First patient dosed with a new eye drop to treat one of leading causes of blindness

Exonate Ltd, a spin-out company of the University of Nottingham, has begun a major clinical trial in its quest to develop a revolutionary new treatment for retinal vascular disease.

Exonate have announced today, that in collaboration with Janssen Pharmaceuticals, Inc. – one of companies of Johnson & Johnson, the first patient has been dosed with Exonate’s lead compound, EXN 407, in a Phase Ib/II clinical trial of patient volunteers with centre-involved diabetic macular oedema (CI-DMO).

Exonate Ltd was ‘spun out’ of the University of Nottingham in 2013 by University of Nottingham academics, Professors David Bates and Lucy Donaldson, with Professor Steven Harper from the University of Bristol and Professor Jonathan Morris from the University of New South Wales.

Dr Catherine Beech, Chief Executive Officer of Exonate, said: “The initiation of our first clinical trial is an important step in the validation of our eye drop approach. This is a unique opportunity to create a drug that may have the potential to improve the treatment of patients with retinal vascular diseases, and transform the lives of those suffering from vision loss. The collaboration with Janssen has been incredibly positive and together, we have designed a study that we believe will deliver meaningful results.”

It is a credit to many people that this complex and potentially game-changing therapy has reached first-in-human studies. This has been an immense team-effort from the original lab discovery work at the Universities of Bristol, New South Wales and Nottingham to the development of the pre-clinical and clinical programmes by the Exonate team, our contractors and collaborators. We look forward to learning the study results in due course.”

By exploiting the alternative splicing of Vascular Endothelial Growth Factor (VEGF), Exonate has developed small-molecules for the treatment of retinal neovascular diseases. EXN 407 inhibits serine/arginine-protein kinase 1 (SRPK1), which enables production of the form of VEGF that stimulates blood vessel formation. CI-DMO is caused by growth of blood vessels into the retina and current treatment options for CI-DMO and other retinal diseases require regular injections into the eyeball. EXN 407 has been designed to reach the retina when given as eye drops and represents a shift in the potential treatment of retinal vascular eye disease away from injections. Pre-clinical studies have demonstrated an effect on neovascularisation and retinal vascular permeability induced by diabetes, without any significant tolerability or safety issues.

The double-blind, randomised multicentre trial of 48 patients is being conducted at retinal centres across Australia. The trial consists of a dose escalation phase during which three doses of EXN 407 and a placebo are tested, followed by an expansion phase with a larger cohort of patient volunteers and a longer drug dosing period. The study aims to demonstrate safety and tolerability and an exploratory end point of efficacy through reduction in retinal thickness in a proportion of patients.

To date, Australia has managed the COVID-19 pandemic such that no major delays are expected in patient recruitment and we anticipate topline results in early 2022.

DMO is the most common cause of vision loss among people with diabetic retinopathy and affects approximately 21 million people worldwide. DMO is a build-up of fluid in a region of the retina called the macula and is associated with an increase in retinal thickness due to leakage of fluid and plasma proteins from retinal vessels, which leads to central vision loss. Although DMO is more likely to occur as diabetic retinopathy worsens, it can happen at any stage of the disease.

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