DNL.L Regulatory News (DNL)

22 February 2018

Diurnal Group plc

("Diurnal" or the "Company")

Diurnal announces grant of first patents for Alkindi® and Chronocort® in Japan

Pharmaceutical composition of matter patents in this key territory provides protection for Alkindi® and Chronocort® to 2032 and 2033, respectively

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces the grant of the Company's first two Japanese patents for Alkindi® (development programme name Infacort®) and Chronocort® by the Japanese Patent Office (JPO).

The Alkindi® patent, entitled "Treatment of Adrenal Insufficiency", is a pharmaceutical composition-of-matter patent protecting Alkindi®'s proprietary formulation as a treatment for adrenal insufficiency in paediatric and elderly adult patients. The patent provides in-market protection until 2032.

The Chronocort® patent, entitled "Hydrocortisone Controlled Release Formulation", protects the product as a modified-release hydrocortisone formulation. The patent provides in-market protection until 2033.

The US and UK counterparts for these patents have already been granted.

These patents provide Diurnal with a proprietary position for Alkindi® and Chronocort® in Japan, where the Company intends to secure a local distribution partner. Japan represents a significant market opportunity for Diurnal with the country being the third largest market for pharmaceutical products after the US and Europe. The Company estimates that there are around 6,700 patients with congenital adrenal hyperplasia and around 58,000 with adrenal insufficiency eligible for treatment with Alkindi® and Chronocort® in Japan, providing an estimated total market opportunity for Alkindi® and Chronocort® of approximately $415 million per annum.

Martin Whitaker, PhD, Chief Executive Officer of Diurnal, commented:

"Japan is a significant potential market for both Alkindi® and Chronocort®. We are therefore delighted that these patents have proceeded to grant and will create the cornerstone of our strong exclusivity position in this territory. We will now look to secure a local partner, in line with our commercialisation strategy outside of the US and Europe, and will liaise with local regulatory authorities to determine the clinical studies that will be required for approval."

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. 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). AI is estimated to affect over four million patients globally.

In the paediatric setting, AI, including the related genetic condition congenital adrenal hyperplasia (CAH), is estimated to affect approximately 1,300 patients in Japan. In Europe, AI has been identified as a rare condition, where there are estimated to be approximately 4,000 sufferers younger than the age of six, where the need for an effective replacement therapy is greatest. Prior to the European approval of Diurnal's product, Alkindi®, paediatric AI was treated by compounding hydrocortisone or crushing/splitting tablets of adult preparations of hydrocortisone (the synthetic version of cortisol) as there was no licensed formulation available specifically designed for children.

Diurnal's products, Alkindi® and Chronocort®, have been granted Orphan Drug Designations in the US for the treatment of AI. Chronocort® also benefits from Orphan Drug Designation for AI in Europe. These orphan drug designations mean Alkindi® and Chronocort® have the potential to be granted market and data exclusivity for seven years in the US and 10 years in Europe for Chronocort® post market authorisation.

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 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 5,400 adult patients in Japan, 47,000 patients in Europe and over 400,000 patients globally.

Current therapy for CAH uses a variety of generic steroids (hydrocortisone, dexamethasone and prednisolone) which, at best, 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.

Diurnal's product, Chronocort®, has been granted Orphan Drug Designations in Europe and the US in the treatment of CAH, providing the potential to be granted market exclusivity for 10 years in Europe and seven years in the US post market authorisation.

About Alkindi®

Alkindi® is the first preparation of hydrocortisone specifically designed for use in children suffering from paediatric AI. Alkindi® is a patented, oral, immediate-release paediatric formulation of hydrocortisone granules in capsules for opening that allows for 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.

On 9 February 2018, the European Commission granted a paediatric use marketing authorisation (PUMA) for Alkindi® as replacement therapy of AI in infants, children and adolescents (from birth to ® in Europe.

About Chronocort®

Chronocort® is a modified release preparation of hydrocortisone that has been designed to mimic the 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). The first planned indication for Chronocort® is CAH in adults.

Chronocort® has completed three Phase I trials in 2011, 2012 and 2015, a Phase II trial in CAH patients in 2014 in the US and is currently in a Phase III trial in Europe. This pivotal Phase III trial for Chronocort® in Europe is scheduled to complete in Q3 2018, with market authorisation in Europe expected in 2020.

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