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 Riyad Sharif, who's CEO of Oculus. And before we get into the Q&A, Riyad, I just wanted to turn over to you for any opening remarks.

Yeah, thank you very much, David, for inviting us. Very happy to be here at Goldman Sachs Conference and very happy to give an update on Oculus.

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 Oculus 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 three, and I would be very happy to give an update about them.

So 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 three diamond trial and 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, an unexpected setback on Lament 1 and 2, which were two phase threes in DME with OCS OCS 1. 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 previous sector and the Caminimab 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 Two, we decided to refocus our resources now on Prevosector with Pioneer 1, which is registrational trial in optic neuritis, and on PREDICT, which is a Likaminimab phase 3 trial as well, a registrational trial in dry eye with the genotype-based development.

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

So on pre-morphic sector, as you said, 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 SJK2 which activates FOXO3 which actually prevent or preserve neuron and oligodontal site from death the product was tested in multiple animal models in fact three models, glaucoma optic neuritis and multiple sclerosis showing consistently then when animals are receiving previous sector they are able to preserve their neurons then we went into phase 1 and then phase 2 phase 2 is called ACQUITY 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 previous sector plus steroids versus steroids alone patients on the 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 release 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 a breakthrough designation with FDA, we got Prime with MEA in Europe, and we went into detail and deep review with FDA on our protocol, we got 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.

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

Yeah. 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 Prevo, operationally, most probably we are enhancing, we have an 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 Prevo. Strategically, it was part of our pipeline and part of our programs.

And you're running currently three trials, correct?

So for PREVO, 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 NAON 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 NAON and Pioneer 3 will be on NAON 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, and 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 and Pioneer 3 will be in the second half, initiation at least.

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

So we do not have any treatment for neuroprotection. In optic neuritis, steroids are used to reduce inflammation, but still patients who are young, patients who 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 steroids, they do not recover LCBA. Therefore, there is a huge unmet medical need, no solution. This is an optic neuritis. In NAON, it's a different disease, the same outcome, loss of vision. And in NAON, we do not have anything, like nothing. I mean, I talk with many KOLs, and they say to them, what do you do when you have NAON? And really, the only thing they say to patients is, I am 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 two diseases, it would be a huge response to a big, massive and mathematical 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 100K in ophthalmology, and you take the number of cases per year, it creates an opportunity of $7 billion market. without anything available. So therefore, a huge opportunity for us, for patients, for our investors, and for the company.

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

So 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 2017, Pioneer 2 in the first half of 28. 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. So this should be done around September, October will be the right timing to refine. But so far, things are on schedule.

Yeah, excellent, great. So, you know, I think we mentioned earlier there's three indications that you're looking at for Prevo. so why don't we turn to potentially the largest indication, so MS, multiple sclerosis, relapse, similar question. What role do you expect PREVO to play in the treatment paradigm, and what do you think about the commercial opportunity there?

Yeah, so there are two types of MS, progressive MS, where we do not have really a solution so far. PREVO might play a role, let's see, and we have relapse-remitting MS. Relapse-remitting MS with the current immunomodulators, which are in fact good, we are able to reduce the number of relapses in a material manner. At the same time, we still have relapses. It is considered that in the U.S. we have between 200,000 to 400,000 relapses per year. The half of them, 200, need the treatment, like actively to be treated on top of the DMTs or immunomodulators. So for this patient, this patient is truly, during the flare-up, losing their neurons. Our product can help them to preserve their neurons and therefore reduce a 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 helped this patient 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 privosector 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 to 200,000 patients. So therefore it's huge, like it's between 6 to 7 times 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 which is super exciting anything you want to say about uh timing on on that particular indication beyond what you've said already or i would say so we are in pre pre ind phase with the neuro division yeah so as soon as we have clarity about pre ind uh 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 can benefit from Prevo. That raises the question strategically as you think about maximization of Prevo and the opportunity and 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 do you think about strategic maximization over time?

I would say the first focus is really 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 two requirements, we will be open to.

Anything more you'd like to add on Prevo, Rian, before we turn to OCSO2?

I think we discussed optic neuritis, we discussed NAOM, we discussed 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?

So this asset went into already three clinical trials, two in symptoms, one in sign. The three 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 hyper-respond to the drug. This genetic biomarker is specific on the TNF, and this patient who has this genetic biomarker hyper-responds to symptoms, and we saw it in the ED2, which is the second trial, and then we did it in a pre-specified manner in the signs, and we see the same thing as patients having this genotype hyper-respond in sign to Osses-O2 or Likaminivab. So this is very encouraging. Why? Because in a disease where there is 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 threes to try to show something. This biomarker allows us to really achieve three goals. One is a much more efficient program because somehow this biomarker helped 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 errors, like let's try, see if it works great, if it does not work, let's change. And in fact, we see that in Tri-Eye, 85 to 90 percent of treatment are stopped after six months so it's huge like the carryover very low yeah because of viability of this of this treatment so therefore first is is a very efficient development plan yeah the 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 errors which actually affect them because they are paying something very expensive without 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 swab like COVID so this is what we are doing, the trial is ongoing, it is a 29 days readout It's a symptoms trial, so it's a global discomfort score. So how we do it, we screen the patient for the TNF-R1. Positive patient, if they are positive, they go into a run-in period of two 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 running, and was randomized. And we are expecting the data to around the end of the year or the beginning of the next year.

Okay, excellent. Good.

And as it relates to this particular trial and clinical strategy, you know just given it's more sort of 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 your eye or yeah so let's perhaps to respond to the question let's come back to the diamond and what we learned so far and we will continue to learn we are expecting to receive the full data set but what we learned so in Diamond as I shared with you we repeated really the stage one the CST which is the biological response was as planned and 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 one 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 will lost efficacy during this like the duration of the treatment maybe that will lost efficacy. So this situation we don't have it with Lica Minimab, we don't have it with Privosector, with Pioneer because for both we are repeating exactly what we did in phase 2 Actually, the symptom for Likaminimab was day 29. We are doing the same symptom at day 29. Same thing. For privo sector, we did equity was month three. We are doing month three. So it is exactly the same thing. So we are not taking any risk in the translation between phase two to phase three. Now, for the rest, 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 them and the rest, nothing at all.

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

So in the context, 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 helped us because we find ourselves now, even with the setback on Diamond 1 and 2, with the portfolio which is very solid, with two phase 3 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 runaway until the second half of 29, and this allows us to deliver all what we say we are going to deliver for both assets, PrivoSector and Likaminimab. 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. Well positioned. It could be better, but it could be worse. Yeah, yeah, 2021. So, therefore, it's good.

No, it's good. Yeah, excellent. Okay, great. Well, look, Brad, that's all the questions that I had for you. Anything else you'd like to add before we depart?

Yeah, no, I would say the conclusion. I mean, as the CEO of the company, clearly Diamond 1 and 2 were the setback for the company, unexpected 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 previous sector 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.

Great. Excellent.

Well, thank you very much for your time, Riyad.

We really appreciate it.

Thank you very much.

Yeah, thank you again.