Okay, ready to go? All right. Thanks very much. My name is David Landers. I'm a Managing Director on the healthcare team at Goldman, and I have the pleasure to introduce Riad Sherif, who's Chief Executive Officer of Oculis. Before we get into the Q&A, Riad, I just wanted to turn over you for any opening remarks. Thank you very much, David, for inviting us. Very happy to be here at Goldman Sachs conference, very happy to give an update on Oculis. Great. Excellent. Well, why don't we start there? 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. Oculis is a public company listed in NASDAQ. It's a biopharma company focusing on neuro-ophthalmology and ophthalmology with a pipeline or two advanced products which are in phase III, I would be very happy to give an update about them. Excellent. why don't we start there then and just work our way through the pipeline? Yeah. Know you recently had an unfortunate outcome for your phase III DIAMOND trial on DME. any additional thoughts on that trial and the outcome before we turn to the forward strategy? Yes. yes, as you said we had actually I would say, unexpected setback on DIAMOND 1 and 2, which were two 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 the licaminlimab. what we saw in DIAMOND 1 and 2, we were able to repeat the Stage 1, which was the previous trial. When we see efficacy of BCVA at week 52, we didn't meet the endpoint at week 52. we decided to refocus our resources now on Privosegtor with PIONEER-1, which is a registrational trial in optic neuritis, and on PREDICT-1, which is a Licaminlimab phase III trial, as well, registrational trial, in dry eye with the genotype-based development. Mm-hmm. Excellent. Great. Why don't we talk a bit more about Privosegtor and why you're excited about it? How does it work mechanistically, and what impact do you expect to have on patients? Yes. On Privosegtor, as you said, we are truly super excited, actually, about this program. First, what this product does. This product is a peptoid. It's a small molecule. It cross brain and retinal barrier. It activates JAK2, which activates FOXO3, which actually prevent or preserve neuron and oligodendrocyte from death. The product was tested in multiple animal models, in fact, three models: glaucoma, optic neuritis, and multiple sclerosis, showing consistently then when animal are receiving Privosegtor, they are able to preserve their neurons. We went into phase I and phase II p hase II is called ACUITY. It was a trial in optic neuritis. What really is super exciting is what we saw in vitro, we see it in patient 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. 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. We see that patients in the active arm have much less neurofilament released in the blood, and therefore, much less neuroaxonal damage. The last point, which is important as well, is the safety looks very good with the dose which is being used. Therefore, in all parameters, efficacy, and safety, the product shows a very solid profile. Based on this profile, we got a Breakthrough designation with FDA. We got PRIME with EMEA in Europe. We went into a detail and deep review with FDA on our protocol. We got the SPA as well on the protocol, 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. Great. It's really event driven. Excellent. Great progress. Maybe staying on Privosegtor. If you think about, again, recent updates with the company, has your guys' and your excitement around Privosegtor and the pathway forward, has the plan for the development of Privosegtor changed at all? Do you see any opportunity to sort of accelerate the development there going forward? Yeah. Strategically, the plan didn't change. It's the same plan. At the same time, because we are putting a very high focus on Privosegtor, operationally, most probably we are enhancing. We have enhancement operationally based on the fact that we have more focus. We have more resources. Therefore this should help us to accelerate our programs with Privosegtor. Strategically, it was part of our pipeline. Right Part of our programs. Right. You're running currently three trials, correct? Yeah. Yeah. For Privosegtor, 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. PIONEER 3 is in NAION, which is a different indication. Still, optic neuropathy is another type of optic neuropathy. We are really targeting two optic neuropathies. One is optic neuritis, and the second one is NAION. PIONEER-3 will be on NAION. PIONEER-2 should be initiated now 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 a typical relapse of MS. We would like potentially to go broader and to go to any acute MS relapse, therefore we are interacting with FDA, and this might have implication of PIONEER-2. We will synchronize the start with the feedback, but this is in the plan. PIONEER-3 will be in the second half of the year. Excellent. Initiation, at least. Okay, great. How do you Maybe tell us a little bit more about the opportunity that you see with Privosegtor. Particularly in optic neuritis and NAION, how would you describe those indications and the role that you expect Privosegtor to play in the treatment paradigm? We do not have any treatment for neuroprotection. In optic neuritis, steroids are used to reduce inflammation, but still patient who are young, we are talking about an average age of 32 years, like the typical patient is a young mother who lose vision, rapid loss of vision and pain. Even in the best-case scenario, when they recover with steroid, they do not recover LCVA. Therefore, there is huge unmet medical need, no solution. This is on optic neuritis. In NAION is a different disease, the same outcome, loss of vision. In NAION, we do not have anything, like nothing. I talked with many KOLs, and I say to them, "What do you do when you have NAION?" Really the only thing they say to patient is, "I am sorry. This is really the only thing they have to say because we don't have anything. Therefore, if this product is approved in these two diseases, it will be a huge response to a big, massive unmet medical need. Just basic math, like just you 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. Therefore, a huge opportunity for us, for patients, for our investors, and for the company. Absolutely. In terms of the timelines, I know you referenced it a bit, but in terms of the timelines for Privosegtor and those particular indications, what are the key things that you're focused on? Basically, in terms of timelines, what we said, we gave, I would say, an overall guidance saying PIONEER-1 should be delivered in the second half of 2027, PIONEER-2 in the first half of 2028. At the same time, and it's really our common practice, each time we refine the timelines and so on three months after the start of the randomization. This should be done around September. October will be the right timing to refine. So far, things are on schedule. Yeah. Excellent. Great. I think we mentioned earlier there's three indications that you're looking at for Privosegtor. Why don't we turn to potentially the largest indication, MS, multiple sclerosis relapse. Similar question, what role do you expect Privosegtor to play in the treatment paradigm? What do you think about the commercial opportunity there? Yeah. There are two types of MS, progressive MS, where we do not have really a solution so far. Privosegtor might play a role. Let's see. We have relapsing-remitting MS. In relapsing-remitting MS, with the current immunomodulators, which are in fact good. We are able to reduce the number of relapses in a material manner. Yeah. At the same time, we still have relapses. Yeah. It is considered that in the U.S., we have between 200,000-400,000 relapses per year. The half of them, 200,000, need a treatment. Like actively to be treated on top of the DMTs or immunomodulators. Yeah. For this patient, these patients are truly, during the flares up, losing their neurons. Our product can help them to preserve their neurons and therefore reduce relapse-associated worsening, which is the worsening we see post relapses. Yeah. We showed that in optic neuritis, in MS patient, we show that our product materially help this patient by improving LCVA, improving the structure a nd reducing neurofilament. 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. Yeah. Therefore, we are really talking about potentially today we are addressing optic neuritis, which is a market of 30,000-35,000 patients per year, to, if we go broader into MS, to be able to address 180,000-200,000 patients. Yeah. Therefore, it is huge. It is between six to seven times more than optic neuritis. Yeah. We want to do it step by step to make sure that first we deliver optic neuritis indication. 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. Excellent Which is super exciting. Anything you want to say about timing on that particular indication beyond what you've said already, or? I would say, we are in pre-IND phase with- Yeah The neuro division. Yeah. As soon as we have clarity about pre-IND, we will be communicating about it. Then after the phase II will be, okay, now we understand the guidance. What are you going to do? We will communicate on both. Okay. Excellent. On the pre-IND, also on the protocol. Excellent. Obviously you outlined the degree to which there is a massive set of patients out there. Benefit from Privosegtor. That raises the question strategically, as you think about maximization of Privosegtor and the opportunity in getting it to the most patients and ultimately value maximization. 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? Yeah. I would say the first focus is really on execution. We want to deliver. We want to deliver a positive study. Therefore, the first focus on execution. The second part, we are a very pragmatic organization. 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. Great. Anything which fits with these two requirements. Yeah We would be open to discuss it. Okay. Excellent. Great. Anything more you'd like to add on Privosegtor, Riad, before we turn to OCS-02? I think we discussed optic neuritis, we discussed NAION. Yeah. Discussed MS. We covered it. Yeah. Pretty good. Excellent. All right, let's turn to the second asset. I know you're currently running a registrational trial on 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? Yeah. This asset went into already three clinical trials. Two in symptoms, one in sign. The three clinical trials were positive. Yeah. What we saw in the second clinical trial in symptoms on an exploratory manner is that certain patient who have a genetic biomarker hyper respond to the drug. This genetic biomarker is specific on the TNF. This patient who have this genetic biomarker hyper respond to symptoms, we saw it in DD2, which is the second trial. We did it in pre-specified manner in the signs. We see the same thing as patient having this genotype hyper respond in sign to OCS-02 or Licaminlimab. This is very encouraging. Why? Because in a disease where there is very high variability between patients You don't know in the end of the day who will respond, who will not respond. You see it in clinical trial, you see it in commercial. Therefore, we tend to have huge phase III to try to show something. This biomarker allows us to really achieve three goals. One is much more efficient program because somehow this biomarker help us to make the clinical trial more efficient- 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. If it does not work, let's change. In fact, we see that in trial, 85%-90% of treatment- are stopped after six months. It's huge, like the carryover, very low. Yeah Because of viability of this treatment. Sure. Yeah. Sure. Yeah. Therefore, first is a very efficient development plan. Yeah. 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. They are paying something very, very expensive without outcomes expected. Yeah. This is what we are doing. Now, this biomarker is not very difficult to do. It is a qPCR test. Yeah. Therefore, it's a saliva swab like COVID basically. Yeah. Yeah. This is what we are doing. The trial is ongoing. It is a 29 days readout. The symptoms trial, it's global discomfort score. How we do it, we screen the patient for the TNFR1. Sure. Of course. Positive patient, if they are positive, they go into a run-in period of two weeks where they are treated with artificial tears. Yeah. If they do not respond to artificial tears, they are randomized. We just announced, I think yesterday, the first patient randomized. Yeah. Therefore, it means that this patient went into the genotyping, went into the running, and was randomized. Of course. We are expecting the data around the end of the year, I mean, end of the year or the beginning of the next year. Okay. Excellent. Good. As it relates to this particular trial and clinical strategy, just given it's more classically ophthalmology, like some of the DIAMOND results, did those DIAMOND study results change the way you think about the strategy that you're currently pursuing around dry eye? Yeah. Yeah. Let's perhaps to respond to this. Yeah. Yeah, please. Question, let's come back to the DIAMOND and what we learned so far. Please. Please. Yeah. We will continue to learn. Expecting to receive the full data set. What we learned. 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. Biologically, this was not translated into BCVA. Yeah. The difference between the DIAMOND program and what we are doing is Stage 1 DIAMOND was 12 weeks, then the full DIAMOND was 52 weeks. We didn't know if the data of 12 weeks will stay in 52 weeks, and most probably we lost efficacy during this. Yeah That we lost efficacy. This situation, we don't have it with Licaminlimab. We don't have it with Privosegtor with PIONEER. Yeah. Cool. For both, we are repeating exactly what we did in phase II. Yeah. Actually, the symptom for Licaminlimab was day 29. We are doing the same symptom at day 29. Yeah. Same thing. Yeah. For Privosegtor, we did ACUITY was month three. We are doing month three. It is exactly the same thing. We are not taking any risk. In the translation between phase II to phase III. For the rest, is really they are completely independent in terms of technology, in terms of execution, in terms of profile. Therefore, I do not see any risk which will be shared between DIAMOND and the rest, nothing at all. Excellent. Great. Yeah. Just you can imagine with the readout, you had expectation being you would do a financing or raise some sort of money. In light of recent events, maybe summarize your guys' financial position and how you think about cash needs and cash on balance sheet going forward? Yeah. In the context, our strategy was always to plan, hope for the best, but plan for the worst. Yeah. Really, this is what we implemented. In the end of the day, it helped us because we find ourself now, even with the setback on DIAMOND 1 and 2, with a portfolio which is very solid. Yeah With two phase III product. Yeah Differentiated. One, the first neuroprotective, and the second one, the first precision medicine in dry eye. Yeah. This is on the pipeline point of view. On the cash point of view, we have cash runway till the second half of 2029. This allows us to deliver all what we said we are going to deliver for both assets, Privosegtor and Licaminlimab. Yeah I would say we are in a good position. Yeah In terms of cash. We are in a good position in terms of project. Yeah. We are in a good position in terms of differentiated, innovative projects. Therefore, no, it's good. Well-positioned. Yeah. It could be better- Yeah. Yeah It could be worse. Yeah. Yeah. 2024 is pretty good. Therefore, it's good. No, it's good. Yeah. Excellent. Okay, great. Well, look, Riad, that's all the questions that I had for you. Anything else you'd like to add before we depart? I would say the conclusion, as the Chief Executive Officer of the company, clearly DIAMOND 1 and 2 were the setback for the company, unexpected, but setback for the company. We will for sure maximize the learning from it. 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. Super excited about the portfolio. Great. Excellent. Thank you. Thank you much for your time, Riad. We really appreciate it. Thank you very much. Thank you very much. Yeah. Thank you again.