Good morning and welcome to the Oculis Update Call. At this time, all participants are in a listen-only mode. A Q&A session will follow the formal presentations. As a reminder, this call is being recorded, and a replay will be made available on the Oculis website following the conclusion of the event. I would now like to turn the call over to your host, Sylvia Cheung, CFO of Oculis. Please go ahead. Thank you, Sarah. Good day, everyone, and welcome Oculis conference call to discuss Privosegtor's development plan after a successful FDA meeting. My name is Sylvia Cheung, and I'm the Chief Financial Officer at Oculis. Joining me today are Chief Executive Officer Dr. Riad Sherif and President of R&D, Snehal Shah. We'll begin our call with a prepared presentation and end with a Q&A session. The slide deck, which accompanies today's presentation, can be viewed using the webcast link provided on our Investors and Media page Oculis website. Before moving on to the presentation, I'll first note that during the course of this conference call, company management may make forward-looking statements, which is on slide two, within the meaning of the U.S. Federal Securities Law regarding future events or performance of the company. We also refer you to the documents the company files from time to time with the SEC. Please note that the forward-looking statements made during this call speak only as of today's date, and we undertake no obligation to update them to reflect subsequent events or circumstances, except to the extent required by law. The words "anticipate," "continue," "estimate," "expect," "intend," "will," and similar expressions are intended to identify forward-looking statements. With that, I would now like to turn the call over to our CEO, Dr. Riad Sherif. Thank you very much, Sylvia. I'm very happy to be here to make an update about our recent interaction with FDA regarding Privosegtor. A snapshot on Oculis. Oculis today, after the recent interaction with FDA, we are very happy to say that we have three registration programs in neuro-ophthalmology and retina indications, which provide multi-billion dollar market opportunities for the company. As a recap, before going into detailed feedback, Oculis is a global biopharma company listed in NASDAQ with an innovative neuro-ophtha and ophthalmology candidate with significant market potential on a market which is over $25 billion, with a key late-stage asset, including Privosegtor, which is a first-in-class neuroprotective candidate advancing to registration programs in two indications: Acute Optic Neuritis, AON, and Non-arteritic Anterior Ischemic Optic Neuropathy, NAION, with potential for broad applications in neuro-ophthalmology and neuro later on. For OCS-01, eye drop, potentially the first non-invasive treatment for DME, is in a registration trial in a Diamond program with readout, which is anticipated in Q2 2026. The company has a strong balance sheet, no debt, and current cash runway into end of 2027 without utilization of the loan facility. Let's go now into the detail of the feedback from FDA. This is the summary. First, we had a successful meeting with the U.S. FDA, which allows us to advance Privosegtor into the registration phase. We have a full alignment on the acute optic neuritis registration trial design, and I will go into the design. We have a full alignment as well on the regulatory pathway for NAION to be evaluated under the same IND. Today, the IND of AON will be the same IND for AON and NAION. In terms of registration programs for AON, we are going to start two registration trials: PIONEER-1 and PIONEER-2. PIONEER-1 is planned to start in Q4 2025. It will be initiated in Q4 2025, and PIONEER-2 will be initiated in the first half of 2026. The design of PIONEER-1 and -2 will mimic the successful phase II ACUITY trial with the same dose, 3mg /kg/ day, the same patient population, MS and non-MS patient as ACUITY. The primary endpoint will be the same endpoint, change from baseline in LCVA at month three, which is the approvable endpoint. Secondary endpoint will be a proportion or percentage of 15 letter gainers at month three and change from baseline in LCVA at month six. This is on acute optic neuritis. On NAION, our plan is to start the PIONEER-3, which will be a registration trial as well, which is planned to start in the mid of 2026. This will allow us to establish a master global optic neuropathy program called PIONEER. PIONEER will help us to drive efficiently pre-registration trials, which target multi-billion dollar market opportunities with AON and NAION. If you recall, this was our status before after the ACUITY readout, but before FDA interaction, these are the advancements we have been able to deliver. First, we are moving from a phase II to a pivotal status with Privosegtor with the start of PIONEER-1 and -2. We are also moving to a registration trial with PIONEER-3, leveraging the same IND with ophthalmology division at FDA. For MS Relapse, we have been also able to advance with Oculis being able to cross-reference Privosegtor AON IND for new IND submission in MS Relapse in 2026 with the neuro division. If we go into the design of the study, you will recognize ACUITY trial. PIONEER-1 and PIONEER-2, which are the registration trials in acute optic neuritis, will mirror those and population in the successful phase II ACUITY trial. It will be as in ACUITY a five-day treatment, a daily treatment, IV infusion of daily treatment, comparing Privosegtor plus steroid versus placebo plus steroid. We'll have a six-month evaluation period with the primary endpoint at month three, which will be LCVA, and then an additional six months of safety follow-up. The study population will be all comers, including as in ACUITY, MS and non-MS acute optic neuritis. In terms of treatment period, it will be mirroring also ACUITY with the treatment within 12 days from the first onset of symptoms. In terms of endpoint, we'll have LCVA change from baseline at month three, which is the primary endpoint. The secondary endpoint, which will be important for our label, are proportions of 15-letter gainers at three months, LCVA change from baseline at six months, LCVA for MS patient, and NFL at month one. To summarize again the feedback and our plan for acute optic neuritis, we are going to implement a similar design to ACUITY with PIONEER-1 and PIONEER-2, which are both registration trials for acute optic neuritis, which is the first indication. In terms of patients, it will be the same patient population, MS and non-MS patient. The study will be statistically powered for the primary endpoint for all comers, but also MS AON. For NAION, we will run a PIONEER-3. The protocol will be presented at a later stage. However, in the same time, we will be able with PIONEER-3 to leverage the same centers, same treatment administration, and data collection techniques. This will create material synergies, which will allow us to have operational synergies for study execution and cost efficiency and optimize enrollment rate with synchronized timing and execution. In the same time, of course, we are running two programs in two different indications, AON and NAION. These studies will be independent with an independent statistical powering of AON and NAION to maximize the probability of success. Now, let's just talk about the opportunities we have and the unmet medical need we have for these. Acute optic neuritis is an acute inflammation of the optic nerve that can lead to permanent visual impairment in young adults with an average age of 32 years. Interestingly, the average age in acute optic neuritis is 32 years. Average age in our trial, ACUITY trial, was as well 32 years. It is an acute optic neuritis with inflammation, with visual loss, and pain. Today, it is treated with high-dose steroids, which can reduce inflammation. However, they do not change the final outcomes, and no neuroprotective treatment is available. In terms of market potential, we estimate just in the U.S. more than 30,000 cases per year. It is a rare disease. In fact, Privosegtor has an orphan status. In acute optic neuritis, we are talking about a similar price analog, which is between $100,000 to $400,000 per treatment per year. The prescriber is very concentrated. We are talking about 450 neuro-ophthalmologists in the U.S., which could represent a market which is $3 billion plus only in acute optic neuritis, where Privosegtor could be the first neuroprotective therapy to improve vision outcomes in this market. Where, again, and I'm really repeating it because it is important, we are talking about young adults of 32 years old in average. If I go to NAION, NAION as well here, no treatment approved, with severe vision loss in 60% of the patients. It represents one of the most important causes of blindness or severely impaired vision in middle-aged and elderly populations. In terms of number of patients, we are also talking about an average of 30,000 - 35,000 patients every year. The vision loss is important. It is mostly between 20/60 to legal blindness. Here, the risk factors are multiple: diabetes, hypertension, sleep apnea, smoking, high altitude, migraine, use of certain medications, and currently, no medical or surgical treatment has been shown to improve the prognosis in case of acute NAION. Here as well, we are talking about a material market opportunity, potentially bigger than AON. We estimate the number of cases between 30,000- 35,000 patients. It's a rare disease as well. It's the same prescriber base for 415 neuro-ophthalmologists in the U.S. and an estimated market of $4 billion plus. You can now see that these two indications, AON and NAION, represent material market opportunity for Privosegtor and Oculis. More importantly, a potential solution which truly can transform the life of this patient by treating, by preserving their retinal ganglion cells and axons and giving them vision back. In conclusion, for our pipeline, Oculis has multiple pivotal milestones focusing on significant unmet medical needs. Acute optic neuritis now, which is on the registration trial with PIONEER-1 and PIONEER-2, with a phased start, Q4 initiation for PIONEER-1, first half for PIONEER-2. PIONEER-3 will start in mid of 2026. In MS relapse, our aim is to cross-reference Privosegtor AON IND for new IND submission in MS relapses. Of course, in parallel, DIAMOND-1 and DIAMOND-2 continue with very solid execution, and we have the President of our R&D here, so more than happy to address questions about DME as well. We expect readout in Q2 2026. We are launching Predict, which is the first phase III in genotype-based development to lead precision medicine in dry eye. Multiple shots on goal, addressing a multi-billion market in a very late stage portfolio with Privosegtor, OCS-01 and Licaminlimab. In conclusion, very pleased with the way our pipeline is advancing. We were able to advance OCS-01 in DME, and now it is in full phase III. As you may recall, randomization is finalized, and we are now in the last cycle of the trial with readout planned in Q2 2026. Licaminlimab with the Predict 1, which is going to be initiated this quarter, and Privosegtor neuroprotection in acute optic neuritis with PIONEER-1, which is going to be initiated this quarter. Next year would be an expansion year for us, with first delivering on what we are doing: DME, dry eye, and AON with PIONEER-2. We will be initiating a PIONEER-3, which will be the first registration trial in NAION. Thank you very much. I am very happy to take questions, and I will turn it to the operator for the questions. Thank you very much. Thank you, Riad. At this time, we will begin conducting our Q&A session. As a reminder to our analysts, if you would like to join the queue, please raise your hand. To those online, please submit your questions below the webcast player in the text box. With that, we'll take our first question from Dan Akschuti from Pareto. Thank you, and congrats on this surprisingly positive news today. Just a few questions. The presentation was very clear, but what kind of centers are you going to go for? I guess you will also include the French ones that you had now. Will you focus in these registration trials more on the U.S., or are you going just generally global? Are you able to... There was no question on a lower dose again, like 2 milligrams or anything like that, or some maximum tolerated dose? It seems very, very straightforward. Yeah. Yeah. Dan, thank you. Good morning, and thank you for the question. First, of course, we don't change a team, which is a winning team. We will keep the French centers, of course, but it will not be only a French study. It will be a global study, and the U.S. will have a key part in the next trial. It will be a global trial, U.S., Europe, and potentially other regions. This is the first part of the question. In terms of dose, we shared, of course, the full CSR with the FDA. The FDA reviewed not only the top-line result, but the FDA reviewed the full CSR, and the FDA is totally confident with our dose, which is the 3 milligrams. Therefore, we are going with the same dose. I completely agree with you. It's pretty straightforward in terms of really replicating what we did with ACUITY. Thank you very much. You're welcome. Thank you for the question. The next question comes from Annabel Samimy at Stifel. Good morning, Annabel. Good morning. How are you? Thank you for taking the question. Given that you're looking at both MS and non-MS, and you've now done it in two trials, does that give you the possibility of putting you into a possible pivotal trial for MS relapse when athe time comes? Are you going to be able to draw anything from these studies that will put you into that pivotal stage for that? Did I hear correctly that all three studies are reading out next year, or did I completely misread that? Thank you. No, no, no. All three programs, rather, DED, DME, a nd this one. Yeah. First, in terms of studies, PIONEER-1 and PIONEER-2 have only one goal, which is registration in acute optic neuritis. It's really the only goal. Now, yes, as you have seen, we are powering the MS subgroup because this could be leveraged later on when we will talk with the FDA about relapse of MS. I would say PIONEER-1 and 2, core goal is approval in acute optic neuritis. Of course, all comers, as we did with ACUITY. With ACUITY, when we analyzed different subgroups, MS or non-MS, as we already publicly shared the data, product worked in both groups. In terms of readout, next year, we'll have two phase III readouts. One is DME, and the second one is dry eye. In terms of acute optic neuritis, as we always did, we will be able to give guidance as soon as we have the first patient dosed. Okay, great. Just to go back to the prior question, you will be also disclosing the various subgroup analyses for each of these so that we can, you know, again, I guess you can validate its efficacy in each of those groups, MS versus non-MS. Didn't we disclose the sensitivity analysis where we showed that actually the product worked in both groups? More than happy to go through them again. Yes, of course. I would say, just to make it very simple, really, the primary endpoint is on all comers. This is the only primary endpoint. This is the only endpoint which is expected from the FDA point of view to get approval in AON. We do not need to, just for clarity, we do not need to show positive in MS and non-MS. The only endpoint, the only primary endpoint is LCVA at three months in all comers. I would say what we are doing in terms of MS patients is an extra. We are doing it just to potentially build on later on when we meet with the neuro division. For today, the goal is all comers to get approval in acute optic neuritis. Great. Thank you. You're welcome. Thanks for the questions, Annabelle. The next question comes from Colleen Kusy at Baird. Great. Good morning. Congrats on the update. Good morning, Colleen. Thank you. Thanks for taking our questions. I know in the phase II study in AON, a pretty striking difference on LCVA. I think it was about 18 letters. Any color on the powering for these phase III studies? What letter difference do you need to show to hit statistical significance? I will. Actually, we are lucky to have our Head of R&D. Snehal, would you like to take this question? Yeah, it's a great question. Based on the ACUITY data, we're more than well adequately powered for the AON registration studies, PIONEER-1 and 2. We'll have, with the sample size, what we presented around 70 patients an arm, which gives us well over 90% power for the primary endpoint. Okay, great. That's helpful. Thank you. A clarifying question for NAION. Would this require a second pivotal study, or could you get away with just one registrational study? It will require a second. Sorry. Go ahead, Snehal. Yeah, our base case is always two adequate well-controlled trials per indication, unless obviously the health authority allows otherwise. Okay, great. Just one more question if I can. As you're moving into a bigger study with more centers, do you expect, is there a difference in how quickly patients are able to start treatment after their onset of disease? Did you see any difference in the phase II study based on, you know, from time to onset to time to starting treatment? I'm just wondering, as you move to a bigger study, if there'd be a longer delay. Thank you. I would say it's the opposite, actually. We learned a lot from ACUITY, and all the learning from ACUITY will be leveraged into the PIONEER-1 and PIONEER-2. I am confident because of our learning in ACUITY, because of huge excitement from the medical community as well about this product. I mean, think about it. This is the only neuroprotective drug showing patient result in development in phase III today. You cannot imagine the excitement around it. Therefore, we are rather optimistic. Of course, we will remain extremely diligent in terms of execution. Execution is always key. I'm very pleased with our R&D team. No, we are confident. Okay, great. Thanks for taking our questions, and congrats again. Thank you. Thank you, Colleen. Thank you, Colleen. I see Jason. Yeah. Yes. I see at least, yeah. The next question comes from Jason Gerberry at Bank of America. Hey, Jason. Good morning. Hey, good morning. Yes, we have just a couple for me. Yeah, please. On your secondary endpoints, the rationale for evaluating retinal structure at one month versus in the pilot studies, I believe you looked at three and six months. In your discussions with regulators, how important was it to showing and confirming maintenance of benefit at three and six months on the retinal structure endpoints? Yeah, I will start to respond to it, and would welcome Snehal adding if I missed something. Basically, NFL here is neurofilament. It's not the structure, actually. Neurofilament is more relevant to dose than the first month instead of three months because these are surrogate indicators of axonal damage, and the damage really happens during the acute phase. This is why one month is more relevant than three months. In terms of structure, I would say really similar to what we see with DME and what IMD. FDA is not interested. Of course, we do it. We do it because it helps us to have a correlation and to see what is happening in the structure. FDA does not ask for OCT at all. Snehal, please complete if I missed something. No, that's correct. The only endpoint that FDA really cares about is the primary endpoint, which is maintained from baseline of LCVA at three months. I see. Will you be capturing some of those retinal structure endpoints that you did in the pilot in this study, even though the FDA is not as focused on those? Yes. Okay. From a timing perspective, can you give some brackets around how long you think it will take to enroll these studies? I assume it's 140 per study, not combine these two studies together, but just confirm that point as well. When you top line, would it be when you unblind at six months or after the full 12 months with the safety assessment? Yeah. I would really say what we said in the past about enrollment. Our assumption is enrollment will take 12 months. We will give more guidance in terms of top line as soon as we have the first dose. You are correct, Jason. The unmasking is at month six for the top line result, yes. Okay, thank you. You're welcome. Thank you, Jason. The next question comes from Daniil Gataulin from Chardan. Hello, guys. Thank you for taking my question. The first question is on the communication channels between the ophthalmology and neuro divisions. Obviously, acute optic neuritis is part of ophthalmology. What is the communication channel within the FDA between those two divisions, and how will your alignment for AON and NAION be or can be leveraged for your indication for MS relapses? I will ask our experts in the [reg], Snehal, to address your question. Yeah, please go ahead, Snehal. Yeah, so when we think about the indications, I mean, these are distinct indications, right? We have acute optic neuritis, and we'll have two studies to support that indication. NAION is a second indication, so we'll have adequate well-controlled trials for that. MS relapse, obviously, we are looking at the MS population in both PIONEER-1 and 2, and we know that acute optic neuritis is one of the most common forms of MS relapse. We believe that that is going to be valuable information in our discussions with the neurology division at the FDA. That's kind of the plan for now. Got it. Okay, thank you. Yeah. I would say really, I mean, as we say, the good news here and the core first indication we are going to focus on is AON. It's a huge indication, huge unmet medical need. We have young patients losing their vision. We have the only product showing result, and this is where we are going to focus. This is really the very first focus with Privosegtor. The second focus is NAION. We are talking about patients who are young, still, at least from my point of view, because they are 50. They are still very young, and they're losing vision. More than 60% of them, so when we go into, I just would like to highlight really the importance of the unmet medical need here on NAION. 60% of them are 20/60 to legally blind. It means that in a best-case scenario, they cannot drive. In the best-case scenario, I'm talking about my patient. They still cannot drive. Therefore, this patient today, we do not have anything for them, nothing. This product can really change the life of this patient. These are our two focus and core indications, and we want to win. This is why also we have this staggered approach in terms of doing our trials with PIONEER-1 being initiated this year, PIONEER-2 being initiated the first half of the next year, and PIONEER-3 in the mid of 2026, because we'll be extremely focused on perfect execution and perfect start. We also believe that there is a true synergy between these three trials, and we would like to be the leader, the leader in neuro-ophthalmology and neuroprotection. Any optic neuritis will be referred to investigator centers we will have in the U.S. and Europe and elsewhere. Next year, when we start this and things are going well, we will start the preparation of MS, which is, of course, an important indication. We believe that with around $7 billion market where we might be the only player, we want to win these two markets first. Got it. All right. Thank you. One more question is a follow-up for AON. Given its acute nature, the patients would benefit from getting the treatment as early as possible. Is there an established treatment window during which they would have to get treatment before they had the irreversible death? I would say, what we had in ACUITY and is really mirroring what we had in ACUITY was less than 12 days. We had an average mean in terms of how many days after first onset was 9.5 days. We already showed that we are able to execute this protocol. We showed it. We are going to replicate, and based on the learning, I am confident that we might be better. Let's see. Within the timeframe of the protocol, we believe that this product will have a material effect as it showed in ACUITY. All right. Thank you. You're welcome, Daniel. Thank you for asking. Next question comes from Yi Chen at H.C. Wainwright. Hey, Yi. Good morning. Good morning. Thank you for taking my question. My question is, has the FDA communicated that as long as the treatment results are statistically different between OCS-05 and placebo, that you can get approval, or you need to show at least a certain amount of delta, and then you can get approval? I mean, which is the case from the FDA's perspective? I would ask our Head of R&D to address it. Go ahead, Jason. Yeah. ahead, Jason. Yeah. ahead, Jason. Yeah. It's a great question. FDA requires statistical significance on the primary endpoint, and the primary endpoint should be relevant, clinically relevant. That's where we agreed LCVA at three months, mean change from baseline is the primary endpoint. Obviously, like any other product, you know, it's a matter of reviewing the data, and that's why we're looking at this clinically relevant endpoint. Okay, got it. My follow-up question is, I guess from the phase II results, you did observe LCVA improvement. Do you expect improvement in HCVA as well? I mean, what is the clinical meaningfulness between HCVA and LCVA? In AON, LCVA is the clinical meaningful sign to measure, basically. Therefore, we will be measuring LCVA. Their HCVA does not deteriorate? It deteriorates. The sign which does not come back to baseline is LCVA, and this is why the FDA is focusing on LCVA in this indication. Okay. Okay, got it. Thank you. You're welcome. Thank you, Yi. The next question comes from Sushila Hernandez at Kempen. Hey Sushila. Good afternoon. Good afternoon. Thank you for taking my questions. At your R&D event earlier this year, you mentioned to start a registrational trial in the first half of next year. How come you're able to accelerate this and already start in Q4 this year? Have you already started prep work and engaged with centers? Yes, I mean, you are totally right. Thank you for following exactly what we said. You are totally right and very pleased to say that we are accelerating. We are finalizing now the startup agreement, and we are already starting to talk with the centers and so on. It is starting earlier than anticipated, yes. Okay. Could you share initial feedback from neuro-ophthalmologists on Privosegtor? Also, what kind of work are you doing to raise awareness for the potential of this drug? We are doing the typical work in being present in congresses, preparing publications, abstracts. We were in X-rays. We were in Medioretina. We are going to have a very bold presence. If you come, you are invited to our booth at AAO, which is taking place in two weeks. Therefore, this is the presence we are having. We are going to be very present in NANOS, where we will be the company of NANOS in the future. Therefore, a very, very bold presence with our neuro-ophthalmic community. The feedback from this community has been extremely positive. They never saw this type of result. They're extremely engaged, extremely helpful, and insightful in terms of what we should do to make this product successful. Therefore, I am confident, but also thankful to the community with their help from neuro-ophthalmology, from retina, from neurologists as well. Okay, great. Just the last question. You mentioned for ACUITY, there was an average 9.5 days after onset of treatment started. This was in France. How can you compare this to the situation in the U.S.? Do you also expect that you can start this soon after onset? Yes. The very first feedbacks we have from investigators, from our SAB, from the neuro-ophthalmology in the U.S. and Canada, is that this is realistic. This is not out of scope. This is totally realistic, yes. I would say what will help us even more this time vis-à-vis ACUITY, so ACUITY, we didn't know if this product will work on. Therefore, in terms of conviction, to convey conviction to patients, we have much more conviction today when you talk to patients and explain what you are doing. We have a conviction that we are going to help the patient if the patient is on active R. In ACUITY, we didn't know. Therefore, we are in a much better shape for three reasons. First, because we have a product which worked, at least showed very clearly that it worked in ACUITY. This is the first point. The second point is because we learned from ACUITY, and we are going to leverage the learning. The third, as I shared with you, we have amazing support from the medical community to make this product successful because they need something. Okay, that's clear. Thank you. You're welcome. Thank you. We have time for one last question from Serge Bélanger at Needham. Good morning. Thanks for speaking in. Good morning, Sushila. I guess the first question, you mentioned the PIONEER studies 1 and 2 will be in an all-comers AON population. Can you just highlight how that may differ from the patient population that was recruited in the phase II study? Secondly, thinking of NAION, you're going straight to a registrational study here, foregoing the phase II. Maybe just give us an idea of your confidence that I assume you think that the drug will perform similarly to how it did in AON, and that gives you confidence to go straight to phase III, but maybe just talk about those assumptions. Thanks. Yeah, yeah, of course. To the first question, the population was all comers. We had two-thirds of MS and one-third idiopathic, and we expect the same population. Therefore, we do not expect a different population. ACUITY already was really the same. It's copy-paste in terms of population. It's really copy-paste. This is on the first question. On the second question about NAION, yes, you are right. NAION is a different disease. However, at the same time, what is happening at the retinal ganglion cell level and axon level is the same. We have axonal damage and retinal ganglion cell death. This product in preclinical work showed consistently, regardless of the type of injury, that retinal ganglion cells and axons were preserved and protected. This is what we would like to replicate in humans in NAION. This is why also in terms of PIONEER-3, we said we will do PIONEER-3, and based on the data, we will do PIONEER- 4, which will happen after PIONEER-3, while PIONEER-1 and -2 are in parallel almost. We are very confident based on the preclinical data we have that this product will also play its role in terms of preserving retinal ganglion cells and axons because in NAION, and you have a picture here, really what is suffering is we have damage of the axon and damage of the retinal ganglion cells. At the cell level, what happens in AON is happening in NAION. Thank you. You're welcome. Thank you, Serge. This concludes the Q&A session. I'll turn the call back to Riad for concluding remarks. I would like just to thank all our analysts for their support, for attending, and the Oculis team and our partners at LifeSci for great collaboration and great work. Let's keep it up. Patients are waiting for us. Thank you.