Exonate Ltd. announced plans to advance its lead candidate EXN407 into a Phase IIb clinical trial, marking a significant step toward developing the first topical therapy for non-proliferative diabetic retinopathy (NPDR). The CLEAR-DE (Clinical Evaluation of a New Eye Drop for Alleviating Retinopathy in Diabetic Eye Disease) trial will evaluate the clinical efficacy, optimal dosing and safety profile of this first-in-class SRPK1 inhibitor eye drop.
Phase IIb Trial Design and Timeline
The Phase IIb study is planned to commence in early 2026, enrolling 140 patients across multiple sites in Australia, the Middle East and China. This progression follows encouraging results from Exonate's Phase Ib/IIa study completed in March 2024, where EXN407 met its primary safety and tolerability endpoints with no drug-related serious adverse events and demonstrated high patient compliance.
Importantly, the earlier study showed exploratory efficacy signals with a reduction in vascular leakage, a key pathological driver in diabetic retinopathy progression.
Addressing Significant Unmet Medical Need
Diabetic retinopathy represents a leading cause of vision loss globally, affecting an estimated one-third of the nearly 500 million people living with diabetes. NPDR, the early stage of diabetic eye disease, can progress to more severe, vision-threatening complications if left untreated.
Current therapeutic approaches present significant limitations, involving monthly intraocular injections that are initiated only after symptoms appear. This reactive treatment paradigm limits opportunities for early therapeutic intervention, and due to the invasive nature and frequency of injections, treatment is often deferred until irreversible retinal damage has occurred.
Novel Mechanism of Action
EXN407 represents a first-in-class, twice-daily topical formulation of a selective SRPK1 inhibitor, offering a minimally-invasive approach with potential to become the first effective eye-drop therapy for both NPDR and diabetic macular oedema (DME). The drug is designed to modulate expression of vascular endothelial growth factor (VEGF) through alternative mRNA splicing, selectively inhibiting the pro-angiogenic isoforms that drive disease progression and cause abnormal, leaky blood vessel formation in the retina.
Clinical Impact and Future Outlook
"The Phase Ib/IIa data demonstrated the clear potential of EXN407 as a non-invasive treatment for diabetic eye disease," said Dr. Catherine Beech, Chief Executive Officer of Exonate. "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."
The company is actively seeking strategic partners to support execution of the CLEAR-DE Phase IIb trial. If successful, EXN407 could represent a paradigm shift in diabetic retinopathy management, enabling early intervention through a patient-friendly topical formulation rather than invasive intraocular procedures.
