DNL.L Regulatory News (DNL)

12 October 2016

Diurnal Group plc

("Diurnal" or the "Company")

Diurnal announces full results from positive European Infacort® Phase III study

As previously disclosed, primary endpoint met with high statistical significance

Results also show Infacort® achieved comparable cortisol levels in children with adrenal insufficiency to those of healthy children

95% of parents/carers preferred Infacort® to current treatment

European market authorisation anticipated in late 2017

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, is pleased to announce full results from the Phase III European study for Infacort® in paediatric Adrenal Insufficiency (AI). Positive headline data from this pivotal study were published on 11 July 2016 and today's release follows a comprehensive analysis of the data.

The Phase III trial was designed in agreement with the European Medicines Agency (EMA) and conducted in a total of 24 neonates and children under the age of six years who require replacement therapy for AI due to Congenital Adrenal Hyperplasia (CAH), primary adrenal failure or hypopituitarism.

Comprehensive analysis of the results confirms that the study met its primary endpoint, demonstrating a statistically significant (p® compared to pre-dose values. The median 60‑minute cortisol level achieved after Infacort® treatment was 535 nmol/L, which is comparable to the mean peak morning cortisol of healthy children.

AI is currently treated by unlicensed preparations of hydrocortisone with no regulated dose or consistent formulation. Infacort® is designed to provide the first regulated, consistent preparation of hydrocortisone to ensure efficacy and safety and ease of use for young children. In this respect, Infacort® was well tolerated with no adverse events reported. As part of the trial, a series of surveys were completed by parents/carers, the results of which showed that 82% of parents/carers agreed that their child found swallowing Infacort® easy, 95% of parents/carers preferred Infacort® to the usual, unlicensed preparations, and 95% of parents/carers would be happy to give their child Infacort® in the future. Furthermore, in the cohort of babies aged 0-28 days, 100% of parents/carers preferred Infacort® to the usual, unlicensed hydrocortisone preparations.

Prof Heiko Krude of Charité-Universitätsmedizin Berlin, one of the leading paediatric endocrine hospitals in Germany, and co-investigator in the trial, commented:

"This carefully controlled study clearly demonstrates, for the first time, the value of a standard dose of hydrocortisone in controlling cortisol levels in children with adrenal insufficiency."

Dr Oliver Blankenstein of Charité-Universitätsmedizin Berlin and co-investigator in the trial, added:

"These important data suggest that Infacort® could be an effective and safe cortisol replacement treatment able to address a significant unmet need for children with adrenal insufficiency. Infacort® also has the potential to increase compliance through the product's taste-masking excipients specifically designed to eliminate the bitter taste of hydrocortisone."

The EMA previously approved a Paediatric Investigation Plan (PIP) for Infacort®, setting out the regulatory pathway to market authorisation via the Paediatric Use Marketing Authorisation (PUMA) route. Diurnal is on track to submit this regulatory dossier to the EMA around the end of 2016. If approved, Infacort® has the potential to be the first licensed treatment in Europe for AI (including CAH) specifically designed for use in children. Diurnal anticipates market authorisation in late 2017.

Martin Whitaker, CEO of Diurnal, commented:

"The successful completion of the pivotal trial programme for Infacort® in Europe is another important step towards realising our vision of improving the lives of patients with adrenal insufficiency and CAH, and building Diurnal into a leading global endocrinology company. We look forward to filing the drug for approval with the EMA in the coming weeks and anticipate approval in late 2017."

Overview of Infacort® pivotal trial design

The pivotal phase III trial was an open-label study of Infacort® in neonates and children less than 6 years of age with adrenal insufficiency carried out at Charité-Universitätsmedizin, Berlin Germany and consisted of three cohorts that were carried out in series:

- Cohort 1: 12 patients with adrenal insufficiency aged 2 - 6 years of age

- Cohort 2: 6 patients with adrenal insufficiency aged 1 month to 2 years of age (infants)

- Cohort 3: 6 patients with adrenal insufficiency aged 0 to 1 month of age (neonates)

The primary objective of the study was to measure peak and four-hour cortisol levels after administration of a single dose of Infacort®. The secondary objective was safety.

Please further information, please visit www.diurnal.co.uk or contact:

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 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. The European Medicines Agency has already approved a Paediatric Investigation Plan (EMEA-001283-PIP01-12) for Infacort®, which sets out the regulatory pathway to market authorisation via the Paediatric Use Marketing Authorisation (PUMA) route.

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.