On this episode of Evidence Based Retina, Rishi Singh, MD, FASRS, sits down with Riad Sherif, MD, and Arshad Khanani, MD, MA, FASRS to discuss Oculis' portfolio, technology, and clinical programs with a special focus on the DIAMOND phase 3 trials of OCS-01 in diabetic macular edema (DME).
Dr. Sherif serves as CEO of Oculis and Dr. Khanani holds the position of Chair of the Scientific Advisory Board (SAB).
Introduction to Oculis Therapeutics and its portfolio
Oculis was established in 2016 as a hospital project in Iceland. The two co-founders are Einar Stefánsson, MD, a retina surgeon, and Thorsteinn Loftsson, PhD, a chemist and pharmacist. Dr. Sherif states that he joined the company as CEO after Novartis Venture Fund invested in it in 2017, intrigued by its technology, OPTIREACH.
The company's portfolio consists of three late-stage product candidates currently in phase 3 trials. Oculis has two areas of focus: ophthalmology, which includes retina and dry eye products, and neuro-ophthalmology.
Diabetic macular edema (DME)
OCS-01 is designed to be the first topical treatment for DME, utilizing OPTIREACH technology to deliver the drop directly to the back of the eye.1 OPTIREACH technology enhances drug solubility in eye drop formulations, increases the residence time on the eye surface, and facilitates drug passage to the posterior segment of the eye.2
It is currently undergoing two phase 3 clinical trials: DIAMOND 1 (NCT05066997) and DIAMOND 2 (NCT06172257),1 with results expected in the second quarter of 2026.
OCS-01 is designed for patients with DME who are not currently being treated due to the risk-benefit balance and treatment burden, as well as for those experiencing persistent lack of visual acuity and edema despite anti-VEGF injections.1
In the phase 3 stage 1 trial:3
- Patients treated with OCS-01 gained 7.2 letters in vision at 6 weeks, compared to 3.1 letters in the placebo group. This effect was maintained over 12 weeks
- 25% of treated patients gained 15 or more letters at 6 weeks, compared with 10% in the placebo group. This effect was maintained over 12 weeks as well
- There was a rapid improvement in central macular thickness, with a reduction of about 60 microns in the treated group at 2 weeks, while the placebo group increased by about 10 microns
Dr. Khanani comments that for many patients, topical administration is beneficial because OCS-01 has been shown to be effective and safe in past trials; furthermore, if needed, it can be stopped to reverse adverse events, unlike an intravitreal injection.
Dry eye disease
Oculis is developing Licaminlimab, a groundbreaking eye drop treatment targeting TNFα. This candidate employs a dual mechanism of action—anti-inflammatory and anti-apoptotic—to address persistent unmet medical needs through a precision medicine strategy.4
In addition, Oculis is using a genotype-based approach to dry eye treatment, leveraging a biomarker to identify patients likely to respond to Licamnilimab. The aim is to develop a "genotype-based" product in which a simple qPCR test (like a COVID test) can determine who will respond. The phase 3 trial, PREDICT1, is currently in progress.4
Neuro-ophthalmology
Privosegtor is a novel peptoid small molecule that can penetrate both the blood-brain barrier and the retinal barrier. It has the potential to be the first neuroprotective therapy for optic neuropathies and other neuro-ophthalmic diseases.5
Privosegtor is a disease-modifying, neuroprotective compound, as it helps prevent neuroaxonal degeneration and promotes neuronal and oligodendrocyte cell survival in multiple injury models, including apoptosis, oxidative stress, and inflammation.5
It has been tested in various in vivo models, including optic neuritis, glaucoma, and multiple sclerosis, and consistently prevents retinal ganglion cell death and axonal damage in the ganglion cell/inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL).5
The ACUITY (Acute OptiC NeUrITis of DemYelinating Origin) trial met the primary endpoint of safety and achieved several key efficacy-based secondary endpoints:6
- Strong efficacy, improving low-contrast visual acuity (LCVA) by 18 letters
- Preservation of the GCIPL and RNFL
- Reduction of neurofilaments in the cerebrospinal fluid and blood, which is a regulatory endpoint and a surrogate biomarker of reduced axonal damage
What’s coming up next for Oculis?
- Phase 3 trials (PIONEER 1) have started for optic neuritis
- A phase 3 trial is also starting in non-arteritic anterior ischemic optic neuropathy (NAAION), which has a huge unmet medical need
