Kala Pharmaceuticals, Inc. Aktie

Hello, and thank you for joining us this afternoon. I'm Todd Bazemore, Interim CEO and President of KALA BIO. We are pleased to welcome you to our Key Opinion Leader event where we will be discussing our lead program, KPI-012 and its potential to transform the treatment of persistent corneal epithelial defect or PCED.

Before we begin, a quick note on disclosures. Today's presentation includes forward-looking statements, which should be considered in the context of our filings with the SEC and materials available on our website. Please also note that KPI-012 is an investigational therapy and has not been approved for use in any jurisdiction.

Turning to our agenda. I will start with a brief overview of KALA BIO and the commercial opportunity in PCED. We'll then turn to our esteemed KOLs. Dr. Francis Mah will discuss PCED and the significant unmet need in this space. Dr. Aldave will walk us through the PCED patient journey. Dr. Pflugfelder will provide insight into the mesenchymal stem cell secretomes and the mechanism of action of KPI-012. And finally, Dr. Toyos, an investigator in our CHASE trial, will share her clinical experience and discuss the CHASE study design. Then I will conclude with some closing remarks and look at some of our upcoming milestones for KPI-012.

Now I'd like to introduce today's speakers. Dr. Francis Mah is Director of Cornea and External Disease & Co-Director, Refractive Surgery at the Scripps Clinic Medical Group. Dr. Anthony Aldave is a Professor of Ophthalmology and Co-Chief of Cornea and Uveitis Division at the Jules Stein Eye Institute. Dr. Pflugfelder is a Professor and James and Margret Elkins Chair in Ophthalmology at the Baylor College of Medicine. And Dr. Melissa Toyos is a Partner and Research Director of Comprehensive Ophthalmology at the Toyos Clinic.

KALA BIO is a leader in the emerging field of mesenchymal stem cell secretomes with a focus on rare ophthalmic diseases. Our proprietary mesenchymal stem cell secretome platform is a cell-free regenerative approach designed to address serious underserved eye conditions. We're currently advancing two investigational therapies for orphan indications.

KPI-012, our lead asset, is in development for PCED, a rare vision-threatening condition with no approved treatments that address all underlying etiologies. Based on its unique multifactorial mechanism, we believe KPI-012 has a pipeline and a product potential, and we're exploring its use in other rare front-of-the-eye diseases, including limbal stem cell deficiency and other corneal diseases. We have made great progress with the KPI-012 development program. The product has received Orphan Drug and Fast Track designations from the FDA.

We recently announced that we have completed enrollment in our Phase IIb CHASE trial, and we are on track to report top line data in Q3 of 2025. If successful, we believe this study could serve as a pivotal trial to support a biologics license application submission to the FDA.

Our second program, KPI-014, is in preclinical development for rare inherited retinal diseases. KALA is well positioned to execute. Our team has a proven track record in ophthalmology, having previously developed and secured FDA approval for two ocular therapies: one for dry eye disease and another for postsurgical pain and inflammation, both of which were transacted to Alcon, allowing us to fully focus on our secretome platform. Importantly, we are well capitalized with runway extending into Q1 of 2026, well beyond our expected data readout.

Before turning things over to our team of KOLs, I want to briefly frame the commercial opportunity in PCED, which we conservatively believe represents a $3 billion and plus market in the U.S. alone. This is based on a few key factors. The only approved product in this space is OXERVATE, which is indicated for neurotrophic keratitis, a subset of PCED, representing only about 1/3 of the total patient population.

OXERVATE, which was developed by a private Italian company, reported $820 million in 2023 in U.S. sales and over $1.1 billion in 2024, demonstrating continued strong growth 6 years into launch, and we don't believe they've reached their peak yet. However, OXERVATE only addresses NK patients, leaving 2/3 of PCED patients without an approved therapeutic option. For this reason, we are pursuing a broad PCED indication that includes NK and all other etiologies, representing an estimated 100,000 patients in the U.S. and approximately 238,000 patients globally when including the EU and Japan.

Based on the multifactorial mechanism of KPI-012 and clinical data from our Phase Ib study, we believe KPI-012 could become the first and only treatment that addresses all underlying causes of PCED, offering rapid and sustained healing, improved tolerability and importantly, more convenient administration compared to OXERVATE, helping reduce treatment burden for patients and providers alike. This is a highly underserved market, and we believe we are well positioned to meet that need with a capital-efficient, scalable commercial model. PCED is predominantly treated by the approximately 1,800 corneal specialists in the U.S. which gives us a focused and manageable path to market entry and adoption.

With that, I'll now turn the call over to Dr. Francis Mah, who has worked closely with KALA as our Chief Medical Consultant for the past 2 years, and he will provide a deeper look at the clinical landscape and unmet need in PCED. Dr. Mah?

Thanks a lot, Todd. And I'd like to thank everybody that's on the call today, especially the other KOLs. We've really got a phenomenal group here today that are going to help address PCED or persistent corneal epithelial defects. And I'll be introducing each one of them. But we, as a collective, I think, have significant experience with PCED. I mean, literally, we've treated thousands of patients if you consider iatrogenic causes as well as obviously, referrals, from peripheral sources. The group represents the top as far as academicians, clinician scientists and clinicians that really are world-renowned cornea people. I have the pleasure of kicking us off in terms of giving an overview of the persistent corneal epithelial defects and then the unmet needs, and then we'll move further on, as Todd had mentioned regarding the rest of the agenda.

So as far as the issues with persistent corneal epithelial defects, in general, the healthy eye, the cornea continuously renews the function as a barrier. And this happens literally blink to blink, hour-to-hour, day-to-day, where you've got this corneal epithelial homeostasis, which involves a complex, really choreographed process of proliferation, migration, adhesion of the epithelial cells, differentiation of those epithelial cells and then stratification. And this is really very sophisticated and very well orchestrated, again, blink to blink, day-to-day. And again, the majority of people -- the vast majority of people will never know how sophisticated this process really is.

In terms of an epithelial defect, so in the normal healing cornea, and again, there are many different causes for epithelial defects. The epithelial defects, whenever there's an injury, usually heals within anywhere from literally 3 to 7 to 10 days. As far as how we know this, again, there are some iatrogenic causes of epithelial defects, for example, post PRK or PTK or cross-linking procedures. And literally within 3 or 4 days, the majority of patients heal. In general, I think anything over 7 days, the comprehensive ophthalmologist or optometrist or eye care person starts getting a little bit nervous. So in general, in the normal situation, the corneal wound will heal within anywhere from 3 to 7 to 10 days. And again, it's -- this very rapid proliferation, this migration, adhesion and stratification that happens, again, within 3 to 10 days.

In the abnormal situation, if there's anything that affects this proliferation or migration or adhesion, then what happens is a persistent corneal epithelial defect can occur. And the definitions will kind of vary a little bit. But I think in general, most people will agree anything over 10 to 14 days would be considered a persistent corneal epithelial defect. And I think in general, the comprehensive or general eye care specialists over 7 days probably starts getting a little bit nervous with an epithelial defect that either does not seem to be progressing or has not healed. And that's usually just with supportive care like preservative-free lubricants topically and then a prophylactic antibiotic.

The issue with persistent corneal epithelial defects is that not only can people experience issues regarding pain, you can imagine that any type of epithelial defect anywhere in the body is going to be pretty uncomfortable. But this can lead to permanent visual morbidity. So you can actually get significant vision loss, you can actually lose the eye. There's a risk of obviously infection any time an epithelial barrier is breached anywhere on the body. Corneal ulceration can occur. That ulceration can lead to stromal scarring, corneal melting and then corneal perforation. So it's really an urgent issue if an epithelial defect is formed. And so we really try, as eye care specialists, to heal these epithelial defects as soon as possible.

So why is PCED or persistent corneal epithelial defects, why is it a burdensome issue with high unmet needs currently? And I think the issue is, as Todd had pointed out, we do have a treatment for neurotrophic keratitis, which is a cause of persistent corneal epithelial defects. But there isn't really a single FDA-approved therapy that addresses multiple different etiologies or potentially all causes of persistent epithelial defects. And again, there could be multiple etiologies for the PCED.

As far as the currently approved neurotrophic keratitis treatment, which is cenegermin or OXERVATE, they did demonstrate mean healing rates of about 41%, 42% over placebo. No non-NK patients that had epithelial defects were part of the pivotal trials. We need something that's going to rapidly and hopefully keep that epithelium healed and sustained long term, which would be, I think, one of the key factors that clinicians are really hoping for. And it's something, obviously, that's very, very well tolerated that helps with compliance. It's easy to administer.

Currently, OXERVATE, again, landmark drug, but it is a little cumbersome to apply the product insert states that there's 19 different steps before the application to the eye. And then number two is the one thing that we all recognize as cornea specialists that treat PCED and NK specifically is that OXERVATE does have an adverse event of eye pain, which occurred in the clinical trials at 16%. So something that would be a little bit more comfortable would also be welcomed in general, and we could hear from the other KOLs. But my experience is that almost everybody experiences some type of discomfort, which is described as pain.

So it's something that really broadens the indication to cover all etiologies of PCED, not just theoretically that 1/3 cause of PCED NK, something that's easy to administer, that does not cause discomfort or has a low AE rate, and then obviously, something that's very rapid with sustained healing would be very welcome.

So with that as kind of some backgrounds, we'll dive deeper. And so the first person that we'll hear from, I have the pleasure of introducing Anthony Aldave, who, as Todd said, is at UCLA, Jules Stein Eye Institute. He's really, again, one of the leaders in our field of cornea external disease, doing excellent work. And he's going to take us through the PCED patient journey. Anthony?

Thank you very much. It's a pleasure to be able to speak with you today and to take you through the patient journey. I think it starts really with a review of the causes of persistent corneal epithelial defects. We've discussed neurotrophic keratopathy as being one, but the fact that the majority of patients with PCEDs have other conditions that may lead to persistent corneal epithelial defect formation.

The first group, defective epithelial adhesion. When you're talking about the epithelium and its normal state, you have a multilayered structure on a basement membrane. So any condition that can affect the healthier epithelium or the substrate on which epithelial cells reside, the basement membrane, can lead to persistent corneal epithelial defect. So the first category, defective epithelial adhesion, these are the things that affect the adherence of the epithelial cells to the basement membrane.

Recurrent corneal erosions, which is a fairly common condition in corneal practices. Toxic keratopathy, which unfortunately is also a common condition. Many times, we see this in patients who are long-term eye drops such as those with glaucoma. Band keratopathy, which is calcium deposition on the cornea, which can be due to many different causes. And in this case, the epithelial cells do not adhere well to the band keratopathy, to the calcium or scarring or trauma. Again, anything that causes an irregularity of the surface layer of the cornea to which the epithelial cells normally reside can lead to persistent epithelial defect formation.

The second category is limbal stem cell deficiency. At the edges of the cornea reside the limbal stem cells whose job it is to proliferate throughout our life, producing new epithelial cells. The corneal epithelium turns over -- just like our skin cells, turn over. So conditions that can affect the health of the limbal stem cells include those that are inherited disorders as well as acquired conditions such as chemical injury, thermal injury or even iatrogenic physician-induced injury from surgery or from long-term medication use.

Inflammatory conditions can also affect the health of the epithelium and the limbal stem cells themselves. These can fall into broad categories such as conditions associated with infection, Sjogren's syndrome, which is an autoimmune disease, that can lead to severe dry eye syndrome. Stevens-Johnson syndrome, again, an autoimmune disease that can be fatal in a significant percentage of patients who acquire this. And those who survive are often left with severe ocular surface disease and in some cases, persistent corneal epithelial defect formation.

Graft-versus-host disease, these are patients who've had a bone marrow transplant where the donor-derived cells can attack the patient's own cells causing an immune condition. Neurotrophic keratopathy, in my practice, I think many of our practice, probably diabetes is the most common cause. Sometimes it's combined with other conditions that can lead to decreased corneal sensation and persistent epithelial defect formation. Herpetic keratitis, so corneal infection, the herpes virus, either a herpes simplex or herpes zoster are conditions that are common in any corneal specialist practice.

Mechanical conditions. Most of these are conditions that affect the ability of the eyelids to close fully, resulting in corneal desiccation and healthiness of the epithelial cells, and thus predisposed to persistent corneal epithelial defect formation. And then there are acquired idiopathic conditions, those of which we don't really understand the conditions or the cause as well as hereditary disorders. Aniridia is a condition that's associated typically with absence of the iris, retinal abnormalities and limbal stem cell deficiency. And these patients very commonly develop persistent corneal epithelial defect formation.

So how do we diagnose persistent corneal epithelial defect formation? Well, like anything else, we start with discussion with the patient, a history of prior diabetes, history of prior ocular surgeries, ocular medication use, prior maybe brain surgery that can affect the trigeminal nerve that provides intervention to the cornea. These are all things that are very relevant in the history to determine why this patient may have a persistent corneal epithelial defect.

Symptoms from the patient. The duration of the symptoms will often tell you how long this condition has been present for. And the symptoms you see on the slide are those that you would assume if somebody had an abrasion of the cornea is not healing, pain, blurred vision, redness, many times light sensitivity. In the office, we use fluorescein dye, as you see in the two pictures, and this very clearly highlights the areas where you have an absence of epithelium. And in this image here, we see it's located in the sort of the junction of the inferior middle [ third ] of the cornea, a very common location for persistent corneal epithelial defect.

So a couple of cases to sort of make this kind of easier to understand. And in this case, we have a patient with Stevens-Johnson syndrome. This patient may be a month out, they may be years out. These patients remain at risk for developing persistent corneal epithelial defects throughout their life after developing Stevens-Johnson syndrome. Again, many times, it can be due to a severe dry eye, because the scarring of the conjunctiva can affect the production of the normal components of the tear film, resulting in an unhealthy tear film. And if you have an unhealthy tear film, you're going to have an unhealthy corneal epithelium.

So we can see very clearly in these images that after putting in the fluorescent dye, that epithelial defect is highlighted quite clearly. How do you treat these patients? Well, many times putting on a soft contact lens, we call that a bandage contact lens can help promote re-epithelialization of the cornea as well as treating these patients, topical cyclosporine is a medication we use. It's approved for treatment of dry eye syndrome as well as artificial tears. We're trying to address the desiccation as best we can, but these can be very challenging patients to treat.

Another patient here, this is actually a patient of mine, who was enrolled in the CHASE trial. This is a woman with a history of diabetic eye disease. She had prior retinal surgery for her diabetes affecting her retinas, and she had significantly decreased corneal sensation. She had the abrasion you see depicted on the image on the right, present for about 5 months prior to enrollment in the CHASE trial. And fortunately, that epithelial defect resolved only about 2 or 3 weeks after starting treatment.

Now what is the typical treatment algorithm for managing persistent corneal epithelial defects? Well, as you see on the left, the current standard management moves from conservative to more invasive. So we need to identify what's causing it. Even if you have somebody using tears, you moisturize ocular surface, if their lids aren't closing either during the day or at night, you're not going to make much headway. So you have to identify, is it from exposure? Is it desiccation? Is it toxicity from ocular medications, et cetera? And many times, these patients who are challenging patients to treat is not just one, but there can be multiple conditions that are leading to the persistent corneal epithelial defect formation.

However, regardless of the etiology, some standard initial treatments include lubrication with tears or ointments, punctal plugs, small plugs, either collagen or a silicon that we can place in the holes in the eyelids through which the tears normally drain from the eye into the nose helps to conserve the tears on the ocular surface. Contact lenses, soft contact lenses usually initially. Amniotic membrane or placental tissue, we have that available commercially in a plastic ring that can be placed on the eye like a contact lens to help facilitate healing. Debridement is sort of freshening up, if you will, the edges of epithelium. If healing is stalled, it gives us sort of a fresh start that can help, in some cases, tarsorrhaphy, a closure of the eyelid with suture. Botox can be injected in the upper eyelid to produce a droopy eyelid to help protect the cornea, increase moisture and facilitate re-epithelialization.

As you know, there's other agents here as well. Tetracyclines taken orally can help in some cases with healing of the epithelium. And cenegermin, as we already spoke about, is a recombinant human nerve growth factor can help in cases of neurotrophic keratopathy. For those patients who do not improve on these initial therapies, the next step is usually to do something such as autologous serum, so the patient's blood is taken. It's diluted with saline and then eye drops are made from it. And the thought here is that we have factors in the blood that can facilitate -- promote healing of the epithelium.

Additionally, the scleral lenses or PROSE lenses are large contact lenses that vault over the cornea. They are placed with fluid beneath them that protect the cornea, which is then based in the fluid throughout the day and not exposed to the drying effects of the environment. If these don't work, then many times we have to do something in the operating room such as suturing amniotic membrane to the ocular surface. We can do limbal stem cell transplantation if the cause is limbal stem cell deficiency. And finally, in the most severe cases, if the persistent epithelial defect formation is associated with corneal scarring and/or perforation, artificial corneal transplantation could be performed. These patients tend not to be good candidates for traditional corneal transplantation.

So in summary, the goal of managing these patients is to really give the epithelium the best chance possible to migrate, to cover the area where there is an absent of epithelial cells to adhere to the basement membrane or substrate on which the epithelial cells are located, and then to maintain the epithelial cell integrity to prevent breakdown of the epithelium once it heals. You want to do this sooner than later. Francis already mentioned the fact that if you have a persistent epithelial defect formation, more times than not, that leads to thinning and scarring of the corneal stroma, the body of the cornea, such that even after the surface heals, you may have a scar that can affect vision.

In the worst-case scenario can lead to corneal perforation. So you want to treat these conditions early, effectively to prevent the sequelae that can follow. And currently, there is no FDA-approved treatment with a broad range of indications or treatment that may address all the conditions that can lead to persistent corneal epithelial defect formation.

Great. Thanks so much, Anthony. I mean, what a great review of not only the etiologies of persistent corneal epithelial defects, but also initial managements. It's my pleasure to introduce another one of my friends and excellent scientists, Stephen Pflugfelder, world renowned. He's at Baylor College of Medicine. And he's really going to help us dive deeper into the mesenchymal stem cell secretome as well as specifically KPI-012. Stephen? I think you're on mute.

Can anyone hear me now? Okay. Sorry about that. I don't know what happened. But well, I'm going to -- I'd like to welcome you all this afternoon, and I'm going to talk a little bit about the biological activity of mesenchymal stem cells and KPI-012.

This is an illustration of the processes that can occur in a persistent corneal epithelial defect that can contribute to abnormal or delayed wound healing. As you've heard, this is a fairly common clinical problem. And as Dr. Mah mentioned, this is a very complex biological healing process, and it's essential that things go in the normal fashion. Otherwise, the cornea can end up being irregular and hazy. So patients have a reduced vision, which can actually lead to functional blindness.

So any impairment in the normal healing process can result in a persistent corneal epithelial defect. And as you can see here in the diagram, normally, the epithelial cells on the side of the defect, which is there in the center, would loosen and migrate and proliferating and quickly heal the central defect. But in persistent corneal epithelial defects, that doesn't happen. The epithelial cells become stagnant at the edge. Clinically, we can see that is an elevated rolled edge. And then the base can actually start to thin or ulcerate, and that can occur from proteases or proteolytic enzymes that are produced by the epithelial cells on the edge and as well as keratocytes that are located in the corneal stroma that produce these enzymes that can degrade the tissue.

The keratocytes or basically the fibroblasts and the stroma can also either die off, which is not good, because they often provide supporting factors or they can become activated and produce inflammatory mediators, which can recruit inflammatory cells. They can produce proteases or they can produce a cytokine called TGF-beta that causes the remaining keratocytes to differentiate into what we call myofibroblasts that produce abnormal and excessive matrix that leads to scarring, but also the cells can contract and cause an irregular corneal surface. So none of those things are good. And as Dr. Aldave mentioned, it's important to get the cornea healed as quickly as possible.

Mesenchymal stem cells are found in multiple tissues in the body, including the bone marrow, muscle, fat and the umbilical cord. And they can differentiate into different cell types in those various tissues, including osteoblasts, which can stimulate bone production, chondrocytes to produce cartilage, myotubes, which can lead to muscles, stromal cells in the bone marrow, fibroblasts in tendons and ligaments, and then adipocytes that produce fat. But those cells do more than just differentiate into the tissue-specific cells. They also can influence the surrounding cells by producing factors that suppress inflammation. So they have immunomodulatory effects. They could promote survival of the surrounding cells, suppress new blood vessel formation, which is good for wound healing. But in the cornea, it's not so good because the blood vessels can lead to cloudiness and they leak -- they can leak blood products into the cornea. They can also suppress scar formation, and they can promote healing and regeneration of wounds.

KALA's product is a proprietary mesenchymal stem cell secretome platform. And the healing and regenerative capacity of the mesenchymal cells is attributed to the multifactorial biological factors that are secreted by these cells referred to as the secretome. And the secretomes are produced by collecting biomolecules that are secreted by these cells into the extracellular space to support their health and viability. And KPI-012 was manufactured from this master proprietary cell bank of human bone marrow-derived mesenchymal stem cells.

And these cells produce a variety of factors, including cytokines and healing growth factors, neurotrophic factors, protease inhibitors and matrix proteins that the epithelial cells can bind to kind of as their scaffold. And benefits have been demonstrated from the secretome by third parties in healing the cornea in suppressing retinal degeneration of the photoreceptors and other cells in the retina, also in preserving retinal ganglion cells in glaucoma models and in dry eye disease. So the mesenchymal stem cell platform is cell-free and it provides a new regenerative approach to disease management.

The KPI-012 is the lead candidate from KALA for the treatment of PCED. And it contains a variety of key secretome biofactors that are associated with wound healing. And some of those are listed here on the right. There are other ones, too. In fact, quite a few have been identified. But among the important ones include protease inhibitors, molecules that can inhibit those enzymes that I mentioned that cause tissue digestion and thinning of the cornea, including TIMP-1 and 2 and SERPINE1. They can produce matrix proteins that can serve as a scaffold for attachment and migration of the corneal epithelium, including fibronectin and collagen.

Growth factors such as hepatocyte growth factor that's been found to be a key growth factor for the corneal epithelium. And neurotrophic growth factors such as PEDF, which is known to support the corneal epithelial nerves and cause the regrowth.

And this provides a multifactorial approach to addressing impaired corneal healing. It's formulated as a topical, nonpreserved, single-unit dose formulation and has the potential to treat multiple rare corneal diseases, including PCED.

So the -- in summary, KPI-012 addresses multiple biological pathways associated with impaired corneal healing in the PCED from the variety of those factors. And one thing to mention is that we have learned that biological factors such as nerve growth factor and OXERVATE can be very effective. But we've also from lots of key basic science research, we've realized that often more than one factor is needed. And that's why you have to sort of reduplicate the complicated processes that contribute to normal wound healing. So a mixture of factors as found in the secretome really makes sense and -- not only in the healing, but also to clinicians would be able to buy into that concept.

Well all, thank you for your time, and I'm going to turn it back over to Dr. Mah.

Great. Thanks a lot, Steve. A fantastic overview of really what happens in a nice short succinct way as far as that proliferation, migration, adherence and so forth. So next, I have the pleasure of introducing Melissa Toyos, who's an excellent ocular surface disease specialist as well as clinical researcher. And she's really going to kind of guide us through the clinical trial experience of KPI-012. Melissa?

Thank you so much. I appreciate the introduction. We've done a great job of expressing the unmet need. I think all of us on this call, all of the clinicians are seeing these patients in our clinics day-to-day. They are some of our toughest to treat patients. These are chronic problems for these patients, spanning over their lifetimes and impacting them in very significant ways, a lot of times hitting them in the prime of their life, impacting families, workabilities, et cetera. So it's been a pleasure to be part of this team and part of this trial.

This is what we came for. So I get the opportunity to talk about the clinical data that has led us up to this point, and we can kick it off talking about the Phase Ib study design. This was -- Dr. Pflugfelder was involved with this, but largely conducted ex U.S. The key inclusion data, they were looking for patients with PCED for at least 10 days without improvements with conservative nonsurgical treatments. There was a lead-in safety cohort of three patients that received twice daily dosing for a week that showed no safety and no tolerability issues. There was an efficacy cohort of patients that were suffering with PCED that were dosed twice daily for 1 to 8 weeks and followed for up to 19 weeks, with the key efficacy endpoint of the healing of the PCED based on corneal fluorescein staining, which highlights any abnormal or damaged corneal epithelial cells.

So let's look at some of the results there. I would say these are scientifically exciting when six of eight participants had complete healing of their PCED or their ulcer with KPI-012 using it twice daily. Four of the six were completely healed as quickly as 1 week. That is fairly remarkable in this field, I would say, extremely remarkable. One of six was completed healing after another week, and then there was another one that healed at 4 weeks' time. This is important because if you take a look to the right, you can see that some of the patients had very significant sized ulcerations or epithelial defects.

And if you consider that the cornea is usually about 12 millimeters. You can see that many of these patients were suffering with about half the loss of their corneal epithelium, and to have this level of healing this quickly is a remarkable indeed. So improvement in lesion side was -- in size was observed in two of the participants who did not heal completely. We saw improvement of 80% and 60%, respectively, and all of the healed participants remained healed. That's important, too, because these patients are at risk for additional degeneration and ulceration later in their life. So they were healed through the end of the follow-up, and we saw no new safety signals. This was very well tolerated for these patients with the treatment.

Okay. This is a graphic that shows how patients were treated. And you can see here there on the left side, the etiology or the cause of the epithelial defect. Many of them were neurotrophic. You can also see a Stevens-Johnson, a post-infectious keratitis, really highlighting that all comers. This medication is helpful for a variety of different indications of PCED, not just one. So we have more latitude here to treat patients that are -- will be coming to us with other issues, etiologies and problems.

And again, you can see that in many cases, these patients were healed as quickly as 1 week. In some cases, the investigator at the time decided to stop the medication at that time. There are some patients that continued on with treatment. And then if you take a look at some of the patients that were included in this trial, we mentioned that we get a little bit nervous when we see people not healing after 10 to 14 days. And you can see that the last patient here was unhealed for 871 days. So these are not cherry-picked patients, these were absolutely very difficult-to-treat patients. And the longer these problems go on, the tougher they are to treat. So the fact that these patients were enrolled that we had this level of success is very important for us scientifically.

In terms of pain, the treatment that is currently available is strongly associated with some sort of discomfort. Sometimes it causes discontinuation of the medication. Patients are unable to tolerate or have to decrease their dosing strategy in order to move forward with that. In the case of this medication, KPI-012, 100% of patients reported a reduction in pain as early as 1 week. That is very significant. 2/3 of the patients that were experiencing pain reported 0 pain score, absolutely no pain at all by week 1, so as early as 7 days. And then 100% of the study population reported no pain at all as early as 3 weeks. So a rapid reduction in pain and also a rapid improvement in the size of the ulcer and healing.

These very strong results supported the CHASE Phase IIb clinical study trial design, and we have been happy to be a part of that as well. So this is a multi-cohort study to evaluate the safety and efficacy of two doses, 1 unit per ml and 3 units per ml of KPI-012 ophthalmic solution compared with its vehicle. It's been dosed 4x daily. So a little bit different from the Phase I study, dosing for 56 days in the study eye of patients with the PCED coming in with at least 14 days of duration.

I want to point out here in this study, the way the trial was designed was a run-in period. So there were 7 days of treatment with antibiotic nonpreserved tears. That is a higher bar and standard than other medications that have been approved for this process. So they absolutely put in a higher bar, so less likely to have a placebo healing, which means that the patients are not likely to heal on their own. These patients were -- had a run-in period. They were treated with conservative therapy. They did not get better. And so we are more likely to have true PCED patients here, again, with a higher bar than what we've currently seen in the market. And then they were randomized to one of the treatment arms, whether it was vehicle, the lower dose of KPI-012 or the 3 units per ml. And the treatment period was 8 weeks.

These patients were followed up for 2 weeks and at 6 months. Now the key inclusion criteria, 18 years of age or older, had to be willing to comply with the study procedures, medically documented PCED of 7 days duration. We've already talked a lot about the causes of PCED, but these were the eligible etiologies for the clinical study. And I'm going to turn this over now to Todd.

Thank you, Dr. Toyos. Now that you've heard from our KOLs, it's clear that PCED is a serious clinically burdensome condition with significant unmet need. Today, the only approved therapy, as our speakers spoke to, OXERVATE, addresses just a subset of these PCED patients, which currently accounts for approximately 1/3 of all the affected patients.

Treatment of OXERVATE is associated with ocular pain, as we've heard, and requires a complex and burdensome administration process. As Dr. Mah pointed out, across the two pivotal trials, OXERVATE demonstrated a mean healing rate improvement of 41.8% over placebo. However, non-NK PCED patients were not included in those trials, and there remains a lack of a benchmark for a clinically meaningful pharmacotherapy treatment across the broader PCED patient population. As a result, we believe that demonstrating statistical significance in this broader PCED patient population in our ongoing CHASE trial will be extremely clinically meaningful.

We believe KPI-012 has the potential to dramatically improve the treatment paradigm in three key areas: a single therapy that leaves no PCED patient behind. KPI-012 is designed to address all underlying etiologies of PCED. Most patients present with multiple causes of disease. And KPI-012's multifactorial mechanism of action makes it uniquely suited to treat the full spectrum of PCED, offering a single comprehensive solution.

Number two, rapid and sustained healing of corneal defects. PCED is not only painful, but it is progressive. Delayed healing can lead to permanent vision loss. Based on our Phase Ib study, KPI-012 demonstrated rapid epithelial closure with 4 of 6 responders healed fully in just 1 week, and sustained healing over time with all six responders fully healed by week 3, highlighting KPI-012's potential to provide fast, durable and effective treatment across etiologies.

And finally, superior tolerability and ease of administration. OXERVATE requires dosing 6x per day and a 19-step preparation involving daily reconstitution of a frozen vial. In contrast, KPI-012 is dosed 4x per day using convenient, premixed preservative-free, single-use vials with no preparation required. Additionally, OXERVATE, as we've heard, is associated with an approximate 16% rate of ocular pain and other AEs like irritation, blepharitis and corneal neovascularization. Many clinicians believe OXERVATE's pain adverse event may stem from nerve regeneration, while the corneal epithelium is still diluted or possibly from a direct action of NGF on pain receptors. In our clinical experience, KPI-012 has not shown these side effects. In fact, in our Phase Ib trial, KPI-012 completely resolved pain over time in those patients that reported pain at baseline.

We have been hard at work laying the foundation for KPI-012's potential future launch, and we're pleased to provide you an update on our progress in manufacturing. KPI-012 is now being produced at full commercial scale with the capacity to support both pivotal studies and early commercialization. On the drug substance or secretome side, we spent a lot of time upfront -- optimizing culture conditions for cost of goods and scale. And as a result, have developed a well-defined, straightforward bioreactor production, harvesting and processing process. This process starts with a working cell bank vial derived from the KALA master cell bank, which in turn was derived from a single healthy donor. This helps to ensure drug substance batch-to-batch consistency.

For the formulated drug product, our manufacturers Woodstock Manufacturing, formerly Catalent, the final drug product is manufactured using industry standard unit dose blow fill seal formulation and filling processes, the same used by many artificial tear products that patients are already familiar and comfortable with. And finally, we've demonstrated batch-to-batch consistency of KPI-012 using a suite of protein critical quality attributes and cell-based potency assays, which are consistent with the feedback we received from FDA at both our pre-IND and Type C meetings. In fact, at our Type C meeting with the FDA last year, we presented our proposed potency assay strategy. The FDA agreed with our recommendations without modification, a strong validation of our approach. We're now actively validating these assays to be BLA ready.

We are looking forward to presenting top line results from the CHASE Phase IIb study later in the third quarter of this year. We have made exceptional progress to date, receiving Orphan Drug and Fast Track designation from the FDA, and we have recently completed enrollment in the Phase IIb pivotal trial. We have taken proactive measures to streamline the efficiency of our program, so we can bring this paradigm-altering treatment to the 200,000-plus patients in need. If results from the CHASE study are positive and contingent on discussions with the FDA, we believe this study could serve as a pivotal trial to support a BLA submission. We have also aligned our CMC and potency assay program with the FDA during our Type C meeting held last year and successfully set CMC expectations for that BLA submission.

We expect to leverage the CMC program for KPI-012 and other IND-enabling activities to support follow-on interior segment orphan indications for KPI-012, as we believe it has pipeline and a product potential. And we have U.S. regulatory exclusivity and IP protection well beyond 2040.

We are progressing a pipeline -- our pipeline based on this proprietary mesenchymal stem cell secretome platform, targeting the treatment of both front and back of the eye orphan indications. As we complete the Phase IIb study of KPI-012 in PCED, we are also exploring the potential of KPI-012 in limbal stem cell deficiency and other rare corneal diseases that have multibillion-dollar orphan indication potential. In addition, we are advancing our preclinical candidate, KPI-014 for rare inherited retinal diseases.

Our secretome platform has broad potential in a number of rare ocular disease segments. We are currently focusing our efforts on some of the most prevalent indications with limited or no treatment options such as PCED and LSCD, but we'll continue exploring its application in additional disease areas and believe that this proprietary platform could continue to generate significant value for many years to come.

I'd like to thank you all for joining us today. I'm now going to turn the call back over to Dr. Mah for Q&A, during which our KOL panel and members of the management team will be available for your questions. Dr. Mah?

Yes. Thanks a lot, Todd. Excellent overview of KALA BIO and the pipeline. And just as Todd said, not only are Anthony, Melissa and Stephen still on the call, Todd is obviously still on the call. We also have several of the other key members of the team. First, I just wanted to thank Bianca Baker for all the help in the slides and arranging things. She's the Executive Director of Clinical and Medical Affairs. Darius Kharabi, who's Chief Business Officer, is also on the line. And then Kim Brazzell, who's Chief Medical and R&D is also on the line, if there are some questions that we need to reach out to them for.

So there are a lot of questions. And so that's exciting, that's great. There's a lot of interest, obviously, in this topic. So we'll try to get through as many of these questions as possible. So the first one is what is the bar for clinical success for the CHASE study?

So I think the quick easy answer is if we get epithelial healing, that's statistically significant in a rapid manner. But I think just some scope is that, number one, this is obviously a study that's not just neurotrophic keratitis is persistent corneal epithelial defects as we have heard. And it's a broad, wide ranging list of etiologies. And so I think with that as background, if we try to compare it loosely to what's available, if we can heal the epithelium as well as cenegermin in their two registration clinical trials, then I think that's obviously going to be a clinically meaningful outcome.

And then number two is especially if what has happened in the Phase IIb holds up in the CHASE trial, meaning that there was not any adverse events. Pain, for example, was part of the cenegermin adverse event profile, 16% was -- is on the label. And then also, it's a lot easier to administer as Todd went through, it's just a vial that we're all familiar with. So I think with those things and if KPI-012 in the CHASE trial holds up with the Phase IIb CHASE trial, then I think, again, clinically meaningful.

The next question is if the study is successful, will you need to run a second pivotal study to support a BLA? Maybe we'll start with Todd for this one.

Sure. Thank you, Dr. Mah. Look, I would say our base case assumption is we'll need to do a confirmatory trial. That having been said, we will build a case to go to FDA and think that if there is a possibility that this could be approvable on a single trial. We're working with some external consultants that used to work at FDA, specifically within the CBER division, which is the division that's managing this current program. And I think it all depends on the strength of the results of this one trial. We will make the case. That is an upside scenario for us. However, we are planning base case will be a confirmatory trial that we would kick off in the first quarter of 2026.

Great. And there has been some indication that from the FDA, Makary. Marty said that there are some scenarios where, especially for rare diseases, a single trial might be acceptable along with that.

All right. So the next question is, if the study is successful, what are the next steps for timing for your communications with the FDA, example, end of Phase II, filing for designations such as RMAT and breakthrough? Again, since Todd is already on, why don't we ask Todd about the strategy here?

Yes, sure. So once we get these results, we will quickly request an end of Phase II meeting. The team is already preparing documents to get ready for that. We would expect it would take typically the 60-day period to grant that meeting. Of course, we'll want the minutes from -- post that meeting. That will take a few weeks after the meeting for those minutes to be published. We do plan to file either for RMAT or breakthrough designation. We're still discussing which one is more appropriate for this specific product and its mechanism of action. But I think we should -- assuming data by the end of Q3, we are hopeful that we will have had our end of Phase II meeting and those minutes back before the end of the year with clarity on next steps.

Great. Next question is it sounds like OXERVATE has penetrated approximately 33% or 1/3 of the NK market so far. And again, KPI-012 is for persistent corneal epithelial defects. Do you expect to have any overlap or competition with cenegermin or OXERVATE? And again, we'll kind of go to Todd based on some of his projections.

Sure. And I'll start off, and I would certainly welcome the thoughts of the panel on this, too, because I think this is a clinical question as well. I agree with your numbers. We estimate that OXERVATE has probably penetrated about 1/3 of the NK market, only about 10% of the overall PCED market. There could be some overlap in the overall PCED market in the sense that some of these patients will present with multiple etiologies. I think we heard that from the KOL panel today. And we believe if we achieve our target product profile that we shared today, that we will be highly competitive, not only in the non-NK PCED market for which there's no therapy today, but also a highly competitive product within the NK-specific PCED market, which is the market that OXERVATE competes within today. But we would certainly welcome any additional thoughts from the panel.

Yes, Stephen, what do you think? You're kind of at the top left of my screen, so.

Yes, I totally agree with Todd. I mean, as Tony showed, there are multiple etiologies for these problems. And to be honest, a lot of -- almost a lot of them or most of them have an NK component. The corneal nerve plexus at the minimum is not normal and sensation may be reduced. Since we don't really have a gold standard diagnostic tool for NK, it's really still a clinical diagnosis. I think there will be an opportunity for the secretome to treat either pure NK or mixed NK.

Yes. Great. I think the same thing. Next question, I think, Anthony, I think your -- people were listening. Are the drivers of disease in PCED etiologies different, but manifestations the same? Would this be a simple way to think about PCED?

Are the drivers different, but the manifestation is the same? The drivers are different and the manifestations are different, meaning that if you have broad categories, as I mentioned, one is think of etiology's poor substrate. So in irregular ocular surface, because of band keratopathy, because of prior -- we see patients who have prior corneal infections in which the Bowman layer on which the epithelial cells normally reside is eroded. The surface is now irregular. Epithelium has a hard time adhering to it.

That's very different than a situation where the substrate is normal like a diabetic patient, but the epithelial cells are not normal or a patient who has dryness from exposure. Again, the substrate may be normal, but the epithelial cells were not. The treatment, as I mentioned, we, as clinicians, try to identify the major contributing causes and address them. Some of the treatments, as I mentioned already, are very much applied to any etiology, moisture to ocular surface, et cetera. But again, we use cenegermin for patients with neurotrophic keratopathy. We may need amniotic membrane transplantation for patients who have an inflammatory component, et cetera.

The condition for which I think we really need something better than what we have right now are the patients who have a partial limbal stem cell deficiency together with one of these other conditions, a poor substrate desiccation, et cetera. In my clinical experience, cenegermin has not really yielded good results in these patients. I think that experience is shared by others. And also in these patients who have partial limbal stem cell deficiency, even if you can get the epithelium to heal, they're prone to breaking down again, developing recurrent epithelial defects. So these are the patients, I think, where it's the greatest unmet need.

So to that point, I mean, Steve went through exactly the secretome, how there are multiple different products. Do you think that would help address the various different clinical scenarios, different manifestations, different etiologies? For example, as you pointed out, it might be a proliferation issue. Well, the secretome has something for proliferation. It might be an adhesion issue. It might be a migration issue. Do you think this strategy of having multiple different components in the treatment would help with exactly what you pointed out with PCEDs and the etiologies?

I do. I mean, because, again, why does your basement membrane break down? It's probably release of proteases. And so if you have protease inhibitors as you do in the secretome, that can address that. Why is it epithelial cells are not migrating even though they have a good platform? Well, because they don't have the sensory inputs, the growth factors that are needed. So if you have a hepatocyte growth factor, PEDF, et cetera, in the secretome, that can help address that issue.

So I do think, as Stephen said, that if you have a sort of a multiple components that can address the varied conditions that result in the formation and persistence of epithelial defects that, that optimizes your chance for having an effective therapy with persistent lasting benefit. I think you're muted, Francis.

Sorry. Next question, I think I'm going to have Melissa answer. So the question is, how burdensome is the dosing regimen of OXERVATE or cenegermin to NK patients dosed 6x a day over 8 weeks. And as you had mentioned, Melissa, this one is 4x a day, for example.

Right, right. There's a huge difference between 6 and 4. 6x a day is a part-time job. People have to carry it with them and they're coolers to work, to school, all of their activities. And then 4x a day, that's breakfast, lunch, dinner and bedtime. So that's significantly easier for our patients. I think this is a growing disease. I would agree with the panel. The diabetic problem in the U.S. is not going away anytime soon. I feel like I'm seeing a lot more autoimmune patients in my clinic.

Dry eye, people are becoming more aware of that. I think patients are seeking out treatment. We have a confocal in our clinics. And I think being able to look into with some newer diagnostic equipment, I think this problem is largely untapped. I think there's a lot more problems than we're even aware of, iatrogenic, even LASIK and SMILE. And I think the idea of a regenerative medication would have very wide appeal to patients as well as clinicians.

Great. Excellent answer. I agree. I think 4x a day is a huge difference compared to 6x a day just in compliance issues, not to mention again the 19 steps that it takes for cenegermin to be administered to the eye.

I think we kind of answered this next question, but if anybody has any additional thoughts. But the question is for our docs. PCED is a complex etiology, just as Anthony had gone through. Could you help us understand which PCED patient would -- or population would benefit the most from KPI-012 and why? Is there an etiology that is more similar in clinical -- manifestations that you would -- I think we kind of answered that. Obviously, with the multiple components, there would be multiple etiologies. But maybe, Stephen, is there anything that you would say would be better treated or...

Yes. I mean one of them obviously would be a postsurgical. A lot of times like pretty much everybody has a corneal transplant is going to have a PCED, and if it speeds that after a delayed healing after refractive surgery might be one that would respond. I think the conditions that are more chronic, obviously, there are more structural changes in the cornea and even changes to the tear film, et cetera. So they may be a little bit harder for anything to heal. So I think the ones that we treat now with autologous blood products that seem to respond well would be the same target for me to use the secretome because obviously, it would be an approved therapy and much easier to get.

That's an excellent thought since it is kind of more akin to that biologic. So with the next question, let's see, would there be a difference between mild and moderate to severe PCED patients? So would there be a difference between mild patients with PCED versus moderate to severe PCED patients, maybe those patients with stromal melting ulceration. Melissa, any thoughts?

Well, I agree with the panel that once we see the breakdown, I mean, there are a lot of factors that are building, and it's a downhill slide. The faster we catch these patients, the faster we heal them, the less long-term damage occurs. So that's important. A lot of these patients have central defects, and that can lead to decreased vision, decreased contrast sensitivity, it can really affect their quality of life. So the faster we can get it turned around and especially if we have a therapy that's comfortable and easy to use, I think that makes a big difference for our patients.

Francis, can I add something to that?

Absolutely.

Because you said, if you talk about severity, I think you can look at it a couple of different ways. One of it is you can look at it in terms of the clinical manifestations, how large is epithelial defect, is there a stromal ulceration? Is there a thinning? How severe is the thinning? So you can look at it that perspective. And yes, obviously, the larger the defect, the longer it's been around, the greater the result in sequelae like stromal thinning, you'd say that's more severe.

You can also look at the conditions that lead to the epithelial defect, persistent corneal epithelial defect and say which of these conditions are going to be harder to treat. A patient with a condition like Stevens-Johnson syndrome that tends to get worse over time, it's going to be a PCED. And that situation is going to be much more difficult than, let's say, a patient who has a PCED from using three glaucoma medications, which can be stopped if that patient then has glaucoma surgery. So a condition that could be addressed or somebody with exposure keratopathy, don't blink well, who could have a partial closure of the eyelids to address that.

And so as a clinician, I kind of think about severity of these PCEDs in both ways, both what am I seeing on exam as well as what is the underlying condition or what are the underlying conditions and how challenging is it going to be to address those.

Yes. That's an excellent point. And do you feel like there's going to be a certain group that's going to respond a little bit better? Or it's just kind of the overall thought process that addressing the things that you can address and then using, for example, the secretome for some of the other scenarios like the Stevens-Johnson? Or is that just kind of a -- meant for kind of food for thought as far as managing PCED?

I think the prognosis is the best for things for which I'm responsible as long as I recognize it. So my LASIK surgery, my corneal transplant, my glaucoma medications, all these iatrogenic conditions, I think more likely, you're going to be able to successfully intervene by modifying that or just giving it time if you've induced an anesthetic cornea because of incisional corneal surgery, the nerves will tend to regrow over time. Again, as compared to a condition such as diabetes, Sjogren's syndrome, graft-versus-host disease, that is something that you may be able to try to control, but you're never going to be able to actually cure.

Yes. I think that was -- so I think everybody agreed with that. So Stephen mentioned iatrogenic, Melissa also spoke about iatrogenic issues. So I do think I agree with the group, obviously, that those would be a little bit more kind of treatable than some of the other ones that are more systemic without a real treatment, the diabetes, Stevens-Johnson's for example.

The next one is interesting. What excites you the most about KPI-012? We talked about several different things, different components, the dosing schedule, the AE profile, the broader spectrum. Maybe we'll just kind of go one by one. Stephen, what excites you the most if you just had one thought?

It's come up a little bit, but in addition to healing PCEDs is the potential regenerative aspects of mesenchymal stem cells. Like, for instance, can we -- we talked about people getting haze in their cornea from a PCED. Well, it's quite possible that treatment with this product will also help to suppress that and regenerate a more normal optically clear cornea stroma and also smoother surface. So I'm excited about that. It's not only just healing the epithelium, but it's also making it healthy again, like very smooth with a good tear film. So to me, that's a really exciting aspect.

How about you, Melissa, that would be exciting?

I can't pick one. Francis, I can't pick one. I think for me, looking at the Phase I data, looking at the variety of different pathologies that came in, I think the size of the ulcers and the length, these patients were well over 10 days. Some of them were a year or longer. Being able to clear that in a week is unheard of. I mean that is remarkable stuff. The pain profile as well differentiates this from everything else on the market that we use to treat this. And I think that is extremely exciting as well. If we could relieve pain and cure things, that's the sweet spot.

And then, Anthony, how about you? What do you think as far as the most interesting aspect, let's say?

My thought is kind of similar to what Stephen just mentioned is I'm just thinking about this -- I have, as you know, a molecular genetics lab, and we often look at diseases by looking at alterations in protein expression. And so we'll do techniques like RNA-seq looking at the pro and RNA level, et cetera. I think that gives you a better view as to what's going on in a disease as opposed to looking at expression of a single protein. These conditions such as persistent corneal epithelial defect formation, there's an initiating event, but then there's a cascade of things that follow, all of which result in the disease that you're seeing.

So the therapies to me ideally would be something that would target multiple targets, multiple factors that are responsible for initiating and perpetuating the disease. And using the secretome to me makes sense in that it's a multipronged therapeutic approach as opposed to only singling out a single aberration as far as protein expression or whatnot. So I like the approach that this represents.

That's excellent. And I do think the potential is very intriguing. Next question is any difference in the assessments and care for PCED between patients in academic and independent sites?

I'll just start off. As far as the assessments and care, I think people that see and treat persistent corneal epithelial defects, just like Anthony had kind of gone through, we try to identify the etiology or the reasons that this person has the epithelial defect. And then as far as going through the treatments, I think we all go through the kind of hierarchical management that Anthony went through, maybe not so structured, but we do use the various different treatments. And it's based on what the patient can do and what the patient allows you to do or wants.

I think there are a couple of things that, for example, I don't have access to our plastics -- oculoplastics people do not yet do the neurotization. So maybe some of the academic centers have an easier access to somebody who could do neurotization. But in general, I think the process is about the same. There are going to be, I think, people that are going to be more comfortable than others. Obviously, the KOLs that are here are going to be extremely comfortable.

Melissa, you're not in an academic center. Do you have any thoughts as far as the assessment and care of PCED in your practice, for example?

I did think I'm going to have to speak for the independent sites because I'm the only one who's not academic here. So I think in general, we are research sites. So we have more tools and diagnostics, investigative equipment than an average eye care provider would. But I think that in general, I don't have a molecular genetics lab. I'm very jealous of you, Dr. Aldave, on that one. But there are a lot of practices like mine that are private practice that are seeing these patients that need available treatments no matter what the etiology is. They are broad etiologies. They may not even have time to investigate exactly what the cause is. But to have a tool that would be applicable in a wide variety of settings, I think, is very important for independent practices and really for academics as well.

Any thoughts, Anthony or Stephen, on the academic side as far as the assessments in the care?

I agree with Melissa. If there are centers, whether they're academic or community that see this type of patients, I think they have similar expertise in diagnosis, and they have all the same tools. I know Melissa has as many or more tools than I have because when we discussed it at meetings. So I don't think there's that much difference really. I think the difference exists between clinicians who don't typically see these types of patients or don't want to see them. And then hopefully, they're going to get them to centers like all of ours.

I would agree with both of you, but I have seen a difference in the way these patients are managed, certainly in Southern California in the community versus academic centers, where I've seen patients have self-retaining embryonic membrane placed again and again and again, maybe weekly 6, 7x before they're referred. Why? I think maybe because that's been effective for that provider in less severe cases, and they don't typically employ other interventions like tarsorrhaphy or whatnot. I hate to say it also because there could be a financial incentive there because that does reimburse fairly well.

Whereas those patients when they come to an academic center, we tend to not use that option as often. These patients are often referred to us after other therapies have failed. So we tend to be further down the road as far as our intervention. So we tend to, I think, go to the operating room sooner or refer for a score lens, use other subspecialists and treatment earlier after they come to us. But again, we're seeing them many of these patients, I think, at a different time point than our colleagues in the community.

Yes. That's an excellent point. I think it's kind of like that hammer in the nail, right? So if that's all you ever do is hammer that nail, then you're going to try to do the same thing. As far as access, I think we have access to everything. And just like Stephen and Michelle (sic) [ Melissa ] said, it behooves us to educate ourselves and then have some experience on the various different management tools.

So I just wanted to wrap up here. I really appreciate all of the speakers. Obviously, Todd and then our KOLs, Anthony, Stephen, Melissa, a phenomenal job with the various different topics. And again, I appreciate everybody that's in attendance. I really appreciate the time and then all of the excellent questions that we had. And hopefully, we'll have excellent news in the coming weeks regarding the CHASE study.

Thank you, Dr. Mah. Thank you, everyone.