I'll sit here.
I don't know why I've just been comfortably sitting over here. All right, everybody, we're going to get started with our next session with Oculis Holdings, and we have Sylvia Cheung, who's the CFO. Thank you so much for joining us.
Thank you for having us.
This has been one of our favorite stories ever since we first met your company a few years ago. I have to say, it's just been playing out really nicely. It's interesting. I remember when we first started, I was like, okay, we've got this lead asset that's really, really interesting. Then we have the second asset that also could be interesting. As the story kind of went along, we got the second asset, became interesting. It's like, yeah, that third asset may or may not, I don't know what to make of it. Now, all of a sudden, we have a third asset that could be even more.
Well it's people's minds.
It could be even more interesting than the first two. We'll obviously get into those three assets and some specifics. Why don't you just give us a quick, how did we get here? What did you all accomplish over the past 6- 12 months to get here? Just to give everybody a quick update.
Absolutely. Thank you. First of all, thank you for having us. It's a great pleasure to be here. We've come a long way in terms of getting to where we are. I think initially, the company, when the company you asked for 12- 18, but I go a little bit back.
You can go back.
The company.
It's fine.
The company had OCS-01, which is very innovative, right? First topical that can go to the back of the eye. We have really good phase II data. Then we had stage one of phase III data, which showed strong efficacy, which is excellent. By design, the company built out a portfolio of innovative novel assets. We added OCS-05, which is a neuroprotective asset. OCS-02 was also an additive asset, which is a biological topical eye drop for dry eye, but it has a precision medicine approach where nobody else has. All these assets are designed with two things in mind. One is it has to be novel in terms of how it works. Two, it has to target large markets with high differentiation.
We have been able to, through really hard work, deliver good news from a clinical standpoint on all those programs. Happy to speak more about whether you all.
Where did you get these programs?
OCS-01 is proprietary, fully developed in-house. It was invented in Iceland. We continue to have a formulation development lab there, which we are leveraging for other applications, other assets, topical application. OCS-02 is in-licensed from Novartis. OCS-05 is in-licensed from Accure Therapeutics about 2.5 , 3 years ago.
Yeah. Kind of bizarre that Novartis would license the product. Why wouldn't they want it themselves? What is the rationale there, do you think?
At the time, my understanding was they had two dry eye products. I think they picked the wrong one, perhaps. We really liked the profile of OCS-02. After we took over, we did a lot of work to advance its clinical development. The latest readout was around mid-year of last year, which showed really strong results on a patient population, which we can get into more details, TNFR1 positive patients, where we saw 5-7 fold improvements in signs and symptoms.
Very exciting. All right, which product do you want to kind of dive into first? Your choice.
It's up to maybe OCS-05.
OCS-05 it is.
Because it's fresh.
Yeah. So talk about what OCS-05 is and what was unique about the data. What was the end points that you're looking at? What did you achieve?
Absolutely. OCS-05 is a complete new molecule, if you will, new mode of action. It is a peptide mimetic small molecule. It is peptide-like. It is an activator, not a blocker. Before we have the clinical studies, we had a lot of preclinical data, which were very promising. In seven animal studies, and those animal studies, those models included glaucoma, multiple sclerosis, and AON, we saw that animals that received OCS-05 had neuroprotection, meaning retinal ganglion cell protection effects after they were administered with OCS-05. On top of that, we also had functional studies on those animals. The animals had better mobility with administration of OCS-05. We saw anatomical improvement as well as functional improvement. The latest study that we did, which was completed in late 2024, was called ACUITY. The study was ACUITY. It was studying acute optic neuritis.
It's an acute disease. The study's primary endpoint was safety. We met the primary endpoint, no issues, nothing to report there. What's interesting and very exciting is that for the efficacy results, there were two anatomical measurements that we did. Both were measured through OCT, and I'll go through what they are. There was also a functional endpoint. The two anatomical endpoints, one is called GCIPL. This one is a biomarker to measure the retinal ganglion cells in the retina. What we saw is the patients with OCS-05 had 43% better improvement in the reduction of retinal ganglion cells compared to the placebo group. Let me perhaps step back a little bit. The two arms of the study, one is OCS-05 plus steroid. The other one is placebo with steroid.
The reason why steroid is in there is because currently there's no treatment for acute optic neuritis. The standard of care is injection of steroid for five days, once daily for five consecutive days. When we did the study, it was OCS-05 plus steroid versus placebo plus steroid. We're not really comparing to a so-called placebo because steroid is there, which is the current standard of care. Back to GCIPL. GCIPL is the biomarker for retinal ganglion cell, which is the neuron in the retina. What we saw is OCS-05 was able to preserve retinal ganglion cells 43% better than steroid, which is quite remarkable. It's statistically significant. On RNFL, the other biomarker, which is a biomarker to measure axon, it's also done through OCT. What we saw there is there was 28% of improvement comparing to the placebo.
The study was six months. We measured it at month three and measured it at month six. We saw strong results in month three, which got carried over to month six as well. Anatomically, we saw both were going in the same direction. The OCS-05 product was able to prevent the loss of retinal ganglion cells and the axonal decrease, which is obviously very important from an anatomical standpoint. What is more interesting is from a functional standpoint, we measured LCVA, which is low contrast visual acuity. For patients with acute optic neuritis, they have low visual acuity issues, meaning they can read perfectly well under daylight, normal lighting environment. If the lighting is not good, they cannot read newspapers. They cannot drive at night. The low visual acuity is a problem for AON patients.
What we saw in the LCVA result is that at month three, we saw an 18-letter gain versus placebo for patients who received OCS-05, which is remarkable. That result also maintained at month six. Between the anatomical and the functional endpoints that we saw, they were all pointing in the same direction, very strongly, very positively. We are very excited and confident in terms of moving to the next stage of development.
What kind of adverse events did we see? This is an eye drop?
This is an IV.
This is an IV.
Correct. The current standard of care is IV.
How long does it take?
I don't know the exact duration, but it's not super long.
Not long.
Yeah. It is daily. The patients do not need to stay in the hospital. It is not inpatient. You go in, you get the infusion, and you go home. You do it for five days.
Okay.
Yep.
Were there anything of note regarding the adverse events?
Nothing. No adverse events related to the drug. The primary endpoint safety was met. There is really nothing surprising to report.
That was reported out at the end of last year. Have there been any additional analyses from the trial? Anything else that you can kind of point to?
Yeah. We are expecting some additional. That was the top-line result, which was announced in the beginning of this year, right before JPM. We are currently waiting to analyze additional more details. As soon as we have that information, we'll be looking to share with the investment community about what they are.
The change in the vision correlates with these anatomical measures.
Exactly.
I mean, is that something that the FDA is going to look to for a pivotal study where you have to have both? Is that the idea?
Yeah. We have stated publicly that our discussions with the FDA on the next stage development of pivotal development will be in Q3. We will have meetings and interactions with them about the next trial in terms of trial design endpoints. We do believe that we have the endpoint, which is a functional endpoint, LCVA, because the FDA typically approves BCVA, LCVA, and visual field. LCVA is a perfectly fine, approvable endpoint. We saw.
As a primary endpoint.
Yeah. Exactly.
Do you think these biomarkers will be secondaries? Or is that.
I think that's to be discussed. Yeah, to be discussed. We have our hypothesis and our preferred design. We'll wait to speak with the FDA in the third quarter. From there, we'll be rapidly looking to commence the trial enrollment.
Is it your guess that this is going to be one study? Or do you think you need two studies for this?
For planning purposes, we're thinking two. We obviously, from a capital efficiency, from a time-to-market standpoint, will do what we can to see how we can optimize it, obviously, with the FDA's approval.
Lastly, just talk about what do these patients do today and how many patients are there? How big a market is this?
Yeah. The market is currently estimated at about 65,000 patients between the U.S. and Europe. It's roughly half-half between those two geographies. It is an acute disease, which means that when it happens, it just happens super rapidly. Pain in the eye and rapid loss of vision. Typically, patients would go to try to figure out what's happening. When they get diagnosed, they'll be told that they have AON. The infusion process will start shortly thereafter for five days consecutive, daily.
Yeah, they've got it. There's really nothing. What are they doing today?
Today is steroid. Yeah, steroid injection. There are no products approved for neuroprotection. The remarkable, I'd say, outcome of the ACUITY study is it allows us to move forward with AON. It can also be viewed as a proof of concept for other potential indications in ophthalmology and beyond ophthalmology.
Like what? Give us a sample.
In ophthalmology, if we talk about the retina, glaucoma and DR can be potential indications. If we talk about cornea, NK, neurotrophic keratitis can be an indication. The product was originally designed with MS in mind. As a matter of fact, 60% of the patients in our ACUITY study had MS. This product can potentially be applicable for MS as well.
Are there any other endpoints that you looked at that would be telling you that it's helping the MS?
I think there are additional data that we'll be getting that can give us more insights to that. Currently, we're in the process of analyzing.
These biomarkers, which most people probably do not know these biomarkers, right? But these are not MS biomarkers as well? Or are they? Are they specific for the eye? I mean, I do not know the answer.
These are specific for the eye. I'm not scientific and technical enough to say what endpoints for MS will be. That is something that we will be continuing to look at, the additional data beyond the top-line results, and see how we can pave a pathway toward additional indications.
Okay. OCS-02?
OCS-02. OCS-02, or Licaminlimab, is a topical, meaning an eye drop for dry eye disease. The uniqueness about OCS-02, one, it is a topical, sorry, biological product. Two, in the previous studies, and we're talking about multiple studies, we had identified a patient group, patients who have a specific genotype called TNFR1, who would super respond to OCS-02. In multiple trials, we saw that the efficacy results were significantly better than people without TNFR1. As I mentioned before, because the FDA requires signs and symptoms from a dry eye approval standpoint, as you know, what we saw is OCS-02 would provide five-fold improvement on signs for this particular genotype patients and seven-fold improvement on symptoms, which is quite remarkable because currently, the market, we know there's a lot of products. They don't work too well.
Study or data shows that 87% of patients would drop their treatment within six months. Physicians are telling us that they're really using this trial and error approach on patients. People come in with a bag, and they just go through and cycle through and see what works. This precision medicine approach is valuable in a sense that you can predict outcome. We don't need, I mean, dry eye patients, there are a lot of them. This genotype is roughly about 20% of the U.S. population. It's roughly about 2 million or so. By being able to identify those patients and predict the outcome, it is welcomed by physicians. From a financial standpoint, it's a better P&L all the way top to bottom, less salesforce, premium pricing, better.
What is that marker?
It's a.
Is it a?
TNFR1.
It's a specific mutation that people have? Is that what this is, or?
Sorry?
Let me go back before you even ask that question. You analyzed both the large regular dry eye population and.
All comers.
The subpopulation.
Correct.
Even before we go to the subpopulation, how did the data look in the full population?
It shows that it works for all comers. The results for the TNFR1 subgroup is significantly stronger across all the exploratory endpoints that we looked at.
Yeah. That's not surprising. I mean, it's a TNF. It's an anti-inflammatory.
Exactly.
Like it should be working on people who have an inflammatory component, which I actually don't know what inflammatory component represents.
It's a very complex disease with multiple factors, which is one of the reasons why it's very hard to treat.
You hit good numbers with respect to the full population, but the subpopulation was even better. Is that right?
Exactly. Exactly right.
How many patients did we have we seen this in?
It was 148 patients, if I remember correctly.
In total, right?
In total, yeah.
Right. The subpopulation was, I do not remember what it was. Was it 20, 30, 40? I do not know. It was a subpopulation.
Sorry, it's 122.
Total.
Right.
I want to say that about 60 or so patients were TNFR1.
Yeah. Yeah. Very exciting. Okay. What's next? What do we do now that we've seen this?
We are speaking with the FDA about testing the TNFR1 subgroup and what the next trial design would look like. I am going to do a little advertisement now. The company is planning on an R&D day coming up in April. We will be giving more detailed information about our plans vis-à-vis the FDA, as well as for OCS-05, what our thoughts are in terms of pipeline development and where we would focus on. More to come on specifics.
You have already met with the FDA.
We have.
You'll disclose.
Correct.
In April is what you're basically saying, the plan.
Exactly.
The goal has always been to focus on the subpopulation where it's a smaller number. How many patients are we talking about? You said it was 2 million.
2 million. Yep. It's 20% of the U.S. general population. The headline of that interaction is we now have clarity to go to the next trial, being able to have the trial to focus on the TNFR1 population.
Interesting. Okay. Any feedback from the physicians on this product and what they think about this precision approach?
The overall feedback is very positive because of the current issue in the market where people are trying and not knowing if it works. Patients, 87% of patients just dropped their treatment within six months.
There was Restasis or.
Whichever.
Yeah.
Yeah. Sometimes the products come with two issues, pain and staining effect. It is not comfortable, which we are not seeing in our study. The last study, from a patient comfort standpoint, it was being, the data suggesting from a qualitative description standpoint, it was described as a placebo-like comfort level, which is very good. From an onset standpoint, products currently on the market will kick into effect in a matter of months. Ours would be in a matter of weeks. The fast onset relief without discomfort is also, from a patient standpoint, very positive.
Are there any side effects here at all? Like what did we see?
No. No side effects.
Nothing related to point two?
No.
Because I know that the, well, Restasis basically, you put it in the eye, it kind of burns and makes your eyes a little bit red for the first, I don't know, few weeks or whatever. Then it's finally starting to.
The safety results from the RELIEF study, which was the last phase to be resolved, was pretty pristine. Being a biologic, I think it also helps as well.
Okay. Okay. Let's flip to the other product, OCS-05, which is when I first met the company, this was really the focus of the company, the exciting part. We kept the best for last. Describe what is O5.
OCS-01.
I'm sorry, OCS-01?
Yeah, OCS-01.
I apologize.
We went reverse.
I apologize. Did I say OCS-05? I meant OCS-01.
OCS-01.
The DME product.
The DME product. Yes, the DME product. The DME product. The DME product, it's the first topical that reaches the back of the eye. That is the excitement, right? We have multiple clinical trials that showed efficacy and safety for that product. Currently, the approved products on the market, as you know, are either injectables or implants. It involves a needle into the eye. There are about 1.8 million patients diagnosed in the U.S. About 500,000 of them are actually treated with these invasive products.
Yeah. VEGF injections. Pretty standard.
Exactly. And roughly, for those who are treated, about 40% are not getting adequate response. It creates an issue where the vast majority of the patients aren't getting treated because of the invasiveness and the not convenience of going into the hospital because these patients are diabetic patients. On average, they spend about 29 days away from work. I mean, these are working group patient population. They spend about 29 days visiting doctors' offices. Asking for diabetes, not for DME, right? Asking them to take another X number of days to go to the retinal specialist to get injected with an invasive product. There's just a lot of issues there. We have a vast population that's not treated because of the invasive nature. At the back end, 40% of the treated patients aren't getting adequate results.
The market has a lot of needs there in the front and in the back that nobody is addressing. OCS-01 is the only product that can address those needs because it's topical. It can deal with early intervention. In the back end, for people who are not responding to anti-VEGF, the product can be used too because the utility can be versatile. It can be used potentially in combination or standalone.
Yeah. Talk about the phase II data.
Okay.
We will move to the phase III program. What did we see?
So phase.
It was so long ago now, right?
Yeah, it's so long ago. I know. The phase II data was statistically significant. And it was I forgot how many patients we did. I apologize.
I don't know how many patients it was either. It was a pretty large group.
It was a large group. It was positive. We moved into phase III.
The number of letters that were improved was so amazing, right? And how many lines of improvement?
Okay. For stage one, phase III, we had 148 patients. The primary endpoint is BCVA, and then we have a secondary endpoint on number of letter gains. The primary end, it was a 12 weeks, so three months study measured at week six, which is the end of induction phase, and at week 12, which is the end of maintenance phase. At week six, we saw the primary endpoint BCVA was at 7.2 at end of week six. It got improved to 7.6 at end of week 12. The secondary endpoint, there are two. The first one is improvement in letter gains. At week six, we saw 23%. At week seven, it was 27% improvement gains. The secondary endpoint is related to reduction in CMT. This is the reverse of AON. In this case, we want the retinal thickness to reduce.
This is done with OCT. It is an imaging.
Exactly. Yeah, exactly. That was statistically significant as well. It was amazing data. I mean, we did not do head-to-head studies. If you look at the product labels from injectables or implants, what we saw is our week 12 results was in line, similar, the same as injectables and better than steroid implants.
Yeah.
It's a topical.
I was going to say the thing that amazed me most is that the OCT imaging correlated with the vision improvement. That is what was amazing. The pictures as the edema was coming down, the patients were seeing.
The letter gains.
More and more letter gains.
Exactly.
That was really amazing. The fact that it's an eye drop is pretty amazing. You started to allude to this before, but I guess there are a couple of different buckets it could be used in, right? It could be used out of the gate before VEGF. You could use it on top of VEGF. You could use it when VEGF fails, which you said 40% of the patients fail. Only 60% are actually working. That is kind of the ways that it would be used.
Exactly. On the early intervention phase, there were studies previously that were conducted that showed if you put placebo-armed patients, once the study is done and switched them to the injectables, you do not get the spike of visual improvement. It improves a little, but it stays at the low level. The beauty and the importance of having early intervention is to start that visual gain earlier before it is lost. Because it is known that one can only, for DME patients, they can only regain up to half of what they lost. If you start later, you cannot gain as much. That is why the early intervention is important. That is a space that no one can claim other than OCS-01 once, obviously, phase III has to complete and we get approval.
Yeah. Let's talk about the phase III. The phase III started a year plus ago.
We started enrollment in late 2023, beginning of 2024 for the study one. The study two started in the February-March timeframe.
When will we get the data for study one?
Both studies, we are in the midst and heat of dashing to enrollment completion. Hopefully, we'll be able to report that in the coming months. 52 weeks from the last patient in will be data readout. We're currently expecting first half of 2026 from a top-line readout standpoint for both one and two.
Both of them, even though one started a little later, they're both running very similarly in timeline.
Yeah. The enrollment pace has been very positive. I think it really speaks to the product is really well receptive by physicians and patients.
Yeah. Okay. So if you announce, yeah, in a couple of months, call it May or whatever, and you're fully enrolled, then one year plus some time to analyze the data.
Exactly.
That's early first half. Yeah. That's the next, do you view that as, that's the next big data point, right, for the three programs as far as data?
Yeah, from a clinical data standpoint, yes. Between now and then, we have R&D day coming up, which will help to showcase our OCS-05 and potential next step developments. We have updates on OCS-02 from a next clinical trial development standpoint. From a data readout, we would have phase III for DME first half of next year. Followed after that, it will be dry eye for the next study, phase II/III. After that, it will be AON. Multiple clinical data points coming up.
Talk about the cash runway, the cash position, just to kind of finalize things here.
Yeah. Sure. We ended the year with $109 million U.S. dollars. We recently raised $100 million U.S. dollars just a few weeks ago off of the very positive OCS-05 ACUITY data.
So 209.
At the time of, yeah, so over $200 million.
Over $200 million.
Over $200 million.
Over $200 million. Yeah.
Runway is to early 2028, covering the key milestones that we talked about.
Excellent. Excellent. Thank you. Thanks for joining us.
Thank you. No, thank you for having us. It's been wonderful.