DNL.L Regulatory News (DNL)

20 November 2019

Diurnal Group plc

("Diurnal" or the "Company")

Successful outcome of oral testosterone clinical study

Primary efficacy endpoint met with DITEST™ in 24-patient study

Potential to be the first effective oral native testosterone treatment in a $4.8bn global market

Diurnal's third product in clinical development; another significant step towards building a global endocrinology franchise

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces positive headline results from the Company's DITEST™ (native oral testosterone formulation) Phase I proof-of-concept clinical trial. This study, which confirms the positive findings in the Company's successful in vivo pre-clinical studies, evaluated the pharmacokinetics, safety and tolerability of DITEST™ in the target patient group of 24 adult men with primary or secondary hypogonadism1.

The estimated $4.8 billion market in US and Europe for testosterone-based products for the treatment of hypogonadism is dominated by topically-available products, which have compliance and safety issues, while key issues with the use of alternative, oral modified testosterone products (testosterone undecanoate) has been the variability in absorption and the requirement for a high-fat meal to achieve therapeutic testosterone levels. The DITEST study was designed to compare both of these properties to an existing testosterone undecanoate therapy in hypogonadism patients.

The primary endpoint of the trial compared the rate and extent of absorption of testosterone from a single dose of DITEST™ 120mg with a single dose of testosterone undecanoate 80mg in the fed state in hypogonadal men. In this respect, DITEST™ was shown to achieve testosterone levels within the healthy young male adult normal range after oral administration, with levels that were less variable than testosterone undecanoate.

Secondary endpoints demonstrated that there was no impact on the rate and extent of absorption of testosterone from DITEST™ 200mg whether taken with either food or in the fasted state, representing a major difference with testosterone undecanoate. The safety and tolerability of two different doses of DITEST™ were also assessed in the study: there were no serious adverse events in the DITEST™ arm of the study, and levels of the potent testosterone derived androgen, dihydrotestosterone (DHT), were lower than with testosterone undecanoate.

Professor John Newell-Price, University of Sheffield and Lead Investigator on the study, commented:

"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 considerable pharmacokinetic variability and a requirement to be taken with a high-fat meal. For hypogonadal men, there is an unmet need for an effective and convenient oral testosterone replacement therapy. I am strongly encouraged by these study results, which demonstrate that the DITEST™ formulation has the potential to address these needs."

Martin Whitaker, CEO of Diurnal, added: 

"The positive outcome of this trial is another meaningful step towards achieving Diurnal's vision of becoming one of the world's leading endocrinology speciality pharma companies. We are excited by the potential of DITEST™ to address a significant unmet patient need for hypogonadal men, which affects over 60 million men globally2. DITEST™ is our next pipeline product in the clinic after our lead programmes, Alkindi® and Chronocort®. We look forward to engaging with regulators in the US and Europe to progress DITEST™ to late stage clinical trials, and to discussing these positive trial data with potential development and commercialisation partners."

1 Clinical Trials ID NCT02966652

2 Datamonitor Report 2015

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

Notes to Editors

About Hypogonadism

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. Diurnal estimates that in Europe and the US the market opportunity is around $4.8 billion per annum. Topical (gel) formulations are the current market leaders due to low bioavailability of testosterone in the body when administered by the oral route. However, these topical formulations have compliance and potential safety issues. Other testosterone replacement therapies for hypogonadism include intramuscular injections, testosterone patches and the only currently available oral forms are modified testosterones (such as testosterone undecanoate) that have limited label scope, well-documented pharmacokinetic variability, a requirement to be taken with a high fat meal and safety concerns.

Therefore, Diurnal believes that there is a patient need for an oral (native) testosterone preparation.

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 (the amount of drug in the body that is able to have an active effect). Diurnal's approach is a proprietary lipid-based formulation that aims to provide improved bioavailability of testosterone. An additional potential feature of the native testosterone formulation demonstrated in both preclinical studies and now in this clinical study is that it shows similar absorption and bioavailability 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 

Date of Preparation: November 2019 Code: CORP-GB-0042