Phase 2 ACUITY Analysis Shows Privosegtor Associated With Smaller Early NfL and GFAP Increases in Acute Optic Neuritis

New translational biomarker data from the phase 2 ACUITY trial (NCT04762017) showed that Oculis’ investigational agent privosegtor was associated with smaller post-onset increases in plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) compared with placebo in patients with acute optic neuritis (ON). Presented as a late-breaker at 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto 2026), held October 21-23, 2026, in Toronto, Ontario, Canada, the company noted that differences were most pronounced at early time points close to ON onset.¹

“These findings are particularly noteworthy because they provide biological evidence that complements the functional and retinal structural improvements previously observed in ACUITY, “ presenting author Céline Louapre, MD, PhD, professor of neurology at Pitié-Salpêtrière Hospital, Sorbonne University, in Paris, France, said in a statement.² “The consistent effects across NfL and GFAP suggest that Privosegtor may be influencing multiple pathways involved in tissue injury following acute optic neuritis, supporting its potential as a neuroprotective therapeutic approach. Together, these data deepen our understanding of the treatment's effects and further support continued clinical evaluation.”

NfL and GFAP Trajectories

Of 33 patients randomly assigned in ACUITY, the analysis focused on those receiving privosegtor 3 mg/kg/day (n = 15) or placebo (n = 14) for 5 days as an add-on to high-dose methylprednisolone; the 2 mg/kg/day group (n = 4) was not analyzed because of its small size. Plasma samples collected at baseline, day 5, and months 1, 3, and 6 were measured centrally using Single Molecule Array technology and analyzed with a mixed model for repeated measures.

At day 5, the least squares mean (LSM) change from baseline in plasma NfL was 5 pg/mL (SE, 2) with placebo vs 0 pg/mL (SE, 2) with privosegtor. NfL remained stable in the privosegtor group through month 6 (LSM, −1 pg/mL [SE, 1]), whereas levels in the placebo group remained elevated at month 1 (LSM, 5 pg/mL [SE, 2]) before returning to baseline by month 6 (LSM, 0 pg/mL [SE, 1]).

At day 5, the LSM change in plasma GFAP was 53 pg/mL (SE, 28) with placebo vs 4 pg/mL (SE, 28) with privosegtor. GFAP then declined below baseline in the privosegtor group (LSM: month 1, −17 pg/mL [SE, 16]; month 3, −11 pg/mL [SE, 17]; month 6, −1 pg/mL [SE, 25]) but remained elevated above baseline in the placebo group through month 6 (LSM, 43 pg/mL [SE, 26]).¹According to the company, lower GFAP levels are consistent with reduced reactive astrogliosis.²

“For patients with optic neuritis, irreversible neuro-axonal damage can occur within days of disease onset, yet there are currently no approved therapies designed to protect retinal ganglion cells and their axons, the neurons responsible for transmitting visual signals from the eye to the brain, and preserve long-term visual function,” Riad Sherif, MD, chief executive officer at Oculis, said in a statement.² “These biomarker findings and translational analyses provide important additional evidence supporting Privosegtor’s neuroprotective potential, strengthening our confidence as we advance the PIONEER registrational program and explore its broader applicability across acute neuro-axonal conditions, including acute multiple sclerosis relapses.”

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Prior ACUITY Findings

ACUITY enrolled adults with unilateral demyelinating acute ON of less than 12 days’ duration, excluding patients positive for aquaporin-4 antibodies.^1,3 As previously reported, privosegtor 3 mg/kg/day improved 2.5% low-contrast visual acuity by 18.2 letters vs placebo at month 3 (90% CI, 8.4-27.9; P = .004) and by 14.8 letters at month 6 (90% CI, 5.4-24.1; P = .012).³ Treatment was also associated with preservation of the ganglion cell/inner plexiform layer and retinal nerve fiber layer on optical coherence tomography.²

Clinical Context and Next Steps

No therapy is currently approved specifically to protect retinal ganglion cells and axons after an acute ON episode; high-dose corticosteroids shorten episodes but do not influence long-term disability. Privosegtor, a peptoid small molecule that crosses the blood-brain and retinal barriers, has received FDA breakthrough therapy designation and EMA PRIME designation for ON.²

NfL and GFAP were prespecified exploratory end points, the analysis included only 29 patients, and no P values were reported; SEs were large, particularly for GFAP. NfL analyses were not adjusted for age or renal function. The relationship between these biomarkers, central nervous system inflammation, and optical coherence tomography measures remains under investigation.¹

Privosegtor is being evaluated in the registrational PIONEER program, including PIONEER-1 (NCT07623668), which is recruiting patients with ON with and without multiple sclerosis (MS) and uses a gain of at least 15 letters in low-contrast visual acuity at month 3 as its primary end point.⁴ Oculis noted that it also plans an investigational new drug submission for acute MS relapses.²

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REFERENCES
1. Louapre C, Bar-Or A, Kupersmith M, et al. Effect of Privosegtor on Plasma Neurofilament-Light and Glial Fibrillary Acidic Protein Levels in the Phase 2 ACUITY Trial in Optic Neuritis. Presented at: MSToronto2026; October 21-23; Toronto, Canada. Abstract 281.
2. Oculis reports new phase 2 ACUITY biomarker data further supporting privosegtor's neuroprotective potential in optic neuritis. News release. Oculis. October 22, 2026. Accessed October 22, 2026. https://investors.oculis.com/news-releases/news-release-details/oculis-reports-new-phase-2-acuity-biomarker-data-further
3. Villoslada P, Louapre C, Bonnin S, et al. Improved low contrast visual acuity, reduction in retinal ganglion cell loss, and neurofilaments-light with privosegtor in acute optic neuritis: results from a multicenter, randomized, placebo-controlled, double-masked trial. Presented at: 2026 AAN Annual Meeting; April 2026; Chicago, IL. Abstract 003177.
4. A randomized, double-masked, placebo-controlled study assessing the efficacy and safety of privosegtor (OCS-05) in patients with optic neuritis (ON) (PIONEER-1). ClinicalTrials.gov identifier: NCT07623668. Updated August 13, 2026. Accessed October 22, 2026. https://clinicaltrials.gov/study/NCT07623668