In this episode of Evidence-Based Retina, Rishi P. Singh, MD, sits down with Riad Sherif, MD, who discusses Oculis' ophthalmic pipeline and the PIONEER program evaluating privosegtor (OCS-05) as a potential neuroprotective treatment in acute optic neuritis.
Dr. Sherif is the CEO of Oculis.
Oculis clinical trials fast facts:
- DIAMOND trials: OCS-01, an investigational topical corticosteroid eye drop, reduced central subfield thickness (CST), but the anatomical change did not translate into an improvement in best-corrected visual acuity (BCVA). Oculis has received the complete trial dataset and is continuing its analysis.1
- PIONEER program: Privosegtor (OCS-05) is a peptoid molecule being developed by Oculis as a neuroprotective drug intended to preserve neurons and axons.2
- PIONEER-1: The trial uses privosegtor 3 mg/kg/day for 5 days and follows the dose, measurements, and 3-month endpoint timing used in ACUITY.3
- Why optic neuritis: Dr. Sherif describes optic neuritis as both an unmet medical need and a useful platform for assessing neuroprotection.
- Measuring neuroprotection: The program evaluates visual function, OCT measures of retinal structure, and neurofilament as a measure of axonal damage.
OCS-01 and the DIAMOND trials
Oculis' phase 3 DIAMOND-1 and DIAMOND-2 trials evaluated topical OCS-01 for diabetic macular edema (DME). Dr. Sherif says OCS-01 reduced central subfield thickness (CST), a measure of retinal swelling, but did not improve BCVA.1
He also points out that the response seen in the earlier stage of development was repeated in DIAMOND-1 and DIAMOND-2, but not through week 52. Oculis had received the complete dataset and was continuing its analysis.
Dr. Sherif explained that the company had reviewed the study's execution and found it sound. Dr. Singh notes that visual acuity is not a perfect measure of functionality and considers the anatomical response encouraging.
Dr. Sherif also briefly discusses licaminlimab (OCS-02), a TNF inhibitor being studied for dry eye. The PREDICT-1 trial uses a genotype-based approach to identify patients with a TNFR1 biomarker before randomization.4
PIONEER program: Privosegtor and neuroprotection
Privosegtor (OCS-05) is Oculis' neuroprotective drug in registrational development. Dr. Sherif describes it as a small peptoid molecule that behaves like a biologic in its binding to receptors and targets and can cross the brain and retinal barriers. It is designed to protect neurons and axons from damage and death.2
Preclinical studies have tested privosegtor in models of apoptosis, inflammation, and oxidation, as well as glaucoma, optic neuritis, and multiple sclerosis. Dr. Sherif says these studies showed preservation of neurons and axons, including retinal ganglion cells and myelin.2,5
“We preserve the retinal ganglion cells, we preserve the axons, we preserve the myelin from being damaged.”
Dr. Singh considers the anatomical findings particularly significant, describing that type of effect as “unprecedented in our field.”
Why optic neuritis is an important proof of concept
Dr. Sherif sees optic neuritis as an important proof of concept for neuroprotection for two reasons.
First, an unmet treatment need exists. Corticosteroids are the standard of care and are effective at reducing inflammation, but there is no treatment specifically aimed at preserving retinal ganglion cells.6 Privosegtor is intended to address that gap by protecting neurons and their axons from damage.
“This product is really meant to be neuroprotective and to preserve axons and neurons from dying.”
The second reason is that optic neuritis allows investigators to assess neuroprotection in several complementary ways:
- Visual function: Visual function can be measured with low-contrast visual acuity (LCVA) and best-corrected visual acuity (BCVA).
- Retinal structure: Optical coherence tomography (OCT) provides structural information about the retina. Dr. Sherif points to the RNFL as providing information about the axons and the GCIPL as providing information about retinal ganglion cells.
- Axonal injury: Neurofilaments serve as biomarkers of axonal injury. When an axon is damaged, neurofilaments are released into the cerebrospinal fluid and blood, where they can be measured.7
Dr. Sherif points to multiple sclerosis, amyotrophic lateral sclerosis, and other neurological diseases as examples in which neurofilaments are associated with damage and prognosis.
“Optic neuritis is a great platform to test and assess neuroprotective drugs.”
From ACUITY to PIONEER
PIONEER is a clinical development program that includes multiple trials, with PIONEER-1 and PIONEER-2 focused on optic neuritis. The program builds on ACUITY, the earlier phase 2 trial of privosegtor in acute optic neuritis. ACUITY primarily assessed safety and tolerability, with secondary measures examining retinal structure and visual function.3
PIONEER-1
Dr. Sherif describes PIONEER-1 as very similar to ACUITY. It uses the same 3 mg/kg/day dose for 5 days and follows the same approach to assessing function, structure, and neurofilament, with efficacy endpoints measured at 3 months.3
PIONEER-1 compares privosegtor plus corticosteroids with corticosteroids alone. Treatment begins the same day or within 24 hours, with both privosegtor and corticosteroids administered intravenously for 5 days.
To learn more about Oculis' ophthalmic pipeline and stay on top of updates, check out the Ophthalmic Clinical Trials Tracker!
Trial design
At month 3, visual assessments include the proportion of patients who gain 15 letters on LCVA, those who gain 30 letters, and the mean change in LCVA.
Ganglion cell-inner plexiform layer (GCIPL) is measured with OCT to assess whether retinal ganglion cell structure is being preserved, while neurofilament is measured to determine whether axonal damage is reduced.3
Patients then continue for another 9 months of safety follow-up through month 12. Dr. Sherif describes this as the typical FDA safety follow-up for a new molecular entity.
At the time of the interview, the study was in the site activation phase. Oculis had also been aligning with the FDA and had received a Special Protocol Assessment (SPA) during the first half of the year. The study planned approximately 75 centers across the United States, Europe, Australia, and Canada.
Dr. Singh describes the study as “avant-garde” and emphasizes the unmet need in optic neuritis.
Key takeaways:
- In the DIAMOND trials, OCS-01 produced an anatomical response (CST reduction) that did not translate into a corresponding gain in visual acuity, which Oculis continues to evaluate as part of its full dataset analysis.
- Privosegtor (OCS-05), a peptoid molecule capable of crossing the brain and retinal barriers, demonstrated preservation of retinal ganglion cells, axons, and myelin in preclinical models.
- The PIONEER program assesses neuroprotection through three measures: visual function (LCVA, BCVA), retinal structure via OCT (RNFL and GCIPL), and axonal injury via neurofilament levels.
- PIONEER-1 uses the same Privosegtor dose (3 mg/kg/day for 5 days) and measurement approach as the earlier ACUITY trial, with efficacy assessed at month 3 and safety follow-up continuing through month 12.
- As of the interview, PIONEER-1 had received an FDA SPA and was in site activation across roughly 75 planned sites in the US, Europe, Australia, and Canada.
This article was written by Sonia Kelley, OD, MS, based on the recorded video from Drs. Singh and Sherif.
