8 October 2019

UCLB has concluded an exclusive agreement to license a collection of pre-clinical small molecule compounds for the treatment of alpha-1-antitrypsin deficiency with a US biotech company.

Alpha-1-antitrypsin deficiency is a rare inherited disorder that results in lung and liver disease. While produced in the liver one of its key functions is to protect the lung and other connective tissue from excessive and uncontrolled degradation. In many patients the deficiency of alpha-1-antitrypsin is caused by a genetic missense mutation (e.g. Z alpha-1-antitrypsin) which leads to the production and accumulation of polymers in liver cells. The build-up of polymers leads to liver damage, which in severe cases, requires liver transplantation. There is currently no treatment for alpha-1-antitrypsin deficiency.

Research leading to the development of these compounds has been the main scientific interest of Professor David Lomas, Vice-Provost (Health), UCL.  Understanding the molecular and cellular mechanisms of alpha-1-antitrypsin deficiency has been the focus of Prof Lomas’ work, since his PhD in the early 1990’s. More recently, Prof Lomas and his team worked with GlaxoSmithKline as part of the DPAc collaboration scheme to develop a small molecule treatment which will prevent the polymerization of the mutant Z alpha-1-antitrypsin in the liver.

Through the very successful collaboration with GSK over five years, the team discovered and developed a number of small molecules which had the desired effects in pre-clinical studies and a number of these were on the path to the clinic. However, in March 2018, the collaboration was terminated by GlaxoSmithKline due to a change in corporate strategy, and all the project IP was assigned to UCL. UCLB have been working alongside Prof Lomas in the identification of a suitable commercial partner to further progress the development of the small molecules to market and ultimately patient benefit.

To this end, UCLB has entered into an exclusive licensing agreement with a leading US biotech company. From this partnership, both parties seek to further develop this potential treatment for conditions mediated by alpha-1-antitrypsin polymerization.

Professor David Lomas said: “My research over 30 years has focused on understanding the mechanism of antitrypsin deficiency with the aim of developing a cure.  We have developed exciting compounds in collaboration with GSK.  This licence agreement will allow us to evaluate the lead compounds in ‘first in human’ studies.”

Dr Richard Fagan, Director of BioPharm, UCLB said: “Prof Lomas’ research has made real progress to enhance our understanding of Alpha-1-antitrypsin deficiency. We’re really pleased to have found a fitting commercial partner to further develop these small molecule compounds. We look forward to seeing both parties work together towards their shared goal of developing treatments for the condition.”