Good morning, and thank you for joining the H.C. Wainwright Fifth Annual Ophthalmology Virtual Conference. For this session, we have a panel discussion, and I'd like to welcome the following panelists to share with us their view on multiple drug candidates currently in pivotal stage of clinical development for retinal disorders. Dr. Hendrik Scholl, Chief Medical Officer of Belite Bio – Dr. Snehal Shah, President of R&D at Oculis Holding AG – Dr. Samarendra Mohanty, President, Chief Scientific Officer, and Co-Founder of Nanoscope Therapeutics – Ms. Reenie McCarthy, Chief Executive Officer at Stealth BioTherapeutics – and Dr. Mark Breazzano at the University of Rochester Medical Center. Welcome to the panel. Dr. Breazzano, could you give us an update on your practice since our last year's conference?
Absolutely. Since last year, I have completed my transition to the University of Rochester , still with a busy clinical practice in upstate New York. I'm Associate Professor and Director of the Retina Surgery and Disease Fellowship, a two-fellow program, and predominantly clinical and surgical.
Got it. In your view, what are the most pressing medical needs in retinal disorders, particularly for indications such as dry AMD, GA, retinitis pigmentosa, and Stargardt disease?
Yeah, absolutely. I think we are in that exciting time where hopefully we have more developments since what we know has happened with the anti-complement in vitro therapy for geographic atrophy. In many ways, it may mimic what happened a couple of decades ago with Macugen at the time for anti-VEGF, which we now know has really dominated the retinal treatment space for diabetic retinopathy and age-related macular degeneration, among others. Hopefully, we can have a therapy that will not only slow down the progression of the disease but can actually halt it or reverse it like we know that anti-VEGF can now. In terms of retinitis pigmentosa and other inherited retinal diseases, it's obviously been groundbreaking with gene therapy, which we have performed in Rochester as well as other medical centers across the country and the world, now, several hundred in the United States for RPE65 with Luxturna.
Hopefully, this will open the floodgates for more treatment options for these patients that are desperately in need for additional treatments, not only for additional mutations but those that are more frequent, including ABCA4 maculopathy or Stargardt disease.
From a clinician's viewpoint, what key clinical endpoints or biomarkers would you prioritize when evaluating the efficacy and safety of pivotal stage therapies? I mean, how do you assess their potential to change the standard of care practice?
Yeah, absolutely. I think first and foremost, we want to do no harm. We want to avoid any drastic safety signals that might be poor. In the back of our mind, we still have Betaview, of course, which is still occasionally used, which can be surprising to some, but has been very effective at drying up the retina with its very powerful anti-VEGF modality. However, the retinal occlusive vasculitis, which we've all been traumatized mentally from, we obviously would like to avoid with any of these other future therapies. Barring that, the efficacy, it's very hard to compete with the gold standard of best-corrected visual acuity, which ideally we can show a benefit for these treatments. Other forms of function, even with something as subtle and isolated as navigating a maze, like with RPE65 gene therapy, for example, is still noteworthy and beneficial for these patients.
Contrast sensitivity is something that can be overlooked in general practice with patients, but it's a very important functional endpoint as well. Of course, with OCT and other imaging, looking at the anatomical biomarkers, which are so effective now with the technology that we have, whether it's the atrophy or C-ROA, complete RPE and outer retinal atrophy, for example, that can be so easily followed, as well as fundus autofluorescence with hypoautofluorescence that's also consistent and co-localizes with that geographic atrophy as an example.
That's very helpful. Thank you. What factors do you believe could drive or hinder the adoption of novel retinal therapies in clinical practice, such as ease of administration, patient compliance, or payer reimbursement?
Yeah, absolutely. I think something that has been used and adopted so far and relatively is invasive is intravitreal injection. However, it is so frequently administered across the country and the world that something that is familiar already to clinicians and is not novel in that standpoint is certainly a favorable one, which although it does have its own risks, is certainly something that is helpful if it's something that we're already used to doing. Of course, if there's other things that are less invasive, that is also going to be helpful too. Then other aspects like subretinal gene therapy, where we have to go in surgically to do it, it's only performed at major academic centers or medical centers in general. It might be a little bit more challenging, but that has already paved the way as well.
In terms of compliance, coming back in for these treatments can be quite burdensome, not only for urban centers but also more rural practices. It's not infrequent in many parts of the country and world where patients are traveling from miles, if not hundreds of miles, from far away and have to do so at such frequent intervals. That can really hurt the compliance. Of course, with rising health care costs, deductibles, all these aspects with insurance have been quite problematic. Often it's complex, socioeconomic issues that play into this, as well as taking caregivers out of work to help provide their care and come into all of these visits. Payer reimbursement has been a major challenge as well, and also under scrutiny, not only by insurance itself but also governmental agencies. As we all know, the geopolitical climate has certainly created a little bit of turbulence.
Some of this, I think, is going to be hard, very, you know, it's going to be quite variable and hard to predict based on administration, based on anything else that's going on in terms of getting these approved. There have been, as you know, a nonprofit organization that has helped finance some and cover some of the costs for these expensive medications, and some of that has been less available in recent months. That might just be a mild fluctuation in recent times, and perhaps it can come back and be more helpful for patients trying to obtain treatments specifically for the anti-VEGF currently. That would be part of that kind of landscape with any sort of retinal treatment, I'd imagine, moving forward as well.
Got it. That's very helpful. Thank you. Ms. McCarthy, I understand elamipretide targets mitochondrial dysfunction in dry AMD. Could you explain how this mechanism addresses the unmet need in intermediate dry AMD and other, you know, mitochondria-related retinal disorders and how it differs from complement-based therapies?
Yeah, thanks. It's a great question. So elamipretide and our next-gen compound, beva-mipretide, both target mitochondria to essentially restore and normalize mitochondrial dysfunction in disease states. We know that in dry age-related macular degeneration, even before intermediate AMD onsets, we see signs and symptoms of mitochondrial dysfunction. We see abnormal numbers of, like, cristae. The structure of the mitochondria becomes irregular in early-stage AMD. That's relative to age-matched controls, leading to deficits in ATP, so bioenergetics, which the retina, particularly the RPE and the photoreceptors, are very dependent on, and also increasing production of oxidative stress, which plays a role in signaling inflammatory cascades.
With treating mitochondrial dysfunction in dry AMD, you know, we are studying early-stage GA, but to your point, we do think that intermediate is really the best place in many ways for this mechanism because what we see is that RPE loss and photoreceptor loss, and really photoreceptor loss, both precedes and predicts the onset of geographic atrophy and the growth patterns of geographic atrophy. What we've seen is that if we can intervene when there are still viable but at-risk photoreceptors, we can significantly reduce the amount of photoreceptor loss, which then eventually, again, will predict geographic atrophy. That has been associated with improvements in low light best-corrected visual acuity in patients in our Phase 2 clinical trial.
Got it. Could you provide us an update on elamipretide's Phase 3 trials for dry AMD, including the key endpoints and expected timelines?
Yeah, so based on learnings from our Phase 2 trial, just to back up, we did a Phase 1 where we saw improvements in low light best-corrected visual acuity, and post-hoc looked to see if there were any physiological predictors of that and really zeroed in on the ellipsoid zone, which is, per FDA, a direct measurement of the photoreceptors. In our Phase 2 clinical trial, that was a pre-specified endpoint, and we gained alignment with the FDA based on improvements in that endpoint, about a 43% protective effect, that that could be a Phase 3 primary. We have one fully enrolled Phase 3 clinical trial, which we completed enrollment in July. We are looking at the rate of loss of the photoreceptors, measured by essentially the distance between the ellipsoid zone and the RPE. If that's zero microns, that is a measurement of photoreceptor loss.
We are looking at the rate of loss over time with the primary readout on that at 48 weeks, but we're also maintaining the masking of the trial out to 96 weeks so that we can look at longer-term therapy. A key secondary endpoint for us remains improvements in categorical, low light best-corrected visual acuity.
Got it. Got it. What regulatory strategies is Stealth pursuing, and how does the FDA's feedback on mitochondrial therapies influence your approach?
Yeah, so I mean, we have feedback from the FDA, again, in the context of our Phase 2 clinical data and our Phase 3 protocol design, that targeting mitochondria to reduce photoreceptor loss is an approach, an acceptable strategy for the treatment of dry age-related macular degeneration. It's pretty early to get labeling guidance, but we did ask about the label given that we are enrolling patients with early-stage GA in our trials, and they told us that the likely label would be dry age-related macular degeneration, not limited to geographic atrophy, since, again, our endpoint is photoreceptor protection, and that is a problem throughout the trajectory of dry AMD. That is kind of where we are from a regulatory perspective, running this first Phase 3 clinical trial. A second one will follow.
We are also in Phase 1 clinical development for a next-generation compound with the same mechanism, but improved retinal distribution via a topical ophthalmic drop. We have active transport to the retina with this next molecule, and that's in Phase 1.
Yeah, that's great. Can you tell us the key commercial considerations for targeting earlier-stage dry AMD patients?
It is a much larger market, right? I think when you kind of look at the number of patients, this is a huge unmet need at the earlier stages. I think the other, you know, commercial challenge, right, that we face in the setting of dry age-related macular degeneration is the approaches that are slowing the progression of geographic atrophy but not really delivering clinical benefit in terms of preventing loss of visual function or actually improving visual function in patients. To Dr. Breazzano's point, lead to compliance concerns and reimbursement concerns. I think that with this approach, where we've seen very significant correlations between the photoreceptor protective effect and the improvements in low light best-corrected visual acuity, that that, you know, again, sort of anchors us in a stronger commercial strategy. I would say the other things Dr.
Breazzano spoke to, which are things like compliance, elamipretide is a once-daily subcutaneous injection. That's at-home therapy. It's been extensively characterized from a safety perspective. We have over 1,700 patients who've been exposed, and we don't see any ocular adverse effects. We do see mild to moderate injection site reactions that can be managed with topical steroids. From a compliance perspective, patients can administer this at home. It reaches both eyes, and there is a convenience factor relative to, you know, intravitreal injections with elamipretide. As we go back in with our next-gen compound as an eye drop, obviously, the compliance burden would come down even further.
Got it. Thank you. Dr. Shah, I understand tinlarebant targets the reduction of toxic bis-retinoids in Stargardt disease and geographic atrophy. Could you tell us how it addresses the needs in these conditions, particularly for adolescent Stargardt patients?
I'm very happy to, as a clinician, I'm still seeing patients, and we use fundus autofluorescence imaging, and we see that there's increased signal in the two diseases, both Stargardt disease and also geographic atrophy around the lesion. These toxic compounds are made of vitamin A, or more specifically, two molecules of vitamin A bound together. We call them bis-retinoids. What tinlarebant does, it is an antagonist of retinol binding protein 4, or RBP4, and it's only the eye that has this unique requirement to essentially suck in vitamin A through this receptor, while all the other tissues in the human body do not need that, which is important because it makes the therapy almost as specific as gene therapy.
You really target that specific protein, and by targeting that protein, you reduce the level of available vitamin A for photoreceptors in retinal pigment epithelium, and that will lead to a reduction of bis-retinoids in the target cells that are greatly increased due to mutations of ABCA4 in Stargardt disease and because of subretinal and sub-RPE pathology in geographic atrophy. By slowing down or even stopping the accumulation of these toxic bis-retinoids, we will preserve vision. Obviously, there is no approved therapy for Stargardt at all, and for GA, as we just discussed, there are no approved oral therapies in the United States. Tinlarebant will specifically address this unmet medical need.
Got it. Thank you. Can you share with us the key findings from the Phase 3 trials and outline the design of the ongoing pivotal trials?
Happy to. In a Phase 2 clinical trial, 12 subjects were treated in an open-label fashion with tinlarebant. These patients would not have late lesions of disease of Stargardt disease. These were adolescent patients, young patients between 12 and 18 years old. As we know, it's a disease that starts relatively early in life. Tinlarebant produced a mean reduction of RBP4 in the circulation, and that is the biomarker for tinlarebant treatment. What was found is that safety was excellent. There was delayed dark adaptation and xanthopsia. These were the most common drug-related ophthalmic adverse events, and they are anticipated since you reduce to a degree, at least, vitamin A in the target cells, namely the photoreceptors. Therefore, you will delay the final threshold of reaching full dark adaptation.
All these instances of delayed dark adaptation and night vision impairment were rated as mild and transient, and there were no severe or even moderate drug-related AEs reported and no AEs requiring discontinuation of the treatment. There were also no systemic clinically significant findings. In terms of efficacy, we have excellent natural history in Stargardt disease. It has to do with the fact that we have the PROXSTAR study. I had the honor to lead that multicenter worldwide natural history study when I was still a professor at Johns Hopkins University. We have excellent natural history, and we have an outcome measure for the disease called decreased fundus autofluorescence, DAF specifically, definitely decreased fundus autofluorescence, DDF.
That lesion growth was compared between the open-label treated subjects, these adolescent Stargardt patients, and they showed a progression rate of pretty much exactly half a square millimeter over the duration of the two years. We could compare that to a subset of age-matched controls out of the PROXSTAR dataset, which showed pretty much exactly one square millimeter per year, per two years. That means if you translate that into a treatment effect, that was a 50% treatment effect to reduce lesion growth in Stargardt patients. That informed our clinical trial design in our Phase 3 clinical trial with the name Dragon, where 104 patients were enrolled. It's a double-masked placebo-controlled clinical trial with a two-to-one ratio. Twice as many patients received tinlarebant – one-third receives placebo.
The main outcome measure is exactly the one that was established by the PROXSTAR study, namely definitely decreased fundus autofluorescence, which is accepted by the FDA as an approval endpoint in Stargardt. We just recently had access to the interim analysis that was provided to the DSMB in February. We submitted the data after the recommendation of the DSMB to regulatory agencies, including the FDA, and were provided a breakthrough designation end of May this year, obviously based on an efficacy signal that the DSMB had seen in February.
Got it. What are the critical regulatory milestones investors should look forward to? How does the breakthrough therapy designation for Stargardt influence the pathway?
We expect the 24-month data by the end of Q4 this year. Last patient last visit will be September 30, so it's six weeks ahead of us. We aim to submit an NDA in the first half of next year. The breakthrough designation would provide some benefits, such as more frequent communication with the FDA, rolling submission, and priority review.
Got it. Okay. Thank you. Thank you very much.
[Crosstalk] Thank you.
I understand Nanoscope's MCO-010 is a mutation-agnostic gene therapy for retinitis pigmentosa as well as Stargardt disease. Can you explain the optogenetic mechanism and how it addresses the unmet needs for vision restoration in patients with advanced retinal degeneration?
That's a great question. I would start with combining those two aspects where we are seeing optogenetics as a disease-agnostic, not just mutation or gene-agnostic. In the IRD space, as you know, there are more than 300 genes and more than 8,000 mutations which cause these diseases. Developing a drug, Luxturna is a great drug for single mutation, as Dr. Mark Breazzano mentioned. Developing for each one of them will take decades, if not centuries. With this mutation and disease-agnostic approach, what it does is instead of using or trying to get the photoreceptors in this advanced stage of disease where the highest unmet need is the photoreceptors or the RP, the outer retina is destroyed. The target cell is not even available for a classical gene therapy or any other small molecule therapy to slow down the progression.
The other alternative is to either have kind of electrical implants, which is not in market currently, or to do cell therapies, which has issues with integration and survival of the cells. You have to put not only RP cells but also photoreceptors. Now bypassing that outer retina, what optogenetics does is target the bipolar cell, inner retinal cells. We have seen in this patient population, bipolar cells are remaining even decades of the lifespan of the patients. We have patients from 20 years of age to 80+ years of age. With OCT, simple diagnosis, you can see the bipolar cells and the ganglion cells being present.
We are taking a very highly bioengineered opsin, which is not rhodopsin or conopsin, which requires dozens of proteins to function, but rather from a simple primitive algal system like algae, taking the protein and making a synthetic protein which can function by itself. When light falls, it can generate electrical current. Putting that into bipolar cells, making the bipolar cells as a new defect of photoreceptors that are already integrated into the retinal circuitry. There is no survival or integration issues. It allows us to utilize the existing retina and the visual processing that happens. When an image is projected with a natural environment, it can generate the visual perception how a patient will see. There have been challenges with optogenetics. With our opsin, it's not only sensitive to all colors of light, from blue to red color.
It has fast kinetics and also sensitivity to low light level with high dynamic range. The patient can see real-world vision in real time without blur and not requiring an external goggle to stimulate to convert the light to different color or intensity amplification.
Can you share with us the key efficacy and safety data from the Phase 2b/3 RESTORE trial for RP, and whether FDA has asked for additional clinical trials after seeing that data?
So going back, how we designed the Phase 2b/3 trial is based on our Phase 1/2 trial where we saw a dose-dependent improvement in BCVA. Of course, these patients are off the chart, so we had to use the validated Freiburg visual acuity test where you can measure count finger, hand motion on those patients. Based on those dose dependencies, we designed the Phase 2b/3 trial with 27 patients in two dose groups with 0.9E11 and 1.2E11 GC per eye and the same control group. Those study designs were agreed upon with FDA before moving forward. Now, even with the small patient population, we see a statistically significant difference in visual acuity change from baseline at multiple time points, starting from 26 months all the way up to now we are seeing.
The study was for two-year duration, and FDA has given us green light to move forward with the BLA submission. That's how we have started our BLA submission. As we announced publicly, I think this data set in this heterogeneous patient population is showing the statistical significance in a small patient population to talk to the large amount of treatment effect that we have seen in these patients. That is very solid, and it will be supported by our Phase 1/2 data as well as related indication in Stargardt disease, which is showing also efficacy. Those will be part of the BLA submission. Most importantly, it's not just the one-year primary endpoint. We have data up to three years currently from that study, and it is showing the durable treatment effect of 0.3 logMAR vision gain.
What we had to show FDA is that how this 0.3 logMAR, which is on-chart patients, is clinically meaningful, how that will be meaningful for the off-chart patients. We had done an observational study in 35 patients to show that how this visual acuity gain of 0.2 or 0.3 logMAR in these low vision patients is very clinically meaningful when you anchor it with respect to visual field, with respect to their functional vision, patient-reported outcomes, all those measures. That gives FDA some more complete data set to evaluate our program for approval.
Got it. That's very helpful. Thank you. Dr. Scholl, I understand Oculis is developing OCS-01 as an eye drop for diabetic macular edema and also OCS-05 for neuroprotection. Can you elaborate on how these approaches differ from existing treatment and address unmet needs in DME and also acute optic neuritis?
Yeah, that's a great question. I'll start with OCS-01. All currently available treatments for diabetic macular edema require invasive delivery, such as intravitreal injections or ocular implants to reach the retina. With OCS-01, it's a topical eye drop, and it has really the potential to transform the treatment paradigm of DME as a non-invasive treatment. We know approximately about 60% of diagnosed DME patients remain untreated, and this is based on the IRIS database. 40% of treated patients have a suboptimal response to the standard of care of anti-VEGF because we know the pathophysiology of the disease is more than neovascularization, and it includes a significant inflammatory component. With OCS-01, there really is a significant unmet need for treatment options for early treatment in patients inadequately controlled on the current standard of care. OCS-01 being a topical eye drop really addresses the unmet need of having a non-invasive treatment.
For OCS-05 in acute optic neuritis, we know steroids are used to resolve acute inflammation. There remains an unmet need, though, for therapies that actually preserve retinal neurons, which are the ganglion cells, and therefore allow preservation of vision and provide neuroprotection after an acute episode of optic neuritis. Privosegtor or OCS-05 is a first-in-class small peptoid molecule being developed as a neuroprotective therapy, really with transformative potential in ophthalmology, neuro-ophthalmology, and neurology. Privosegtor showed neuroprotection benefits both anatomically and biologically and really showed clinically meaningful visual function improvement as defined by low-contrast visual acuity in the recently completed Phase 2 acuity study, which read out at the beginning of this year.
Got it. Can you provide us with an update on the Phase 3 Diamond trial of OCS-01 in DME? What regulatory challenges do you expect in the near term, particularly for a novel topical therapy like OCS-01?
We have two Phase 3 trials, Diamond-1 and Diamond-2 , and enrollment is ongoing in both 52-week trials. Enrollment has been completed with over 800 patients enrolled. It's fully enrolled. The study is ongoing. We expect top-line results second quarter of next year. We've had very, very good randomization. In fact, double, twice as what we predicted with benchmarks for diabetic macular edema trials, which showed the great interest of our investigators and our patients to enroll into a trial with a non-invasive treatment. Following the positive results of the Phase 2 acuity trial in acute optic neuritis, we're also planning to meet with FDA to initiate registration trials for acute optic neuritis for OCS-05.
Also, going back to your question with OCS-01 and the Diamond program, some of the risks really for a Phase 3 registration trial, like any other registration study, study execution and oversight are absolutely critical to success. This includes driving strong adherence to the protocol and really ensuring patient compliance and retention throughout the study. We're able to do this with very close monitoring. We collaborate closely with highly experienced investigators. We have a steering committee consisting of world-renowned retina specialists and clinical trialists. What we know is patients are really motivated to be part of a DME study where they receive a non-invasive treatment. This, again, as I stated, is really supported by the rate which we fully recruited our Diamond studies, which was over two times faster than benchmarks. As a topical treatment, you know, we really learned from four previous clinical trials.
We had two exploratory studies in DME and two Phase 2 studies. We don't really see any risk or surprising for the data for safety and efficacy given the positive and consistent results of all those trials. We're really just trying to confirm what we already know with the Phase 3 registration program for OCS-01.
Got it. Thank you. Dr. Brezzano, so based on the mechanisms and the clinical data presented so far for these drug candidates, how do you assess their potential to address specific unmet needs in indications such as dry AMD, Stargardt disease, retinitis pigmentosa, as well as DME? I mean, in terms of patient outcomes and disease progression.
Yeah, I think it's definitely important. It's a great question, and it's certainly multifactorial, of course. All these approaches I do believe are reasonable, including oral, intravitreal, and subcutaneous as well. Some of them are more common in other branches of medicine than ophthalmology, but certainly adaptable, I think, to our field as well. Even other ones, even a pill, which is pretty novel. I mean, we already do have recommended for intermediate non-exudative age-related macular degeneration, AREDS2, for example, which is something that is very common and people are often doing even if they don't have macular degeneration and the thought that it might benefit what they have, even though there's not really data to support it. That's a different topic.
I think in terms of these outcomes, as many have already sort of pointed to, certain aspects in addition to preservation of vision, including visual acuity, it's really that contrast sensitivity at nighttime, which does plague a lot of retinal disease that is important. It's that compliance. It's that issue with being able to come back for those visits. Anything that's going to be able to facilitate that is going to be important, not only for clinical trials, where often we do have much higher return for treatment rates than we do in normal everyday practice, including, as was pointed out, with diabetic retinopathy. There are so many socioeconomic factors in place and many other conditions that often make it challenging for these patients to come back, particularly in that disease cohort. Anything we can do to sort of reconcile that, I think, is going to be particularly helpful.
Some of these, so again, some of these treatment approaches, while novel for that particular disease, is not necessarily a new aspect in a positive way in how it's already been known and tried and true in other diseases.
Got it. From a clinician's perspective, how do the administration methods, such as oral or topical versus intravitreal or subcu, impact their feasibility in real-world clinical settings, particularly regarding patient compliance, practice workflow, or payer reimbursement?
Absolutely. There are often, for intravitreal injections, certainly a lot of logistics involved in terms of numbing process and post-injection calls. There are certain burdens that are known to these sorts of procedures. At the same time, there are systems set up to accommodate that as well, despite these negative setbacks. It is obvious that monitoring, usually on a monthly basis, intraocular pressure, any inflammation that fortunately is rare but not unheard of and certainly will happen at some point over a practice's time horizon, are important and shouldn't be neglected. Versus a pill, often with AREDS, one of the biggest complaints, for example, is just stomach upset. Different formulations, like gummy formulations, for example, can often offset that. There is the cost associated with it. Often, it has its own pros and cons, but typically, AREDS, for example, is over-the-counter.
Unless you're a veteran in the VA system where they will often cover that for the veteran patients, most people do not have that luxury and will have to pay out of pocket themselves for the supplement, which isn't necessarily nearly as expensive as an injection would be, but it's certainly something that they have to factor into their budget. Each one has its own pros and cons for sure.
Got it. We've discussed here various clinical endpoints such as visual acuity, retinal thickness, or functional vision improvement. Which of these endpoints do you consider most critical for validating the efficacy of novel therapies in clinical practice? Are there any emerging biomarkers or imaging techniques that could further enhance the evaluation of these treatments for retinal disorders?
Absolutely. I think a few were touched upon earlier. I think the ellipsoid zone has been recognized as a marker of photoreceptor health and a very important one. The advancement of OCT has really highlighted that. Of course, the fundus autofluorescence, which is also noted too, these are both very important modalities in assessing retinal health. We know more about, in terms of the rollout of competitor medications or the anti-complement therapy with the mixed response that our field has had, depending on who you ask in terms of whether people will administer it or not. A lot of it does come back to that sort of gold standard in terms of vision preservation. Depending on who you ask, you will probably get a different answer.
That is why I think this is a great question because I think what's really going to get people in the field over that hurdle and more in a unified agreement would be trying to achieve, you know, that whether scientifically it makes sense or not, psychologically for our field in terms of physicians and clinicians getting behind these treatments, hitting that hurdle, there's nothing that can necessarily beat that, although these other metrics are certainly important and scientifically valid.
Got it. That's very helpful. Thank you. Dr. Scholl, can you comment on the key risks in the ongoing Diamond trials for OCS-01? How is Oculis addressing potential challenges such as variability in topical drug delivery from patient to patient?
Like I said in the previous question, right? Like any registration study, execution and oversight are absolutely critical to success. This is the challenge, right, for pretty much any Phase 3 study. Again, driving strong adherence to the protocol, ensuring patient compliance, retention, minimizing missing data, that's something FDA and health authorities are very keen for. We're able to do this with very close monitoring of the trial and collaborating closely with very experienced investigators. We have a world-renowned steering committee with the top retinal specialists and clinical trialists. As we progress the trial to our data readout, which would be second quarter of next year, world-class execution is the challenge and the opportunity here for OCS-01. As far as the topical delivery, patients are really motivated to be in the DME study. They can receive a non-invasive treatment. This is supported by a high recruitment rate.
We're able to completely randomize the trials over two times faster than our benchmarks in DME studies. We are learning from what we've learned in Phase 2, and we're really confirming in these Phase 3 pivotal studies. We have agreements with FDA on all the endpoints, the study design through close collaboration over the years with FDA. We're really looking forward to completing the trials with world-class execution and confirming what we've learned in the previous trials.
Got it. Thank you. Dr. Mohanty, based on the Phase 2b data for MCO-010, what are the key long-term efficacy and safety considerations for patients with RP or Stargardt disease? How will these be addressed in your future trials?
That's a great question. Safety is paramount. As you know, we are talking about, I didn't mention MCO-010 is a single intravitreal injection providing durable expression and functional vision. We have monitored our RP patients in our phase I/II trial, which is now over five years. None of the trial phase I/II or the Restore Randomized Control Trial or Stargardt trial have any SAE related to treatment, no ocular or systemic. That gives us a, of course, we have prophylactically treated these patients with a short course of, you know, tapered steroid profile. Occasionally, there is inflammation which has been treated and patients have responded to steroids. We believe with the highest unmet need in severe vision loss patients across these indications, RP or Stargardt and other indications in our pipeline, they will be amenable to occasional steroid eye drops. We have not seen any SAE.
In that context, we have solid data of 100% years of exposure to our drug across these three trials. We have full alignment with FDA about our Phase 3 trial on Stargardt disease, which we are going to begin shortly towards the end of this year. We believe to further put both oral and topical steroid maybe to further control any inflammation or safety event, that transient event that has happened in the past. We do not foresee this to be a rate limiting for treatment in the real world because we did not see any correlation with existing neutralizing antibody levels or other ways. The safety events were not correlated to any of those. We believe we can treat patients in the real world in a commercial setting after approval without requiring even their neutralizing antibody being screened. That's a very safe profile, I think.
We have to have close monitoring of that. We should not feel comfort from the patients. We have treated so far around 35 patients. When it's a mass, when it's big in a commercial setting, we have to watch closely.
Are there any logistical challenges associated with delivering the therapy to ensure broad patient access, and how is Nanoscope addressing those potential issues?
That's a very good question. As I mentioned, it's a disease-agnostic approach. We are seeing we have multiple animal models which have shown that. Now, clinically, we are showing in both RP and Stargardt. We are removing that access barrier by we have not seen any gene mutation-dependent efficacy outcome that we have seen, safety or efficacy. The same way, as I mentioned, there is no neutralizing antibody-related safety or efficacy. Even that said, a patient can now be clinically diagnosed without, so all the patient journey will be very simple from starting from diagnosis to treatment to follow-up outcome assessment. Reimbursement is very much simplified, similar to a biologics rather than a gene therapy. One-time treatment, not requiring a drop of blood to be drawn for genetic testing or for neutralizing antibody testing.
As we know, intravitreal injection is a very common procedure in medical science, not just in ophthalmology. The clinicians are trained. Once we provide this either through with a bill and buy model or it's with a white glove service with specialty pharma, the patient can be treated one time in an in-office setting. Diagnosis is simplified, treatment is simplified, and our outcome assessment is done through a computerized vision chart. As I mentioned, it takes very small space, like your computer is only required. The patient's outcome can be assessed in a very, very easy way instead of a big mobility course and stuff like that. I think when we're talking to our payers and other organizations, we see there's a wide adoption. We'll have a wide adoption of this because of this reason, because it's not about the price.
It's more about the value and how we are assessing with ease. The administration, assessment, and diagnostic all are at ease in this our program. It will be more like a biologics launch that we are planning.
Thank you. Dr. Scholl, does tinlarebant's advanced mechanism of action position it to compete or complement the existing complement inhibitor treatment in the GA space, GA market?
Yeah, that is a good question, right? I actually can claim that my group was the first to show systemic complement activation in AMD in 2008. A year later, we published a paper that there was no correlation at all between SNPs in complement genes and progression of GA. A couple of years later, it came as a surprise that there is some signal when you target complement by intravitreal injections. I believe there is a real signal. The drugs do something, right? As an example, they triple the risk to develop CNV, to develop bad AMD, which shows that those drugs actually do something. They have a treatment effect, but they have to be delivered intravitreally. We target a completely different mechanism. The two mechanisms may be synergistic. This is possible. Our drug tinlarebant is not anti-inflammatory.
It's rather antitoxic, if you will, and it preserves retinal tissue from damage. As a clinician, right, you look at retinal images, you see accumulation of waste materials in AMD, in Stargardt disease, and you see these areas at risk that light up by fundus autofluorescence imaging. That's exactly where tinlarebant actually targets the root problem of the disease.
Thank you. Ms. McCarthy, how does Stealth plan to position elamipretide for earlier stage R&D patients? What clinical data, in your view, will support its differentiation?
Yeah, I mean, so really what we're seeing an effect on is the photoreceptors. Not geographic atrophy, which really kind of moves into areas of dead photoreceptors, but the photoreceptors themselves. There's a protective effect there. There was data recently presented at ASRS, which showed photoreceptor death predicts GA growth. Before that, photoreceptors at risk, so photoreceptors that are somewhere between 0 and 20 microns in height, about half of their normal height but not dead yet, those are the ones most likely to convert to photoreceptor death in our data set over one year. Treatment with elamipretide, as presented at ASRS, and this was a post hoc, essentially eliminated that relationship between at-risk photoreceptors and their eventual death at one year. You sort of see a flattening of that. We think we can protect those struggling photoreceptors and potentially improve vision.
I think that just fundamentally differentiates, right, from where complement inhibition is being utilized, which is in later stage diseases, larger lesion sizes, and probably at a point where the disease may actually be too progressed for our mechanism to be as effective. We, again, think that we're more at that intermediate to early stage GA sweet spot based on the data we have.
Got it. Thank you. Breazzano, I think you may have touched upon this in your previous remark, but my next question is, how do you foresee the delivery of various delivery approaches influencing patient and clinician preference in real-world treatment settings for retinal disorders? I mean, particularly in terms of balancing efficacy with practical considerations such as the cost of the therapy?
Yeah, absolutely. I think it's that balance between how effective it is, how safe it is, and then, of course, the cost and is insurance going to be paying for it? What's the current financial landscape in terms of budgeting personally for these patients as well? It certainly is complex. Anything that can make things easier, both physically, financially, time-wise, other caregivers being involved, I think, are all going to be important. Certainly, other aspects as well in terms of the mode of treatment itself. Certain things are going to be more favorable if they can be done at home, for example, like eye drops. Some of that will have to be off-balanced by what we know, for example, with steroids, which is arguably even more effective than anti-VEGF.
At the same time, monitoring for intraocular pressure increases and glaucoma long-term is also a consideration, just as GI upset and other, maybe skin reactions with oral or injectables. Everything has pros and cons, of course, that we'll obviously want to be mindful of. The financial considerations is a big enigma and black box, I think, moving forward for everyone and everything, not just health care.
Got it. Thank you. Dr. Mohanty, could you share with us your expected catalysts in the coming quarters for Nanoscope?
Yeah, there are many. In common quarters, as I mentioned, our Phase 3 registration trial is beginning towards Q4 of this year. Our completion of our BLA submission is in Q1, as we publicly announced, followed by approval hopefully in the Q4 timeframe. As you know, we are fast track or fund designation with priority review potential. We anticipate launching that drug towards the end of next year. Besides that, we are also moving fast in geographic atrophy space secondary to wet and dry age-related macular degeneration where there is a loss of photoreceptors to restore vision. We will be advancing that program. We have recently data on NHPGM model as well as from Stargardt macular degeneration patients, a great improvement, later improvement in ETDRS chart. We believe that's a mass indication that we'll be starting a new clinical trial late-stage program directly. Those are the key milestones, I think.
Okay. Thank you. Dr. Shah, could you share with us your upcoming catalysts from Belite Bio ?
Very happy to. We expect a 24-month readout of the Dragon trial, the registration trial in Stargardt disease, by Q4 this year. We aim for an NDA submission in the first half of 2026, and potentially the approval of tinlarebant for treating Stargardt disease before the end of 2026.
Thank you. Ms. McCarthy, the upcoming catalyst from Stealth?
Yeah, so we've just completed enrollment of our renewed clinical trial. The 48-week readout, so the full completion of that trial will be in mid-2027. Sorry, the 96-week readout, the 48-week readout, which is the primary, is mid-next year that we'll be crossing that milestone. Our phase, our beva-mipretide asset, which again is a topical ophthalmic drop, which we are progressing for dry age-related macular degeneration. It's also shown neuroprotection in glaucoma models. That has completed the first part of a phase I study. We've completed the SAD portion and moving into the MAD portion. With that, hope to be starting Phase 2 clinical trials second half of next year.
Got it. Dr. Scholl, upcoming catalyst from Oculis?
Yeah, so we're in a really exciting time for Oculis and catalysts before the end of 2026. We're going to really include the fully enrolled Phase 3 Diamond studies. We'll read out top-line results second quarter of next year, and then we will follow that up with an NDA submission in the second half of next year. As I discussed, following the positive Phase 2 acuity results for OCS-05 in acute optic neuritis, we're preparing to initiate a registrational trial in the first half of next year. We're also looking to expand into two new indications as the first potential neuroprotective treatment for non-arteritic anterior ischemic optic neuropathy, NAION, and acute treatment of multiple sclerosis relapse.
We also have a third program, Licaminlimab, which is OCS-02, and we're preparing for the first genotype-based registrational trial by the end of this year to really drive personalized medicine in a multifactorial disease like dry eye disease.
Got it. Thank you. Dr. Brezzano, of all those anticipated milestones mentioned, including Phase 3 data readout, regulatory submission, or potential FDA approval, in your view, which kind do you could potentially have the most significant impact on clinical practice?
Yeah, absolutely. You know, it's hard to definitively say, oh, this one is certainly more than others. I think all of them can be quite exciting and informative. I think each one has its own special caveats that we can look back into the recent history on those that have been particularly helpful and informative as well. I think each one is going to be critical. Phase III, of course, we're looking for primary outcome measures that are significant and beneficial. The approvals, of course, you know, sometimes there are surprising things from the FDA that they're approved. All of a sudden, you know, wow, that's a pretty wide open label for this. Then others that, you know, you're surprised, oh, why wasn't this part approved? It will be interesting and unique to each circumstance, I think.
Thank you. We are getting towards the end of this panel discussion. I would like to ask the panelists to provide some closing remarks to our audience. Maybe starting with Dr. Scholl? Dr. Scholl from Oculis?
Thank you for the opportunity. I couldn't agree more with Dr. Breazzano. It's an exciting time for drug development. There are a lot of exciting things on the horizon. There are going to be a lot of fireworks this year and next year with new data. What you heard today is really companies are working to really focus on unmet need, right, and really, really understanding what the patient needs and doing trials to get new treatment options for our patients and our physicians. Thanks again for the opportunity today. I really appreciate it.
Thank you. Ms. McCarthy?
Yeah, thank you so much for the opportunity to join. I echo what Dr. Scholl said, right? There's tremendous unmet medical need for patients living with retinal diseases. It can be one of the most significant disease burdens in terms of impacting patients' ability to live independently, contribute meaningfully to life, very isolating to live with some of these diseases. I think that the more we can do to identify treatments that may actually improve clinical outcomes for patients, slow the loss of vision or improve vision, as well as reducing compliance burdens, we start to get closer to improving the lives of these patients.
Thank you. Dr. Mohanty?
You're on mute, Sam.
First of all, thank you for the opportunity to participate. It's great to have the panelists here. We are all working cohesively on the mission of restoring vision. It will be an exciting time for Nanoscope , as well as each one of you. We are looking forward to work together to make it better for the patients in the future. Thank you.
Thank you. Dr. Shah?
It was great to participate in that meeting. In ophthalmology, we sometimes stay in this compounded space. We should be proud of leading the way of targeting neurodegeneration, right? This has been an obstacle in the whole field of medicine, right? Obviously, working on the retina, we are the first that show that we can slow down, maybe even stop neurodegeneration in the retina. Obviously, tinlarebant will be a key player in that game. Thank you very much.
Thank you. I would like to thank all our panelists for participating in our conference and best wishes to all your clinical endeavors. Thanks again.
Thanks, you.
Thank you.
Thank you.
Yes.
Thank you.