DNL.L Regulatory News (DNL)

02 March 2022

Diurnal Group plc

("Diurnal" or the "Company")

Regulatory update on oral native testosterone

Targeting H2 2022 start for Phase 1 study with DNL-0300

Diurnal Group plc (AIM: DNL), the specialty pharmaceutical company targeting patient needs in chronic endocrine (hormonal) diseases, announces that it has received feedback from the US Food and Drug Administration (FDA) for its native oral testosterone treatment (DNL-0300, previously referred to as DITEST™) in response to the Company's Investigational New Drug (IND) application submitted towards the end of January 2022.

As announced in July 2020, the FDA has previously indicated that the registration programme for DNL-0300 for the treatment of male hypogonadism can progress via the 505(b)(2) regulatory pathway, which means potentially only two further clinical studies are required before filing for market approval via a New Drug Application (NDA): a Phase 1 multiple-ascending dose (MAD) study followed by a single pivotal Phase 3 trial.

In the latest feedback, the FDA has stated that Diurnal's Phase 1 study can proceed subject to a protocol modification, primarily relating to additional clinical safety data from the two lowest dose groups. Diurnal expects to file an amended protocol for the MAD study as soon as possible with a view to initiating dosing in H2 2022. DNL-0300 will remain on partial clinical hold until the revised protocol has been agreed with the FDA.

Martin Whitaker, Chief Executive Officer of Diurnal, commented: 

"We are pleased to have received greater visibility and certainty regarding the exact nature of studies required to satisfy the FDA as we move DNL-0300 towards registrational submission in the US. We will file an amended protocol in the coming weeks and we look forward to starting the next study for our native oral testosterone product in H2 2022."

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This announcement contains inside information for the purposes of the UK Market Abuse Regulation (UK 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 $5 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 administration 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 native oral testosterone

Native oral testosterone (DNL-0300 previously referred to as 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 requirement with many alternative oral modified-testosterone formulations.

Patents protecting DNL-0300 have already been granted in the US, Europe and other major territories worldwide.

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: March 2022 Code: CORP-EU-0028