Phase Ib/IIa trial of EXN407 eye drops from Exonate demonstrates safety and tolerability


In addition to the primary safety and tolerability endpoints, the study also saw signals of biological response from EXN407

Image credit: AdobeStock/megaflopp

(Image credit: AdobeStock/megaflopp)

In early March of 2024, Exonate shared that the data from the Phase Ib/IIa trial for lead candidate EXN407 demonstrated safety and tolerability, as well as clear indications of biological activity. These results position the candidate well for further development as the first topical treatment for retinal vascular diseases such as diabetic retinopathy (DR) and diabetic macular edema (DME).

Following this news, Exonate plans to progress EXN407 to the CLEAR-DM (Clinical Evaluation of a New Eyedrop for Alleviating Retinopathy in Diabetic Macular Oedema) Phase IIb clinical trial.


This topical eye drop is a twice-daily formulation, comprised of a small molecule SRPK1 inhibitor, which is involved the alternative splicing of vascular endothelial growth factor (VEGF). 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.1

Safety and tolerability

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 edema. The independent Dose Escalation Committee characterized 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. Additionally, EXN407 exhibited high levels of tolerability, with drop comfort scores similar to that of placebo and artificial tears.1

In addition to the primary safety and tolerability endpoints, the study also saw 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).1

Exonate’s CEO shares hope for EXN407

In the press release1, Catherine Beech, chief executive officer of Exonate, noted that the positive data could provide hope and reduce the treatment burden for patients and providers. She said, “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. 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.”

Upcoming data presentation

Full results of the Phase Ib/IIa will be presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in May 2024:

1. 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. Published March 5, 2024. Accessed March 26, 2024.
Related Videos
© 2024 MJH Life Sciences

All rights reserved.