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 secretome and the mechanism of action of KPI-012. Finally, Dr. Toyos, an investigator in our CHASE trial, will share her clinical experience and discuss the CHASE study design. I will conclude with some closing remarks and look further at some of our upcoming milestones for KPI-012. Now I'd like to introduce today's speakers. Dr. Francis Mah, Director of Cornea and External Disease and Co-Director of 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 Margaret Elkins Chair in Ophthalmology at the Baylor College of Medicine. 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 secretome 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 etiology. Based on its unique multifactorial mechanism. We believe KPI-012 has pipeline and product potential and we're exploring its use in other rare front-of-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 at our phase II-B 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 BIO 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 post-surgical 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 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 six 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 considering 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 E.U. and Japan. Based on the multifactorial mechanism of KPI-012 and clinical data from our phase I-B 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 BIO as our Chief Medical Consultant for the past few years. He will provide a deeper look at the clinical landscape and unmet need in PCED. Dr. Mah. Thanks a lot, Todd. 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. I'll be introducing each one of them. 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 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 the unmet needs, and then we'll move further on, as Todd had mentioned, regarding the rest of the agenda. As far as the issues with persistent corneal epithelial defects in general, the healthy eye, the cornea continuously renews the function as a barrier. 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. This is really very sophisticated and very well orchestrated, again, blink to blink, day to day. The majority of people, the vast majority of people, will never know how sophisticated this process really is in terms of an epithelial defect. In a normal healing cornea, there are many different causes for epithelial defects. The epithelial defects, whenever there's an injury, usually heal within anywhere from literally three to seven to 10 days. As far as how we know this, there are some iatrogenic causes of epithelial defects, for example, post PRK or PTK or cross-linking procedures, and literally within three or four days, the majority of patients heal. In general, I think anything over seven days and the comprehensive ophthalmologist or optometrist or eye care person starts getting a little bit nervous. In the normal situation, the corneal wound will heal within anywhere from three to seven to 10 days. It's this very rapid proliferation, this migration, adhesion, and stratification that happens again within three 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. The definitions will kind of vary a little bit, but I think in general, most people will agree anything over 10- 14 days would be considered a persistent corneal epithelial defect. I think in general, the comprehensive or general eye care specialist over seven days probably starts getting a little bit nervous with an epithelial defect that either does not seem to be progressing or is not healed. 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. This can lead to permanent visual morbidity. You can actually get significant vision loss. You can actually lose the eye. There's a risk of obviously infection anytime 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. It's really an urgent issue if an epithelial defect is formed. We really try as eye care specialists to heal these epithelial defects as soon as possible. Why is PCED, or persistent corneal epithelial defects, a burdensome issue with high unmet needs currently? 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. There isn't really a single FDA-approved therapy that addresses multiple different etiologies or potentially all causes of persistent epithelial defects. There could be multiple etiologies for the PCED. As far as the currently approved neurotrophic keratitis treatment, which is cenegermin-bkbj or OXERVATE, they did demonstrate mean healing rates of about 41%- 42% over a 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. It's something obviously that's very, very well tolerated, that helps with compliance. It's easy to administer. You know, 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. Number two is the one thing that we all recognize as cornea specialists that treats PCED and NK specifically is that OXERVATE does have adverse events of eye pain, which occurred in the clinical trials at 16%. Something that would be a little bit more comfortable would also be welcomed in general. We could hear from the other KOLs, but my experience is that almost everybody experiences some type of discomfort, which is described as pain. 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 adverse event rate. Obviously, something that's very rapid with sustained healing would be very welcome. With that as kind of some background, we'll dive deep, deep, deeper. 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. He's going to take us through the PCED patient journey. Anthony. Thank you very much. It's a pleasure 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. Now, 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 as normal state, you have a multilayer structure on a basement membrane. Any condition that can affect the health of the epithelium or the substrate on which epithelial cells reside, the basement membrane, can lead to persistent corneal epithelial defects. The first category, defective epithelial adhesion. These are 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 on long-term eye drops such as those with glaucoma. Band keratopathy, which is calcium deposition on the cornea, can be due to many different causes. In this case, the epithelial cells do not adhere well to the band keratopathy, to the calcium, or scarring or trauma. 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 stem cells turnover. 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. Sjögrens 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 percent 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 practices, 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, herpes virus, either 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, unhealthiness of the epithelial cells, and thus predispose to persistent stem cell defect formation. There are acquired, excuse me, idiopathic conditions, those for 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. These patients very commonly develop persistent corneal epithelial defect formation. How do we diagnose persistent corneal epithelial defect formation? 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 innervation 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 symptoms will often tell you how long this condition has been present for. The symptoms you see on the slide are those that you would assume if somebody had an abrasion of the cornea that's not healing: pain, blurred vision, redness, many times light sensitivity. In the office, we use fluorescein dye, as you see in the two pictures. This very clearly highlights the areas where you have an absence of epithelium. In this image here, we see it's located in sort of the junction of the inferior and middle thirds of the cornea, a very common location for persistent corneal epithelial defect. A couple of cases to sort of make this easier to understand. 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. Many times it can be due to a severe dry eye because the growing of the conjunctiva can affect the production of the normal components of the tear film, resulting in an unhealthy tear film. If you have an unhealthy tear film, you're going to have an unhealthy corneal epithelium. We can see very clearly in these images that after putting in the fluorescein dye, that epithelial defect is highlighted quite clearly. How do you treat these patients? 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 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 five months prior to enrollment at the CHASE trial. Fortunately, that epithelial defect resolved only about two or three weeks after starting treatment. What is the typical treatment algorithm for managing persistent corneal epithelial defects? If you see on the left, the current standard management moves from conservative to more invasive. 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. You have to identify is it from exposure, is it desiccation, is it toxicity from ocular medications, et cetera. Many times these patients who are challenging patients to treat, it's not just one, but it 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, tarsal plugs, small plugs, either collagen or silicone that we can place in the holes in the eyelids through which the tears normally drain from the eye into the nose, which 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 dulled, 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 are other patients here as well. Tetracyclines taken orally can help in some cases with healing of the epithelium, and some, as we already spoke about, the 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. The patient's blood is taken, it's diluted with saline, and then eye drops are made from it. The thought here is that we have factors in the blood that can facilitate and promote healing of the epithelium. Additionally, the scleral lenses or PROSE lenses are large contact lenses that vault over the cornea. They're placed with fluid beneath them that protect the cornea, which is then bathed in 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 outer surface. We can do limbal stem cell transplantation if the cause is limbal stem cell deficiency. Finally, in the most severe cases, if the persistent epithelial defect formation is associated with corneal scarring and/or perforation, artificial corneal transplantation can be performed. These patients tend not to be good candidates for traditional corneal transplantation. 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 absence 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 rather than later. Francis already mentioned the fact that if you have a persistent corneal epithelial defect formation, more times than not that leads to thinning and scarring of the corneal stromal, 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, it can lead to corneal perforation. You want to treat these conditions early and effectively to prevent the sequelae that can follow. Currently, there is no FDA-approved treatment with a broad range of indications or treatments that 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 management. My pleasure to introduce another one of my friends and excellent scientists, Stephen Pflugfelder. World renowned, you said. Baylor College of Medicine. He's really going to help us dive deeper into the mesenchymal stem cell secretome as well as specifically KPI-012. Stephen. Brand new. Make your unmute. Can anyone hear me now? Oh yeah, you're there. Okay. Sorry about that. I don't know what happened. I would 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. As Dr. Mah mentioned, it's 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 reduced vision, which can actually lead to functional blindness. Any impairment in the normal healing process can result in a persistent corneal epithelial defect. 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 proliferate, quickly healing the central defect. In persistent corneal epithelial defects, that doesn't happen. The epithelial cells become stagnant at the edge. Clinically, we can see that as an elevated rolled edge, and then the base can actually start t o thin or ulcerate, and that can occur from proteases or proteolytic enzymes that are produced by the epithelial cells on the edge, as well as keratocytes that are located in the cornea stromal that produce these enzymes that can degrade the tissue. The keratocytes are basically the fibroblasts. The stromal 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 to produce abnormal and excessive matrix that leads to scarring. The cells can also contract and cause an irregular corneal surface. None of those things are good. 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. 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 muscle, 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 can promote survival of the surrounding cell, suppress new blood vessel formation, which is good for wound healing. 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 BIO's product is a proprietary mesenchymal stem cell secretome platform. 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. The secretomes are produced by collecting biomolecules that are secreted by these cells into the extracellular space to support their health and viability. KPI-012 was manufactured from this master proprietary cell bank of human bone marrow-derived mesenchymal stem cells. 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 k ind of as their scaffold. 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. The mesenchymal stem cell secretome platform is cell free and it provides a new regenerative approach to disease management. KPI-012 is the lead candidate from KALA BIO for the treatment of and it contains a variety of key secretome biofactors that are associated with wound healing. Some of those are listed here on the right. There are other ones too. In fact, quite a few have been identified. 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 TIMP-2 and Serpin E1. 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 regrowth. This provides a multifactorial mechanism of action to addressing impaired corneal healing. It's formulated as the topical non-preserved single unit dose formulation and has the potential to treat multiple rare corneal diseases including PCED. So. In summary, KPI-012 addresses multiple biological pathways associated with impaired corneal healing in PCED from the variety of those factors. One thing to mention is that we have learned that biological factors such as nerve growth factor and OXERVATE can be very effective. We've also, from lots of key basic science research, 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. A mixture of factors as found in the secretome really makes sense, not only in the healing but also to clinicians who would be able to buy into that concept. Thank you for your time and I'm going to turn it back over to Dr. Mah. Great, thanks a lot, Steve. Fantastic overview of really what happens in a nice, short, succinct way as far as that proliferation, migration, adherence, and so forth. Next, I have the pleasure of introducing Melissa Toyos, who's an excellent ocular 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. Great. 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 clinical are seeing these patients at our clinic 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, work abilities, et cetera. It's been a pleasure to be part of this team and part of this trial. This is what we came for. 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 I-B study design. This was Dr. Pflugfelder was involved with, 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 non-vertical 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 one to eight weeks and followed for up to 19 weeks, with the key efficacy endpoint, the healing of the PCED based on corneal fluorescein staining, which highlights any abnormal or damaged corneal epithelial cells. 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 one week. That is fairly remarkable in this field, I would say. Extremely remarkable. One of six was complete healing after another week and then there was another one that healed at four 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 size ulcerations or epithelial defects. If you consider that the cornea is usually about 12 mm, you can see that many of these patients were suffering with about half the loss of their corneal epithelium. To have this level of healing this quickly is remarkable indeed. Improvement in lesion size was observed in two participants who did not heal completely. We saw improvement of 80% and 60% respectively. 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. 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. This is a graphic that shows how patients were treated. 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, post-infectious keratitis. This really highlights that all comers, this medication is helpful for a variety of different indications of PCED, not just one. We have more latitude here to treat patients that will be coming to us with other issues, etiologies, and problems. You can see that in many cases these patients were healed as quickly as one 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. 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- 14 days. You can see that the last patient here was unhealed for 871 days. These are not cherry-picked patients. These are absolutely very difficult to treat patients and the longer these problems go on, the tougher they are to treat. 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 one week. That is very significant. Two-thirds of the patients were experiencing absolutely no pain at all by week one, so as early as seven days, and then 100% of the study population reported no pain at all as early as three weeks. Improvement in the size of the ulcer and healing, these very strong results supported the phase II-B clinical study trial design and we have been happy to be a part of that as well. This is a multi-cohort study to evaluate the safety and efficacy of two doses, one unit per milliliter and three units per milliliter of KPI-012 ophthalmic solution compared with its vehicle. It's been dosed four times daily, a little bit different from the ones from the phase I-B study. Dosing for 56 days in the study eye of patients with a PCED, the antibiotic, non-preserved tears, that and other medications that have been approved for this process. They absolutely put in a higher bar, so less likely to have a placebo healing on their own. These patients were treated with conservative therapy. They did not get better, 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. They were randomized to one of the treatment arms, whether it was vehicle, the lower dose of KPI-012, or the three units per milliliter. The treatment period was eight weeks. These patients were followed up for two weeks and at six months. The key inclusion criteria: 18 years of age or older, had to be willing to comply with the study procedures, medically documented PCED of seven days duration. We've already talked a lot about the causes of PCED, but these were the eligible etiologies for the clinical study. I'm going to turn this over now to Todd. Thank you, Dr. Toyos. Now, as you heard from our KOLs, it's clear that PCED is a serious, clinically burdensome condition with significant unmet need. Today, the only approved therapy is OXERVATE, which is just a subset of these PCED patients, which currently accounts for approximately 1/3 of all affected patients. Treatment with 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 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 I-B study, KPI-012 demonstrated rapid epithelial closure with four of six responders healed fully in just one week and sustained healing over time with all six responders healed by week three, highlighting KPI-012's potential to provide fast, durable and effective treatment across etiologies. Finally, superior tolerability and ease of administration. OXERVATE requires dosing six times per day and a 19-step preparation involving daily reconstitution of a frozen vial. In contrast, KPI-012 is dosed four times per day using convenient premixed preservative-free single-use vials with no preparation required. Additionally, OXERVATE, as we've heard, is associated with approximately 16% rate of ocular pain and other adverse events like irritation, blepharitis and corneal neovascularization. Many clinicians believe OXERVATEe's pain adverse event may stem from nerve regeneration while the corneal epithelium is still denuded or possibly from a direct action of rhNGF on pain receptors. In our clinical experience, KPI-012 is not showing these side effects. In fact, in our phase I-B trial, KPI-012 completely resolved pain over time in those patients that reported pain at baseline. We've 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 up front optimizing culture conditions for cost of goods and scale and as a result have developed a well-defined, straightforward bioreactive production, harvesting, and processing process. This process starts with the working cell bank derived from the 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 manufacturer is 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. 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 the 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're looking forward to presenting top-line results from the CHASE phase II-B 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 had recently completed enrollment in the phase II-B 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+ patients in need. If results from the CHASE trial 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 all anterior segment orphan indications for KPI-012 as we believe it has pipeline and product potential, and we have U.S. regulatory exclusivity and IP protection well beyond 2040. We are progressing 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 II-B 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 studies. We are currently focusing our efforts on some of the most prevalent indications with limited or no treatment options such as PCED and LSCD. We will 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. Yeah, thanks a lot Todd. Excellent overview of KALA BIO and the pipeline. 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. 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. There are a lot of questions and 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. The first one is what is the bar for clinical success for the CHASE trial? I think the quick, easy answer is if we get epithelial healing that's statistically significant in a rapid manner. I think just some scope is that, number one, this is obviously a study that's not just neurotrophic keratitis, it's persistent corneal epithelial defects, as we have heard. It's a broad, wide-ranging list of etiologies. 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 OXERVATE in their two registration clinical trials, then I think that's obviously going to be a clinically meaningful outcome. Number two is especially if what happens in the phase II-B holds up in the CHASE trial, meaning that there were not any adverse events. Pain, for example, was part of the OXERVATE adverse event profile. 16% was on the label. It's a lot easier to administer as Todd went through. It's just a vial that we're all familiar with, getting some feedback. I think with those things and if KPI-012 in the CHASE trial holds up with the phase II-B 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. 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 there is the 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. 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. There has been some indication from the FDA. Makari Marty said that there are some scenarios where, especially for rare diseases, a single trial might be acceptable along with that. All right, 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? Yeah, sure. 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 they 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. I think we should, excluding data, by the end of Q3. We are hopeful that we will have had our end of phase II meeting and those minutes 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. Again, KPI-012 is for persistent corneal epithelial defects. Do you expect to have any overlap or competition with cenegermin or OXERVATE? Again, we'll kind of go to Todd based on some of his projections. Sure. I'll start. I would certainly welcome the thoughts of the panel on this, Chief, because I think this was 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, 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. We'd certainly welcome any additional thoughts from the panel. Yeah, Stephen, what do you think? You're kind of at the top left of my screen. Yeah, I totally agree with Todd. I mean, as [Sjögrens], there's multiple etiologies for these problems. To be honest, almost a lot of them or most of them have an NK component. You know, 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. Yeah, 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 manifestations 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, poor substrate. In irregular ocular surface because of band keratopathy, because of prior, you see patients who have prior corneal infections in which the Bowman's layer on which the epithelial cells normally reside is eroded, the surface is now irregular, the 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 are 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 the ocular surface, etc. We use, for patients with neurotrophic keratitis, we may need amniotic membrane transplantation for patients who have an inflammatory component, etc. 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, measurement has not really yielded good results in these patients. I think that experience is shared by others. 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. These are the patients, I think, where it is the greatest unmet need. To that point, I mean, Steve, you know, went through exactly the secretome, how, you know, 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. You know, the secretome has something for proliferation. It might be an adhesion issue, it might be a migration issue. Do you think, you know, this strategy of having multiple different components in the treatment would help with exactly what you pointed out with PCEDs and etiologies? I do. I mean, because again, why does your basement membrane break down? It's probably release of proteases. If you have protease inhibitors, as you do in the secretome, that can address that. Why is it that the fulfilled cells are not migrating even though they have a good platform? They don't have the sensory inputs, the growth factors that are needed. If you have a parasite growth factor, PEDF, et cetera, in the secretome, that can help address that issue. I do think, as Stephen said, that if you have multiple components that can address the varied conditions that result in the formation and persistence of epithelial defects, that optimizes your chance for having an effective therapy with persistent lasting benefit. These are muted. Francis. Sorry, next question. I think I'm going to have Melissa answer. The question is how burdensome is the dosing regimen of OXERVATE or [Synergy meant] to NK patients? Dose six times a day over eight weeks. As you had mentioned, Melissa, this one's four, four times a day, for example. Right? Right. There's a huge difference between six and four. Six times a day is a part-time job. People have to carry it with them in their coolers, to work, to school, all of their activities, and then four times a day, you know, that's breakfast, lunch, dinner, and bedtime. 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, 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 a s well as clinicians. Excellent answer. I agree. I think four times a day is a huge difference compared to fixed times a day just in compliance issues. Not to mention again the 19 steps that it takes for OXERVATE to be administered to the eye. I think we kind of answered this next question. If anybody has any additional thoughts, 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 or population would benefit the most from KPI-012 and why? Let's see, 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. Yeah, I mean, one of them obviously would be a post-surgical. You know, a lot of times, like pretty much everybody who has a cornea 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. They may be a little bit harder for anything to. 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. The next question, let's see. Would there be a difference between mild and moderate to severe PCED patients? 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? I agree with the panel that once we see the breakdown, there are a lot of factors that are building and it's a downhill flight. The faster we touch these patients, the faster we heal them, the less long-term damage occurs. 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. 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. Chris, can I add something to that? I was going to say, if you talk about severity, I think you can look at it a couple different ways. One of it is you look at it in terms of the clinical manifestations. How large is the epithelial defect? Is there a stromal ulceration? Is there thinning? How severe is the thinning? You can look at it that perspective. Yes, the larger the defect, the longer it's been around, the greater the resultant sequelae, like stromal thinning, you 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. This could be a PCED. In that situation, it's 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. A condition that could be addressed or somebody with exposure keratopathy, don't blink, who could have a partial closure of the eyelids to address that. 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. 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, you know, 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 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. 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, Sjögrens 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. Yeah, I think that was so. I think everybody agreed with that. Stephen mentioned, you know, iatrogenic bullet, also spoke about iatrogenic issues. 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's interesting. What excites you the most about KPI-012? We've 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. You know, it's come up a little bit. In addition to healing PCEDs is the potential regenerative aspects of mesenchymal stem cells. For instance, can we— we talked about people getting haze in their cornea from a PCED. It's quite possible that treatment with this product will also help to suppress that and regenerate a more normal, optically clear corneal stromal and also a smoother surface. I'm excited about that. It's not only just healing the epithelium, but it's also making it healthy, you know, like very smooth with a good tear film. To me that's a really exciting aspect. Yeah. 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-B data, looking at the variety of different pathologies that came in, I think the size of the ulcers and the length, you know, 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. I think that is extremely exciting as well. If we could relieve pain and cure things, that's the sweet spot. Yeah. Anthony, how about you, what do you think as far as the most interesting aspect, l et's say. My thought is kind of similar to what Stephen has mentioned. I'm just thinking about this. I have a, as you know, molecular genetics lab and we often look at diseases by looking at alterations in protein expression. We'll do techniques like RNA seq, looking at the 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. The therapies to me ideally would be something that would target multiple targets, multiple factors that are responsible for initiating and perpetuating the disease. Using the mesenchymal stem cell secretome to me makes sense in that it's a multi-pronged therapeutic approach as opposed to only singling out a single aberration as far as protein expression or whatnot. I like the approach that this represents. That's excellent. I do think the potential is, you know, very intriguing. Next question is any difference in the assessments and care for PCED between patients in the 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, you know, just like Anthony had kind of gone through, we try to identify the etiology or the reasons that this person has the epithelial defect. As far as going through the treatments, I think we all go through, you know, the kind of hierarchical management that Anthony went through. Maybe not so structured, but we do use the various different treatments. It's based on, you know, what the patient can do and what the patient allows you to do or wants. There are a couple of things that, for example, I don't have access to. Our plastics oculoplastics people do not yet do, you know, the neurotization. Maybe some of the academic centers, you know, have an easier access to somebody who could do neurotization. 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 site because I'm the only one who's not academic here. I think in general, we are a research site, so we have more tools and diagnostics, investigative equipment than an average eye care provider would. I think that, you know, in general, I don't have a molecular genetics lab. I'm very jealous of you, Dr. Aldave, on that one. 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, their broad etiology. They may not even have time to investigate exactly what the cause is. 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 and 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 m ore tools than I have because when. We discussed it in meetings. 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 community versus academic centers, where I've seen patients have self-retaining amniotic membrane placed again and again and again, maybe weekly, six, seven times 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 paracentesis 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. We tend to be further down the road as far as intervention. We tend to, I think, go to the operating room sooner or refer for a scleral lens, use other subspecialists and treatments earlier after they come to us. We're seeing them, many of these patients, I think at a different time point than our colleagues in the community. That's an excellent point. I think it's kind of like that, you know, hammer and a nail, right? 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. Just like Stephen and Melissa said, it behooves us to educate ourselves and then have some experience on the various different management tools. I just wanted to wrap up here. I really appreciate all of the speakers, obviously Todd and then our KOLs, Anthony, Stephen, Melissa, phenomenal job, you know, with the various different topics. I appreciate everybody that's in attendance, really appreciate the time and all of the excellent questions that we had. Hopefully we'll have excellent news in the coming weeks regarding the CHASE trial. Thank you, Doctor.