A Phase IIb clinical trial is set to begin for EXN407 – a novel eye-drop therapy for non-proliferative diabetic retinopathy and diabetic macular oedema (DME).
Developed by the biotechnology company Exonate Ltd., it is hoped that this minimally invasive therapy may one day provide clinical benefit while avoiding the burden of injections.
The CLEAR-DE trial will evaluate the drug’s efficacy, optimal dosing, and safety in 140 patients across Australia, the Middle East, and China, starting in early 2026. This follows promising Phase Ib/IIa results from March 2024, where 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.1
EXN407 is… a minimally-invasive approach with potential to become the first effective eye-drop therapy for NPDR and diabetic macular oedema
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,2 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.
Dr Catherine Beech, Chief Executive Officer of Exonate
“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. We’re excited to progress to the CLEAR-DE Phase IIb trial and are actively seeking strategic partners to support its execution.”
References
- Press Release (5th March, 2024): Exonate first-in-class eye drop Phase Ib/IIa trial data demonstrate safety and biological activity in treatment of diabetic retinopathy and diabetic macular oedema
- Wong TY, Tan TE. The diabetic retinopathy “Pandemic” and evolving global strategies: The 2023 Friedenwald Lecture. Invest Ophthalmol Vis Sci. 2023;64(15):47. doi: 10.1167/iovs.64.15.47.
