Exonate plans 'CLEAR-DE' Phase IIb clinical trial of lead candidate EXN407 for diabetic eye disease

Exonate Ltd., a biotechnology company developing novel, non-invasive, small-molecule therapeutics for patients with retinal vascular diseases, today announced plans to initiate a Phase IIb clinical trial for its lead candidate EXN407. The CLEAR-DE (Clinical Evaluation of a New Eye Drop for Alleviating Retinopathy in Diabetic Eye Disease) trial will further evaluate the clinical efficacy, optimal dosing and safety profile of EXN407 in patients with non-proliferative diabetic retinopathy (NPDR).

The progression to a Phase IIb clinical study follows encouraging results from Exonate's Phase Ib/IIa study in March 2024. In the study, lead candidate EXN407 met its primary safety and tolerability endpoints, with no drug-related serious adverse events, and high patient compliance. Importantly, exploratory efficacy signals showed a reduction in vascular leakage, a key pathological driver in diabetic retinopathy. The Phase IIb trial to investigate the efficacy of EXN407 in NPDR patients is planned to begin in early 2026, with 140 patients currently enrolled across multiple sites in Australia, the Middle East and China.

Diabetic retinopathy (DR) is a leading cause of vision loss globally. An estimated one-third of the nearly 500 million people living with diabetes are affected by NPDR, the early stage of diabetic eye disease, which can lead to more severe, vision-threatening complications. Current therapeutic approaches involve monthly intraocular injections, initiated only after symptoms appear. This limits opportunities for early therapeutic benefit, and due to the invasive nature and frequency, is often deferred until irreversible damage has occurred.

EXN407 is a first-in-class, twice-daily topical formulation of a selective SRPK1 inhibitor - a minimally-invasive approach with potential to become the first effective eye-drop therapy for NPDR and diabetic macular oedema (DME). Designed to modulate expression of vascular endothelial growth factor (VEGF) via alternative mRNA splicing, EXN407 selectively inhibits the pro-angiogenic isoforms that drive disease progression, causing abnormal and leaky blood vessel formation in the retina.

The Phase Ib/IIa data demonstrated the clear potential of EXN407 as a non-invasive treatment for diabetic eye disease.

This therapy could transform the treatment landscape for early-stage disease by providing clinical benefit while avoiding the burden of injections, representing a significant advancement for patients and physicians alike. We're excited to progress to the CLEAR-DE Phase IIb trial and are actively seeking strategic partners to support its execution."

Dr. Catherine Beech, Chief Executive Officer, Exonate