Evaluating ER-100 for Safety in People With Glaucoma or Non-Arteritic Anterior Ischemic Optic Neuropathy (Optic Nerve Conditions)

This first-in-human (FIH), Phase 1 clinical trial is designed to evaluate the safety and tolerability of ER-100, an investigational epigenetic therapy candidate intended for age-related optic neuropathies, such as Open Angle Glaucoma (OAG) and Non Arteritic Anterior Ischemic Optic Neuropathy(NAION) Over time, factors such as age, disease, injury, and lifestyle can leave marks on cells that affect how genes function. These marks, known as epigenetic changes, may contribute to cellular decline. ER-100 is designed to address cellular aging through epigenetic reprogramming. It works by delivering genetic instructions for producing three proteins-collectively referred to as OSK-that may help reverse these changes and restore cells to a more youthful state. The therapy deployed in this trial uses a modified adeno-associated virus (AAV) vector to deliver OSK to retinal cells. The AAV has been engineered to remove its ability to cause infectious disease. Systemic doxycycline is administered for 8 weeks (56 days) to activate OSK expression. ER-100 does not alter the participant's existing genes. The study includes two sequential cohorts: a dose escalation phase in participants with OAG, followed by a dose expansion phase in participants with NAION. In OAG, optic nerve damage is caused by increased intraocular pressure; in NAION, it results from sudden loss of blood flow. Both conditions lead to retinal cell damage and vision loss. ER-100 is intended to reduce this damage by reprogramming affected cells, potentially preserving or restoring vision. At least two dose levels will be evaluated in the OAG cohort. The first ("sentinel") participant at each new dose level will receive ER-100 and be monitored for 28 days with review of data by an independent Data Safety Monitoring Board (DSMB) prior to granting administration of ER-100 to 2 additional participants at that dose level. Dose escalation/reduction will proceed for subsequent participants in accordance with safety data and oversight from the DSMB. Once the dose escalation in OAG is complete, a dose will be selected for NAION after a consultation between the DSMB and Sponsor. Initially only up to 3 NAION participants will be enrolled at the selected dose. After at least one NAION participant has completed 28 days of follow-up, the DSMB will review safety data. All participants' data available at that time will be provided to the DSMB for the review. Upon recommendation from the DSMB, NAION enrollment may then continue up to a total of 6 NAION participants. Up to 18 participants are planned for enrollment: 12 with OAG and 6 with NAION. A total of 15 clinic visits is planned for the study: 10 in the first 6 months, then one visit per year through Year 5. Additionally, there will be approximately 2 remote (telephone) visits. This study represents the first administration of ER-100 in humans, following preclinical evaluation in laboratory models. In this study, results are compared to baseline, which refers to assessments and study procedures at the first study visit and prior to ER-100 administration.