"**Diurnal (in conjunction with its sub-contractor Quotient Sciences) aims to change the paradigm for the treatment of hypothyroidism by developing a, first-of-a-kind, modified release formulation of** **triiodothyronine (T3) and demonstrating physiological thyroid hormone replacement in Phase 1 clinical trials.** This project directly addresses the first wave challenges set out by the Industrial Strategy Challenge Fund (ISCF) of developing first-of-a-kind technologies for the development of new medicines to accelerate patient access to new drugs and treatments. This experimental development project builds upon existing scientific evidence that T3 could offer a better treatment option for the estimated 400,000 UK hypothyroid patients who don't feel well on levothyroxine (T4) monotherapy. These patients suffer from persistent depression, fatigue, obesity and poor quality of life as highlighted by current clinical guidelines and patient organisations, and there has been no product innovation in over 50 years. There is evidence that combination therapy with T4 & T3 would improve health however, current T3 options do not restore physiology because of a lack of appropriate formulations and patients often seek to complement the treatment with supplementary T3 sourced from off shore pharmacies. Available T3 formulations provide un-physiological T3 levels because of a very short serum half-life, which means patients require up to three doses of T3 per day and are at risk of high T3 levels that can cause cardiac arrhythmias. Diurnal will develop a modified release T3 formulation that will overcome the short half-life of T3 and provide the physiological level and rhythm of T3\. This will be done using the Quotient RapidFACT technology and the formulation will be tested in healthy volunteers in a Phase 1 clinical trial. A successful outcome, in conjunction with Diurnal's product development experience, would allow the project to move rapidly to later phase clinical trials and improve the health outcomes of patients in the UK and potentially millions of suffers worldwide who are afflicted by hypothyroidism."

This project aims to develop, validate and introduce new salivary tests into the NHS (and worldwide) to simplify the diagnosis and treatment of patients with adrenal insufficiency. The adrenal produces the essential stress hormone cortisol without which patients die from circulatory collapse in what is called an adrenal crisis. Adrenal insufficiency may be caused by prolonged steroid treatment which is commonly used in inflammatory disorders such as asthma, rheumatoid arthritis and most recently Covid-19\. Currently, diagnosis of adrenal insufficiency requires a day case visit to hospital, however Professor Brian Keevil, at the Manchester University NHS Foundation Trust, has developed a salivary test that will greatly simplify the diagnosis and treatment of adrenal insufficiency. Salivary testing will save lives through early diagnosis, reduce the need for unnecessary clinician-patient contact, reduce the burden to patients and reduce cost through home sampling and remote testing in hospital laboratories. The secondment of Professor Keevil to Diurnal, a UK Company with world-leading expertise in developing hormone pharmaceutical products, through the Innovation Scholars award the Manchester University NHS Foundation Trust will allow the project to examine the validation of the specific salivary steroid (cortisone and cortisol) assays and their introduction in to the everyday care of patients. It is critical that good ideas that will benefit patients find a way to move through to clinical practice in the shortest timeframe possible. Without the correct infrastructure and support many projects fail to reach completion. The key to introducing medical innovation to healthcare is collaboration and early involvement with industry. The Innovation Scholars secondment is the ideal vehicle to develop Professor Keevil's innovation at **Manchester University NHS Foundation Trust,** providing a pathway to accelerate the new salivary diagnostic tests directly into clinical practice with the appropriate industry forethought and backing.