OCS-01 Eye Drops in Development for DME and Inflammation and Pain following Ocular Surgery

Lead candidate OCS-01 is currently in Phase 3 development as a potential topical treatment for diabetic macular edema (DME) and as a once daily treatment for inflammation and pain following ocular surgery with further benefit in potentially treating cystoid macular edema (CME), a significant complication following ocular surgery.

Using Oculis’ proprietary Optireach® technology, OCS-01 is developed to reach the retina via an eye drop, a route of administration for DME treatment that may enable earlier treatment intervention and thereby significantly increase the proportion of patients being treated as well as increase the prescribing physician base by providing a treatment option to general ophthalmologists. This approach contrasts with currently available therapies, which require the use of more invasive treatments such as ocular implants or intravitreal injections to deliver medication to the retina.

OCS-01 eye drops successfully completed Stage 1 of the DIAMOND phase 3 trial in DME with 148 patients randomized. Top line results show a significant increase in visual gains, a higher percentage of patients achieving ≥15-letter improvement in BCVA and a reduction of retinal edema, all with robust statistical significance, re-affirming the effect observed in the phase 2 trial. The start of Stage 2 of the DIAMOND Phase 3 clinical program is planned before the end of 2023.

In Inflammation and Pain following cataract surgery, the OPTIMIZE Phase 3 trial met both hierarchical primary efficacy endpoints, reduction of pain and inflammation, with robust statistical significance (p < 0.0001) with once daily OCS-01 eye drops.

OCS-02, A TOPICAL BIOLOGIC anti-TNFα TO TREAT OCULAR INFLAMMATION

OCS-02 is a next-generation biologic eye drop treatment in development for both DED and non-infectious anterior uveitis. It is expected that OCS-02’s anti-TNFα mechanism of action and topical route of administration can benefit patients suffering from dry eye, many of whom do not receive adequate relief with current options, as well as patients suffering from non-infectious anterior uveitis and for whom OCS-02 can be a powerful option with a significantly lighter toxicity profile than current options.

Differentiating OCS-02 is the topical delivery of an anti-TNFα construct at increased concentrations. The anti-inflammatory and anti-necrotic properties of therapeutics inhibiting TNFα activity are well established with anti-TNF pharmaceuticals already approved as systemic treatments for ocular disease. In addition, Oculis is advancing the development of OCS-02 in conjunction with the development of a potentially novel genetic biomarker intended to identify patients who may have a greater response to OCS-02 therapy.

Two Phase 2 clinical trials in patients with symptoms of DED were conducted (the first with the predecessor of OCS-02, and the second with OCS-02), as well one Phase 2 clinical trial in acute anterior uveitis. Topical ocular administration of OCS-02 was associated with improvements in the global ocular discomfort score versus vehicle in patients with DED, and with reaching a pre-specified responder rate in patients with non-infectious anterior uveitis, as well as being well tolerated in all three studies. Oculis is preparing to commence two Phase 2b trials for OCS-02 (one in DED in signs, and one in non-infectious anterior uveitis).

OCS-05, A POTENTIAL DISEASE MODIFYING CANDIDATE FOR NEURO-OPHTHA DISORDERS (OR DISEASES)

OCS-05, a novel serum/glucocorticoid-regulated protein kinase 2 (SGK2) activator peptidomimetic small molecule, is in development as a potential disease modifying neuroprotective agent against neurological damage to the optic nerve. Oculis is initially developing OCS-05 as a potential therapeutic to treat AON, a rare disease with high medical need as currently, there is no treatment which is approved by the FDA or the European Commission for AON. OCS-05 has been granted Orphan Drug Designation by both the FDA and the European Commission for this indication.

Pre-clinical studies suggest that OCS-05 is neuroprotective and has remyelinating activity. A UK Phase 1 clinical trial (with 48 healthy volunteers) showed that OCS-05 was well tolerated with good pharmacokinetics (PK) correlation with its pre-clinical animal studies. The results of these studies have enabled the advancement of OCS-05 into a First-in-Patient clinical proof-of-concept trial in France. The Acute OptiC NeUrITis of DemYelinating Origin (ACUITY) trial, a randomized, double-masked, placebo controlled, multiple center trial, is enrolling patients diagnosed with AON.

Should the clinical results of the AON trial prove sufficiently compelling, Oculis intents to evaluate the promise of OCS-05 to treat other neuro-ophthalmic disorders such as geographic atrophy, glaucoma, diabetic retinopathy, and neurotrophic keratitis.