GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - OCULIS HOLDING AG

All right, good afternoon. Welcome to Guggenheim's third annual healthcare innovation conference. My name is Yatin Suneja, I'm one of the biotech analysts here at the firm. Our next presenting company is Oculus Holding. From the company we have Chief Executive Officer Riyadh Sharif. Riyad, why don't you make some opening comments, you know, tell us about the company, the programs that you have, some of the upcoming milestones, and then we'll go into the Q&A. Thank you, Thank you very much for inviting us. So, Oculis is a biopharma company focusing on neuro-ophthalmology or neuro-protection company actually. It has also in the same time product which is reading out very soon in precision medicine in ophthalmologists which is called Likaminimab. If I go one by one, so two late stage asset, prevom sector which is really the mid-term value driver driven by three programs. The first is in optic neuritis disease which is an orphan indication, often a complication of MS without any treatment and we are talking really about a young adult. The second indication is NAON which is orphan indication. In fact this This indication is actually increasing because of complications of other therapies, as you may know. And the third indication is acute MS relapse, where the treatment will be treatment of the flares of any acute MS or relapse. And then with Likaminib-Limab, as I said, it is a precision medicine genotype-based development focusing on a subset of population which represent 1.5 million patients, which is already huge, and it's reading out in a matter of weeks. In terms of upcoming milestone, I would say the first milestone which is upcoming is the IND for the neuroindication. We submitted already, and we are waiting for the confirmation. This should come in the upcoming days, weeks. Then we have an R&D day planned, December 8. And then we have the top line result. And of course, during the R&D day, we will be able to give an update on the execution of Pioneer One, fine tune the timing for Predict One, and explaining really the, I would say, the blueprint of multiple indications we are going to develop with previous sector. Got it, very good then. So let's start with like a mini-map, the anti-TNF drops that you have. Can you maybe put in perspective the phase two data that you have generated? This is, I think, going to become much more of a central focus for investors because you're going to get data relatively soon. So walk us through the phase 2 data, then talk about the predict one study that's going to read out what is a good data, what we'd like to see there. Yeah. So licaminimab is a TNF inhibitor, anti-inflammatory, anti-necrotic, is a fragment of the antibody which has a benefit of having high concentration and good ocular tissue penetration and it comes with really something very unique which is a biomarker which allows us to select patients who hyper respond to the TNF inhibition. Product went into three phase twos, two in symptom, one in sign. The most recent in symptoms showed in an exploratory manner that TNFR1 patients showed much better response in symptoms than all comers and really multiple. In most recent trial in science as well we saw that a patient, it was pre-specified secondary endpoint, patient TNFR1 in signs improved much more than all commerce and it's matter just to give a magnitude in sign it was like five times what we saw in all commerce six times with with what we so in the best phase three from the competition so really meaningful response versus what we see in our all commerce and in all other product so in terms of predict predict is a study in symptoms and we expect as well to see much better response in terms of efficacy but also in terms high responders like patient who are responding with more than 20 20 point vis-a-vis all commerce so therefore expectation from PREDICT-1 is really we are doing a precision medicine and the assumption is to have a precision in the same type of response which is which should be higher than what we see in our all comers and what we see with the competition. Got it. So in this study you recently completed enrollment of 176 patients. So first question is what percentage are TNF-R1 with the TNFR1 genotype? Yeah. And then you mentioned about the efficacy on the primary endpoint which is global ocular scale discomfort scale and then the responder rate what do we know about placebo like how does the placebo sort of or the expectation there for placebo and the drug effect yeah yeah so you are you are totally totally right so we randomize 176 page patient the plan which randomized 160 patient we went slightly higher because it's typical if you have patient who are in the running or patient in the screening you do not stop them is for ethical reasons so therefore you over overshoot slightly so therefore it's good very happy screening was really very fast very simple is a saliva swab is a covet type of test very rapid in terms of a placebo response you are totally totally right we see placebo response in dry eye because it's the lubrication and if you lubricate the eye the eye will feel better and and therefore you see it in symptoms, absolutely. The way to address it is the following. First, we have a run-in period, where during two weeks, we give to everybody artificial tears. And patients who are responding to artificial tears will not be randomized. So therefore, you clean the baseline, basically. The second, we had a threshold of between 100 to, between zero to 100 points in the discomfort scale. We have a threshold of 60, so patients need to stay above 60. If they are below 60, it means they improved, and therefore they are not randomized. So therefore you enrich also with the symptom score. And the last, we have the enrichment based on the TNFR1. So therefore we believe that we are handling what we typically see with the placebo. Got it, got it. And then I don't know if you just said it. What was the TNFR1 proportion in this study? Yeah, two-thirds. Two-thirds of the patients are TNF1 patients. Okay. And then in terms of a drug effect, actually two questions. In the overall patient population, what is a drug effect that will be good or meaningful? In TNVR1, what will be a good result? And then how does it disinform the next steps? Yeah. So basically, this is a phase three. So therefore, if this study is positive, we will repeat this. Now, what do we expect as a good result? If we take the previous phase two in symptoms, the difference between, in all comers, the difference between the drug versus placebo was 4.3 point. I would say good response will be doubling this in the TNFR1. I see. same in all commerce double in the TNFR one the same in responders in all commerce we had 18 percent who gained more than 20 point I would say we would need to see something which is higher than 25 percent 25 percent I see like 50 percent more yeah yeah basically doubling or 50 percent more effect yeah Okay, and then how is the study? So the study is powered on first the TNF-R1 subset? Yes. That's how the powering works and is there a minimum delta that you could detect there? So we didn't disclose actually this. The plan is to disclose further during the R&D to give a full picture on the execution of the trial and what to expect. I was trying to get some answer here so that you don't have to disclose it on December 8th. So you need two and two studies, right? Two symptoms and two signs. If this study is successful on the symptom front, you need three more studies or there is still room for negotiation? So you are totally correct. The base scenario is two and one. And we are separating them. So we are doing symptoms and signs separately. Now we will see the result, meet with FDA, and see what FDA wants us to do. But I would say the minimum will be at least to do one in science. This is the minimum. But the base case scenario is really two and two. Now, the advantage of the biomarker and the drug effect we have with the biomARKER, a typical phase three in dry eye is 2,000 patients. The whole four trials, two and to, in our program, will be around 650 patients. So it's a much lower number of patients, it's much more efficient, and we are talking about trials which are actually less than 10 million trials. Got it. Oh, wow. It's efficient. It's very efficient. And these are fast. Even this one unrolled very fast. It's unrolled extremely fast, actually. And it shows that, actually, when you look for these patients who are severe patients, not responding to artificial tear, TNFR1 positive, it's very easy to find them and when we think about the population like when you take the whole population of dry 40 million patients in dry in the US the population we are targeting is 1.5 million but this 1. 5 million are populations who are moderated to severe who are higher than the 60 point in discomfort score TNFR1 positive patient so it stays actually meaningful 15%, as you know, TNFR1 is published in terms of incidence is between 13% to 19%. So Aprox is 15%. It gives us the 1.5 million. Very interesting. What are drugs that are approved for this? I mean, not specifically for TNF1. I'm just trying to understand for our audience what is the commercial opportunity for a product like this. So the five last drugs which have been approved the last five years, the price is, if I recall well, between $132,000 to $1,004,000 per month. So therefore, I would say an average of $900. And this is without precision medicine. So even without precision medication, you assume this price. You assume $1.000 per year. You get 20% of the $1.,000. five with the precision medicine is much stronger value story for payers actually when you say to them if you test patients you have much higher likelihood that this patient is responding is a much better for for access so therefore it's really like the the the trans the transformation we want to implement here in dry eye which is a typical trials and error type of treatment is to to move from trials and error to test and treat. Got it, got it. And then these products, like what are the biggest product in the space in dry eye disease? I would say the two biggest products now are most probably Mibo and Restasis. Yeah, I see. Sorry, and Xydra. Restasis is perhaps the cyclo franchise, yes, but not Restasis alone. So this product could have that level of peak potential. Potential? I would say higher. I will tell you why. I truly believe it's higher, assuming the same pricing. So assuming the same price, we have leeway to be in better price. But assuming the highest same price pricing, we should deliver much more revenues for the following reason, is when you see today, after six months, only 10 to 15% of patients are staying with the drug is mainly because the drugs are not good enough. If we have a better efficacy, if we have a higher responder rate, then our adherence to the treatment will be higher and therefore for the same number of patients, the value per patient will be the double or the triple and therefore precision medicine should drive much higher value in fact. Got it, very good, very helpful. All right, good luck with those results and we'll see what additional information you provide on December 8th. Let's move to previous sector. How is that, number one, maybe just orient everybody, the disease a little bit, what is optic neuritis and what is the mechanism, anything that you've seen in previous study and then how is the ongoing phase three study going? Yeah, so pre-pop sector is based on the clinical data. first neuroprotective drug ever. We are addressing, we are starting with optic neuritis because optic neurosis has two or three shot on goal, at least two shot on call. One, it is an orphan indication without a treatment. It affects a young woman in general, 32 years. So really the young mother who is losing vision. So therefore without a treat. And we have potentially treatment for this patient so amazing but the second shot on goal is is the optic neuritis is the best model to measure neuroprotection why because we have the function we have structure with OCT so just to give you an idea the precision of OCT is two microns precision of MRI is 200 microns so what we see in four weeks we see it in four years in MRI so it's an amazing model And then we do neurofilament and the GFAPs, which are actually a typical biomarker we use in MS and ALS and so on. So, therefore, amazing proof of concept. So, we are starting with optic neuritis. The aim is to go to acute MS relapse and to NAON. How PioneerOne is going? Pioneer One is going well. Pioneer one is going, well, it is tracking on plan in terms of activation, in terms of enrollment. our really aim is to finish the year with 50% of the site activated which means 30 30 site our aim is you have 60 in total the goal is to finish the Year at 30 site it gives us a very strong solid critical mass because the the relapses and optic neuritis are mainly seasonal because this virus is driven. And therefore, the season really starts in December and in May. So I would like, I mean, we would like to make sure that we are well prepared with like referral system in place, the ER in place everything in place to maximize our enrollment. Got it. Got It. So in the maybe just going back first to the equity study, the phase two study that you conducted, What was the defining data set that you saw there? Was it just the improvement in LCVA? Or just curious, number one, what was appealing from an efficacy standpoint? And then also, now you go into Pioneer One. Are the patient population exactly similar to what you enrolled in ACUTI? Yeah. So in equity, what was really exceptional is positive benefits and end point in every efficacy measure we did. So we started with the function with LCVA, 18 letters difference, maintained over time till month six. And we know based on the natural story that what we get at month three is sustainable over time. And in fact, the proof is FDA accepted in phase three, an endpoint at month three. This is the first point. The second point in terms of structure, we were able to measure the structural preservation of the neurons in the retina by measuring GCIPL and measuring RNFL. And then the third, in terms OF biomarker, we showed that we had less neurofilament release in the blood, which means less axonal damage. And we showed that we had less GFAPs releasing in the blood and CSF, which means less glial activation or injury. So therefore, consistently, what we see in the function is actually supported by the structure and supported by the neurofilament. And really, all this data set gave us both breakthrough at FDA and prime at EMEA. I see. I see it. So with the endpoints, what is the endpoint now? Is it the same endpoint as ACQUITY? So the endpoint is LCVA in ACQUTY, is LCVAs in PioneerOne. We will do also on top of LCVA, we will do LCVA2 mean end responders. We will GCIPL as well and NFLs. These are the secondary endpoints. Exploratory, we'll have GFAPs. Okay. How many studies are needed? What about pioneer two? And then what about pioneer three? When are those going to start? So this is a new molecular entity. We need 300 patients exposed to the drug. One study will give us 140. So therefore, we need two studies. And this is what is aligned with FDA. We needs two studies, pioneer one and pioneer two. Now, the program we are doing with Pioneer 1, 2, 3 is really with three trials, we will get two labels. One is optic neuritis, which will be supported by Pioneer 1 for all optic neurritis, all comers, and Pioneer 2 for optic neurosis in MS. But then Pioneer 3 will serve actually two purposes. One is optical neuritis and one is acute MS relapse. I see, I see. So in the acute, so isn't that a separate study, the acute MS? So in acute MS relapse, it will be supported by two trials, Pioneer 2 in optic neuritis MS and Pioneer 3 in ambulatory relapse. So it's like pain, and we are showing that we can reduce pain in two locations, basically, I mean, if I illustrate. Got it. I see. And then, so with regard to the acute MS relapse, I think the IND is expected this quarter, right? I think you sort of provided a little bit more color there. How did you come up with that? Like, what is the evidence to go into acute MS? So the evidence should go to acute MS is because optic neuritis is an MS relapsed. relapse. In fact, even in our trial, in acuity trial, we have two-thirds of patients who were already MS, like known as MS, treated for MS. And the last two-third of them, it was the first onset of MS. So therefore, it's heavily MS-driven. And when we did the sensitivity analysis and we compared, the product worked in the MS group as well as in the rest of the group. So, therefore, And the translation is really direct. So I think in the fourth quarter or most likely next month is when you're going to disclose the protocol for the MS study? Yes. What will be the size of the scope? Do you need one study or do these other studies support the approval? I would say the Pioneer 2 will be one study. One that supports. Pioneer 3 will be a second trial. I see. Okay. And FDA, as you may recall, and this is what we disclosed, FDA in pre-IND meeting, they said we don't need preclinical data, we can go directly to a three-month study endpoint, the same regimen, the same dose, so therefore same regimens, the same dose in in ambulatory MS, yes. Okay, very good. Wow, there's a lot going on. Okay Maybe then finally on the financials, how is the financial, what is the cash runway, how much of the stuff is already factored into your bond rate? Yeah. So basically, so what we published, I think the last week, so end of September, we had $252 million in the bank without taking into account debt facility we have with the Black Rock of 100 million Swisses. so this this covers us till the second half of 2029 and covers us really on all what we are saying in terms of predict one and pioneer one two three very good for very good Riyadh that's all I had for you well thank you so much thank you looking forward to the December 8th investor day yes thank you very much thank you