Good afternoon, and thank you for joining the H.C. Wainwright 5th Annual Ophthalmology Virtual Conference. For this panel discussion, I'd like to welcome the following panelists to share with us their view on multiple novel drugs for front of the eye indications. Mr. Mark Baum, Chief Executive Officer and Chairman of the Board of Harrow, Dr. Kim Brazzell, Chief Medical Officer of KALA BIO, Dr. Gary Jacob, Chief Executive Officer of OKYO Pharma, Mr. Thurein Htoo, Chief Executive Officer and Co-Founder of Qlaris Bio, and Dr. Timothy Khater at West Texas Eye Associates. Welcome. Thank you. Dr. Kather, could you give us an introduction of yourself and your practice? Good morning everybody, or good afternoon, wherever you may be. I am an ophthalmologist. I practice in West Texas. Right now, I'm a fellowship- trained cornea, cataract, and refractive specialist. I've been in practice for about 26 years. I started a practice 26 years ago and grew it to about seven or eight doctors. A couple of years ago, we were acquired by a private equity corporation, and I continue to practice there. I'm the lead cornea and cataract and refractive specialist there. Thank you. Based on your practice, what are the most pressing needs in front of the eye conditions, such as dry eye disease, persistent corneal epithelial defects, or neuropathic corneal pain, or glaucoma? That is a very broad, broad question. As you know, the front of the eye is a very complicated part of the eye, and there are many areas that need help. Dry eye is a very big part of our practice, and living in West Texas, we take care of a bunch of dry eye patients. Our environment is not very good for patients with dry eye because we live in a relatively low- humidity area. We take care of the normal complement of patients with corneal diseases, and treatment of corneal diseases is a very big, also a big part of our practice, as is glaucoma and cataract and refractive. The front part of the eye is a problem area, and it's not going away. Thank you. Could you tell us how do you evaluate the potential of emergent treatment options compared to standard options, and what key clinical endpoints would influence your adoption of these new therapies? Emergent treatments are very interesting only because they allow us new methodologies to help our patients. The way I like to evaluate them is to stay abreast of the literature. I don't do research myself, so I really depend on my colleagues to be able to manage and stay at the forefront. When I look at emergent treatments, the number one thing I look at is how am I going to be able to make my patients' lives easier and less problematic, and that's how I like to look at emergent treatments. Okay. With advancements in precision therapies for anterior segment eye diseases, what barriers do you foresee in integrating novel treatment into clinical practice? I mean, including patient compliance or diagnostic challenges, and how could these impact broader adoption among ophthalmologists, in your view? Barriers are far and wide. First, you have to develop the treatment. You have to find where the need is, and once you have identified a need, you can proceed with doing whatever manipulation you want to do to improve the need. Once you've found the need, you need to develop the treatment, and the treatment needs to be applicable to your patient population. After you've found that need and found that it works, you need to find a way to implement it, find a way to implement it safely, and find a way to implement it cost-effectively. In addition, there are lots of regulatory barriers that I'm probably not the right person to discuss, but there are a lot of regulatory barriers as well. Any particular diagnostic challenges in identifying, I mean, a specific segment of patients? I guess I'm not understanding the question. There are certain indications that do not have FDA-approved therapies. I'm just asking, are there any challenges in terms of diagnosing these patients for the indications that do not have FDA-approved therapy yet? Yes, there are plenty of barriers for diagnosing these patients. In order to diagnose these patients, you have to have a methodology to understand that your patient has the actual problem, and then after you've found that methodology to understand that your patient has the problem, you need to go about the therapeutic manipulation to fix the problem. Thank you, Dr. Kather. Mr. Baum, I understand VEVYE utilizes a novel water-free, semi-fluorinated alkane technology to deliver cyclosporine for dry eye disease. Could you explain how its mechanism addresses unmet needs compared to traditional therapies, and also what specific advantage sets VEVYE apart from other cyclosporine products? Thanks for the question, Yi. Look, cyclosporine is not a new thing to ophthalmologists. It's not a new active ingredient. In fact, I would say it's the most trusted active ingredient in the U.S. market. The original product that was developed not necessarily to treat the signs and symptoms of dry eye disease, but for increased tear production, is RESTASIS, which is a cyclosporine-based product. I think, though, if you talk to patients and you look at the refill data related to products like RESTASIS, they really don't stay on therapy that long, and a lot of that has to do with the burning and stinging associated with those products, the fact that they don't work very quickly, and there's not a lot of data in terms of showing the duration of therapeutic effect for products like that. Even other cyclosporins in the category suffer from the challenge of burning and stinging. I think from our perspective, what consumers want is not only a product that's both accessible and affordable, but they want something that works quickly, that lasts a long time, and gives them that therapeutic benefit. We think VEVYE is that product. It's the first and only water-free cyclosporine in the category, and it is approved for both the signs and symptoms of dry eye disease. What makes it different is its vehicle, which, as you said, is a semi-fluorinated alkane. It delivers 22x more cyclosporine into the cornea relative to RESTASIS, as an example, and it works quickly, as soon as two weeks, and there is data demonstrating sustained benefit out to 56 weeks. It is extremely well tolerated. I think if you put it on your eye, you would see that you feel sort of a puff of air. There's no burning or stinging. In fact, there was a 52-week extension study of this Essence II study that was used to get the product approved, and only one out of over 200 patients dropped out of the study. Very well tolerated. With the legacy products characterized as I described them, I think VEVYE and its unique vehicle offer a lot to the market, and that's being demonstrated in the commercial success that we're seeing. Yeah, yeah. I mean, could you provide us with an update on VEVYE's latest commercial performance, and what is your commercial strategy to maximize market penetration going forward? We actually just reported our numbers yesterday, and TRXs are total prescriptions. Q1- Q2 grew 66% quarter- over- quarter, nearly 120,000 prescriptions. NRXs are new prescriptions, grew 62% quarter- over quarter, and I'm excited to say that about 50,000 of those 120,000 prescriptions were new prescriptions. That's 62% growth, and that's largely due to our unique access program, which is called VEVYE Access for All. As of the end of Q2, we had just under 8 percentage points of the total dry eye disease market in the U.S., increasing just under 3 percentage points quarter to quarter from Q1 to Q2. Our primary goal is to win the cyclosporine market. We are now number two in the U.S. We just surpassed CEQUA, and we're beginning to gain ground even on MIEBO, which is not a cyclosporin-based product, but we're making progress there. More and more practitioners are adopting Vivai. I think according to IQVIA data, among U.S. prescribers, we are number one in terms of prescriptions, dry eye prescriptions per prescriber, ahead of everyone. When doctors adopt it and patients come in happy, physicians seem to be more prone to use VEVYE on more of their patients. Thank you. Thank you, Mark. Dr. Brazzell, I understand that KALA BIO's KPI-012 leverages a mesenchymal stem cell secretome to promote corneal healing. Could you elaborate on its methods of action and how it addressed the pathophysiology of persistent corneal epithelial defects? Sure, and thank you, Yi, for inviting me again this year. To start out, you know, impaired corneal healing, such as that seen in persistent corneal epithelial defects and other conditions, can involve any of a number of impaired biological pathways. For example, we know epithelial cells play a major role in healing, and any impairment in the function of epithelial cells, such as the impairment of their ability to differentiate, proliferate, migrate, can have a significant impact on the ability of the cornea to heal. In addition, even if you have a number, right amount of epithelial cells that are healthy, you have to have an intact basement membrane because those epithelial cells have to get to the wound bed. They have to attach to the basement membrane in order to kick off the healing process. Any condition that can affect the basement membrane or degrade the basement membrane is something that can be a key component of the persistent defect. We know that proteolysis can play a major role as well. We know proteolysis has the ability to chew up or degrade the basement membrane and also has the ability to degrade or destroy growth factors that are important for the healing process. Being able to control proteolysis is important. Of course, we know that there's a very significant crosstalk between the corneal nerves and the health of the ocular surface. I'm sure that's an evolutionary process. The cornea is the most highly innervated organ in the body, and when it starts, when those pain receptors start firing, it signals the eye to start healing itself. Any disruption of corneal nerves, such as that seen in neurotrophic keratitis, can have a significant impact on the healing and the development of epithelial defects. We think effective treatments of persistent corneal epithelial defects across multiple pathways are important to be able to address these persistent defects across different etiologies. Our product is a secretome, as you said, manufactured from human bone marrow-derived mesenchymal stem cells. We culture those up under very controlled conditions. We then remove the cells and are left with an aqueous solution containing a mixture of a number of different biomolecules and biomolecules that can impact epithelial regeneration. Examples that we have in our product, growth factors such as hepatocyte growth factor, platelet epithelial derived factor that can help to stimulate migration, proliferation of epithelial cells, neurotrophic factors such as platelet epithelial derived factor, BDNF, CNTF that can help to regenerate the nerves and re-energize that crosstalk between the nerves and the healing process. We have protease inhibitors such as TIMP1 and different serpins that help to avoid the proteolytic activity that tends to chew up the matrix proteins as well as chew up some of the other growth factors. We are providing back matrix components such as fibronectin, collagen, and others to provide a scaffold to rebuild this basement membrane and get an intact matrix so you can initiate the progress. We think that these all work together in a multifactorial way to address impaired healing, and we think administering these components can help provide essential biomolecules that can stimulate healing at multiple points in the biological pathway. We know that a number of patients may have more than one of these pathways that are impaired, so we think that to address persistent defects across a number of etiologies requires the ability to impact the healing process through these various pathways. Yeah. I understand you recently completed enrollments for the pivotal Phase II-B CHASE trial in persistent corneal epithelial defects, and the data readout is going to be in the near term. Can you talk about your expectation about the efficacy or safety results, I mean, particularly regarding the endpoint about complete epithelial defect resolution? Yes, we are targeting a top-line readout at the end of September. First of all, I want to clarify that we haven't looked at any efficacy data even in a masked fashion, so all the data is masked. We do have the results from a Phase I-B trial that was conducted in eight patients with PCED s of different etiologies, and we're able to provide complete healing in six of eight of these patients, and in the other two patients, saw a reduction in lesion size. This was measured using corneal fluorescein staining photographs, which is the way we're evaluating it in the Phase III trial. Seeing healing in 75% of patients, we think is a good signal. That's similar to what OXERVATE showed in their Phase 3 trial, a little greater than that. We think that's a very good omen for our efficacy as well. On safety, in the Phase I-B trial, we saw no significant safety signals. Again, all the data is masked on the ongoing trial, but we haven't seen any significant safety or tolerability issues to date. We're hopeful that when we get our readout at the end of September, we'll see the efficacy we want, and certainly without the safety profile that could impair the uptake. Thank you. Dr. Jacob, OKYO Pharma's Urcosimod is a novel peptide targeting neuropathic corneal pain, right, through its anti-inflammatory mechanism. How does it address unmet needs in NCP patients lacking approved therapies and compared to opioids or other off-label treatments currently in use? Certainly. Thanks, Yi and Sadali, for the opportunity to speak on this panel. To your point, we're developing a drug. Again, it's called Urcosimod. This is a drug that initially we were exploring in dry eye, incidentally, because it's anti-inflammatory, as you say. The reason for that is our drug is a lipidated peptide that hits a receptor, a well-known class of receptors, the G-protein coupled class of receptors. In our case, the particular subclass receptor is called ChemR23. It's present on white blood cells, and of course, because we were very interested in its potent anti-inflammatory activity, we naturally thought of its potential in possibly treating dry eye. The other interesting element is that receptor is not only present on these white blood cells that are involved in immune surveillance, for example, in the eye, but it's also present, was discovered to be present on the spinal cord neurons, nerve cells, and glial cells. In a very important series of studies that we did with Dr. Petra Mohammad, a leading expert in neuropathic corneal pain at Tufts Medical Center, he had an animal model that involves basically ciliary ligation of the general ganglion, which produces this severe nerve pain. Neuropathic corneal pain is not like an inflammatory pain. I tend to think of it as like a spinal cord injury in your eye because of the highly innervated nature of the cornea, which is chock full of nerves. What you're dealing with are patients who are suffering that kind of nerve pain, which basically can be generated from people who have dry eye, for example, who get drying on the eye and get severe inflammation. They get some damage. There is a certain percentage of people with dry eye who experience neuropathic corneal pain. There was a celebrated case, incidentally, about a month ago, that got national attention about a 28-year-old former policeman who had LASIK surgery and developed such an intense neuropathic corneal pain that he committed suicide. These patients with neuropathic corneal pain suffer this kind of nerve pain, for which there is no FDA-approved drug to treat neuropathic corneal pain. Our drug, which is a topical drug, is given in the eye. We were very excited to open the first ever trial in neuropathic corneal pain. This was a trial that was run as a Phase II trial, a randomized placebo-controlled trial, and we were very excited to see if this drug that actually had been through a 240-patient trial in dry eye and was showing a benefit in reduction in ocular pain, the statistic is significant, would be benefiting these people with this severe neuropathic corneal pain. These patients have failed every other therapies, medical interventions. They fail on opioids. They fail on NSAIDs. They even try autologous serum tears. They take their own serum and they generate it to actually do something to reduce that terrible pain. We enrolled these patients using what's called IVCM. That's a confocal microscopy method, so we could definitely look for damage to the nerves by imaging the cornea. You're looking at micro neuromas, changes in density of the neuron. What we did was initiate a 48-patient trial, Phase II, randomized placebo-controlled, and we stopped that trial in April with only 18 patients because even though this was a blinded trial, double masked, we were seeing some remarkable reductions in what's called the visual analog scale, a scale from 0- 10, where patients at nine, and 10, and 8 are suffering severe pain. What we were seeing in that blinded data were remarkable reductions, and we really didn't want to wait another half year to get to finish that trial. In July, we just announced data, and we were very excited because these kind of patients we were seeing who were suffering from this constant pain were showing dramatic reductions. We are right now poised with that trial finished to move forward. First of all, one of the things we would want to do, Yi, is open a dialogue with FDA. We do have fast-track designation with this drug because we need to establish what is an approvable drug to treat neuropathic corneal pain. Number two, we want to establish what is our registration dose. We're looking for a very quick multiple ascending dose trial, and that's why we're so excited about where we are right now, and we're really looking forward to moving this in a fast-track way and no pun intended as we look to develop a drug we believe would be the first with a label of approving of treating neuropathic corneal pain. Thank you. Do you expect you could start the next trial sometime in 2026, and is there a potential for accelerated approval pathway? Certainly, because we are fast-track, there's always the, yeah, and that enables you to go for an accelerated approval, priority review, rolling review, all of that. There's the potential that in our discussions with FDA that we would be looking at maybe a breakthrough therapy designation. I think what's more important would be if we could have a SPA in place, a special protocol assessment with FDA, which would indicate that they, particularly for an indication where there's no FDA-approved drug, as the gold standard, if you will, for what is approval, it's a negotiating with FDA on exactly what they're looking for for an approval. To us, it's very important to have this. We're looking at a Type C meeting with FDA that we can get a quick turnaround, and then we are going to do a small trial, Yi, to actually look for what is the key registration dose. We only did this trial in two doses, 0.05% and 0.1%. The 0.05% gave us great data. 0.1%, we understand why it wasn't showing what you might think as you go to higher, because this is a drug that has unique characteristics, which I won't go to in the interest of time, but we want to do a small multiple ascending dose trial. We'd like to get that trial done by the end of the year, begun by the end of this year with readouts sometime by the summer or autumn of next year, and then looking forward to registration trials. Got it. Thank you. Mr. Htoo, I understand that Qlaris Bio's QLS-111 is a preservative-free, ATP-sensitive potassium channel opener that lowers intraocular pressure by targeting episcleral venous pressure. Could you explain its unique mechanism of action and how it addressed the unmet needs in glaucoma and ocular hypertension compared to the standard of care therapies? Yeah, absolutely, Yi, and again, thank you as well for inviting me to join this panel as well, so thank you for that. Just with respect to QLS-111 current program, as you mentioned, Yi, QLS-111 is a first-in-class formulation of a well-characterized ATP-sensitive potassium channel modulator. That mechanism actually allows us to, what we consider to be, vasorelaxing or vasodilating vascular and vascular-like tissues of the eye. By doing so, that allows us to actually lower and selectively target what's called episcleral venous pressure or EVP. It just happens that EVP is the only one component of IOP that seems to be unaddressed by the products that are currently available on the market. What's interesting about that, and if you may know a little bit about the Goldman equation that builds up all of intraocular pressure in the eye, there are four components. Of the four components, as I mentioned, three out of the four are addressed by the currently available therapeutics out there. That includes everything from uveoscleral outflow to aqueous humor infiltrate to conventional outflow facility, but none of those products target episcleral venous pressure, as I mentioned earlier. Because of that, what we find is that QLS-111 may be an ideal complementary therapeutic to be used second- line in combination with the other products that are currently available, either as a free or a fixed-dose combination product, and that can go across not only primary open-angle glaucoma, but also ocular hypertensive patients. Importantly, because of that mechanism, as I was just explaining earlier, because nothing happens to lower EVP itself, currently EVP happens to set the floor for IOP- lowering in patients with glaucoma, whether or not they have hypertensive glaucoma like primary open-angle glaucoma or even normotensive glaucoma such as normal tension glaucoma, where interestingly enough, because we can lower EVP, QLS-111 may afford itself the opportunity to be the first approvable drug therapy to lower pressure in patients with normal tension glaucoma since nothing is currently approved, and interestingly enough, also disproportionately affects people of Asian descent, where people may not necessarily appreciate as much, but normal tension glaucoma in Asia, that includes East Asia, Southeast Asia, and South Asia, 80%- 90% of all glaucoma sufferers have normal tension glaucoma and not high-pressure glaucoma such as ocular hypertension or primary open-angle glaucoma. Thank you. You mentioned fixed-dose combination. In your future trials, even including considering the potential future commercialized product, do you think it would be better to have a fixed-dose combination of QLS-111 with latanoprost? Yes, actually, that's a great question, Yi, and that's absolutely the case. Given its complementary mechanism, we feel very confident that for the market and based on the feedback from our stakeholders and others, the fixed-dose combination product of QLS-111 combined with latanoprost is going to be something that's going to be very much a go-to product, one that could be used right after patients who are on latanoprost currently and are seeking better IOP control will immediately move to. One of the things that gives us quite a bit of confidence in that approach is that we recently just completed two Phase II studies, one in a dose range finding around monotherapy use of QLS-111, which was called the Osprey study, and the second study called the Aptrix study where we actually combined the use of QLS-111 in patients who are already stable on latanoprost monotherapy. In that study, what we saw was that the actual IOP- lowering horsepower of QLS-111 is nearly fully complementary and additive to the use of latanoprost. We were able to see in the Apteryx study IOP- lowering incremental of 3.2 mm- 3.6 mm of additive IOP- lowering on top of latanoprost itself. What gave us even more confidence and comfort around this is that our safety profile appears to be second to none in terms of its side effect profile. There was no incremental and no seen ocular or systemic side effects seen at our most optimal dose, and importantly, no added hyperemia when used on top of latanoprost, which juxtaposes us against some of the other combination products that are out there right now. Hence, we believe we have a product that not only provides a substantive amount of clinically meaningful incremental IOP- lowering, but also one that, to the comments that were made earlier, also provides a safety profile and a tolerability profile that allows us to have better patient compliance, a product that patients would want to not only start, but they can stay on because they don't have compliance-limiting side effects. Thank you. Dr. Kather, based on the discussion so far and from your clinical perspective, which of the mechanisms of the drugs or drug candidates we just discussed do you find most promising for addressing unmet needs for in front of the eye indications, and how well do their prospective benefits, such as faster corneal healing or targeted IOP reduction, align with the practical needs of your patients in your practice? Wow, that's a tough question. I actually love all the different approaches that I've been exposed to today. Firstly, I really like the QLS-111 medication. As we were educated, the episcleral venous pressure is absolutely the floor of intraocular pressure. Anytime when we treat glaucoma patients, we cannot get below episcleral venous pressure because that is the absolute lowest you can get. Episcleral venous pressure drives the system, and surgically speaking, when I operate on a patient and do glaucoma treatment, you can see evidence of that because I will operate on the patient's trabecular meshwork, and you will get reverse blood flow, which is exactly related to episcleral venous pressure. If we can indeed lower episcleral venous pressure, then there are lots of patients that we can drop their intraocular pressure and potentially slow down the progression of their glaucoma. That's just absolutely fascinating. The medication to decrease neuropathic corneal pain is also very intriguing to me. As a surgeon, I do a lot of treatments on patients, and one thing I would wonder is if we can provide them with some pain relief in the post-surgical period. I'll do cataract surgery, I'll do corneal surgery, I'll do pterygium surgery, and so on and so forth. One of the problems that we have with treating corneal pain is if you use a pain medication such as proparacaine, which is like lidocaine, that can inhibit corneal healing. It would be very, very interesting to me if we have another tool in our toolbox that can treat corneal pain without inhibiting corneal healing, and I'd really like to know if that's going to be a feature of the new medication. As far as VEVYE is concerned, I love that medication because, as I understand it, and perhaps I can be educated a little bit further, that medication is a two-pronged sort of medication. The vehicle works for dry eye, and the medication works for dry eye. Dry eye is considered basically an inflammatory disease, okay. That inflammation leads to a situation where the eye cannot hydrate itself, commonly because of increased evaporation. ViEVYE's medication, cyclosporine, is an anti-inflammatory, and it has been shown that the anti-inflammatory effect of cyclosporine is to increase tear generation. In addition, the vehicle of VEVYE, which is a fluorinated hydrocarbon, is an incredibly good barrier to evaporation. The fact that you're giving somebody VEVYE tells us you can not only treat the evaporative problem, but you can also treat the inflammatory problem, and thus you can have a two-pronged approach to treating the patient's dry eye disease. I think that's an excellent way of using the medication. In addition, for us, solubility of cyclosporine in a water-based solution has always been a problem. Cyclosporine does not dissolve well in water, and the vehicle of VEVYE, I think, really aids to the solubility of cyclosporine, so you can actually deliver a significantly higher concentration of the medication to the target tissues. Finally, the tissue growth factor medication is interesting to me. We have a lot of patients with neurotrophic keratitis that have commonly been a problem because they are very hard to heal up their epithelial defect, and that epithelial defect can expose them to infection, can expose them to breakdown. If we have another tool to re-epithelialize patients' corneas, especially a tool that can work in conjunction with the tools that we currently have, I think that that would be an excellent addition for our ability to care for our patients. Thank you, Dr. Kather. Mr. Baum, I think, as Dr. Kather just mentioned, he could probably use more tools for post-ocular surgery control of inflammation and pain. I think Harrow has another new product that could be launched in the coming quarters for that indication. Is that correct? For? Post-ocular surgery inflammation and pain. Yeah, so we're actually going to be leveraging a product that he probably has used for many years called TRIESENCE. We acquired TRIESENCE from Novartis about a year and a half or so ago. We invested heavily to make sure that it was now available because it had really disappeared. It was extinct from the U.S. market. There were no units available. Now it is in inventory, and importantly, we were able to get a pass-through status for it so that it can be used in both the ASC and the hospital outpatient department, that J- code that exists. There's pervasive coverage, by the way, not only in the office and in the hospital and outpatient setting, but if you have a patient that can benefit from TRIESENCE, they certainly will have access to it, which is really the hallmark of Harrow's commitment in the U.S. market to make sure those in need have access to an affordable medication. Importantly, also for consumers, for patients, the out-of-pocket for a patient for TRIESENCE is about $37, and from an affordability perspective, it's extraordinary. The launch of TRIESENCE in the ocular inflammation market, specifically for injuries associated with surgery, is going to start here in the fourth quarter. October 1st, we're going to kick that off. We've just hired a gentleman named Chad Bryans who joined us. He formerly led the sales organization for Ocular Therapeutix and their Dextenza product, but he's joined us, and we're building out his team, and we're excited to talk to U.S. ophthalmologists who do cataract surgery about the benefits that TRIESENCE can offer their patients and their practices. Thank you. Dr. Kather, can you give us some comment regarding what are the key barriers to adoption that you foresee in integrating novel therapies into routine ophthalmology practice, particularly regarding patient compliance, diagnostic requirements, or payer reimbursement? We have multiple, multiple barriers. Firstly, as physicians, we commonly can be a little slow to adapt to or to adopt new treatments, and once new treatments are made available, a lot of times we as physicians would like to get some experience and some feedback from our colleagues that the treatment works. After we, as physicians, decide to want to use it, there are lots of regulatory and third-party payer barriers that we have to address. It is very common that we will get a new treatment, we will ultimately decide that we want to use the treatment, but we find that the payers are not cooperating with our ability to utilize the treatment. In addition, these newer treatments tend to have a higher price tag associated with them. Our owners and our partners sometimes want to get a little bit more clarity as to how the financial aspects of the new treatments are going to be addressed. Thirdly, after we've utilized them for a while, a lot of times we will discover that there are additional things that we need to think about that we didn't know about prior to the adoption of the new treatment. An example is one of our companies came out with a device to help lower intraocular pressure. It was an implantable device. People had used it for a year, and subsequently, it was found that that device caused problems with the corneal endothelium, so that device had to be removed from the market. Those are all different barriers. Unfortunately, we live in a system where, number one, there's a lot of regulatory stuff, and number two, we have to learn a lot by doing, and a lot of times, you know, even when a company has a great idea, the pitfalls can sometimes prevent that idea from coming to fruition. Thank you. That's helpful. Mr. Htoo, following QLS-111's Phase II results, what are the primary clinical risks in advancing to Phase III in your view, such as achieving consistent IOP- lowering efficacy in all the patients? That's a great question, Yi. I think in terms of what we're doing right now, as I mentioned a little bit earlier, one of the things that comforts us going forward into further development is that our safety profile appears to be quite exceptional at this point in time. That is not in and of itself limiting to us. What we are trying to do right now is to demonstrate then, to the points that were just made a little bit earlier, and Dr. Kather, to your point around access and reimbursement, to help to make sure that we develop the products that we think that not only people would want, but that payers would also want to reimburse because the value is there. Leading with that, we have actually two different areas, one of which is to demonstrate the effect, the incremental effect of the fixed-dose combination product, which we've just developed and will be developing further going into Phase III. That product will be aimed to show superiority versus latanoprost alone, which is really the key right now in terms of being able to help to, and as Dr. Kather put earlier, to lower episcleral venous pressure to help patients who need to achieve better IOP- lowering goals to get there. That actually goes across a number of different areas, which then starts to span a bit more into areas such as normal tension glaucoma, where none of the actual other products are actually fully approved. In there, we want to show actual incremental gains in terms of being able to manage and lower intraocular pressure in that patient population, where other products simply don't perform as well as they do at higher pressures. We're actually initiating that Phase II study called the Nightingale study. It's in South Korea just right now as we're speaking, and we look forward to demonstrating some of that data going forward. Again, Yi, to your point, at the end of the day, it is to consistently show that across the board and across all these patients, we're able to show that by targeting episcleral venous pressure, we can incrementally lower IOP. Thank you. Dr. Jacob, what clinical risks remain in confirming efficacy across a larger diverse population for NCP, particularly given the subjective nature of pain points or potential placebo effects? To begin with, our drug is topical, of course, and it's virtually non-systemic. Issues around unexpected toxicity, some kind of organ-specific toxicity has not been an issue. In fact, in our 240-patient trial in dry eye, we saw excellent drop comfort. We actually saw virtually obviously no SAEs, very few AEs. The drug is extremely well- tolerated. I think what's also important is that this drug, basically, the patients who have neuropathic corneal pain are highly motivated. These are patients who suffer this kind of pain. We're not concerned about compliance. In terms of risk and further development, I don't see an issue around safety. Obviously, what we're looking for as quickly as we can is to demonstrate statistically significant reduction in that visual analog scale and to actually negotiate with FDA what is an approvable drug, the first drug that would be approved to treat neuropathic corneal pain. I see that this has a very low risk profile, but for us, we really need to negotiate with FDA what they're looking for. In our view, this is obviously a drug that could really benefit these people with this severe pain. As Dr. Kather had mentioned in his discussion, these patients, whether it's after surgery, whether they've been on dry eye or they've had LASIK, these patients are just looking for a drug that will benefit them, and they haven't been able to find any. We believe that there's very little other than establishing that this drug really works, as well as negotiating with FDA what they're looking for for a drug to be the first drug, topical drug to treat neuropathic corneal pain. Thank you. Dr. Brazzell, with KPI-012's CHASE trial data pending, what are the primary clinical risks, such as variability in patient response across diverse PCD etiologies, that could potentially jeopardize meeting the efficacy endpoint? Yes, certainly the variability across the etiologies is something that is a potential issue. A couple of issues that have occurred with other in-case studies, one in particular, is a high placebo rate, a patient's healing while on placebo. We added a component to our trial to mitigate that. Once patients are screened, they go into a one-week run-in where they get only non-preserved artificial tears and non-preserved moxifloxacin, and if they improve by more than 10%, then.