Hi, all. Good afternoon, and thanks for joining us for the Oculis Fireside Chat. It's our pleasure to have Sylvia Cheung, CFO of Oculis, with us today. Oculis has a relatively diversified and unique ophthalmology pipeline. Sylvia, maybe you want to give us a quick overview and just lay out how these programs came about and how you've sort of developed such a diversified ophthalmology and unique ophthalmology pipeline. Thank you. Thank you, Annabel. Thank you to Stifel as well for giving us the opportunity to present today. As you said, our portfolio is really diversified and unique, and it was really built by design, aiming to address large unmet needs in ophthalmology and neuro-ophthalmology diseases with novel and differentiated assets. We have three core assets. Perhaps I can go to this slide here with the three core assets. OCS-01 is based on our OptiReach technology. Privosegtor, OCS-05, is a neuroprotective innovation. OCS-02, which is Licaminlimab, is also novel. It is a TNF blocker, anti-inflammatory, and anti-necrosis mode of action. Maybe a quick word on each of the three. OCS-01 is based on our proprietary OptiReach technology. It is an eye drop that will penetrate to the back of the eye, to the retina. OCS-01 is a treatment for DME, diabetic macular edema. Our aim is really to target the early intervention group as well as the non-responders of the currently treated population. Today, only 500,000 of the 1.8 million diagnosed patients are treated and with well-controlled results. Tomorrow, the 1.3 million who are not receiving treatment or adequately responding to VEGF will be addressed. We are very pleased with what OCS-01 can do to DME. Licaminlimab is OCS-02 on the right-hand side. It is the first precision medicine approach product for dry eye disease, biological eye drop with genotype-based development to treat dry eye. You may know that roughly about 10 million patients are moderate to severe patients in the dry eye disease area. About 20% of those patients have a gene that is called TNF-R1. For people with that particular genotype, they respond five times and seven times better in signs and symptoms, respectively. Our aim is really to develop a product not only good for everybody, but for those genotype-positive patients who will be able to offer a much more profound and significant outcome. Last but not least, an exciting asset, OCS-05, or Privosegtor. It's a novel peptide aminamide with neuroprotective properties. We recently announced very positive data at the beginning of the year showing biological, anatomical, and functional efficacy. We're initially focusing on AON, acute optic neuritis, which is an orphan-indicated disease. We recently, in our R&D day, also announced adding NAION and MS relapses to it. Privosegtor really helped us to unlock neuroprotection in neuro-ophthalmology and neurology. It is by design that we have a diverse, innovative, and differentiated portfolio for patients who are in need. Excellent. Maybe we can start with OCS-05 because that is the newest molecule data. It is an indication that is a little bit less well-known. Maybe you can talk first about how you sourced this product and what got you excited about this program. Originally, it started as an IV; it still is an IV program. As an ophthalmology company, how did you really get excited about this? What is it that you saw? Yeah, absolutely. Peripheral sector is a novel asset, as you said. In preclinical, as well as our phase two acuity trial, we saw neuroprotective benefits. The asset was brought into Oculis in 2022. It was built out as part of our development strategy to add this particular asset focusing on neuroprotection. It's being investigated for acute optic neuritis, which today has no neuroprotective treatment available. It's an orphan indication. Typically, the patient is a female in her 30s, young, active, and in childbearing period that who suffers from inflammation of the optic nerve, typically have severe ocular pain. Their retinal ganglion cell is in distress, and cells are in distress and dies. The current standard of care is IV, IV of steroid. In our acuity trial, we have an active arm, which is peripheral sector plus steroid. The placebo arm is basically vehicle plus steroid. The acuity phase two trial were designed with those two arms. The results really showed biological, anatomical, and functional benefits. This particular treatment, as in its current form, can also be used for other indications as well. Okay, great. I guess the data that emerged from the study recently, you said it hit both anatomical and biomarker anatomical functional. Is this unusual? When physicians saw this, what made them excited about the potential versatility of that that allows you to expand into so many different indications? Yep. When physicians and experts in neuro-ophthalmology and even in neurology saw the results from the ACUITY trial, phase two trial, they were all very excited. Several of those actually reached out to us to discuss more about the implications of Privosegtor. In the ACUITY trial, which is a phase two trial for acute optic neuritis, we basically here have the summary. I'd be happy to go through very quickly each of the efficacy endpoints to give a little bit more background. Basically, the study achieved primary safety endpoint. Because it's a new class and a new molecular entity, it's normal to have that as a primary endpoint. The outcome also showed visual improvement, anatomical efficacy, as well as biological. On the safety side, it's very clean. You can see the summary at the bottom of the slide here. First, let's talk about GCIPL. GCIPL is basically a measurement to measure the health of retinal ganglion cells. What we can see here is at month three, the patients treated with Privosegtor had 43% improvement, betterment of reduction in thickness of that layer, GCIPL layer, which is important because they are indicating that the retinal ganglion cells are preserved versus dying. We see that that outcome actually maintains through month six as well. The next one is looking at RNFL. RNFL is the measurement of the axon layer. In this particular measurement, we saw that approximately 30% betterment, meaning less reduction in thickness in RNFL layer, which is also good because it shows that the product Privosegtor can preserve the axonal health. Not only retinal ganglion cell, we also see that in the axon health. Now, on top of that, from a functional standpoint, we measured LCVA, which is low-contrast visual acuity. Here, we're even more encouraged because at month three, we saw an 18 letters betterment comparing to the placebo arm in terms of letters, which was maintained to month six as well. Biologically, functionally, we saw all going in the same direction that there is better health and preservation of retinal ganglion cells, axons, and better functional in terms of LCVA letters. On top of that, we looked at the subgroups within the study. We saw that no matter how we looked at it, whether or not our patients with MS or non-MS or HCVA lower than 60 or equal to or higher than 60, we consistently saw benefits across those groups as well as across the time points, month three and month six. Now, what's even more exciting is in the area of neurofilament, which you may know that neurofilaments are typically released to the cerebrospinal fluid. In our case, in the study, when we looked at neurofilament, we saw that there is less in the active arm versus the placebo arm, which is very good because it shows that there is less neuronal and axonal damage in the patient groups who are treated with Privosegtor. These are really the reasons why the community and Oculis as well are super excited about the outcome and the potential applications of Privosegtor. Okay, great. Now, the indications that you're pursuing right now are, I would say, more acute indications. Acute optic neuritis, I think NAION, which is please forgive me for not getting the entire spell. Maybe you can lay that out for us. It's neuro-optic, acute, ischemic. I can't even remember. Those are more acute indications, as is the MS-related indication as well. As a neuroprotectant, you know this is also potentially applicable to, say, glaucoma further down the line or other indications that have optic nerve damage. Is this something that you're also seeking? Are you sticking with these smaller acute conditions because they're so you can see an endpoint of patients sees that they are getting better, whereas other indications are more prophylactic and they don't necessarily feel themselves getting better, but maybe they won't develop acute, I'm sorry, optic nerve damage in the future. How do you sort of juxtapose both types of areas that you can move into? Yep. Yep. We definitely are going full steam ahead with acute optic neuritis, which is an orphan indication, as you mentioned. We are expanding into NAION and MS relapses. I'll explain kind of the patient prevalence and the size and address your question about longer term, what can we expect. Acute optic neuritis is a disease currently, it's estimated, let me perhaps, it's estimated that roughly about 65,000 or so patients in the U.S. and in Europe and roughly 50/50 split between the two geographies. The core symptoms are pain and loss of vision. Today, there are no approved products. Physicians basically use steroids to reduce and suppress inflammation. Sadly, the prognosis with those patients is they could potentially improve high visual contrast HCVA and V, but not low contrast vision. They would not go back to normal on LCVA, which is where Privosegtor can come into play and address this on the very nice LCVA data that we saw, as well as neuron and axon preservation efficacy. We are moving into a registrational study going ahead with that based on the phase two results. The two indications that we are adding, the first one is NAION, non-arteritic anterior ischemic optic neuropathy. Yeah, I was close. You were spot on. I have to slow myself down every time I name it. NAION. It also is an orphan indication. It is a condition causing a sudden vision loss, rare disease, and it has approximately 20,000-30,000 patients here in the U.S. and mainly affecting patients over 50 years of age. Again, no approved therapy today, and the unmet need is high. For relapse, MS relapses, which currently is treated by steroid IV, but recovery is incomplete. It typically leads to neurodegeneration and can cause permanent disability. The application of Privosegtor is broad. The three that I just mentioned here are a start. They do have similar pathophysiological characteristics, which allow us to be able to extend from AON into NAION and multiple sclerosis. Longer term, there are many other applicable indications or indications that we can work on. We will try to phase in as we get through these three, and we will announce which are the next ones. I think right now, what we have shared and discussed publicly are really just the tip of the iceberg in terms of what Privosegtor can bring to the ophthalmology and neurology communities. Okay. And just on the MS relapse indication, I guess it's interesting that you're technically an ophthalmology company, neuro-ophthalmology, and MS is more considered a CNS condition. Are you looking at an ophthalmic aspect to MS relapse? How should we sort of bridge the two between the CNS and the ophthalmology indication that you're typically going after? Yeah. Yes, the short answer is yes. From a mode of administration standpoint, the three are the same IV, the current where the state of the product is currently. In terms of you had asked about us being able to do it internally, I think with the very positive data, as well as the similarity between the three diseases, we have what we need to carry on the next step, immediate steps for those three indications. We also have planned interactions with the FDA coming up in the second half of this year to basically align on the clinical and regulatory pathways for these indications. We are confident, and we are moving ahead with these three indications. As to future additional indications, we'll be doing more work and make an announcement at the right time in the future. Okay. It was interesting that you were able to jump really quickly from AON into a registrational trial. Is it specifically because of the, I'm sorry, it was a proof of concept into a registrational trial. Are you still waiting to hear from FDA if that is a viable path? Do you expect the same pathway in the future for the others? Yep. For AON, we have a meeting scheduled the second half of this year to discuss the registrational steps. We're pretty confident in terms of what that trial design will look like. After alignment with the FDA, we'll look to start the activities on that particular registrational study. In the second half of this year and into next year, we'll also be performing IND enabling activities for MS relapses and NAION alongside FDA interactions. Based on those discussions, it will inform us of the next development activities. We will be updating the street about what those conversations and outcomes are and what the next step development milestones to expect. Hopefully, next year, we'll be filing INDs for those two newer indications. Okay. Maybe we can move on to OCS-01. Obviously, OCS-05 is a very interesting program and a pipeline and a program. OCS-01 is your most advanced development program that's completed enrollment, I guess, pretty quickly. Maybe you can go a little bit more into details about where it fits into the DME market that is generally pretty well served by anti-VEGF and steroid implants. I guess some are skeptical that a topical can actually reach the back of the eye. You've seen some pretty interesting data here. I guess from enrollment completion, the physicians also got excited about the potential here. Maybe you can talk about just how we should think about this market. Yep. Absolutely. The market is huge. It is very large. The state of the situation is only invasive therapies are approved today, meaning a needle into the eye, right, anti-VEGFs or second-line steroid implants. Extremely high burden of treatment and low compliance. What we ended up with is a market where 60%, close to 60%, is diagnosed. Of that diagnosed population, 44% are treated. As you know, patients are diagnosed with OCT. When patients are diagnosed, 56% of diagnosed patients do not currently receive treatments at all. Forty-four percent of them are diagnosed and treated. Of this group, 60% of the 44%, they are not getting adequate response, meaning that they are not responding well to anti-VEGF. This really leaves us with two voids in the market. One is the early segment where there is nothing available, and our product can be first in line and have no competition. On the back end, because OCS-01 is versatile, it covers the entire continuum of care, and it can be really viewed as a new option of treatment in the diagnosed and treated segment, meaning people who are responding well to anti-VEGF, we should keep them on anti-VEGF because it works well. What we do know is they're not coming in as often as they should. They should be coming in 10, 11 times a year, but they're only coming in three, four times a year. Physicians have told us that they would prefer and would welcome having a topical treatment to be sent together with the patient home during those long parsed-out visits to help patients to maintain that efficacy, right? It can be used in combination, or it can be used as standalone. It is versatile. The result is we will be able to address 1.3 million of the 1.8 million that is currently diagnosed. This is how we will be positioning OCS-01 as first line in the early segment where there is no treatment and as a versatile treatment option, whether it be standalone or in combination in the diagnosed and treated section. Okay. You did not bake in any kind of interim look at any of the data? I know that you have an induction period and a maintenance period. Is there any? The full trial is going to be a year long. You did not bake in any interim look or any look after the initial induction period? We did not bake in, as you said, any interim look into stage two. Stage two, as you know, is 52 weeks. It is exactly the same design as stage one. One can actually view stage one as an interim look because the design is exactly the same. Stage one, phase three, we had 12 weeks of data, which was very positive. Happy to go over the results if you like. Stage two, which is currently ongoing, is 52 weeks with over 800 patients. The design is exactly the same as stage one with the exception of two things. One is duration, 52 weeks. The other is number of patients. Instead of 148 patients, we have over 800 patients. We expect readout in Q2 of next year. We were extremely pleased with the pace at which the stage two of phase three came about. It really surpassed industry benchmark in terms of enrollment pace. I think this really speaks to, and it's a good indicator of how patients and physicians really accept the product, so acceptance and their enthusiasm on OCS-01, which I think largely speaks to the need for non-invasive, as well as, and perhaps more importantly, the data that we saw in terms of efficacy and safety. Yeah. I guess that also speaks to the concerns that people might have that six drops a day for induction period might be too onerous, but it looks like they were very willing to accept that. They are. That is a very good point. The induction phase is six weeks as six drops per day, and the maintenance is three drops per day. The good outcome of the phase three, stage one really speaks for itself. In prior studies, we also saw over 90% compliance based on, I mean, the last study was the same induction phase and maintenance phase. We saw over a 90% compliance rate. From our standpoint, it's really not a concern. Yeah. And just one last, in the last minute, I want to touch on the dry eye program. This is going to be the first precision medicine treatment. The FDA was okay with you moving forward with that because the results were so strong. What is your phase three design going to look at? You will have four programs or four studies, two for signs and two for symptoms. And it would be only in the treatment or TNF-R1 positive patients? Yep. Yeah. So yeah. So I mean, currently, the dry eye treatments, the issue is really, and this is per discussion with physicians, it's really trial and error. Patients are not happy. Only 13% of dry eye disease patients report lasting reliefs after 12 months. It is a hugely unsatisfied patient and physicians population. What we saw in our previous studies was that TNF-R1 positive patients showed five times and seven times better efficacies on signs and symptoms, respectively. We met with the FDA in Q1, and we aligned on the trial design, which you can see here on this slide. The aim is really to study these particular patients with TNF-R1 genotype positive patients and look at, in this case, symptoms. The last study was on sign, and this study is on symptom. We're looking at 160 or so patients in this study. The TNF-R1 genotype patients will be roughly about two-thirds of this study. The measurement primary endpoint is the global ocular discomfort score at day 29. The secondary endpoint is for all patients. Primary endpoint for TNF-R1 positive patients, and the secondary endpoint will be for all population. Okay. Great. We're just going to wrap it up. Just one quick comment on your next catalyst? We have multiple catalysts coming up. We have regulatory interactions with the FDA on Privosegtor, the OCS-05 programs across all three indications: acute optic neuritis, multiple sclerosis relapses, and NAION. Following that, we would be starting our phase two, I'm sorry, phase two, three study. In Q2 of next year, we'll have top-line results from our DME trial. In the second half of next year, we would have our dry eye results. Sorry, I'm trying to show the slide on the timelines. Q2 2026, top-line results from our phase three DME trial. Second half of this year, we would have interactions with the FDA on Privosegtor. The dry eye study will start second half of this year with readout in the second half of next year. Okay. Great. We're out of time, unfortunately. So thank you so much. Thank you. I appreciate it. It was great hearing the overview. Thank you very much, Annabel. All right. Take care. All right. Bye. Bye.