Exonate plans to initiate phase 2b CLEAR-DE trial for EXN407 topical formulation for NPDR

The Clinical Evaluation of a New Drop for Alleviating Retinopathy in Diabetic Eye Disease (CLEAR-DE) trial will evaluate the clinical efficacy, optimal dosing, and safety profile of EXN407 in patients with NPDR. Image credit: AdobeStock/Kwangmoozaa

Biotechnology company Exonate has announced plans to initiate its phase 2b clinical trial for its lead candidate EXN407, a twice-daily topical formulation for the treatment of non-proliferative diabetic retinopathy (NPDR) and diabetic macular edema (DME).¹ The Clinical Evaluation of a New Drop for Alleviating Retinopathy in Diabetic Eye Disease (CLEAR-DE) trial will evaluate the clinical efficacy, optimal dosing, and safety profile of EXN407 in patients with NPDR, according to a news release.

“The phase 1b/2a data demonstrated the clear potential of EXN407 as a non-invasive treatment for diabetic eye disease,” said Catherine Beech, MB, ChB, OBE, CEO of Exonate, in the release. “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 2b trial and are actively seeking strategic partners to support its execution.”

The phase 2b study follows the company’s phase 1b/2a study from March 2024, which resulted in EXN407 meeting its primary safety and tolerability end points, 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 release stated. Now, the phase 2b trial is planned to begin in early 2026, with 140 patients currently enrolled across several sites in Australia, China, and countries in the Middle East.¹

EXN407 is a first-in-class topical formulation of a selective SRPK1 inhibitor, providing a minimally invasive approach that has the potential to become the first effective eye drop therapy for NPDR and DME. The formulation works by selectively inhibiting the pro-angiogenic isoforms that drive disease progression and cause abnormal and leaky blood vessel formation in the retina. EXN407 is designed to modulate expression of vascular endothelial growth factor via alternative mRNA splicing, according to the company.¹

“[EXN407] has the potential to become the patients treatment of choice in an area of high medical unmet need,” the company stated.²

References:

1. Exonate plans ‘CLEAR-DE’ phase 2b clinical trial of lead candidate EXN407 for diabetic eye disease. News release. Businesswire. July 29, 2025. Accessed July 29, 2025. https://www.businesswire.com/news/home/20250728228819/en/Exonate-plans-CLEAR-DE-Phase-IIb-clinical-trial-of-lead-candidate-EXN407-for-diabetic-eye-disease

2. Pipeline Overview. Exonate. Accessed July 29, 2025. https://www.exonate.com/technology/