All right, good afternoon. Welcome to Guggenheim third Annual Healthcare Innovation Conference. My name is Yatin Suneja, one of the biotech analysts here at the firm. Our next presenting company is Oculis Holding. From the company, we have Chief Executive Officer Riad Sherif. Riad, why don't you make some opening comments, 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, Yatin. Thank you very much for inviting us. So, Oculis is a biopharma company focusing on neuro-ophthalmology, or neuroprotection company, actually. It has also, at the same time, a product which is reading out very soon in precision medicine in ophthalmology, which is called licaminlimab. If I go one by one, so two late-stage assets, privosegtor, which is really the midterm value driver, driven by three programs. The first is in optic neuritis, a disease which is an orphan indication, often a complication of MS without any treatment, and we are talking really about young adults. The second indication is NAION, which is also an orphan indication.
Yeah.
In fact, 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 relapse. With licaminlimab, 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 milestones, I would say the first milestone which is upcoming is the IND for the neuro indication. 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 8th, and then we have the top-line result.
During the R&D Day, we will be able to give an update on the execution of PIONEER-1. Fine-tune the timing for PREDICT-1, and explaining really the, I would say, the blueprint of multiple indications we are going to develop with privosegtor.
Got it. Very good then. Let's start with licaminlimab, the anti-TNF drops that you have. Can you maybe put in perspective the phase II 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 II data, then talk about the PREDICT-1 study that's going to read out. What is a good data? What would you like to see there?
Yeah. So licaminlimab is a TNF inhibitor, anti-inflammatory, anti-necrotic.
Yeah.
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 patient who hyper-respond to the TNF inhibition. Product went into three phase IIs, two in symptom, one in sign. The most recent in symptom showed in an exploratory manner that TNFR1 patient showed much better response in symptoms than all-comers.
And really multiple. In most recent trial in signs as well, we saw that patient, it was pre-specified secondary endpoint, patient TNFR1 in signs improved much more than all-comers. It's a matter, just to give a magnitude, in sign, it was like five times what we saw in all-comers, six times with what we saw in the best phase III from the competition. So really meaningful response versus what we see in our all-comers and in all other product.
Got it.
In terms of PREDICT is a study in symptoms, and we expect as well to see much better response in terms of efficacy, but also in terms of high responders, like patient who are responding with more than 20 point vis-à-vis all-comers. Therefore, expectation from PREDICT-1 is really, we are doing a precision medicine, and the assumption is to have a precision medicine type of response, which should be higher than what we see in our all-comers and what we see with the competition.
Got it. In this study, you recently completed enrollment of 176 patients. First question is, what percentage are TNFR1, with the TNFR1 genotype?
Yeah.
And then you mentioned about the efficacy on the primary endpoint, which is global ocular discomfort scale, and then the responder rate. What do we know about placebo? How does the placebo sort of, or the expectation there for placebo and the drug effect?
Yeah. You are totally right. We randomized 176 patients. The plan was to randomize 160 patients.
We went slightly higher because it is typical, if you have patients who are in the running or patients in the screening, you do not stop them. It is for ethical reasons, so therefore you overshoot slightly. Therefore, it is good, very happy. Screening was really very fast, very simple. It is a saliva swab, it is a COVID type of test, very rapid. In terms of placebo response, you are totally right. We see placebo response in dry eye because it is lubrication, and if you lubricate the eye, the eye will feel better, and therefore you see it in symptom, 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.
Patients who are responding to artificial tears would not be randomized. Therefore, you clean the baseline, basically. The second, we have a threshold of between 0 to 100 points in the discomfort scale. We have a threshold of 60. Patients need to stay above 60. If they are below 60, it means they improved, and therefore they are not randomized. Therefore, you enrich also with the symptom score. The last, we have the enrichment based on the TNFR1. Therefore, we believe that we are handling what we typically see with the placebo.
Got it. What was the TNFR1 proportion in this study?
Yeah, it is two-thirds.
Two-third.
So two-thirds of the patient are TNFR1 patient.
Okay. 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 TNFR1, what will be a good result? How does this inform the next steps?
Yeah. So basically, this is a phase III, 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 II in symptoms, in all comers, the difference between the drug versus placebo was 4.3 point.
Yeah.
I would say good response would be doubling this.
in the TNFR1.
I see.
Same in all comers, double in the TNFR1.
Got it.
The same in responders. In all comers, we had 18% who gained more than 20 points. I would say, we would need to see something which is higher than 25%.
25%. I see.
Like 50% more.
Yeah. So basically doubling or 50% more effect than that. Okay. How is the study? The study is powered on first the TNFR1 subset?
Yes.
That's how the powering works. Is there a minimum delta that you could detect there?
We didn't disclose actually this. The plan is to disclose further during the R&D Day 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. 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 study, or there is still room for negotiation?
You are totally correct. The base scenario is two and two, 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 want us to do. But I would say the minimum will be at least to do one in signs. 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 III in dry eye is 2,000 patients.
The whole four trials, two and two, in our program will be around 650 patients. So it's much lower number of patient, it's much more efficient, and we are talking about trials which are actually less than $10 million per trial.
Got it.
Therefore, it's
Oh, wow.
It's efficient. It's very efficient.
These are fast. Even this one enrolled very fast.
It's enrolled extremely fast, actually.
Yeah.
It shows that actually when you look for this patient who are severe patient, not responding to artificial tear, TNFR1 positive, it's very easy to find them.
Yeah, exactly.
When we think about the population, like when you take the whole population of dry, 40 million patients in dry in the U.S., the population we are targeting is 1.5 million. But this 1.5 million are population who are moderate to severe, who are higher than the 60 point in discomfort score, TNFR1 positive patient.
Mm-hmm. Got it.
It stays actually meaningful. 15%, as you know, TNFR1 is published in terms of incidence is between 13%-19%. So approx is 15%. It gives us the 1.5 million.
Very interesting. What are drugs that are approved for this? I mean, not specifically for TNFR1. I am just trying to understand for our audience what is the commercial opportunity for a product like this?
Yeah. The five last drugs which have been approved the last five years, the price is, if I recall well, between CHF 132 to CHF 1,004 per month. Therefore, I would say an average of $900. This is without precision medicine. Even without precision medicine, you assume this price, you assume $1,000 per month.
Yeah.
You get 20% of the 1.5. With the precision medicine, it is much stronger value story for payers actually, when you say to them, if you test patient, you have much higher likelihood that this patient is responding. It is much better for access. Therefore, it is really like the transformation we want to implement here in dry eye, which is a typical trials and error type of treatment, is to move from trials and error to test and treat.
Got it. Got it. These products, what are the biggest product in the space in dry eye disease?
I would say the two biggest product now are most probably MIEBO and RESTASIS.
Yeah. I see. Okay.
Sorry, and XIIDRA. RESTASIS, perhaps the cyclo franchise, yes, but not RESTASIS alone.
This product could have that level of peak potential?
Potential, I would say higher.
Yeah.
I will tell you why. I truly believe it's higher, assuming the same pricing. Assuming the same pricing, we have leeway to being better price. But assuming the highest same pricing, we should deliver much more revenues for the following reason. When you see today, after six months, only 10%-15% of patients are staying with the drug, it's 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 patient, 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.
Thank you.
We'll see what additional information you provide on December 8th. Let's move to privosegtor.
Yeah.
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 have seen in preclinical and previous study, and then how is the ongoing phase III study going?
Yeah. privosegtor is, based on the clinical data, the first neuroprotective drug ever. We are addressing, we are starting with optic neuritis because optic neuritis has two or three shot on goal, at least two shot on goal.
One, it is an orphan indication without a treatment. It affect a young woman in general, 32 years, so really the young mother who is losing vision. Therefore, without a treatment, and we have potentially treatment for this patient. Amazing. But the second shot on goal is the optic neuritis is the best model to measure neuroprotection. Why? Because we have the function, we have the structure with OCT. 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
Yeah.
in MRI. It is an amazing model. And then we do neurofilament and the GFAP, which are actually typical biomarker we use in MS and ALS and so on. Therefore, amazing proof of concept. So, we are starting with optic neuritis. The aim is to go to acute MS relapse and to NAION. How PIONEER-1 is going? PIONEER-1 is going well. PIONEER-1 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 site. Our aim is to have 60 in total. The goal is to finish the year at 30 site. It gives us a very solid critical mass because the relapses and optic neuritis are mainly seasonal because it is virus-driven, and therefore the season really start in December and end in May.
We would like to make sure that we are well prepared with referral system in place, the ER in place, everything in place to maximize our enrollment.
Got it. Got it. In the, maybe just going back first to the ACUITY study, the phase II study that you conducted, what was the defining data set that you saw there? Was it just the improvement in LCVA? Just curious, number one, what was appealing from an efficacy standpoint? Then now you go into PIONEER-1, are the patient population exactly similar to what you enrolled in ACUITY?
Yeah. In ACUITY, what was really exceptional is positive benefits and endpoint in every efficacy measure we did.
Yeah.
We started with the function with LCVA, 18 letters difference, maintained over time till month six. We know based on the natural story that what we get at month three is sustainable over time. In fact, the proof is FDA accepted in phase III, 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. 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 GFAP release in the blood and CSF, which means less glial activation or injury. 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 EMA.
I see. I see. So, with the endpoints, what is the endpoint now? Is it same endpoint as ACUITY?
The endpoint is LCVA in ACUITY, is LCVA in PIONEER-1.
Okay.
We will do also on top of LCVA, we will do LCVA 2.5%, mean and responders.
Yeah, mean and responders, yeah.
We will do GCIPL as well.
Okay.
NFS. These are the secondary endpoint. Exploratory, we will have GFAP.
GFAP, okay. Okay. How many studies are needed? What about PIONEER-2, and then what about PIONEER-3? When are those going to start?
This is new molecular entity. We need 300 patient exposed to the drug. One study will give us 140, therefore we will need two studies. This is what is aligned with FDA. We need two studies, PIONEER-1 and PIONEER-2. The program we are doing with PIONEER-1, 2, 3 is really with three trials. We will get two labels.
Yeah.
One is optic neuritis, which will be supported by PIONEER-1 for all optic neuritis, all comers, and PIONEER-2 for optic neuritis in MS. PIONEER-2 will serve actually two purpose. One is optic neuritis
Yeah.
and one is acute MS relapse.
Acute MS, yeah. I see. Is that a separate study, the acute MS?
An acute MS relapse will be supported by two trials.
Yeah.
PIONEER-2.
Oh, I see.
in optic neuritis MS.
In MS.
And PIONEER -3 in ambulatory-
Ambulatory
relapse.
I see.
It is like pain, and we are showing that we can reduce pain in two locations, basically. I mean, if I illustrate.
Got it. I see. Then with regard to the acute MS relapse, I think the IND is expected this quarter, right?
Yes.
You sort of provided a little bit more color there. How did you come up with that? What is the evidence to go into acute MS?
The evidence to go to acute MS is because optic neuritis is an MS relapse.
Yeah.
In fact, even in our trial, in ACUITY trial, we have two-thirds of patients who were already MS, known as MS, treated for MS.
The last two-thirds of them, it was the first onset of MS. Therefore, it's heavily MS driven. 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. Therefore, the translation is really direct.
Yeah. Yeah. I think in Q4 or most likely next month is when you're going to disclose the protocol for the MS study?
Yes.
What will be the size or scope? Do you need one study, or these other studies support the approval?
I would say, the PIONEER-1, the PIONEER-2 will be one study.
One that support.
PIONEER-3 will be the second trial.
I see. Okay. Okay.
FDA, as you may recall, and this is what we disclosed FDA in pre-IND meeting, they said, "We don't need preclinical data.
Yeah.
We can go directly to a three months study endpoint, the same regimen, the same dose.
Same regimen?
Same regimen, the same dose 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 burn rate?
Yeah. So basically, what we published, I think last week, so end of September, we had $252 million odd in the bank, without taking into account debt facility we have with BlackRock of CHF 100 million. This covers us till the second half of 2029, and covers us really on all what we are saying in terms of PREDICT-1 and PIONEER-1, 2, 3.
Okay. Very good. Well, very good, Riad. 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.