Welcome, welcome everyone to the 44th Annual J.P. Morgan Healthcare Conference. My name is Tessa Romero, and I'm one of the senior biotech analysts here at J.P. Morgan. Our next presenting company is Oculis, and presenting on behalf of the company, we have CEO Riad Sherif. Riad, over to you. Thank you. Thank you, Thank you, Tessa. Very happy to be here and very pleased to introduce Oculis to you. Thank you, Tessa and JPM, for a great meeting and conference. We are a public company, Nasdaq-listed. Here our safe harbor statement. Oculis is a global biopharma Nasdaq-listed company with late advanced registration candidates, three candidates in phase III, two franchises of ophthalmology and neuro-ophthalmology. I'm starting in a chronological order in terms of upcoming readout. Ocular franchise with two candidates: OCS-01, which is the first non-invasive eye drop, self-administered eye drop for retina for DME with readout planned in Q2 this year. Licaminlimab, first product in precision medicine, genotype developed in an indication which is difficult, which is dry eye disease. I will go into the details after, with readout in Q4 2026. The second franchise, which is neuro-ophthalmology with OCS-05. As you know, neuroprotection has been a buzzword for 40- 50 years. People speak about it, but we never, never, never cracked it and never found something which works. Privosegtor is the first product ever which works in neuroprotection. I will show you the data which consistently preserve neurons from dying, and we showed it in all endpoints, functionally, in the anatomy, and biologically. Starting with two indications, optic neuritis and NAION. Optic neuritis and NAION is really only the tip of the iceberg of what Privosegtor could bring to not only Oculis, but to the pharma industry. Financially, we have a strong balance sheet, no debt, cash into 2029 without using or excluding a facility loan we have with our partner, BlackRock, for CHF 100 million or $125 million. In terms of pipeline, we have a catalyst reached 12 months, or I would say 24 months, of consistently bringing new milestones with the late-stage asset in phase III. The first one will be ophthalmology with OCS-01, with DIAMOND 1 and 2 readout in Q2 this year and planned to be submitted this year as well in Q4. The second is Licaminlimab, which is first precision medicine in ophthalmology in dry eye with readout for the first phase III in Q4. And then on OCS-05, which is the neuro-ophthal franchise, we started already PIONEER 1, which is the first phase III in optic neuritis. We are activating centers currently. We are starting in the U.S. and we'll go to Europe after. Pioneer 2 is starting this year as well. And Pioneer 3 in a second indication, NAION, starting in the mid of 2026. We are also, as I said, optic neuritis is just neuropathies, is just the tip of the iceberg. Our aim is to go beyond, and we are starting with MS, and we are starting with the treatment of relapse of MS. Optic neuritis is a relapse of MS. We show that this product brings material benefit to patients in relapse of MS when the relapse of MS takes place in the optic nerve. Our aim is to go broader, to go to all relapse of all types of relapse of MS. We are planning to meet with FDA this year, and we will be informing the market once this meeting takes place. Let me now start with OCS-01. So OCS-01 in ophthalmology, so DME is a huge market. 1.8 million patients diagnosed, not sick, sick and diagnosed in the U.S. Only half are treated. And with invasive therapies, which are actually good. Personally, I launched the first one of them. They're good, but they come with a high burden of treatment, low patient compliance, and in a situation of DME, not all patients respond appropriately to standard of care. If we go to what OCS-01 can bring here, and you see the patient groups, the pools are divided into we have 900,000 patients in the U.S. who are diagnosed and not treated, and now 900 who are diagnosed and treated. The first segment where we do not have a solution, we do not have any non-invasive treatment which we can start with, which is early intervention. This is the first segment we would like to address with OCS-01. If in the future we have a product which is efficacious, safe, and self-administered as an eye drop, this is the first segment we will go with. Here we do not have any competition. The second segment where we have a high unmet medical need, who are almost the half of patients who are treated today are not adequately responding in DME because there are two components, as you know, in diabetic macular edema, neovascularization on one hand, and inflammation on the other hand. OCS-01 could address these two segments without actually challenging the status quo and without having a competition in front of us. One is early intervention. As soon as we are sick, we can treat patients. Today, basically in DME, we are saying to patients, when it becomes worse, come back to me. We would do it rarely in diseases. With OCS-01, we can treat them early, and the second segment is when they are on the standard of care, which is mainly anti-VEGF. If they are not responding appropriately, we can combine with the product, and we know that there is a synergistic effect between these two mode of actions in DME, so OCS-01 can truly broaden the patient pool like multiple fold and broaden the prescriber pool by addressing these two unmet medical needs. Consistently, this product showed the benefit in terms of BCVA, which is the function, vision, and CMT in the four last clinical trials. I'm going to go rapidly to just the most recent trial. The most recent trial was the stage one of the phase III, which was completed. I will show you the data. Stage two is ongoing, and the data is planned on Q2 this year. In terms of functional, the product showed 7.6 letters gain versus baseline at week 12, and 27% of patients who gained more than 15 letters, which means they doubled their vision after week 12 with OCS-01. Retina was rapidly and sustainably reduced in terms of thickness, reducing the edema, and the good news is, if you remember, I said we are going to address two segments, naive early intervention or already treated in both segments in the study because we went to all comers and we ended up with these two groups in both segments. The product brings benefit in naive patients, but also in patients previously treated with the standard of care. The safety was. The product was well tolerated and no unexpected adverse event. This is just to give a profile. OCS-01 is an optic formulation of dexamethasone eye drop. Ozurdex is an approved product, which is a dexamethasone implant. It does $500 million in sales. We offer a product which is, in terms of efficacy, if I compare, of course, these studies are two different studies, but we offer a product which has high efficacy, 27% and 14%-15% in the Ozurdex trial. At the same time, same population, same API, different route of administration. So highly efficacious product. And the most important here as well is a product which is an eye drop, which is accessible for all patients, which can go to segment where we can be alone as early intervention or combination. So in conclusion for OCS-01, the top line results in two studies, Diamond 1 and Diamond 2, with more than 800 patients. The top line result is planned for Q2. The submission is planned for the second half of this year, and the approval is planned for 2027. So very excited about this program, and let's stay tuned on it. So Licaminlimab. Licaminlimab is a novel anti-TNF eye drop specifically designed for ophthalmology with the clinically proven mode of action. Enhanced ocular penetration is smaller. It's just a fragment. And what is really unique here is the product comes with a biomarker which allows us to identify high responders. So we know in advance by testing, by doing a very simple test, which is QPCR test with the saliva sample, who will hyper-respond to Licaminlimab. Why this is important? As you know, dry eye has two challenges. One is development. We have high variability between patients. We end up with phase IIIs of 600 patients to try to show something. So high risk, costly phase IIIs. After commercially, we end up with the situation which you saw, which you see in the picture, where we keep only 10%-15% of patients. To address this challenge, if you have a biomarker which allows you to know who will respond, then it allows you to reduce the cost for phase III, to make it much higher chance of success. This is on the development side. Smaller phase III, more efficient, higher probability of success. Commercially, the payer will be reimbursing something which works. This is what we are doing. First time precision medicine in ophthalmology. This is the primary endpoint is TNFR1 positive patient. This is what we are doing in PREDICT One, which is ongoing. In the last three trials, the product showed efficacy in signs and symptoms, but also what we saw in the TNF R1 positive patients who are the patients responding to our biomarker is five- to sevenfold better efficacy than any other product and versus our all comers as well. So very differentiated profile, which should be a win for us in terms of capital deployment for phase III, but also win for the payer. This is on ophthalmology. Let's talk about Privosegtor, which is a unique asset today in the field. So Privosegtor is a novel neuroprotective candidate with broad potential for all neuroaxonal diseases. It is a small molecule. It penetrates blood, brain, and retinal barriers. It was selected by high throughput screening where we looked in three injury models, inflammation, apoptosis, and oxidation, to see a candidate which promotes cell survival on neurons and oligodendrocyte. In these three injury models, oxidation, inflammation, and apoptosis, Privosegtor preserved neurons and oligodendrocyte from dying. We went to in vivo, and we tested in glaucoma, optic neuritis, and MS, and consistently product protected neurons in the case of glaucoma, retinal ganglion cells from dying, protected axons and protected the myelin of the axon. On the function in multiple sclerosis, showed a better function than without Privosegtor. Product is an activator. It activates SGK2 as a protein which activates itself for FOXO3, which promotes survival of the neuron and the oligodendrocyte. Just recently, we received the Breakthrough Therapy Designation. We are extremely happy. It validates what the company has done so far. It validates also our recent trial, which I'm going to share with you, which is called ACUITY. But this mode of action here, what I shared with you in terms of so really compelling preclinical data showing preservation of retinal and ganglion cells, preservations of axons, and preservations of the myelin in different animal models. The great news is what we see here. We saw it now in humans, in patients. So this benefit translates if I start only with the neuro-ophthalmic diseases in multiple clinical applications, acute and chronic. Our aim now is to focus on acute neuro-ophthalmic indications. We will go to chronic in neuro-ophthalmic. And at the same time, we are preparing plans to go to neuroscience. And as I shared with you, and I will be repeating it because this is what we believe. What we see here is just the tip of the iceberg with Privosegtor. On the first wave of indication, we are targeting the two main optic neuropathies, which are being advanced under the same IND, optic neuritis and NAION. Optic neuritis and NAION, we are talking about between 60 to 70 cases every year in the U.S. If you apply the lowest price analog in all four indications, we end up with a market of $7 billion where we do not have any solution for patients. We are the only product which showed benefit, so no competition and no solution available. Amazing opportunity on an acute indication, which we are advancing as fast as we can. What is optic neuritis? Optic neuritis is an acute inflammation of the optic nerve. It is directly linked to MS. In fact, two-thirds of patients have already MS when they come with optic neuritis. The last third, 80% of them, optic neuritis will be the first onset of MS. So highly directly linked with MS. It's a relapse of MS, in fact. It is an inflammation. It mainly affects young adults, mainly women, 32 years of age. So 32 years of age, a young woman coming who lost vision, had pain, and didn't have anything before. What happens? We have inflammation in the optic nerve, demyelination, the retinal and ganglion cells suffer, dies, atrophy of the optic nerve, atrophy of the retina. NAION is a different disease leading to the same thing, retinal and ganglion cell death, but coming from a different pathophysiology, which is hypoperfusion of the optic nerve, which leads to retinal and ganglion cell and axonal death. We do not have any solution here as well. NAION, in fact, I don't know if you read multiple publications publicly available. This is a complication which we have with the GLP-1 class, the seven-fold risk of GLP-1 of this NAION. This is very severe. 60% of patients have material impairment, and we do not have any solution, zero. I mean, the only thing really the ophthalmologists say to patients is, "I'm sorry for you." This is the only thing we can say. We have zero solution today. So what we did, we did a phase II, which is called ACUITY, where it was first in patient, not first in human, but first in patient. The key endpoint where safety is a primary endpoint, and then the secondary endpoint where BCVA, which is the function, anatomy with OCT, which is GCIPL and RNFL, and biology with the neurofilament. The treatment was, it is an acute treatment, so it's five days IV infusion every day with two arms, one arm, Privosegtor plus steroid versus steroid alone. These are the results. In terms of function, we have been able to improve function for 100% of patients. 18 letters difference mean between steroid alone versus Privosegtor plus steroid. We doubled, more than doubled the vision for patients. This will be the regulatory endpoint for phase III. Second, did we preserve retinal and ganglion cells? Yes, we preserved the retinal and ganglion cells. We preserved the retinal and ganglion cells as per OCT measurement in the GCIPL thickness, which measures the retinal and ganglion cell layer. And here we avoid atrophy basically and reduced the atrophy or preserved retinal and ganglion cells. Did we preserve the axons? Yes, we preserved the axons as well per OCT measurement on RNFL. And then the last, which is extremely well studied in neuroscience, a regulatory endpoint for ALS, very well studied in MS, which is directly correlated to MS progression, which is neurofilament. Did we show that we reduced axonal damage by reducing the neurofilament? And the response is yes. Neurofilament, as you know, is a skeleton of the axons. When the axons are damaged, the neurofilaments are released into the CSF and into the blood. Here is amazing what Privosegtor is able to do by reducing the axonal damage of the optic nerve. So amazing result in terms of function, structure, and biology. This is the first time ever where we have this result. In In an indication where I remember, I can share with you during three years, people were telling us, "We were crazy to go to NAION. This is a very difficult disease." I agree. This is a very difficult disease, but Privosegtor is pretty unique. On the safety point of view, safety profile reported in phase II showed no AEs leading to drug withdrawal or study discontinuation, and we were very pleased with the dose we are going to use, which is the three milligram in the next trial, so now what is the plan? First, extremely happy with the last week breakthrough therapy designation. We started the Pioneer One, which is the first phase III in acute optic neuritis. We are activating centers, and this will be top line for 2027. Pioneer Two, which is the second phase III starting, and Pioneer Three, which is the phase III for NAION, is starting in the middle of the year, and during this year, we are going to consult with FDA to discuss about a treatment, new treatment, which today does not exist. It is the same thing as NAION. We do not have treatment for relapse of MS. We have treatment for MS, which is meant to reduce the frequency of relapses, and it's good. And actually, I actually launched also one of them, recent one. At the same time, when we have relapse, we don't have treatment of relapse. And it's exactly the same thing of optic neuritis. We have neuroaxonal damage. OCS-05 can materially change the life of MS patients in the future. It could be a disease which is under control without the worsening of the function of the patient. We are planning to meet with FDA, and we will be informing the market once we have feedback from FDA. So in conclusion, extremely pleased with what Oculis has been achieving since its establishment, starting with ophthalmology, now broadening to neuro-ophthalmology. And really remember, because I am very serious when I say it, what we are doing with Privosegtor and what you see is only the very small part of what is coming. So I am finishing with this slide. In the next 12 months or 24 months, late-stage asset differentiated, three first products, first eye drop in DME, first precision medicine in ophthalmology, and first neuroprotection, which is really what is being visible here, just the tip of the iceberg of what we are planning to come up with with Privosegtor to change completely the face of neuroprotection, which will impact ophthalmology, neuro-ophthalmology, and neuroscience. Thank you very much. Thank you. Great. Great. Great. Great. Thanks so much, Riad, for the presentation. So we're going to kick off about 15 minutes or so of Q&A. And your presentation did a nice job of explaining the key priorities for the company. How do you specifically prioritize investment across your pipeline? And do you intend to lead the commercial efforts across your lead assets, or could there be opportunities for out-licensing over time? Yeah. So basically, in terms of differentiation, the great news is we have a portfolio which is pretty differentiated. We believe that commercial success starts with designing the right profile, which should be innovative and differentiated. And this is what we have been consistently doing because then it makes your commercial launch easier, cheaper, and more successful. So it's really very important to spend time in how you design your profile. This is the first point. The second point in terms of differentiation, we always said we will focus only on the U.S. and we partner ex-U.S. And this didn't change. The third point, we will be ready to launch in the U.S. successfully in a very bold manner. At the same time, I know that we have a lack of great product in the market and we'll be always open to partner, but it needs to make sense for both parties and for our investors as well. Okay. And maybe let's just dive right into your DME program for a couple of questions here. It sounds like you're still on track to report top-line results in the second quarter. What level of detail do you plan to disclose here? And will there be one or two disclosures to encompass both their trials? Yeah. So, we are planning to have one disclosure for both trials, for Diamond One and Two. We will be disclosing, of course, the typical top-line result, the data, demographic, BCVA, mean, responders, thickness of the retina, and the safety. Okay. And can you describe what you would think would be a positive outcome here? And what are the relevant benchmarks to consider in this setting for this approach to be considered competitive with anti-VEGF injections? So when you ask all the retina and the ophthalmology community, they all tell you, they all say to us, "Listen, any profile, if we have an eye drop, will change our life because we really need an eye drop to treat our patients. They are not compliant. They don't want to have a needle into the eye. They are not coming to each visit. So we need something else." Because even if we will not stop injecting, at least we need something to bridge for compliance or something to bridge for efficacy or something to allow us to start. So therefore, it's amazing that actually the expectation from the medical community is very low. Just give us something which is approved. Now, what we showed in our studies, we showed actually a pretty efficacious profile, which is if I compare with Ozurdex, which might be the right benchmark because it is just the same API, we have a more efficacious profile. We assume the safety will be the same. It's the same API. The safety will be the same, more efficacious profile with an eye drop. And we believe that if we have this, if we just have the same data we got in our stage one, this is a fantastic profile actually. Yeah. Okay. And can you just describe briefly the statistical analysis plan and hierarchy? Any key nuggets you can give us on the. Yeah. So So basically, we are assuming three letters difference between the active versus placebo. The hierarchy, we have mean BCVA first, and responders second. These are the only regulatory endpoint for FDA. CMT is not a regulatory endpoint. We do it for the medical community, but it is not a regulatory endpoint. Okay. So as you think about these studies, how do you characterize the risk? Yeah, so I would say, so when you analyze the risk of a product, you go regulatory risk, biological clinical risk, CMC risk, and then the last one, which remains always, is execution. This product, we know that it works. In terms of biology, actually, it's approved, so it works. On a CMC, it's validated. It's fine. We are at commercial stage. It's fine. So therefore, really the only risk, which always remains till the last moment of a study, is execution, and the team is, and we as a company and our team in development is obsessed about execution, and we will continue to be obsessed till the last moment because execution is important in any clinical trial. I am very happy to say that vis-à-vis our KPIs, we are doing extremely well vis-à-vis our KPIs so far. It's great, but we just need to continue obsessive execution. I really call it obsessive execution to bring the highest quality possible of the trial. And the highest quality possible of the trial brings good results actually. Okay. And any other kind of color or commentary you would give us on what you specifically hear from physicians about how they would incorporate an eye drop? I will give you one really KPI, which shows how the community is excited about it. When we started Diamond 1 and 2, our plan was to have a global trial to go to the U.S., South America, Asia, Europe, and so on. The U.S. was so fast, it was twice as fast as any other DME clinical trial that we didn't need to open all markets actually. I would say it's just a validation that this patient exists and investigators are very motivated to use our product. Any relevant comps in your view to think about that could be helpful in framing time to peak sales and anything you think about there? Yeah. So basically, when you see the market, we really have a huge pool of patients. We have the half of patients who are treated, so we know them. They are monitored by the retina. We have their picture of their eye, their name, and their address, and they are not responding to the current treatment. This patient can immediately combine with our product. So actually, in our mind, the speed to peak sales will be very rapid because we don't need to educate the market. We don't need to go to the market and say, "You know what? DME is a really bad disease. You need to do the diagnostic. And when you see these people, you need to do this and this." No, we are at the stage, thanks to anti-VEGF and Ozurdex and so on, where these patients are diagnosed, they exist, they are into the address book of the doctor, and they are not responding well and they are losing vision. In fact, DME is the first reason of blinding disease in the U.S. for working-age population. So it's serious. So therefore, the speed to peak sales will be very rapid. Okay. Moving along now to Privosegtor. For Pioneer One and Pioneer Two, how quickly do you believe you can enroll these studies? And when could we see data? Yeah. So for Pioneer One, which was initiated in Q4 last year, we are activating the centers. We said it will take us between 12- 15 months to randomize. So we will be announcing, of course, as soon as we have the first patient, first visit. And we believe that we will have a readout in 2027 for Pioneer One. And then Pioneer Two and Pioneer Three will just follow. For each of these studies, can you, actually? Sorry. And maybe just to address Pioneer Three as well, pardon me, which is expected to initiate in mid-2026, how quickly can you enroll this trial and when could we see data? I think it will take the same time in terms of enrollment. So we believe that between 12 to 15 months will be the time to enroll for Pioneer One, for Pioneer Two, and for Pioneer Three. Perfect. Okay. And any broad strokes in why you think the designs of these registrational trials are de-risked and what is a win scenario? Yeah, so I don't know any trial which is de-risked. It's untrue. I mean, if somebody tells you it's zero risk, it is not true because you have always execution risk. On a scale of. A scale. A scale. Yeah. So the risk, yes. So the risk actually is very low. The risk is very low because this product consistently on the bench in animals, in patients, understanding the mode of action consistently showed what was expected to be seen. So therefore, we feel extremely confident about the biology of this product. We learned a lot from the previous trial, from ACUITY in terms of patient profile, in terms of response. You cannot imagine how many cuts and how many analyses we did to understand better our drug, to understand better the patient profile, to understand better the benefit. The great thing with Privosegtor is just amazing because regardless of how you cut the data, this product works consistently all the time. So therefore, the efficacy seen in ACUITY, but also all the preclinical data, really everything is going toward the same direction. So very confident about it. Seriously, I am very confident about it. Now, as I said for DME, we need to continue to be obsessed about execution. Oh, actually, maybe just for a little bit of housekeeping, what are the next steps in development for MS relapse? For MS relapse, our aim is just perhaps stepping back to give a big picture. Optic neuritis is a relapse of MS. Basically, we showed a benefit in one type of relapse of MS, which is optic neuritis, which is neuroinflammation and demyelination taking place in the optic nerve. Our aim is to broaden this and to go to all relapse of MS. Basically broadening the market between 30,000 to 35,000 optic neuritis in the U.S. every year to a market which will be 170,000 to 180,000 relapses every year. It's really like six times. It's huge. Our aim is to meet with FDA and to discuss how we can achieve this. This is a new indication. Nobody has this indication. The immunomodulators who are approved in MS are meant to reduce the frequency of relapse, but not to treat the relapse. Our aim is to treat the flares as we did in optic neuritis. So the aim is really to sit with FDA, make a proposal about the protocol we are working on it, and get their feedback, and then execute. Okay. And maybe just turning to your dry eye disease program, maybe a set of questions here just on how to think about the top-line results in the second half of 2026 for Predict One. And what are you ultimately looking for that would be competitive data? Yeah. So basically on the Licaminlimab program, really the approach is totally different from any other product because we want to have a precision medicine. We recognize the variability of patient in dry eye. And we said, "Okay, why doing what many others did and failed? Let's do it totally differently." And therefore, we have a biomarker which allows us to identify, to know who will hyper-respond. This allows us to have a phase III. So the typical phase III in dry eye is around 600 patients. Our phase iii is 160 patients. So it's like four times less patients. So four times cheaper, basically. Second is much more secured in terms of probability of success because when we compare, it's between five to seven times better response. So it's four times cheaper, at least four times more efficacious, the more probability of success. So it's a material change in the way we are developing it. What we expect now, we do not expect something which will be 10% or 20% better than the competition. We want much more. Yeah. Yeah. Therefore, the success for us is to have something which is transformative for dry eye. Yeah. Okay. Okay, great. And maybe we can just in the last minute or so here, if you can just review the manufacturing capabilities that you have with the company and any changes that you need to make over the near and long term. On the manufacturing, first, strategically, we do not have manufacturing competencies. This is also capital-intensive type of business. Therefore, we have partners. We have partners who are very solid partners, global partners with footprint in the U.S. and in Europe. Therefore, O1 is both Europe and the U.S., will be manufactured in the U.S. as well. O2 is today in Europe, and we are exploring potentially to come to the U.S. Therefore, I would say our strategy in terms of manufacturing, and it's really not recent, is to always have the best partner possible and to make sure that we keep our flexibility in terms of manufacturing. This is what we have been doing. We do it in any partnership. We look for the best partner, and we make sure we keep flexibility. This is what we do for manufacturing on the three assets, by the way. Okay, great. All right. I think we're about at time here, so I want to thank the Oculis team, Riad. Thank you for doing this and being here, and thanks to all the listeners for joining as well. Thank you, Tessa. Thank you, PM. Thank you.