DNL.L Regulatory News (DNL)

11 December 2018

Diurnal Group plc

("Diurnal" or the "Company")

Regulatory package for Chronocort® submitted for Scientific Advice in Europe

Further analysis of data from European Chronocort® Phase III and safety extension study demonstrate significant benefits for patients sustained for at least 12 months

Analyst meeting to discuss the data to take place today

Subject to the outcome of the Scientific Advice request, Diurnal anticipates filing a Marketing Authorisation Application for Chronocort® in Q4 2019

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, today announces that it has submitted a regulatory package requesting Scientific Advice to the European Medicines Agency (EMA) for Chronocort® (modified release hydrocortisone) based on detailed analysis of data from the largest ever clinical trial programme in congenital adrenal hyperplasia (CAH). Subject to a favourable outcome from the request, Diurnal anticipates submitting a Marketing Authorisation Application (MAA) for Chronocort® in Q4 2019, including a potential application for Orphan Drug Designation in the treatment of CAH.

Following the Company's announcement on 8 October 2018 that Chronocort® had not met the primary endpoint in its European Phase III trial for the treatment of congenital adrenal hyperplasia (CAH) based on an analysis of the primary endpoint, Diurnal has undertaken further post-hoc analysis of the clinical trial data, based upon methods previously discussed with the EMA, identifying clinically important differences between Chronocort® and the control arm of the trial, in particular:

· Using the primary outcome measure, Chronocort® achieved statistically significantly better control of the androgen 17-OHP during the period 0700-1500 when androgens are typically high

· Chronocort® achieved statistically significantly lower overall levels of the androgen 17-OHP over 24 hours using an area under the curve (AUC) analysis.

In addition, the following benefits were seen with Chronocort® compared to the standard-of-care arm:

· Levels of the androgen 17-OHP were less variable on Chronocort® over 24 hours;

· Androgen control (both 17-OHP and A4) was achieved on a lower dose of steroid in the Chronocort® arm;

· More episodes of unexpected therapeutic benefit were seen with Chronocort®;

· Fewer sick day rules, where patients have to supplement their daily replacement treatment with additional steroid doses, were seen with Chronocort®;

· No adrenal crises were seen with Chronocort®

An interim analysis of data from the ongoing safety extension study in Europe, an open-label, 'roll-over' trial in which patients from the Phase III trial have continued Chronocort® treatment, also highlighted sustained benefit for patients treated with Chronocort®, in particular:

· Androgen control (17-OHP and A4) was maintained over the period, up to 24 months;

· There were further steroid dose reductions of approximately 20% over the period of treatment.

Diurnal will hold an analyst meeting today to discuss the challenges and current treatment options for CAH, and the current situation with Chronocort®. The meeting will be led by Martin Whitaker, Chief Executive Officer of Diurnal, with speakers including Professor John Newell-Price, an investigator in the clinical trials of Chronocort®, and Dr. John Porter, Medical Director of Diurnal.

A copy of the presentation will be made available on Diurnal's website (https://www.diurnal.co.uk/non-healthcare-professionals/investors/shareholder-information/) following the analyst meeting.

Professor John Newell-Price MA PhD FRCP, Department of Oncology & Metabolism, Chair of Endocrinology and Honorary Consultant Physician, The University of Sheffield, commented:

"Congenital adrenal hyperplasia requires life-long treatment to replace cortisol and to normalise excessive androgen secretion. Current hydrocortisone therapies fail to mimic natural circadian variation and as a result congenital adrenal hyperplasia still results in significant increased morbidity and mortality for patients worldwide. New therapies, such as Chronocort®, that have been designed to mimic the body's natural circadian cortisol release are needed to improve patient outcomes."

Martin Whitaker, Chief Executive Officer of Diurnal, added:

"We have extensive experience of working with patients with congenital adrenal hyperplasia, including performing the largest ever clinical trial programme in the condition. Having now performed a multi-faceted analysis of the complete data set beyond the pre-specified primary endpoint, we believe the data supports Chronocort® as a potential valuable treatment option for congenital adrenal hyperplasia. There continues to be a significant unmet need to improve patient outcomes in this debilitating disease and we therefore look forward to discussing our data package with European regulators to agree a pathway forward."

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

Notes to Editors

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) to control androgen excess and chronic fatigue in patients with diseases of cortisol deficiency. The first planned indication for Chronocort® is Congenital Adrenal Hyperplasia (CAH) in adults. Chronocort® has been extensively studied in humans 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.

In Europe, Chronocort® has been granted Orphan Drug Designation in the treatment of CAH, which, if confirmed at marketing authorisation, provides market exclusivity for 10 years. The market authorisation of Chronocort® in Europe is anticipated in 2020.

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.

Current therapy for CAH uses a variety of generic steroids (hydrocortisone, dexamethasone and prednisolone). 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 47,000 patients in Europe, with over 400,000 in the rest of the world.

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

Date of Preparation: December 2018 Code: CH EU-GB-0025