Oculis to launch PIONEER trials for privosegtor in acute optic neuritis and NAION

Oculis is advancing privosegtor into a registrational program for neuro-ophthalmology indications after a meeting with the US Food and Drug Administration (FDA).

Privosegtor (also known as OCS-05) is a “first-in-class peptoid small molecule” for neuroprotective therapy for acute optic neuritis (AON), non-arteritic anterior ischemic optic neuropathy (NAION), and other neuro-ophthalmic diseases.¹

After the meeting with the FDA, Oculis plans to commence its PIONEER (Privosegtor Investigation in Optic Neuropathies Efficacy Evaluation Research) program by the end of the year. The program will consist of 3 pivotal trials to support registration plans for privosegtor in AON and NAION. The first 2 of the 3 trials in PIONEER will evaluate privosegtor following the acute onset of optic neuritis in a broad population of patients with multiple sclerosis (MS) and those without MS. PIONEER-1 is planned to take place in Q4 of 2025, while PIONEER-2 is planned to happen in the first half of 2026.¹

The primary endpoint will be measured as low-contrast visual acuity (LCVA) at 3 months. According to the company, dosing and patient enrollment criteria will mirror its previously completed phase 2 ACUITY trial. ACUITY was a randomized, double-blind, placebo-controlled, multi-center trial evaluating privosegtor administered intravenously once daily (2 mg/kg/day or 3 mg/kg/day) for 5 days in patients with AON also receiving steroids. The trial randomized 36 eligible patients aged between 18 and 60 with a recent onset of unilateral acute optic neuritis with a demyelinating origin.²

ACUITY achieved its primary safety endpoint in addition to highlighting neuroprotective structural benefit and the ability to improve visual function in patients suffering from AON.²

The company noted that the FDA provided guidance that privosegtor can be evaluated in other neuro-ophthalmology indications, such as NAION, under the current IND. Therefore, PIONEER-3 will evaluate privosegtor after the acute onset of NAION and is planned to take place in mid-2026. The company noted that PIONEER-3 will share the core design and operational elements with PIONEER-1 and PIONEER-2.

Mark Kupersmith, MD, chief medical advisor, neuro-ophthalmology, and Leonard A Levin, MD, PhD, professor, departments of ophthalmology and visual sciences and neurology and neurosurgery at McGill University, commented on the PIONEER program in a press release from the company.

“I am very pleased that [Oculis] is accelerating its development plan with privosegtor in optic neuropathies, including acute optic neuritis and NAION, given the critical unmet medical needs remaining. Neuroprotection represents a promising therapeutic approach across multiple neuro-ophthalmic conditions, and although the cause of optic nerve injury can be different, patients experience permanent loss of optic nerve axons and retinal ganglion cells, causing permanent visual deficits,” said Kupersmith.

While Levin added, ““The positive ACUITY topline results represent a remarkable step forward in neuroprotection trials. I have been involved in this area for more than three decades, and this candidate is the first to show significant improvement in clinical, biological, and imaging measures of the disease in a single trial.”

Privosegtor has received Orphan Drug designation from both the FDA and the EMA.

References:

1. Oculis accelerates Privosegtor into registrational trials in acute optic neuritis, pioneering the path for a potential first-in-class neuroprotective therapy. Published October 6, 2025. Accessed October 6, 2025. https://investors.oculis.com/news-releases/news-release-details/oculis-accelerates-privosegtor-registrational-trials-acute-optic

2. Harp MD. Oculis releases positive topline results from phase 2 ACUITY trial evaluating OCS-05 in acute optic neuritis. Published January 6, 2025. Accessed October 6, 2025. https://www.ophthalmologytimes.com/view/oculis-releases-positive-topline-results-from-phase-2-acuity-trial-evaluating-ocs-05-in-acute-optic-neuritis