Following on from stage 1 phase 3 pivotal clinical data presented at both EURETINA (Paris) and the Retina Society Annual Congress (Chicago), we sat down with Riad Sherif, CEO of Oculis, to discuss how the company’s lead assets — OCS-01 and Privosegtor (OCS-05) — could potentially redefine how ophthalmologists treat diabetic macular edema (DME) and acute optic neuritis.
Can you talk about Oculis’ high-concentration dexamethasone eye drop, OCS-01?
Oculis currently has three clinical stage assets, and OCS-01 is the lead asset in phase III, in a program called DIAMOND with 2 trials, DIAMOND One and DIAMOND Two. The first indication for OCS-01 is diabetic macular edema (DME). OCS-01 is the first candidate coming from a proprietary technology which was developed by Oculis called OPTIREACH®. This technology allows us to deliver products topically as an eye drop, and so OCS-01 is able to cross multiple barriers in the eye and reach the retina. This really is the Holy Grail – it’s the first time ever where we have a product which is able to treat the retina (specifically DME in our case) and be delivered as an eye drop.
The product was tested in four clinical trials – two exploratory trials and two double-masked controlled trials – and consistently showed benefit, in terms of improving the number of letters in BCVA (Best-Corrected Visual Acuity), as well as showing a reduction in retinal thickness.
What benefits does OCS-01 offer when compared with current injection-based DME therapies?
In terms of biology, anti-VEGF and steroids are both good treatments. But the challenge is the invasiveness of these treatments, and the burden on DME patients who generally have other complications as well. If we take the US as an example, and look at the IRIS Registry, we see that more than 60% of DME patients diagnosed are not treated in the first twelve months of their diagnosis.
What this tells us is that there is a huge population left untreated, and we know that when we don't treat them, the future prognosis for this type of patient is not good. Therefore, it’s really important to treat them early. And if we have a product which is efficacious, safe, and easy to access, where we can basically treat the DME patient on the same day of their diagnosis, this situation will change dramatically, and we will be able to enhance and improve these patients’ prognosis.
In DME patients who are treated with anti-VEGF, we know that 60% will respond appropriately and 40% will not respond adequately. And so this 40%, which is almost half of the current market, might need something else.
The pathophysiology of DME is really driven by two drivers: neovascularization and inflammation. Anti-VEGF are extremely good in neovascularization, but they are not anti-inflammatory products, and this is probably why almost half of these patients need something else. Here, OCS-01 can be combined or used alone to offer a versatile solution to retina specialists, who will be able to customize their treatment to treat patients who are not adequately responding to anti-VEGF.
How do you think OCS-01 might fit into current treatment algorithms and health system workflows?
What we envision — based on more than 100 formal interviews with experts, payers, and patients across three independent studies — is quite clear. The conclusion, and I’m really just repeating what retina specialists told us, is this: if OCS-01 becomes available, they would start with it and it would serve as a first-line treatment.
The reasoning is straightforward. If OCS-01 works, patients can remain on it. If it doesn’t, patients are more motivated and open to moving on to intravitreal injections. At present, because there’s nothing in between observation and injections, both physicians and patients often postpone injections. OCS-01 would fill that gap. If it works, great; if not, then patients can transition more readily to injections.
In addition, OCS-01 could be used for the roughly 40% of patients who are currently not responding adequately to treatment. So it isn’t just an alternative — it could also be used as a complementary tool. It allows retina specialists to treat earlier, more effectively, and with greater flexibility.
Beyond the US, the implications are even broader. In many countries, access to retina specialists is severely limited, and large numbers of DME patients go untreated. A product like OCS-01, with its topical administration, could provide a solution for those countries as well.
Could Oculis' OPTIREACH technology be applied to other retinal or neuro-ophthalmic diseases?
Yes, this technology was developed by Oculis, and we might leverage it in our next compound – OCS-05 (or Privosegtor) – in neuro-ophthalmology. OCS-05 is a peptoid product that was tested in three animal models: glaucoma, acute optic neuritis, and multiple sclerosis (MS). What we measured consistently in these models is ganglion cell survival, or preservation. Consistently, regardless of the injury, we have been able to show in these animal models that we were able to preserve or protect retinal ganglion cells from dying.
For OCS-05, we started with an indication called acute optic neuritis (AON). AON involves inflammation of the optic nerve, which can lead to visual impairment through axonal loss and retinal ganglion cell degeneration. Privosegtor (OCS-05), a peptoid small molecule, has shown neuroprotective activity in several experimental animal models and is being studied as a treatment for individuals with AON. AON serves as a predictive model for evaluating neuroprotective therapies – it is often the earliest manifestation of neurological disorders such as multiple sclerosis (MS) and neuromyelitis optica (NMO). A phase 1, randomized, double-masked, placebo-controlled, single- and multiple-ascending-dose study demonstrated safety and tolerability with privosegtor in healthy participants (N=48; privosegtor, n=36; placebo, n=12). The phase 2 ACUITY trial investigated the safety and efficacy of privosegtor plus steroid versus placebo plus steroid in individuals with AON.
In ACUITY we measured three key efficacy endpoints: function (using LCVA - Low Contrast Visual Acuity); retinal structure (via OCT), and a surrogate biomarker called neurofilaments (NFL). The good news is that LCVA, in the active arm, showed an 18-letter improvement compared to the placebo plus steroids. This is especially encouraging because LCVA is a regulatory endpoint for the FDA.
The second measurements we took involved two layers of the retina: GCIPL and RNFL. GCIPL indicates the status of ganglion cells in the retina, and RNFL indicates the health of the axons in the retina. In both of these layers, we were able to demonstrate that privosegtor was able to preserve retinal ganglion cells from dying.
The third measurement we used was neurofilaments. Neurofilaments are structural proteins which act like a skeleton of the axons to help maintain axonal integrity. When axons are damaged, these neurofilaments are released into the cerebrospinal fluid and blood. That means their levels directly correlate with axonal damage. In our study, we measured the increase in neurofilament levels. When levels rise, it’s a clear indication that axonal damage is occurring. What we showed is that patients treated with our therapy had about half the axonal damage compared to the placebo, as reflected in neurofilament levels. This finding aligns perfectly with our other results. On OCT, we saw anatomical protection of the retina.
Taken together, all three measures — retinal anatomy, biomarker evidence, and functional vision— point in the same direction. That consistency is what gives us real confidence in the results. For decades, “neuroprotection” has been a buzzword in ophthalmology and neurology. People have talked about it for nearly 30 years, but until now we’ve never had clinical evidence showing true neuroprotection. This is the first time we have ever been able to demonstrate it in this way. It’s exciting not just for patients, but also for the entire scientific and medical community. Lastly, and very important as well, Privosegtor showed a very good safety profile in the study.
What are the next steps for these treatments?
For Privosegtor, we will be meeting with the FDA in Q3 of this year, and our aim is to discuss a registration plan and initiate the pivotal trial as fast as possible. We'll see the feedback from the FDA and we will take it from there, but we are very excited about this program.
