Exonate Ltd., a biotechnology company developing novel, non-invasive, small-molecule therapeutics for patients with retinal vascular diseases, today announced the data from a successful Phase Ib/IIa trial for lead candidate EXN407. These data demonstrate the safety and tolerability of EXN407, as well as clear indications of biological activity, positioning it well for further development as the first topical treatment for retinal vascular diseases such as diabetic retinopathy and diabetic macular oedema. Exonate is now planning to progress EXN407 to the CLEAR-DM (Clinical Evaluation of a New Eyedrop for Alleviating Retinopathy in Diabetic Macular Oedema) Phase IIb clinical trial.

EXN407 is a twice-daily formulation, comprised of a small molecule SRPK1 inhibitor. The eye drop formula exploits SRPK1 involvement in the alternative splicing of vascular endothelial growth factor (VEGF), a protein heavily involved in the regulation of blood vessel growth. Through inhibition of SRPK1, EXN407 can selectively target pro-angiogenic isoforms of VEGF that lead to vascular retinal disease progression via aberrant growth of leaky blood vessels within the eye.

The mild NPDR/DME (NCT04565756) clinical study assessed the safety, tolerability and signals of biological response to EXN407 monotherapy in a double-masked, placebo-controlled Phase Ib/IIa dose-ranging clinical trial in treatment-naïve patients with mild/moderate non-proliferative diabetic retinopathy (NPDR) and mild diabetic macular oedema. The independent Dose Escalation Committee characterised EXN407 as safe and well-tolerated, with 100% of patients completing the study without requiring anti-VEGF rescue, and no major or serious adverse events reported relating to EXN407. Moreover, EXN407 exhibited high levels of tolerability, with drop comfort scores similar to placebo and artificial tears.

In addition to the primary safety and tolerability endpoints, the study concluded that there were promising signals of biological response from EXN407, demonstrating sustained decreases in macular thickness, relative to the placebo group and comparable to previously reported anti-VEGF injections. The trial further noted that EXN407 treatment led to a significant decrease in vascular leakage (60% of EXN407-treated patients relative to 20% placebo) and that EXN407 inhibited further increases to vascular leakage (10% of EXN407-treated patients relative to 50% placebo).

“The Phase Ib/IIa data demonstrate the clear potential of EXN407 as a non-invasive treatment for these devastating, sight-threatening conditions, and the favourable safety profile and biological activity of EXN407 support its continued clinical development in retinal vascular diseases,” said Catherine Beech, chief executive officer of Exonate. “The results suggest that topical ocular EXN407 may provide clinical benefit and substantially reduce the injection burden for patients with diabetic eye disease. We look forward to engaging with strategic partners to support the CLEAR-DM phase IIb trial, which has been designed to fully demonstrate the clinical benefits of EXN407 in NPDR/DME.”