Welcome to the H.C. Wainwright 27th Annual Global Investment Conference. For this session, we'll have a fireside chat with Dr. Riad Sherif, MD, Chief Executive Officer of Oculis Holding AG. Welcome to join us.
Thank you. Thank you, and very happy to be here. Thank you for the invitation.
Riad, I understand Oculis has three active clinical programs: OCS-01 for DME, OCS-02 for dry eye disease, and OCS-05 for AON. Could you tell us how the company is prioritizing resource allocation across these three clinical programs given their different stages of clinical development and market potentials?
Yeah, yes. Yeah, so as you said, we have three clinical stages: OCS-01 in development in DME, which is the first eye drop in DME; OCS-02 on Licaminlimab, which is a fragment of TNF in ocular inflammation with the lead program in dry eye, with a very different way to do it with what we call genotype-based, and I will explain it; and OCS-05, or Privosergtor, which is a neuroprotective drug. The way we prioritize is, I would say, pretty typical, based on the likelihood of success, the potential of the product, and how well we believe we can bring it to the market, basically. When you see our portfolio, the good news is we have a late-stage portfolio. OCS-01 is in phase 3. I would say it's simple. This is priority number one. It's a phase 3. Enrollment is finished. Readout is planning Q2. Product is very differentiated.
The only topical in the market going to address a pool of patients, which is actually two times bigger than patients who are treated today, which represents just in the U.S. $3 billion. We are going to address more than the double. Therefore, by the definition, it's really number one. The second asset, which is Privosergtor, which is in neuroprotection, we released the data of the phase 2 in January this year. As you may have seen, the data are not good. They're amazing. I mean, it's just amazing the type of data we have been able to deliver with this product in an indication which is very difficult. I remember during the two years, everyone told me that we were crazy to go to acute optic neuritis. No one showed anything.
The good news is we showed consistently function, 18 letters difference, which is doubling the vision for all patients. We are really talking about patients who are young, average age 32 years. The second good news from the trial is consistency. We see functional improvement, structural improvement in the anatomy of the retina by protecting ganglion cells from dying. The third is consistent with neurofilament, which are surrogate biomarkers, which are aligned with the damage of the axon, which was reduced. When you see this type of data in a disease where we don't have anything, where patients are losing vision, it becomes important. This is what we said in the beginning of the year. We said this program, based on the data we have, is becoming very important for us. We are now consulting FDA in this quarter.
It means it's coming to discuss about the registration plan in acute optic neuritis with Privosergtor. We said also that we are going to initiate two new programs in NAION, which is also an optic neuritis, a different etiology, but optic neuritis. We said we would like to target an unmet medical need, which is relapse of MS. I will explain exactly what we mean by relapse of MS versus MS. The third asset, Licaminlimab. As you know, dry eye is a huge market, but still totally underserved. It's a trial and error in the way we develop drugs, a trial and error in the market. Today, if you take the leader in the market in dry eye, the rate of renewal of the first prescription, of the first script, is 14%, one fourth. It tells you that actually it's not good.
The way we are doing it, learning from this, we said, OK, is there a way to identify patients who will respond better to our drug? The good news is yes. We sat with FDA again, and we agreed with FDA. FDA actually is supportive for our genotype-based development, which is identifying patients before randomizing them. The primary endpoint will be in this genotype-positive patient. Therefore, yes, there is clear prioritization. In the same time, we have been able to develop a portfolio of very unique, very differentiated assets.
Got it. Regarding the DME program, were the top-line results from the phase 3 DIAMOND trials of OCS-01 expected in the second quarter of 2026?
Yes.
Can you tell us what specific endpoints do you expect to meet, and how confident are you for meeting those endpoints, particularly given the current competitive landscape of anti-VEGF therapies for DME?
Yeah. So basically, the endpoints which are aligned with the FDA are mean change of BCVA, which is how many letters better we have versus placebo. This is the primary endpoint. The secondary endpoint is how many patients gained 15 letters, which is the clinical impact. The readout is planned in Q2 next year. Now, I am very confident, actually. I mean, this product was tested four times, consistently showing BCVA improvement, CSC improvement, and gains. Now, how this profile compares with others, actually, we are really addressing the different unmet medical needs. We are addressing patients who are early, so recent onset. In the U.S. today, based on IRIS, the database, which is AAO, the database, which is the American Academy of Ophthalmology, which is called IRIS. IRIS follows more than 200,000 eyes.
More than 60% of DME patients are not treated 12 months after the diagnostic today in the U.S. These patients, we can treat them immediately the day of the diagnostic, which we cannot do today. This is the first group. So 60% of the diagnosed patients, we can treat them. 900,000 patients in the U.S., we can treat them immediately. For the other 900,000 who are treated, 60% will respond appropriately to anti-VEGF, and 40% will not respond appropriately to anti-VEGF, and they might need something else. The advantage with OCS-01, without actually competing with anti-VEGF, you can switch them, or you can combine. Now, how it compares, we compare very well. If you compare with Lucentis, at the same time point, we have the same gains, the same BCVA gains, same. If you compare with Ozurdex, which is an implant, a steroid implant, actually, we compare much better.
If you compare at month three with Ozurdex, the primary endpoint of Ozurdex was gainers. They are between 14% to 15% gainers. We are 27% plus gainers. Much, much better. APR is the same, most probably because we are able to deliver a stable PK to the target versus Ozurdex, which is an implant, is a reservoir. Therefore, you have a peak, and it goes down. It compares well. The profile is differentiated, the only topical, addressing unmet medical needs, which is huge in terms of patients who are not addressed actually by anyone, by anti-VEGF or steroid.
Is it fair to say that you plan to position OCS-01 as a first-line treatment for DME?
Absolutely, yes.
OK.
Yes.
Have you evaluated the potential adoption rate by ophthalmologists by using OCS-01 as a first-line treatment? Because given the historical fact that topical steroid was not, currently is not, the current first-line treatment option.
Yes. I would say the surrogate, which is really the indicator which gives us the confidence, is the pace we had in randomizing in our study. We had KPIs, and the KPI, we're comparing the rate of randomization for all anti-VEGF, average anti-VEGF trials in DME for the last 10 years, since Lucentis, Eylea, and Vabysmo. When you compare with this rate, our rate of randomization was twice, the double. In the beginning, we were going to more than 20 countries. We limited, actually, we went to five countries just because the rate was fast. This gives us the confidence that the patient we are looking for exists, and the prescriber is willing to test our drug, and the patient is willing to be tested with this drug. Yes, we are very confident.
What are the primary risks associated with the OCS-01 development? I mean, in terms of clinical development, regulatory pathway, and manufacturing?
In drug development, at least as you know, you have CMC risk, you have clinical risk, you have regulatory risk, and you have execution. CMC, we are fine. We had the final marketing image. Clinical, this product was tested four times. This is the fifth time in phase 3. We are confident about it. Regulatory, we have clear interaction, clear support from the FDA. The last is execution. Execution is always a risk, and it will remain till the end of the trial. This is really where we are focusing, is execution, like obsessive execution. It's always a risk. I will not lie to you. Anyone who will run a clinical trial knows that there are risks in clinical trials, which are just execution. This is why we are obsessed in the company about execution.
I recall the original plan for OCS-01 was to submit the NDA for postoperative pain and inflammation, correct?
Yes.
What is the current status regarding this indication?
Yeah, really following the result of ACUITY and Privosergtor (OCS-05), we decided in terms of prioritization to postpone the submission of ocular surgery to after DME. This is our plan. Submission is ready. We'll submit after DME.
Regarding Privosergtor (OCS-05), you talk about OCS-05 has shown promising results in AON and also the potential application in MS and NAION. What is your current estimate timeline for targeting these indications in terms of the next initiation for clinical trials?
Yeah, so really consistent with what we said. We said we will meet with the FDA. The meeting is taking place. Our first goal is to focus on AON and to advance this program. We said we hope it will be a phase 2-3. We hope it will be a phase 2-3. Let's see the discussion with the FDA. We said we would like to discuss also with the FDA on two new indications, NAION and MS relapse. We would like to initiate NAION and to discuss with the FDA to have the IND for NAION. The meeting is this year, and we should start, we should at least achieve IND for NAION next year.
Will AON be the lead indication of phase 3?
Absolutely, yes.
When can investors know the final trial design for AON?
October.
October?
Regarding the Licaminlimab (OCS-02) in dry eye, so if I recall correctly, few drugs.
May I just clarify when we say relapse of MS versus MS? As you know, in MS treatment, first we have good new treatments in MS, which are mainly driven by CD40 and immunomodulators, which are actually good. In fact, I personally launched the first oral MS, which is Gilenya a while ago. I know pretty well this market. Current MS treatments, which are immunomodulators, are able to reduce materially the number of relapses, which is good. In the U.S., we have around 850,000 patients. We were able to reduce the number of relapses from one to two per year to around two per every five years. It's really a material improvement, which is good for patients. Still, if you take 850 and you have two relapses every five years, it means you have 850, we divide them by 2.5, you have more than 200,000 relapses per year.
When you have relapses, as you know, the function is impacted, and we lose the function. AON is a type of MS relapse, actually, and we lose vision. If we have another relapse, we lose mobility or any other function. This is what we want to treat. Our treatment will not replace immunomodulators. Our treatment will treat relapse as we treated AON to avoid the relapse worsening effect. For AON, it's vision. For other types of relapses, it will be, I would say, customized to the function itself. This is really what we are aiming for. We are aiming for perhaps the last unmet medical need in MS. With immunomodulators, we are able to reduce relapses. With Privosergtor, we can truly treat the relapse as we treat it in acute optic neuritis to reduce the relapse worsening effect. This is what we are aiming for.
It will be similar to what we did in acute optic neuritis, which is an acute treatment of relapse to protect the neuron during the injury of inflammation, as we did in acute optic neuritis. In terms of concept, it's really the same concept. What we are going now to do is, instead of just focusing on AON, which is anyway the first indication, will be broadened, but with the same pathophysiology in terms of what is happening in the relapse. It's just protecting the neuron during the injury phase, which is in MS inflammation.
What percentage of MS patients will relapse with AON?
In our study, 2/3 of AON patients were MS.
OK.
Yeah, we compared, actually, we did sensitivity analysis, and we compared MS patients versus non-MS patients. Both groups responded extremely well.
OK. These AON patients are currently managed by steroids, correct?
These AON patients today, if they have MS, they are receiving immunomodulators, and they are taking steroids when they have an AON.
Is it fair to say that it's relatively easy for Privosergtor (OCS-05) to demonstrate benefits or better safety profile compared to steroids?
The comparison we did is Privosergtor plus steroids versus placebo plus steroids, and our results are much better than steroids alone, much better.
OK, got it.
I mean, significant.
OK. Regarding the other two indications, do you plan to advance into clinical development next year, sometime next year?
Yes.
OK, got it. With respect to the dry eye program, yes, a few drugs have explored a genotype-based approach, which is the approach of Licaminlimab (OCS-02). Can you elaborate the TNFR1 pathway in this, the mechanism of action?
Yeah. First, if I may, we are really the first doing a genotype-based in ophthalmology at least. This is well established in oncology, for example. In ophthalmology, we are the only company doing it, and so far the first company actually doing it. The TNFR1 receptor SNP is present in 20% of the population. We are speaking about 2 million patients who are moderate to severe dry patients in the U.S. This population had this SNP on the TNFR1 receptor. When they have this SNP, what we showed, we identified, and then we validated again. In two trials, we showed that this patient improved symptoms by sevenfold, all comers, and signs by fivefold, all comers. This patient responds, and when they respond, they respond extremely well, much better than all comers. What it gives us, it gives us certainty that the trial will be most likely positive.
It also makes the program much more efficient because we need much less patients to show a benefit. FDA is totally supportive for a primary endpoint in this population. This is our primary endpoint will be in this population. We will run signs and symptoms trials based on this population.
OK. Can you give us an estimated timeline as to the initiation of the next?
Yeah, the initiation will be this year, with the readout in the second half of next year.
OK, thank you. Does Oculis have any ongoing discussions with larger pharmaceutical companies for either potential licensing or co-development opportunities?
As you can imagine, I cannot respond to this question. Our portfolio is appealing for many strategies.
OK. What is the company's current cash runway?
Our current cash runway is the beginning of 2028.
Therefore, it means that the DME is financed till NDA. The next trial, dry eye, is financed, and AON is financed till NDA.
Could you give us a summary of the upcoming catalyst within the next 12 months?
The next catalyst is really regulatory about clarification of the registration plan for Privosergtor (OCS-05) in acute optic neuritis, the IND enabling and IND for NAION, and IND enabling and IND for MS relapse. In terms of clinical, we have the readout of the phase 3 DME for the first half of the next year, and we have the readout of the phase 3 dry eye in the second half of the next year. Pretty rich, yeah.
OK, got it.
Yeah.
Any questions from the audience? Any closing remarks?
No, thank you for a well-organized meeting.
Thank you for joining us.
Thank you. Thank you very much.