DNL.L Regulatory News (DNL)

11 January 2022

Diurnal Group plc

("Diurnal" or the "Company")

Operational update

First clinical trial sites initiated in both CONnECT and CHAMPAIN studies for Chronocort®

DITEST™ IND application to be submitted during January 2022

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, provides an operational update on its ongoing clinical trial activity.

Operational updates

CHAMPAIN: Chronocort® (hydrocortisone modified-release hard capsules) Phase 2 line extension study in adrenal insufficiency (AI) in Europe. The Directors believe this study will facilitate submission of a line extension to AI in Europe (and support any US regulatory submission in due course). AI represents a significant market opportunity of approximately $2.9bn across Europe and the US. 

· The Company reports that the first clinical study site for the CHAMPAIN study was initiated and open to recruitment in the UK in December 2021, as planned. Further UK sites are planned to open in early 2022 and Diurnal anticipates first patient enrolment to occur shortly.

· Regulatory approval for the CHAMPAIN study in Germany was received from the Federal Institute for Drugs and Medical Devices (BfArM) at the end of 2021. Diurnal is now awaiting final ethics committee approval allowing German clinical sites to open for recruitment and participate in this study.

· The CHAMPAIN study remains on track to provide headline results in H2 2022.

CONnECT: Chronocort® Phase 3 registrational study in congenital adrenal hyperplasia in US and Japan

· Following successful completion of a Special Protocol Assessment (SPA) with the US Food and Drug Administration (FDA) during H2 2021 for the CONnECT study, Diurnal reports that the first clinical study site was initiated and open to recruitment in the US in December 2021, as planned. The Company anticipates first patient enrolment shortly.

· During H2 2021, the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) agreed that the CONnECT study can act as the registration study for Chronocort® in Japan. Prior to year-end 2021, ethical and regulatory approvals were granted in Japan allowing site initiation to commence in early 2022.

· The US and Japanese registrational trial of Chronocort® will be conducted in the US and Japan with international centres in Turkey and France. Following initiation of the first clinical study site, further US and international sites are planned to open for patient recruitment from early 2022.

· The CONnECT study is expected to provide headline results in H1 2024.

DITEST™: Investigational New Drug (IND) application in US

· The DITEST™ IND application will be filed with the FDA during January 2022. The Company anticipates that should the IND application be successful, this would enable the initiation of a Phase 1 multiple ascending dose study of DITEST™ (native oral testosterone) in 24 human volunteers in the US.

A further detailed update on clinical trial activities will be provided at the Company's R&D Day taking place in London (UK) on 02 February 2022. To register to attend in person, or to receive a link to the webcast, please contact diurnal@fticonsulting.com.

Martin Whitaker, Chief Executive Officer of Diurnal, commented: 

"We are pleased to be able to demonstrate continued advancement of our clinical trial activities despite recent headwinds caused by the Omicron COVID-19 variant and its impact on healthcare systems around the world. We remain hopeful that as COVID-19 pressures begin to ease, recruitment of patients into the clinic will accelerate significantly. In addition, we look forward to providing a full R&D update at the beginning of February 2022."

This is a business press release containing financial information and/or data for the benefit of shareholders and potential investors. Data are included to allow informed investment decisions.

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

Notes to Editors

About the FDA's Special Protocol Assistance

The SPA process documents the FDA's official evaluation and written guidance on the design and size of proposed protocols and agreement that the design and planned analysis of a study can adequately address objectives in support of a regulatory submission. Final determinations for marketing application approval, however, are made after a complete review of a marketing application and are based on the entire data in the application. The agreed SPA may only be changed through a written agreement between the sponsor and the FDA, or if the FDA becomes aware of a substantial scientific issue essential to product efficacy or safety.

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 glucocorticoid (steroid) preparations including hydrocortisone, dexamethasone, prednisolone and prednisone in the US, 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 16,000 patients in the US, with over 400,000 in the rest of the world.

About adrenal insufficiency

Adrenal insufficiency (AI) is an orphan condition caused either by failure of the adrenal gland to produce cortisol (primary AI) or can result from many factors that lead to suppression of the hypothalamic- pituitary axis (secondary AI). The result is a decrease / absence of cortisol production resulting in a number of comorbidities for patients such as lack of energy, weakness and a low mood.

AI may also lead to adrenal crisis, particularly during times of increased cortisol requirements (e.g. surgery, infection, or trauma) as patients are unable to mount a stress response. Life-threatening symptoms such as severe dehydration, hypotension, hypovolaemic shock, altered consciousness, seizures, stroke, or cardiac arrest may develop; if left untreated, adrenal crisis may lead to death or permanent disability. The condition is estimated to affect 298,000 patients in Europe and the UK.

Current therapy in Europe and the UK for AI either uses generic hydrocortisone or Plenadren® (modified-release hydrocortisone). However, these preparations are unable to replicate the physiological overnight rise of cortisol in AI patients leading to fatigue and poor quality of life, especially in the morning.

About Chronocort® (hydrocortisone modified-release hard capsules)

Chronocort® is a preparation of hydrocortisone that has been specifically designed to mimic the circadian rhythm of cortisol when given in a twice-a-day "toothbrush" regimen (administered 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 targeted indication for Chronocort® in the US is congenital adrenal hyperplasia (CAH) in adults. Chronocort® has been extensively studied in 239 human subjects including 138 CAH patients who have taken part in clinical trials in Europe and the US.

Chronocort® (commercial name Efmody®) was approved by the European Commission in May 2021 and by the UK Medicines and Healthcare Regulatory Agency (MHRA) in July 2021 and is commercially available in Europe and the UK.

The human medicine European Public Assessment Report (EPAR) for Efmody® can be viewed here and the Summary of Product Characteristics (SmPC) here.

About Diurnal Group plc

Diurnal Group plc is a European, UK-headquartered, specialty pharmaceutical company dedicated to developing hormone therapeutics to aid lifelong treatment for rare and chronic endocrine conditions, including congenital adrenal hyperplasia, adrenal insufficiency, hypogonadism and hypothyroidism. 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.com 

Date of Preparation: January 2022 Code: CORP-GB-0164