTH (adrenocorticotropic hormone).

About Alkindi® (hydrocortisone granules in capsules for opening)

Alkindi® is the first preparation of hydrocortisone specifically designed for use in children suffering from paediatric adrenal insufficiency (AI), including congenital adrenal hyperplasia (CAH). Alkindi® is a patented, oral, immediate-release paediatric formulation of hydrocortisone granules in capsules for opening that allows for accurate age-appropriate dosing in children. This therapeutic approach has the potential to help young patients less than eighteen years of age suffering from diseases due to cortisol deficiency including paediatric AI and CAH. AI requires life-long treatment and Diurnal's novel approach to product development has the potential to significantly improve these young patients' lives. The European Commission has granted a paediatric use marketing authorisation (PUMA) for Alkindi® as replacement therapy of AI in infants, children and adolescents (from birth to ® is approved and known as Alkindi® Sprinkle in the US where it is licensed and marketed by Eton Pharmaceuticals. Alkindi® is also approved in Israel and Australia.

The human medicine European public assessment report (EPAR) for Alkindi® can be viewed here and the Summary of Product Characteristics (SmPC) here.

About congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is an orphan condition caused by deficiency of adrenal enzymes, most commonly 21-hydroxylase. This enzyme is required to produce the adrenal steroid hormone, cortisol. The block in the cortisol production pathway causes the over-production of male steroid hormones (androgens), which are precursors to cortisol. The condition is congenital (inherited at birth) and affects both sexes. The cortisol deficiency and over-production of male sex hormones can lead to increased mortality, infertility and issues during sexual development including ambiguous genitalia, premature (precocious) sexual development and short stature. Sufferers, even if treated, remain at risk of death through an adrenal crisis.

Current therapy for CAH uses a variety of generic glucocorticoid (steroid) preparations including hydrocortisone, dexamethasone, prednisolone and prednisone in the US, with no standard treatment regimen. Approximately two-thirds of CAH patients are estimated to have poor disease control, leading to elevated androgen levels. The condition is estimated to affect a total of approximately 41,000 patients in Europe and the United Kingdom, with over 400,000 in the rest of the world.

About Efmody® (hydrocortisone modified-release hard capsules)

Efmody® is a preparation of hydrocortisone that has been specifically designed to mimic the circadian rhythm of cortisol when given in a twice-a-day "toothbrush" regimen (administered last thing at night before sleep and first thing in the morning on waking) to control androgen excess and chronic fatigue in patients with diseases of cortisol deficiency. The first indication for Efmody® is Congenital Adrenal Hyperplasia (CAH) in adults and adolescents (children older than 12 years of age). Efmody® has been extensively studied in 239 human subjects including 138 CAH patients who have taken part in clinical trials in Europe and the US.

The European Commission approval of Efmody® was based on a Phase 3 study conducted in a total of 122 patients enrolled across 11 clinical sites, the largest ever interventional clinical trial completed in CAH. The Phase 3 data was supported by detailed analysis of data from an open-label safety extension study for patients completing treatment in the Phase 3 study, which is assessing the impact of treatment with Efmody® over an extended period, with a number of patients on this trial having been treated for over five years.

The human medicine European public assessment report (EPAR) for Efmody® can be viewed here and the Summary of Product Characteristics (SmPC) here.

About Diurnal Group plc

Diurnal Group plc is a European, UK-headquartered, specialty pharmaceutical company dedicated to developing hormone therapeutics to aid lifelong treatment for rare and chronic endocrine conditions, including congenital adrenal hyperplasia, adrenal insufficiency, hypogonadism and hypothyroidism. Its expertise and innovative research activities focus on circadian-based endocrinology to yield novel product candidates in the rare and chronic endocrine disease arena.

For further information about Diurnal, please visit www.diurnal.com 

About ExCEEd Orphan

ExCEEd Orphan was founded in 2018 by five rare disease experts from multiple Central and Eastern European (CEE) countries. The Company is focusing on innovative treatments for rare diseases and has extensive experience in launching innovative medicines in this field. The portfolio of ExCEEd Orphan includes products in therapeutic areas like haematology, neurology, immunology, and metabolic diseases.

For further information about ExCEEd Orphan, please visit www.exceedorphan.com

Date of Preparation: October 2021 Code: CORP-GB-0153