First Patient Dosed in Testosterone Trial

21 November 2016

Diurnal Group plc

("Diurnal" or the "Company")

First patient dosed in testosterone replacement therapy for hypogonadism

Potential to be the first effective oral native testosterone treatment

Data expected in mid-2017

Represents third product into clinical development, another significant step towards building a proprietary endocrinology franchise

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that it has successfully dosed the first patient in the Company's native oral testosterone formulation (DITEST) Phase I clinical trial. This study will evaluate pharmacokinetics, safety and tolerability of DITEST in the target patient group of males with hypogonadism (Clinical Trials ID NCT02966652).

Dr Martin Whitaker, CEO of Diurnal, commented: 

"The start of this trial is another meaningful step towards achieving Diurnal's vision of becoming one of the world's leading endocrinology speciality pharma companies. DITEST is our next pipeline product to enter clinical development after Infacort® and Chronocort®, our lead programmes. Currently available topical formulations of native testosterone have significant compliance and potential safety issues while, to date, attempts to create oral preparations of modified testosterone have resulted in products with unacceptable pharmacokinetic variability. Therefore, there is an unmet need for an effective oral testosterone treatment for hypogonadism that we believe can be met by our oral proprietary formulation. We look forward to reporting data from this important proof-of-concept study in patients in mid-2017."

DITEST - a proprietary lipid based formulation to overcome the fast metabolism of native testosterone

DITEST is a novel formulation developed by Diurnal comprising native testosterone adapted for oral delivery for the treatment of hypogonadism. The main challenge with oral delivery of native testosterone is that, whilst the hormone undergoes rapid and complete absorption, there is considerable metabolism in both the gut wall and during first hepatic pass which accounts for up to 98% reduction in testosterone bioavailability. Diurnal's approach is a proprietary lipid based formulation that aims to provide improved bioavailability. Patents protecting DITEST have already been granted in the US, Europe and other major territories worldwide.

Proof-of-concept trial will evaluate pharmacokinetics, safety and tolerability of DITEST

This proof-of-concept, randomised trial, which builds on the Company's successful in vivo pre-clinical studies, will evaluate the pharmacokinetics, safety and tolerability of DITEST in both fed and fasted states compared to testosterone undecanoate (an approved oral modified testosterone treatment) in 24 adult men with primary or secondary hypogonadism. The trial is scheduled to complete by mid-2017.

The primary endpoint of the trial will compare the rate and extent of absorption of testosterone from a single dose of DITEST with a single dose of 80 mg testosterone undecanoate in the fed state in adult male patients with primary or secondary hypogonadism. The secondary endpoints will assess the impact of food on the rate and extent of absorption of testosterone from DITEST and to assess the safety and tolerability of two different doses of DITEST.

Hypogonadism - a large but fragmented multi-billion dollar market

Hypogonadism results from failure of the testes (primary gonadal failure) or from failure of stimulation by the pituitary (secondary hypogonadism) resulting in testosterone insufficiency. In primary hypogonadism, failure of the testes can be congenital (inherited) or acquired during life due to a variety of causes (failure of the testes to descend into the scrotum, inflammation due to infections such as mumps, chemotherapy or radiotherapy affecting the testes, and following removal of the testes for testicular tumours). Secondary hypogonadism usually results from a benign tumour of the pituitary gland that causes hypopituitarism and may occasionally be congenital.

The hypogonadism market is a large and fragmented market. In Europe and the US, it is primarily driven by topical formulations, which Diurnal estimated to be of a value of $5.8 billion in 2015. Topical formulations are the current market leaders due to low bioavailability of testosterone in the body. However, these topical formulations have compliance and potential safety issues; there is therefore a need for an oral (native) testosterone preparation.

Current treatment for hypogonadism is testosterone replacement therapy via intramuscular injections, testosterone patches and testosterone gels. The only currently available oral forms are therapies that present well-documented significant pharmacokinetic variability. 

Notes to Editors

About DITEST

DITEST is a novel formulation developed by Diurnal comprising native testosterone adapted for oral delivery for the treatment of hypogonadism. The main challenge with oral delivery of native testosterone is that, whilst the hormone undergoes rapid and complete absorption, there is considerable metabolism in both the gut wall and during first hepatic pass which accounts for up to 98% reduction in testosterone bioavailability. Diurnal's approach is a proprietary lipid based formulation that aims to provide improved bioavailability. An additional potential feature of the native testosterone formulation demonstrated in preclinical studies is that it shows similar absorption in both the fed and fasted state and therefore potentially can be taken without a substantial meal, which is a problem associated with alternative oral modified-testosterone formulations.

Patents protecting DITEST have already been granted in the US, Europe and other major territories worldwide.

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