Alkindi approved in Israel

05 August 2020

Diurnal Group plc

("Diurnal" or the "Company")

Alkindi® approved in Israel

Significant market opportunity to address an unmet need in paediatric AI

Further validates strategy to optimise market access outside of Europe and US

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that Alkindi® (hydrocortisone granules in capsules for opening) has received approval from the Ministry of Health in Israel as a replacement therapy of adrenal insufficiency (AI) in infants, children and adolescents (from birth to

Israel represents a significant potential market opportunity, given the estimated higher than global average prevalence of paediatric AI and congenital adrenal hyperplasia (CAH)1. There are approximately 1,000 patients in Israel (paediatric AI and CAH), providing a total market opportunity for Alkindi® and Chronocort® estimated by the Company to be approximately $7 million per annum. Diurnal anticipates the first sales in Israel will be in H1 2021 following completion of pricing and market access activities. In Israel, Medison Pharma is Diurnal's marketing and distribution partner for Alkindi® and Chronocort® and will hold the marketing authorisations.

Diurnal submitted its Marketing Authorisation Application (MAA) dossier for Chronocort® to the European Medicines Agency (EMA) in December 2019. Assuming the EMA approves Chronocort® as expected by Diurnal in Q1 2021, the European dossier will be used to submit Chronocort® for regulatory approval in Israel.

Martin Whitaker, CEO of Diurnal, commented:

"We are thrilled to announce the approval of Alkindi® in Israel, an important market for us, and would like to thank Medison Pharma for their efforts in obtaining this approval, which further validates the quality of our products and, in line with our strategy, gives us the ability to provide Alkindi® to patients outside of our core territories in Europe and the US."

1 Speiser et al Am J Hum Genet 37: 650-667 (1985)

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

Notes to Editors

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). 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 congenital adrenal hyperplasia (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

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 Chronocort®

Chronocort® is a modified release preparation of hydrocortisone that has been specifically 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) to control androgen excess and chronic fatigue in patients with diseases of cortisol deficiency. The first planned indication for Chronocort® is currently under review by the EMA. Chronocort® has been extensively studied in human subjects having completed four Phase I trials, a Phase II trial in 16 CAH patients in the US in 2014, and a Phase III trial in 122 CAH patients in Europe and the US.

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 steroids (hydrocortisone, dexamethasone and prednisolone) 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, 17,000 in the US, with over 400,000 in the rest of the world.

About Diurnal Group plc

Founded in 2004, Diurnal is a UK-headquartered, European specialty pharma company developing pharmaceutical 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

About Medison Pharma Ltd

Medison is one of the world's largest commercial partner of leading global biotech companies, providing the complete spectrum of integrated services for international companies looking to enter or expand their presence in Israel, Canada and CEE markets. Medison operates a corporate venture arm with a dedicated research and evaluation team boasting deep scientific and commercial backgrounds. Medison also operates a scouting program to cater its partners and is an active investor in life science projects around drug development and digital health.

For further information about Medison, please visit www.medison.co.il 

Preparation: August 2020 Code: CORP-GB-0063