Oculis Aktie

Okay. Ready to go. All right. Thanks very much. My name is David Landers. I'm a Managing Director on the health care team at Goldman, and I have the pleasure to introduce Riad Sherif, who's CEO of Oculis. And before we get into the Q&A, Riad, I just want to turn it over to you for any opening remarks.

Yes. Thank you very much, David, for inviting us. Very happy to be here at the Goldman Sachs Conference and very happy to give an update on Oculis.

Great. Excellent. Well, why don't we start there? So how about you just for those who are perhaps less familiar with the company, why don't you give an overview of the company and its programs?

Yes. So Oculis is a public company, listed in Nasdaq is a biopharma company focusing on neuro-ophthalmology and ophthalmology with a pipeline of 2 advanced products, which are in the Phase III, and I would be very happy to give an update about them.

Excellent. So no -- why don't we start there then and just work our way through the pipeline. So I know you recently had an unfortunate outcome for your Phase III DIAMOND trial in DME. So any additional thoughts on that trial and the outcome before we turn to the forward strategy?

Yes. So yes, as you said, we had actually, I would say unexpected setback on DIAMOND-1 and 2, which were 2 Phase IIIs in DME with OCS-01. Based on the data we have so far in hand, and we didn't receive the full data set, but based on the top line results, we decided to refocus our resources on privosegtor and licaminlimab.

Now what we saw in DIAMOND-1 and 2, we were able to repeat the Stage 1, which was the previous trial. But when we see efficacy of BCVA at week 52, we didn't meet the endpoint at week 52. So we decided to refocus our resources now on privosegtor with PIONEER-1, which is a registrational trial in optic neuritis and on PREDICT, which is a licaminlimab Phase III trial as well as registrational trial in dry eye with the genotype based development.

Excellent. Great. So -- why don't we talk a bit more about privosegtor and why you're excited about it? So how does it work mechanistically? And what impact do you expect to have on patients?

Yes. So on privosegtor, as you say, we are truly super excited actually about this program. So first, what this product does. This product is a peptoid. It's a small molecule. It crosses brain and retinal barrier. It activates SGK2, which activates FOXO3, which actually prevents or preserve neuron and oligodendrocyte from death. And the product was tested in multiple animal models, in fact, 3 models, glaucoma, optic neuritis and multiple sclerosis. This is showing consistently then when animals are receiving privosegtor, they are able to preserve their neurons.

Then we went into Phase I and then the Phase II. Phase II was -- is called ACUITY. It was a trial in optic neuritis. And what really is super exciting is what we saw in vitro, we see it in patients with improvement in function measured per LCVA, where we see that patients receiving privosegtor plus steroid versus steroid alone, patients on active have more than the double in terms of vision. So material improvement in vision, material improvement in structure. We see in the OCT that retinal ganglion cells in the retina are being protected. We see as well in the neurofilament, which are, as you may know, it is part of the skeleton of the axon. And when the axon is being damaged, the neurofilament are released into the CSF and the blood, and we can measure them.

And we see that patients in the active arm have much less neurofilament released in the blood and therefore, much less neuroaxonal damage. And the last point, which is important as well, is the safety looks very good with the dose which is being used. So therefore, in all parameters, efficacy and safety, the product shows a very solid profile. Based on this profile, we got breakthrough designation with FDA. We got prime with EMA in Europe. And we went into detailed and deep review with FDA on our protocol. We got the SPA as well on the protocol and then PIONEER-1 starting, very happy to say that we were able to activate the first centers the last week, and now we should see first patient first visit in the upcoming days. It's really event-driven so.

Excellent. Great progress. So maybe staying on Privo. If you think about, again, recent updates with the company, has you guys and your excitement around Privo and the pathway forward, has the plan for the development of Privo changed at all? Do you see any opportunity to sort of accelerate the development there going forward?

Yes. So strategically, the plan didn't change. It's the same plan. At the same time, because we are putting a very high focus on Privo, operationally, most probably we are enhancing -- we have enhancement operationally based on the fact that we have more focus. We have more resources. And therefore, this should help us to accelerate our programs with Privo. But strategically, it was part of our pipeline and part of our programs.

Right. And you're running currently 3 trials correct?

Yes. So for Privo, we have PIONEER-1, PIONEER-2, PIONEER-3. PIONEER-1 is the first study in optic neuritis, which is ongoing. PIONEER-2 is the second trial in optic neuritis. And PIONEER-3 is in NAION, which is a different indication, still optic neuropathy -- is another type of optic neuropathy. We are really targeting 2 optic neuropathies. One is optic neuritis and the second one is NAION.

And PIONEER-3 will be on NAION. PIONEER-2 should be initiated now very, very soon. In fact, we are interacting with FDA to discuss potentially about an indication which is broader than optic neuritis. As you know, optic neuritis is part of -- is a typical relapse of MS. We would like potentially to go broader and to go to any acute MS relapse, and therefore, we are interacting with the FDA, and this might have implication of PIONEER-2. We will synch it -- synchronize the start with the feedback, but this is in the plan. And PIONEER-3 will be in the second half of the year.

Excellent.

Initiation at least.

Yes, yes. Okay. Great. And so how you maybe tell us a little bit more about the opportunity that you see with Privo. So particularly in optic neuritis and NAION, how would you describe those indications and the role that you expect Privo to play in the treatment paradigm?

Yes. So we do not have any treatment for neuroprotection. And in optic neuritis, steroids are used to reduce inflammation, but still patients who are young patients we are talking about an average age of 32 years, like the typical patient is a young mother who lose vision, like rapid loss of vision and pain. And even in the best case scenario, when they recover with steroid, they do not recover LCVAs. So therefore, there is huge unmet medical need, no solution. This is an optic neuritis.

And NAION is a different disease, the same outcome, loss of vision. And in NAION, we do not have anything like nothing. I mean, I talked with many KOLs and I say to them, what do you do when you have an NAION? And really, the only thing they say to patients is, I'm sorry. This is really the only thing they have to say because we don't have anything. So therefore, if this product is approved in these 2 diseases, it will be a huge response to a big massive unmet medical need. And just basic math, like just to take an orphan indication type of treatment and you take the lowest orphan indication cost, which is around $100,000 in ophthalmology and you take the number of cases per year, it creates an opportunity of $7 billion market without anything available. So therefore, huge opportunity for us, for patients, for our investors.

Absolutely. Absolutely. And in terms of the time lines, I know you referenced it a bit, but in terms of the time lines for Privo in those particular indications, what are the key things that you're focused on?

So basically, in terms of time lines, what we said, we gave, I would say, an overall guidance saying PIONEER-1 should be delivered in the second half of '27, PIONEER-2 in the first half of '28. At the same time, and it's really our common practice, each time we refine the time lines and so on 3 months after the start of the randomization. So this should be done around September, October will be the right timing to refine. But so far, things are on schedule.

Yes. Excellent. Great. So I think we mentioned earlier, there's 3 indications that you're looking at for Privo. So why don't we turn to potentially the largest indication, so MS, multiple sclerosis relapse. Similar question, what role do you expect Privo to play in the treatment paradigm? And what do you think about the commercial opportunity there?

Yes. So -- so there are 2 types of MS, progressive MS, where we do not have really a solution so far. Privo might play a role, let's see. And we have relapse remitting MS. And relapse remitting MS with the current immunomodulators, which are, in fact, good, we are able to reduce the number of relapse in a material manner. At the same time, we still have relapses. We have -- it is considered that in the U.S., we have between 200,000 to 400,000 relapses per year. The half of them, 200,000 need a treatment, like actively to be treated on top of the DMTs or immunomodulators.

So for this patient, these patients are truly during the flare-ups losing their neurons. Our products can help them to preserve their neurons and therefore, reduce relapse-associated worsening, which is the worsening we see post relapses. We showed that in optic neuritis in MS patients, we showed that our product materially help these patients by improving LCVA, improving the structure and reducing neurofilament. So therefore, if we apply this concept to any relapse, it could really open the door for multiple more patients to be treated with privosegtor to protect their neurons. So therefore, we are really talking about potentially today, we are addressing optic neuritis, which is a market of 30,000 to 35,000 patients per year to -- if we go broader into MS to be able to address 180,000 to 200,000 patients. So therefore, it's huge, like it's between 6 to 7x more than optic neuritis.

Now we want to do it step by step to make sure that, first, we deliver optic neuritis indication and the second potentially acute MS relapse. We are in exchanges with FDA. And as soon as we have clear feedback, we will be able to communicate about it and to start the program. It's super exciting.

Anything you want to say about timing on that particular indication beyond what you said already or...

I would say -- so we are in pre-IND phase with the Neuro Division. So as soon as we have clarity about pre-IND, we will be communicating about it. And then after the second phase will be, okay, now we understand the guidance, what are you going to do? And we will communicate on both, on the pre-IND, but also on the protocol.

So obviously, you outlined the degree to which there's a massive set of patients out there who benefit from Privo. That raises the question strategically, as you think about maximization of Privo and the opportunity in getting it to the most patients and ultimately value maximization, does do you think about partnership or some sort of strategic relationship? Or are you focused just on execution? What's your view, whether in the near term or long term, how you think about strategic maximization over time?

I would say the first focus is really -- is on execution because we want to deliver. We want to deliver a positive study. So therefore, the first focus on execution. The second part, we are a very pragmatic organization. And our aim is to create value to bring this product as fast as possible to the patient and to create the greatest value possible to our investors. And anything which fits with these 2 requirements, we will be open to discuss it.

Okay. Excellent. Great. Anything more you'd like to add on Privo, Riad, before we turn to OCS-02?

I think we discussed optic neuritis, we discuss NAION, discuss MS.

We covered it. Excellent. All right. Well, then let's turn to the second asset. So I know you're currently running a registrational trial in dry eye disease. Can you briefly summarize some of the data that you've seen thus far and how you think about how this asset addresses the unmet need in the dry eye space.

Yes. So this asset went into already 3 clinical trials, 2 in symptoms, 1 in sign. The 3 clinical trials were positive. But what we saw in the second clinical trial in symptoms on an exploratory manner is that certain patients who have a genetic biomarker hyperrespond to the drug. This genetic biomarker is specific on the TNF. And this patient who had this genetic biomarker hyperrespond to symptoms, and we saw it in ED2, which is the second trial. And then we did it in a prespecified manner in the signs, and we see the same thing as patients having this genotype hyperrespond inside to OCS-02 or licaminlimab.

So this is very encouraging. Why? Because in a disease where there is a very high variability between patients. And you don't know in the end of the day who will respond, who will not respond. And you see it in clinical trial and you see it in commercial. And therefore, we tend to have huge Phase IIIs to try to show something. This biomarker allows us to really achieve 3 goals. One is much more efficient program because somehow this biomarker help us to make the clinical trial more efficient and higher probability of success. This is the first point. The second point, it makes more sense for the doctor or the patient because we will really have a paradigm shift if this product is approved from trials and error like let's try, see if it works great, it does not work, let's change. And in fact, we see that in dry eye, 85% to 90% of treatment are stopped after 6 months. So it's huge, like the carryover very low because of viability of this treatment. So therefore, first is a very efficient development plan.

The second is really a paradigm shift in terms of treating patients. And the third in terms of payer. Payers will be paying a product which works instead of trials and error, which actually affect them because they are paying something very, very expensive without the outcomes expected. So this is what we are doing. Now this biomarker is not very difficult to do. It's a qPCR test. So therefore, it's a saliva like COVID.

So this is what we are doing. The trial is ongoing. It is a 29 days readout. The symptoms trial, so it's a global discomfort score. So how we do it? We screen the patient for the TNFR1 positive patient. If they are positive, they go into a run-in period of 2 weeks where they are treated with artificial tears. And if they do not respond to artificial tears, then they are randomized. So we just announced, I think, yesterday, the first patient randomized. So therefore, it means that this patient went into the genotyping, went into the run-in and was randomized. So -- and we are expecting the data to around the end of the year, I mean, end of the year or the beginning of the next year.

Good. And as it relates to this particular trial and clinical strategy, just given it's more sort of classically ophthalmology like some of the DIAMOND results, did those DIAMOND results change the way you think about the strategy that you're currently pursuing around dry eye or...

So perhaps to respond to your question, let's come back to the DIAMOND and what we learned so far. And we will continue to learn. We are expecting that to receive the full dataset, but what we learned. So in DIAMOND, as I shared with you, we repeated really the Stage 1. The CST, which is the biological response was as planned and was reduced till week 52. And biologically, this was not translated into BCVA.

Now the difference between the DIAMOND program and what we are doing is Stage 1 DIAMOND was 12 weeks and then the full DIAMOND was 52 weeks. So we didn't know if the data of 12 weeks will stay in 52 weeks and most probably we lost efficacy during this -- like the duration of the treatment that we lost efficacy.

So this situation, we don't have it with licaminlimab. We don't have it with privosegtor with PIONEER because for both we are repeating exactly what we did in Phase II. Actually, the symptom for licaminlimab was day 29. We are doing the same symptoms at day 29, same thing. For privosegtor, we did ACUITY was month 3. We are doing month 3. So it is exactly the same thing. So we are not taking any risk in the translation between Phase II to Phase III. Now for the rest, it's really they are completely independent in terms of technology, in terms of execution, in terms of profile. So therefore, I do not see any risk which will be shared between and the rest, nothing at all.

Excellent. And then just you can imagine with the readout like you had expectation being you would do a financing or raise some sort of money. So in light of recent events, how do you think about -- maybe summarize your guys' financial position and how you think about cash needs and cash on balance sheet.

So in the context, we really -- our strategy was always to plan like hope for the best, but plan for the worst. And really, this is what we implemented. And in the end of the day, it helps us because we find ourselves now even with the setback on DIAMOND-1 and 2 with a portfolio, which is very solid with 2 Phase III products differentiated, one, the first neuroprotective and the second one, the first precision medicine in dry eye. This is on the pipeline point of view.

On the cash point of view, we have cash runway till the second half of '29. And this allows us to deliver all what we said we are going to deliver for both assets, privosegtor and licaminlimab. So therefore, I would say we are in a good position in terms of cash. We are in a good position in terms of projects. We are in a good position in terms of differentiated innovative projects. So therefore, no, it's good. It could be better, but it could be worse. Therefore, it's good. No, it's good.

Yes. Excellent. Okay. Great. Well, look, that's all the questions that I had for you. Anything else you'd like to add before we depart.

Yes. No, I would say the conclusion, I mean, as the CEO of the company, clearly, DIAMOND-1 and 2 was a setback for the company, unexpected, but setback for the company. We will, for sure, maximize the learning from it, but we are fully now committed with the full resources, energy, diligence on delivering PREDICT-1, which is the next clinical readout, PIONEER-1 and PIONEER-2 and PIONEER-3, but also potentially really broadening the privosegtor into MS, which can be truly transformational for the company. We are in the discussion with FDA. Hopefully, we'll be able to announce and inform the market as soon as we know. But super excited about the portfolio.

Yes. Great. Excellent. Well, thank you so much for your time, Riad. We really appreciate it.

Thank you very much.

Yes. Thank you again.

Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Tess Romero, and I'm one of the senior biotech analysts here at JPMorgan. Our next presenting company is Oculis. And presenting on behalf of the company, we have CEO, Riad Sherif. Riad, over to 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.

So we are a public company, NASDAQ listed, here our safe harbor statement. So Oculis is a global biopharma NASDAQ-listed company with late advanced registrational candidates, 3 candidates in Phase III, 2 franchises, ophthalmology and neuro-ophthalmology, I'm starting in a chronological order in terms of upcoming readout.

Of the franchise with 2 candidates, OCS-01, which is the first noninvasive eye drop, self-administered eye drop in for retina for DME with a 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. And I will go into the details after with readout in Q4 2026.

And the second franchise, which is neuro-ophthalmology with privosegtor, as you know, neuroprotection has been a buzzword for 40 to 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 2 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-rich 12 months or I would say 24 months of consistently bringing new milestones with a late-stage asset in the Phase III. The first one will be ophthalmology with OCS-01 with DIAMOND-1 and 2 reading into Q2 this year and plan 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 privosegtor, which is a neuro-ophtha 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 -- neuropathy 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 the 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 the 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 900,000 who are diagnosed and treated. The first segment where we do not have a solution, we do not have any noninvasive treatment, which we can start with, which is early intervention. This is the first segment we would like to address with OCS-01. And 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. And here, we do not have any competition.

The second segment where we have a high unmet medical need where almost half of patients who are treated today are not adequately responding in DME because there are 2 components, as you know, in diabetic macular edema, neurovascularization on one hand and inflammation on the other hand. So OCS-01 could address these 2 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 will 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 2 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 2 unmet medical need. Consistently, these products show the benefits in terms of BCVA, which is the function, vision and CMT in the 4 last clinical trials. I'm going to go rapidly to just the most recent trial. The most recent trial was the Stage 1 of the Phase III, which was completed. I will show you the data. Stage 2 is ongoing and the data is planned on Q2 this year.

In terms of functional, product showed 7.6 letters gain versus baseline at week 12 and 27% of patients who gained more than 15 letters, which means they double 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 2 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 2 groups in both segments, 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 optimist formulation of dexamethasone eye drop. OZURDEX is an approved product, which is a dexamethasone implant. It does $0.5 billion sales. We offer a product which is in terms of efficacy, if I compare -- of course, these studies are 2 different studies, but we offer 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 segments where we can be alone as early intervention or combination. So in conclusion for OCS-01, the top line results in 2 studies, DIAMOND-1 and DIAMOND-2 with more than 800 patients, the top line result is planned for Q2, the submission 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 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 hyperrespond to licaminlimab.

Why this is important? As you know, dry eye has 2 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. And after commercially, we end up with the situation, which you saw -- which you see in the picture where we keep only 10% to 15% of patients. By -- 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 a Phase III to make it much higher chance of success. This is on the development side. So smaller Phase III, more efficient, higher probability of success. And 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 patients. This is what we are doing in PREDICT-1, which is ongoing.

In the last 3 trials, the product showed efficacy in signs and symptoms, but also what we saw in the TNFR1 positive patients who are the patient 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 a 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 3 injury models, inflammation, apoptosis and oxidation to see a candidate which promotes cell survival on neurons and oligodendrocyte. And in these 3 injury models, oxidation, inflammation and apoptosis, privosegtor preserve neurons and oligodendrocyte from dying. Then we went to in vivo, and we tested in glaucoma, optic neuritis and MS, and consistently protected neurons in the case of glaucoma, retinal ganglion cell from dying, protected axons and protected the myelin of the axon.

And on the function in multiple sclerosis, it showed a better function than without privosegtor. Product is an activator. It activates SJK-2 as a protein, which activates itself for FOXO3, which promotes survival of the neuron and the oligodendrocyte. And just recently, we received the breakthrough therapy designation. We are extremely happy. It's validated -- 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 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 translate, if I start only with the neuro-ophtha diseases in multiple clinical applications, acute and chronic. Our aim now is to focus on acute neuro-ophtha indications. We will go to chronic in neuro-ophtha. And at the same time, we are preparing plans to go to neuroscience. 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.

So on the first wave of indication, we are targeting the 2 main optic neuropathies, which are assessed 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 3 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. So 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's directly linked to MS. In fact, 2/3 of patients have already MS when they come with optic neuritis. And the last 1/3, 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, have pain and didn't have anything before. What happens? We have inflammation in the optic nerve, deminimization, the retinal ganglion cells suffer, dies, atrophy of the optic nerve, atrophy of the retina.

NAION is a different disease, leading to the same thing, retinal ganglion cell death. But coming from a different pathophysiology, which is hyperperfusion of the optic nerve, which leads to retinal 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 that is sevenfold the risk of GLP-1 of this NAION. This is a very severe 60% of patients have material impairment. And we do not have any solution, 0. I mean the only thing really ophthalmologists say to patients is, I'm sorry for you. This is the only thing we can say. We have 0 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 endpoints were safety as a primary endpoint and then the secondary endpoint were LCVA, 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 5 days IV infusion every day with 2 arms, 1 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 ganglion cells? Yes, we preserved the retinal ganglion cells. We preserved the retinal ganglion cell as per OCT measurement in the GCIPL thickness, which measures the retinal ganglion cell layer. And here, we avoid atrophy basically and reduced the atrophy or preserved retinal 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 neurofilament 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 results in terms of function, structure and biology. This is the first time ever where we have this result. In an indication where I remember, I can share with you during 3 years, people were telling us, we were crazy to go to AON. 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 the 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 3 milligrams in the next trial. So now what is the plan? First, extremely happy with the last week breakthrough therapy designation. We started the PIONEER-1, which is the first Phase III in acute optic neuritis.

We are activating centers, and this will be top line for 2027, PIONEER-2, which is the second Phase III starting and PIONEER-3, which is the Phase III for NAION 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 AON. 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. Privosegtor can materially change the life of MS patients in the future. It could be a disease which is under control without worsening of the function of the patient. We are planning to meet with FDA, and we will be informing market once we have the 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'm 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'm finishing with this slide, rich next 12 months or 24 months, late-stage assets differentiated 3 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 privosegtor to change completely the face of neuroprotection, which will impact ophthalmology, neuro-ophthalmology and neuroscience. Thank you very much.

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?

Yes. So basically, in terms of prioritization, so 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 prioritization, we always say 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. And at the same time, I know that we have 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 different -- 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 1 or 2 disclosures to encompass both their trials?

Yes. So we are planning to have one disclosure for both trials for DIAMOND-1 and 2. 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's 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 1, this is a fantastic profile actually.

Yes. Okay. And can you just describe briefly the statistical analysis plan and hierarchy, any key nuggets you can give us on the...

Basically, we are assuming 3 letters difference between the active versus placebo. The hierarchy, we had mean BCVA first and responder 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, like what is the -- like how do you characterize the risk?

Yes. 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 until the last moment because execution is important in any clinical trial.

I am very happy to say that vis-a-vis our KPIs, we are doing extremely well, vis-a-vis our KPIs so far is great. But we just need to continue obsessive execution. I really call it obsessive execution to bring highest quality possible of the trial. And the highest quality possible of the trial brings a good result actually.

And any other color or commentary you would give us on what you specifically hear from physicians about how they would incorporate an eye drop?

So I will give you one really KPI, which shows how the community is excited about it. When we -- so when we started DIAMOND-1 and 2, our plan was to have global trial to go to U.S., South America, Asia, Europe and so on. U.S. was so fast. It was twice as fast as any other DME clinical trial that we didn't need to open our market actually. So I would say it's just a validation that this patient exists and investigators are very motivated to use our product.

And 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?

Yes. 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 like 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, the -- in our mind, the speed to peak sales will be very rapid because we don't need to educate the market, like we don't need to go to the market and say, you know what, DME is 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-1 and PIONEER-2, how quickly do you believe you can enroll these studies? And when could we see data?

Yes. So for PIONEER-1, which was initiated in Q4 last year, we are being -- we are activating the centers. What we say we said it will take us between 12 to 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 '27 for PIONEER-1 and then PIONEER-2 and PIONEER-3 will just follow.

For each of these studies, can you -- or actually -- sorry, and maybe just to address PIONEER-3 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-1, PIONEER-2, and PIONEER-3.

Perfect. Okay. And any broad strokes in why you think the designs of these registrational trials are derisked? And what is a win scenario?

Any -- like I don't know any trial, which is derisked. It's untrue. I mean if somebody tells you it's 0 risk, it is not true because you have always execution risk.

At scale and spectrum...

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 analysis we did to understand better our drug, to understand better the patient profile, to understand better the benefit.

The great thing is with privosegtor is just amazing because regardless 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 towards 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 the execution.

And actually, maybe just for a little bit of housekeeping, what are the next steps in development for MS relapse?

So for MS relapse, our aim -- so just perhaps stepping back to give a big picture. So 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 deminimization taking place in the optic nerve. Our aim is to broaden this and to go to all relapse of MS. So basically broadening the market between 30,000 -- 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. So it's really like 6x. So 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-1? And like what are you ultimately looking for that would be like competitive data?

Yes. So basically, on licaminlimab program is really the approach is totally different from any other product because we want to have a precision medicine. We recognize the variability of patients in dry eye. And we said, okay, why doing what many other did and failed? Let's do it totally differently. And therefore, we have a biomarker, which allows us to identify to know who will hyperrespond. 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 4x less patients. So 4x cheaper basically.

Second is much more secured in terms of probability of success because when we compare, it's between 5 to 7x better response. So it's 4x cheaper, at least 4x more efficacy, 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. So therefore, the success for us is to have something which is transformative for dry eye.

Yes. 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 at the company and any changes that you need to make over the near and long-term?

So on the manufacturing, so first, our strategically, we do not have manufacturing competencies. This is also capital-intensive type of business. So therefore, we have partners. We have partners who are very solid partners, global partners with footprint in the U.S. and in Europe. So therefore, 01 is both Europe and the U.S. will be manufactured in the U.S. as well. 02 is today in Europe, and we are exploring potentially to come to the U.S.

So 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 are not -- we keep our flexibility in terms of manufacturing. And this is what we have been doing. And we do it in any partnership. We look for the best partner, and we make sure we keep flexibility. And this is what we do for manufacturing on the 3 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, and thank you. Again, thank you.