Twelve week data from the Ph1b/2a AMARONE trial reveals Restoret to be well-tolerated in patients with diabetic macular edema and neovascular age-related macular degeneration. Proof of concept established with strong visual and anatomic outcomes
Treatment-naïve DME patients treated with Restoret monotherapy experienced a mean reduction in excess retinal thickness of 80% and a mean vision gain of 11.2 letters at 12 weeks
February 13, 2024 08:30 AM Eastern Standard Time
NEW YORK & LONDON--(BUSINESS WIRE)--Eyebiotech Limited (“EyeBio” or “the Company”) announced today the presentation of Week 12 data from its first-in-human Phase 1b/2a AMARONE trial of Restoret in patients with treatment-naïve diabetic macular edema (DME) and treatment-naïve neovascular age-related macular degeneration (NVAMD). The analysis was presented by Charles C. Wykoff, MD, PhD, Director of Research at Retina Consultants of Texas and Chairman of the Research and Clinical Trials Committee, Retina Consultants of America on February 8, 2024, at the Macula Society Meeting in Palm Springs, California.
“There is a great deal of preclinical evidence that agonizing the Wnt pathway in the retina results in reduction in vascular leakage, and so it is very gratifying to generate the first clinical evidence that validates this pathway in the eye.”
The presentation of Week 12 data from AMARONE demonstrated that Restoret was well-tolerated, with no drug-related adverse events, drug-related serious adverse events, or intraocular inflammation reported. Patients with DME (n=26) received Restoret as monotherapy, manifesting a mean improvement in best-corrected visual acuity of +11.2 letters and a mean reduction in retinal thickness of -143 microns, as measured by optical coherence tomography (OCT). Similar outcomes were observed in patients with NVAMD (n=5), who received Restoret in combination with aflibercept. The data demonstrated that multiple monthly doses of Restoret, as both monotherapy and in combination with aflibercept, were well-tolerated.
“These data from AMARONE are unique and impressive,” stated Charles C. Wykoff, MD, PhD. “While anti-VEGF monotherapies have proven valuable, many patients still do not achieve optimal outcomes and there remains substantial unmet need for therapeutics with alternative mechanisms of action that can improve outcomes for patients with exudative retinal diseases including diabetic macular edema and wet macular degeneration. While early data thus far, it is exciting to see these meaningful anatomic and visual improvements using this differentiated and fascinating Wnt agonist, especially in the absence of VEGF inhibition.”
“We are thrilled to be sharing first-in-human data from the Restoret development program,” said David R. Guyer, MD, Chief Executive Officer of EyeBio. “The AMARONE trial represents the first ever clinical use of a Wnt pathway agonist to address retinal disease, and we are encouraged by the preliminary safety and efficacy data we’ve seen thus far.”
“Retinal diseases impact millions of people worldwide, and so we need to continue to innovate to help drive better outcomes for these patients,” said Tony Adamis, MD, Chief Scientific Officer of EyeBio. “There is a great deal of preclinical evidence that agonizing the Wnt pathway in the retina results in reduction in vascular leakage, and so it is very gratifying to generate the first clinical evidence that validates this pathway in the eye.”
About the AMARONE Clinical Trial
The Phase 1b/2a AMARONE (Anti-permeability Mechanism and Age-Related Ocular Neovascularization Evaluation) clinical trial is a multi-center two-part trial consisting of an open-label multiple ascending dose (MAD) safety study, and a single-masked comparative safety and preliminary efficacy study of intravitreal (IVT) Restoret (EYE103) in participants with diabetic macular edema (DME) and neovascular age-related macular degeneration (NVAMD).
Four increasing doses of Restoret were tested sequentially in cohorts of 3 patients each during the MAD portion, and the three highest doses were subsequently tested in a larger cohort of patients during the proof of concept portion of AMARONE. Patients with DME received intravitreal Restoret monotherapy every month for three months, while patients with NVAMD received Restoret in combination with aflibercept 2mg every month for three months. All patients were followed for 12 weeks from their first dose.
Quality control of the trial database and data cleaning were successfully performed by IDDI/EyeBio. Of note, one participant had their end of study visit erroneously substituted for their safety extension injection visit, which was corrected. Another participant’s final visual acuity measurement was felt to be erroneous by the Principal Investigator (PI) on 11/20/23 (35 letters vs. 53 letters at month 2). Because the patient had noted subjective improvement of their vision and the PI had observed clinical improvement on OCT and exam, the PI felt the recorded vision loss was not medically plausible. He brought the subject back for recheck 4 days later (after Eylea) on 11/24/23, at which time the patient’s visual acuity was restored to 59 letters. The PI corrected the final visit input to that measured on 11/24/23, which he felt was accurate and documented with a note to file.
About Restoret, a Wnt agonist tetravalent tri-specific agonist antibody
Restoret is an investigational tri-specific Wnt agonist antibody designed to address urgent unmet medical need in patients with back-of-the-eye diseases. Restoret aims to eliminate leakage in vascular diseases by activating the Wnt pathway to both restore and maintain the blood-retinal barrier. The result of a breakthrough in protein engineering and manufacturing, Restoret may enable the clinical translation of the extensively studied Wnt pathway for the first time in the eye. Published research has shown that Wnt signaling in the retina plays a central role in the maintenance of vascular integrity, and defects in Wnt signaling cause retinal vascular leakage. Restoret has demonstrated activity in preclinical ophthalmic models, including validation in genetic models.
About EyeBio (Eyebiotech Limited)
Eyebiotech Limited (EyeBio) is a clinical-stage, privately held ophthalmology biotechnology company dedicated to developing and delivering a new generation of therapies to protect, restore, and improve vision in patients with sight-threatening eye diseases. Founded in August 2021 by David Guyer, M.D., and Tony Adamis, M.D., EyeBio has a leadership team with a world class track record in ophthalmology drug development. With operations in the United States and the United Kingdom, EyeBio is building and advancing a pipeline of ocular therapies that combine scientifically robust targets with innovative translational approaches. EyeBio was seeded and created by SV Health Investors and raised a Series A in February 2022 led by SV Health Investors, alongside Samsara BioCapital and Jeito Capital, with additional financial backing from MRL Ventures Fund, the therapeutics-focused corporate venture fund of Merck & Co., Inc., Rahway, N.J., USA. EyeBio doubled the size of its original Series A raise in November 2023 with new investors Bain Capital Life Sciences, Omega Funds and Vertex Ventures HC. For more information, please see www.eyebiotech.com.