Investigating the Role of LRG1 in Disease

With TRO support, researchers within the UCL Institute of Ophthalmology have successfully developed their project to spinout.

Unmet Need

The formation of abnormal blood vessels occurs in several ophthalmic conditions, including the wet form of age-related macular degeneration, the most common form of blindness in older people, along with diabetic macular oedema and proliferative diabetic retinopathy.

Solution

Research carried out by Professors John Greenwood and Steve Moss to identify genes showing abnormal expression in affected blood vessels in the eye, led to the discovery of LRG1, a potent stimulator of vessel dysfunction and aberrant blood vessel growth (neovascularisation) whose expression was upregulated. Angiogenesis and vascular abnormality are also the target of several cancer therapies, where blocking the formation of new blood vessels or improving their function is the clinical objective.

How We Helped

The TRO has worked closely with the project team to develop the translational strategy and has supported and managed two MRC DPFS awards. The first award (£741K) was to generate and humanise an anti-LRG1 monoclonal antibody (mAb) and deepen understanding of the mechanism of action and the role of LRG1 in disease. The second £6.1M award, enabled the team to develop a large scale GMP manufacturing process and to test the anti-LRG1 mAb in GLP safety, and toxicology studies. These studies informed the decision to generate a Fab version of the anti-LRG1 biologic for ophthalmic indications. 

Where is the project now?

Professors Greenwood and Moss worked with UCL Business (UCLB) to patent their work and with a UTF award (£550K) have formed a spinout company, PanAngium Therapeutics.

The TRO has continued to manage the preclinical work being undertaken by the spinout in generating an anti-LRG1 Fab fragment and safety testing the tolerance of this biologic in an animal model. These studies have demonstrated improved safety over the original full length mAb. A further UTF award (£1.1M) is investigating the role of LRG1 in tumour vascular dysfunction.