Developmental Clinical Studies - Phase 1 studies on an analogue of peptide YY as a treatment for obesity

When humans eat, the bowels naturally secrete chemicals into the bloodstream which make people feel full and which stop eating. One of these chemicals is known as Peptide YY (PYY). We have previously shown that injections of human PYY reduce appetite and food intake. We have now developed a very similar chemical, Y242, as a treatment for obesity. Y242 has been tested in animals and has been shown to be safe, and to reduce their appetite. This study will test Y242 for its safety and tolerability in humans.

Obesity causes 600 premature deaths per week in the UK and is a serious risk factor for cancer, diabetes and cardiovascular disease. The only licensed drug on the UK market is neither powerful nor free of side effects. In contrast, gastrointestinal bypass surgery provides sustained, major weight loss and works mainly by elevation of potent satiety gut hormones such as peptide YY3-36 NH2 (PYY3-36). Intravenous infusion of PYY3-36 significantly reduces food intake in humans. However, its effects only last for a few hours and rapid elevation causes nausea. Following a five-year development programme culminating in a DPFS-funded project, we have successfully designed a long-acting peptide analogue of PYY, named Y242. Given subcutaneously (SC), it has a profile of action of at least 72 hours in rodents without any burst release, allowing a smooth cumulation of effect. It produces a powerful inhibition of food intake, impressive weight loss in every animal model tested and no apparent behavioural side effects. Formulation of Y242 produces prolonged plasma elevation, with the possibility of weekly dosing. Under MRC DPFS funding, pre-Good Manufacturing Practice (GMP) production has been achieved and Y242 is currently undergoing formal Good Laboratory Practice (GLP) toxicology testing for Medicines and Healthcare products Regulatory Agency (MHRA) Clinical Trial Authorisation (CTA). We now seek funding through the MRC DCS scheme to establish the safety, tolerability and pharmacokinetics of Y242 in man, in a combined single ascending dose and multiple ascending dose Phase 1 clinical study.