Oculis: Advancement for acute optic neuritis patients

Oculis Holding AG (Nasdaq: OCS / ICX: OCS.IC) (“Oculis”), a global biopharmaceutical company purposefully driven to save sight and improve eye care, today announced positive topline results with OCS-05 in the Phase 2 ACUITY trial, which met the primary endpoint of safety and achieved statistical significance on several key efficacy-based secondary endpoints. The trial evaluated the safety, tolerability and efficacy of OCS-05, a neuroprotective candidate, in patients with acute optic neuritis.

The Phase 2 ACUITY (Acute OptiC NeUrITis of DemYelinating Origin) trial was a randomized, double-blind, placebo-controlled, multi-center trial, designed to evaluate OCS-05 (2mg/kg/day or 3mg/kg/day) administered intravenously once-daily for five days in patients with acute optic neuritis also receiving steroid. The study randomized 36 patients with recent onset (visual loss symptoms) of unilateral acute optic neuritis with a demyelinating origin, of which 33 patients received treatment and were included in the pre-specified modified intent-to-treat (mITT) analysis.

Positive results from the ACUITY trial showed that OCS-05 achieved primary safety endpoint in addition to highlighting neuroprotective structural benefit and the ability to improve visual function in patients suffering from acute optic neuritis.

Primary Endpoint was Safety-Based
The percentage of patients with a shift from normal (baseline) to abnormal in electrocardiogram (ECG) parameters after study drug administration until Visit 4 (Day 15) was measured to evaluate cardiac safety. The results showed no difference in the percentage of patients with abnormal ECG parameters between the two treatment arms.

• Two patients in the OCS-05 arms (2 and 3 mg/kg/day) and one patient in the placebo arm had a shift from normal to abnormal in any ECG measures between baseline and Visit 4 (Day 15), both equivalent to 12.5%. Events observed in the OCS-05 arms were mild and transient and qualified as not clinically significant by central review reading center.

Secondary Efficacy Endpoints Assessed Changes in Retinal Structure
Optical Coherence Tomography (OCT) imaging was used to objectively measure the thickness of two different retinal segments in the affected eye to evaluate the potential neuroprotective effects of OCS-05 compared to placebo: 1) Ganglion Cell-Inner Plexiform Layer (GCIPL) and 2) Retinal Nerve Fiber Layer (RNFL). Results showed:

• A 43% improvement in GCIPL thickness mean change from baseline in favor of OCS-05 (3mg/kg/day) + steroid compared to placebo + steroid at month 3 which was maintained through month 6 with p-values* of 0.049 and 0.052 at 3 and 6 months, respectively.
• A 28% improvement in RNFL thickness mean change from baseline in favor of OCS-05 (3mg/kg/day) + steroid compared to placebo + steroid at month 3 reaching 30% improvement at month 6 with p-values* of 0.045 and 0.033 at 3 and 6 months, respectively.

Secondary Efficacy Endpoint Assessed Changes in Visual Function
Changes in 2.5% ETDRS low contrast letter acuity (LCVA) were measured to assess visual function improvement. Results showed:

• A favorable difference in LCVA mean change from baseline of approximately 18 letters at month 3 and approximately 15 letters at month 6 with OCS-05 (3 mg/kg/day) + steroid compared to placebo + steroid, with p-values^ of 0.004 and 0.012 at 3 and 6 months, respectively.

Treatment emergent adverse events (TEAEs)

• No drug-related serious adverse events (SAEs).
• No AEs leading to drug withdrawal or study discontinuation.
• Most frequently reported drug related AEs > 10% in the OCS-05 (2 or 3 mg/kg/day) + steroid treatment group were headache: 2 patients (10.5%), and acne: 2 patients (10.5%).

Riad Sherif, MD, Chief Executive Officer of Oculis, commented: “These positive safety and efficacy results from ACUITY represent a significant milestone in bringing the first potential neuroprotective treatment in ophthalmology to patients. The improvement in vision is especially encouraging, and the consistent improvement in retinal structure highlights the therapeutic potential of OCS-05 across multiple ophthalmic and neurological conditions. We are excited to further advance OCS-05’s development in acute optic neuritis, while actively exploring its potential in additional neuro-ophthalmic indications with the aim to deliver a first-in-class neuroprotective treatment option to patients.”

Mark Kupersmith, MD, Professor, Vice chair translational research, Chair NORDIC at Icahn School of Medicine at Mount Sinai Hospital, New York, added: “These groundbreaking results represent an important advancement for acute optic neuritis patients. Steroids have been used to treat the inflammation seen in acute optic neuritis, but don’t prevent persistent visual impairments or reduce structural loss. There remains a critical unmet need for neuroprotective therapies to preserve vision and the potential neuroprotective properties of OCS-05 observed in the ACUITY trial and its impact on visual function could offer significant hope for patients. These results, if replicated in larger clinical trials, could have profound implications, not only for this condition, but potentially for MS and other optic nerve disorders as well as glaucoma.”

Pablo Villoslada, M.D., Chair of the Department of Neurology at Hospital del Mar, Pompeu Fabra University in Barcelona, Spain, Oculis’ Scientific Advisory Board Member, said: “I am excited to see that the ACUITY results are consistent with the robust effects observed in animal models of neuroinflammation and neurodegeneration in the prevention of retinal ganglion cell damage and that OCS-05 has shown promising results in the improvement of vision. I look forward to the additional studies that can now be initiated for acute optic neuritis while further exploring the full potential of this promising neuroprotective candidate in both ophthalmology and neurology indications.”

OCS-05 has received orphan drug designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for acute optic neuritis, a rare condition characterized by acute inflammation and demyelination of the optic nerve, often affecting young adults, in which retinal thinning is directly associated with vision loss and permanent visual impairment. There are currently no approved therapies specifically indicated for acute optic neuritis and despite steroids being used to treat inflammation and improve recovery, steroids are unable to provide neuroprotection to prevent vision loss.

In addition, the Investigational New Drug (IND) application for OCS-05 has also been cleared by the U.S. Food and Drug Administration (FDA), enabling the initiation of clinical development in the United States to support the global potential of OCS-05.  The encouraging ACUITY trial results, Oculis’ positive development momentum and a solid balance sheet, including approximately $105 to 110 million in cash, cash equivalents and short-term investments, provide Oculis with a strong start in 2025 to focus on delivering additional development and business milestones.

About OCS-05
OCS-05 is a novel peptidomimetic small molecule candidate with the potential to become a first-in-class neuroprotective therapy for acute optic neuritis and other neuro-ophthalmic diseases. In animal models of neuroinflammation and neurodegeneration, OCS-05 has shown positive results in prevention of retinal ganglion cell damage and was associated with improvements in mobility (clinical function disability). OCS-05 is currently in Phase 2 development for the treatment of acute optic neuritis and has received orphan drug designation from both the FDA and the EMA. In addition to acute optic neuritis, a neuroprotective treatment could potentially have wide applicability in neuro-ophthalmic indications such as glaucoma, diabetic retinopathy and other vision-threatening diseases.

OCS-05 is an investigational drug and has not received regulatory approval for commercial use in any country.

About Acute Optic Neuritis
Acute optic neuritis is a rare condition characterized by an acute inflammation of the optic nerve that can lead to permanent visual impairment. It affects up to 8 in 100,000 people worldwide and often represents the first sign of multiple sclerosis. It mainly occurs in adults between the age of 20 and 40 years and is more frequent in women (2:1). The acute inflammatory process of acute optic neuritis leads to the loss of myelin covering the optic nerve and the axons. At the onset, patients often suffer from ocular pain that increases with eye movement and vision loss. Once the inflammation recedes, remyelination often occurs but it is incomplete. Without the myelin sheath protecting the axon, neurons located in demyelinated segments become fragile and prone to death. Unfortunately, damaged axons cannot regrow, leading to permanent visual impairment. To date there is no specific therapy approved for acute optic neuritis and unmet needs remain for therapies that can prevent vision loss after an acute episode of optic neuritis.