DNL.L Regulatory News (DNL)

2 March 2017

Diurnal Group plc

("Diurnal" or the "Company")

Diurnal signs marketing and distribution agreement for the commercialisation of Infacort® and Chronocort® with Israel's leading commercial group for niche healthcare products

Further validation of lead products in diseases of cortisol deficiency

Significant market opportunity for Diurnal, given the estimated higher prevalence of CAH in Israel

Agreement exemplifies Company approach to marketing and distribution outside of core territories

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces a marketing and distribution agreement with Medison Pharma Ltd (Medison), Israel's leading group for the marketing of innovative niche healthcare solutions. The agreement covers the commercialisation in Israel of Diurnal's novel therapies for adrenal insufficiency, Infacort® and Chronocort®. Infacort® is expected to be submitted for marketing authorisation in Israel once approved by the European Medicines Agency (EMA). Diurnal anticipates EMA marketing authorisation approval for Infacort® could come towards the end of 2017 with the potential of approval in Israel during 2018, based on the European regulatory submission package and clinical trial data.

Under the terms of the agreement, Medison will receive the exclusive rights to market and sell Infacort® and Chronocort® in Israel. This agreement forms part of Diurnal's ongoing activities for commercialisation of its lead products in diseases of cortisol deficiency. Infacort® has the potential to be the first preparation of hydrocortisone (the synthetic version of cortisol) specifically designed for use in children suffering from adrenal insufficiency (AI), including the related disease, Congenital Adrenal Hyperplasia (CAH). Chronocort® is a modified release hydrocortisone preparation that has been designed to mimic the natural circadian rhythm of cortisol when given in a twice-a-day "toothbrush" regimen for the treatment of adult CAH.

Israel represents a significant market opportunity for Diurnal, given the estimated higher prevalence of CAH in Israel1. There are around 1,000 patients in Israel (paediatric AI and CAH), providing a total market opportunity for Infacort® and Chronocort® estimated by the Company to be approximately $7m per annum.

Prof. Naomi Weintrob, MD, MHA, Senior Pediatric Endocrinologist, Scientific Advisor, Israeli CAH Association, commented:

"Infacort® and Chronocort® have the potential to address a significant unmet medical need for patients with adrenal insufficiency and congenital adrenal hyperplasia who are not currently being treated satisfactorily. Infacort® allows delivery of hydrocortisone in accurate and small doses, which are best suited for infants and young children, and Chronocort® is designed to imitate diurnal physiologic cortisol secretion. I therefore look forward to the introduction of these innovative products in Israel."

Dr Martin Whitaker, CEO of Diurnal, added: 

"Medison is uniquely qualified to provide the complete spectrum of integrated sales and marketing services Diurnal requires to enter the Israeli healthcare market. Given the estimated higher prevalence of CAH in Israel1, this market represents a significant opportunity for Diurnal. The agreement with Medison marks a further validation of the quality of our products and provides us with the ability to distribute Infacort® outside our core territories of Europe and the US. We believe that our strategic objectives and global ambitions are aligned with this important new partner, which also provides a blueprint for other similar agreements, addressing selected high value markets, in the future."

Notes to Editors

About Adrenal Insufficiency

Adrenal Insufficiency (AI) is a condition characterised by deficiency in cortisol, an essential hormone in regulating metabolism and the response to stress. AI has been identified as a rare disease in Europe where there are estimated to be approximately 4,000 sufferers younger than the age of six. Currently there are no licensed hydrocortisone preparations in Europe specifically designed to treat these young patients. These children are often administered compounded adult tablets or other unlicensed products. Poor control of disease can result in precocious puberty in young children, virilisation in girls and chronic fatigue leading to a poor quality of life in adulthood resulting in increased morbidity and mortality.

About Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia ("CAH") is an orphan condition usually caused by deficiency of the enzyme 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 severe development defects including ambiguous genitalia, premature (precocious) sexual development and short stature. Sufferers, even if treated, remain at risk of death through an adrenal crisis.

Approximately two thirds of CAH patients are estimated to have poor disease control, leading to elevated androgen levels. The condition is estimated to affect approximately 71,000 patients in Europe (51,000) and the US (20,000), with approximately 405,000 in the rest of the world.

Current therapy for CAH uses a combination of generic steroids (hydrocortisone, dexamethasone and prednisolone) and, at best, these adequately treat approximately one third of CAH patients. Other therapies being developed are at an early stage of development and not expected to receive approval in the short-term.

About Infacort®

Infacort® represents the first preparation of hydrocortisone specifically designed for use in children suffering from AI. It is a patented, immediate-release, oral, paediatric formulation of hydrocortisone that allows for age-appropriate dosing in children. This therapeutic approach has the potential to help young patients less than six year of age suffering from diseases due to cortisol deficiency including adrenal insufficiency and congenital adrenal hyperplasia. AI requires life-long treatment and Diurnal's novel approach to product development has the potential to significantly improve these young patients' lives. Diurnal has already submitted for market authorisation to the European Medicines Agency via the Paediatric Use Marketing Authorisation (PUMA) route in late 2016.

About Chronocort®

Chronocort® is a modified release hydrocortisone preparation that has been designed to mimic the natural circadian rhythm of cortisol when given in a twice-a-day "toothbrush" regimen (last thing at night before sleep and first thing in the morning on waking). Chronocort has been granted orphan drug designations in Europe and the US in the treatment of Congenital Adrenal Hyperplasia ("CAH") and Adrenal Insufficiency ("AI"). The first planned indication for Chronocort® is CAH. Chronocort® has completed three Phase I trials in 2011, 2012 and 2015 (food effects study) and a Phase II trial in CAH patients in 2014, and is currently in Phase III trials in Europe.

Phase II

Data from the Chronocort® Phase II trial demonstrate that the trial met its primary endpoint of fully characterising the pharmacokinetic profile of Chronocort® in 16 male and female adult subjects with CAH. The results show Chronocort® provides circadian levels of the stress hormone, cortisol, similar to the healthy population mimicking the overnight rise in cortisol levels, such that patients wake with a normal cortisol level.

In addition, the secondary objective of examining the effect of Chronocort® on the morning biochemical efficacy markers of the disease showed significant control in 94 per cent. of the patients having their morning levels of the androgens, 17-hydroxyprogesterone (170HP) and androstenedione (A4), brought into the optimal range after six months' treatment with titrated Chronocort®, compared to poorer control (only 31 per cent. controlled) on standard treatment at the beginning of the study. Chronocort® was well-tolerated during the six month trial.

About Medison Pharma Ltd

Medison is Israel's leading specialty pharmaceutical company, focused on delivering innovative healthcare solutions to the Israeli market. Medison is uniquely qualified to provide the complete spectrum of integrated services, including early access programs, regulatory affairs, registration and reimbursement, medical, marketing and logistics. Backed by three generations of experience in the healthcare industry since 1937, Medison is the exclusive Israeli partner for leading global pharma companies such as Amgen®, Biogen®, Shire® and Ipsen®. Medison also operates a fully owned subsidiary in Romania based on replicating its success in Israel.

For more information, please visit www.medisonpharma.com

About Diurnal Group plc

Founded in 2004, Diurnal is a UK-based specialty pharma company developing high quality products for the global market for the life-long treatment of chronic endocrine conditions, including Congenital Adrenal Hyperplasia and Adrenal Insufficiency. 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.co.uk