Heptares Orphan disease program awarded grant from UK Biomedical catalyst

The grant, with additional funding from Heptares, will support a three-year research project aimed at developing first-in-class, selective and orally available small molecule GLP-1 receptor antagonists for the treatment of severe hypoglycaemia (low blood glucose) in rare diseases including congenital hyperinsulinism (CHI).

These, often inherited, conditions are characterized by inappropriate and unregulated insulin secretion, causing severe hypoglycaemia, and are associated with poor clinical outcomes including long-term nerve and brain damage.

GLP-1 is a hormone that regulates insulin production in response to blood glucose levels. The activation of its receptor is an important approach for treating diabetes with several products approved.

No GLP-1 receptor antagonists are licensed for treating CHI or other related conditions, however experimental and clinical studies with an intravenous peptide antagonist strongly indicate their prospective effectiveness.

The support of the MRC and Innovate UK through this grant will enable Heptares to optimise a series of novel small molecule GLP-1 receptor antagonist compounds identified and developed using its GPCR structure-based development platform.

Heptares, in collaboration with the University of Manchester and Great Ormond Street Hospital, London, will then carry out the preclinical development of candidates with the goal of providing novel safe, effective and orally available molecules for clinical studies for CHI with anticipated additional potential in other areas associated with intractable hypoglycaemia; including neonatal hypoglycaemia, hypoglycaemia occurring as a consequence of gastric bypass surgery and insulinoma-associated hypoglycaemia.

Fiona Marshall, Heptares Chief Scientific Officer and co-founder, said: "The ability to precisely drug and regulate the activity of the GLP-1 receptor and thereby regulate and normalize blood glucose levels is an important and validated approach to the treatment of many diseases. We are delighted to receive this grant from the Biomedical Catalyst to fund work that combines the expertise in structure-based drug design at Heptares and the disease expertise of our academic partners to identify new oral treatments for these diseases."

The Biomedical Catalyst is a funding programme jointly operated by the UK Medical Research Council and Innovate UK (formerly the Technology Strategy Board – TSB) providing responsive and effective support for the best translational life science opportunities arising in the UK.

Grants are available to UK academics and small and medium enterprises (SMEs) seeking to move their research more quickly from discovery to commercialisation.