Diurnal has created its pipeline of enhanced product opportunities by evaluating therapeutic indications within the endocrine area where current therapies are considered to be sub-optimal and could be superseded with more effective physiological hormonal replacement products.

• Chronocort^® - first-in-class physiological cortisol replacement product for the life-long treatment of adrenal insufficiency and congenital adrenal hyperplasia.
• Rheumacort™ – anti-inflammatory treatment to alleviate the symptoms of rheumatoid arthritis.
• Native Oral Testosterone - first-in-class physiological native oral testosterone replacement treatment for hypogonadism.
• Tri4Combi™ - goal to be the best-in-class thyroid hormone replacement treatment for patients with hypothyroidism.

Chronocort^® is the first-in-class physiological cortisol replacement product for the life-long treatment of adrenal insufficiency and congenital adrenal hyperplasia.

The body’s inability to produce the important metabolic hormone cortisol comes in two forms: adrenal insufficiency (acquired) and congenital adrenal hyperplasia (genetic). There are over 250,000 patients worldwide who are unable to produce the healthy required amounts of cortisol.

Cortisol has a distinctive daily rhythm and, currently, there are no effective products for the treatment of cortisol deficiency. Chronocort® is specifically designed to provide physiological cortisol replacement over the whole day. Chronocort® is administered at bedtime and provides overnight coverage of cortisol as well as sustained replacement during the following day.

Diurnal has successfully completed pre-clinical development of Chronocort® and has initiated a Phase 1 trial in humans, the results of which are expected in 2010. It is expected that Chronocort® will be on the market by the end of the 2014.

Rheumacort™ is a novel anti-inflammatory treatment aimed at alleviating the symptoms of rheumatoid arthritis.

Rheumatoid arthritis is a disease that affects over 1% of western populations and there are more than 2.5M sufferers in the US alone.

Alleviating the symptoms of rheumatoid arthritis, such as morning stiffness, is a key goal in this area.

Rheumacort™ is currently undergoing pre-clinical evaluation by Diurnal and our partners.

Diurnal is developing a first-in-class physiological native oral testosterone replacement treatment for patients suffering from hypogonadism.

Hypogonadism (testosterone deficiency) is estimated to affect 1% of men and has an estimated market size of at least £800M (USD $1.25B; Euro €900M) per annum worldwide. Often hypogonadism is under-diagnosed and recent studies show that the patient and market size could be significantly higher.

Currently, there is no oral formulation of native testosterone available because testosterone is quickly removed by the liver. The only currently available oral forms are either alkylated or esterified and are sub-standard therapies that present well documented significant pharmacokinetic variability and long-term safety issues.

Diurnal has successfully completed in vivo pre-clinical studies of its novel formulation and expects to initiate Phase 1 studies in humans during 2011.

Tri4Combi™ will be the first physiological combination therapy of the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) for patients suffering from hypothyroidism.

Hypothyroidism is common affecting up to 5% of people over 60 years and has an estimated market size of £800M (USD $1.25B; Euro €900M) per annum worldwide.

Despite conventional thyroxine replacement being widely available, more than 25% of patients with hypothyroidism report significantly impaired quality of life with medical and social economic consequences. Commercially available combination products of T3 and T4 do not provide physiological replacement and at best are titrated empirically (by the physician) based on symptomatic responses.

Diurnal has completed an initial formulation development programme to enable the selection of a suitable drug delivery technology to underpin its clinical development programme in this area. Diurnal is actively seeking partners to progress the Tri4Combi programme.