Hello everyone. Thank you all for attending the Jefferies Healthcare Conference today. My name is Isi Martini. I'm with the Jefferies Healthcare Investment Banking team, and it is my greatest pleasure to introduce you all to Kim Brazzell, today's speaker.
Thank you very much. We'd like to thank the Jefferies team for inviting us to give an update on Kala Bio. Let's see if this works. There may be some forward-looking statements here, so I won't read through the whole series here, but you've seen all this. Kala is a leader in the emerging field of mesenchymal stem cell secretomes, with a particular focus on rare ophthalmic diseases. Our lead product of our proprietary secretome platform, KPI-012, which we'll touch on in a minute, is in a phase IIb pivotal trial currently for the treatment of persistent corneal epithelial defects, which are a serious and potentially blinding condition, that where there's a significant amount of unmet need. We also see KPI-012 as a, as a...
Sorry, as a pipeline and a product, and we have additional indications that we're looking at for the front of the eye. The current trial is targeted to read out at the end of 2024, so we're looking forward to the end of the year. Based on that, with a positive success, we think it will be a pivotal trial, and we'll have one more trial to go with. We're also looking at utilization of the secretome platform for treating diseases of the back of the eye, which we won't talk much about today, but we'll go into if you want more detail. We've had a significant amount of progress in the last 18 months. At the end of 2022, we filed and had accepted our IND.
We initiated our current phase II trial in Q2 of last year, and as we said, are looking for top-line data by the end of this year. We also, in 2023, received a $15 million grant from the CIRM, the California Institute for Regenerative Medicine, which we think further advances the program and talks about its importance and potential impact. So, we have an experienced—we also have cash and equivalents that will take us into the third quarter of 2025. We have an experienced team, management team. We've been together for a number of years.
We have successfully and developed and approved two ophthalmic products, one for dry eye disease, one for ocular inflammation, which we subsequently divested to Alcon to focus on the secretome platform. As I said, we're a leader in the emerging field of mesenchymal stem cell secretomes, and for those who don't know much about secretomes, they're basically the biomolecules that are secreted by cells into the extracellular space to maintain the viability of the cells. In our case, we use human bone marrow-derived mesenchymal stem cells. We have a master cell bank of that, and basically, the production involves culturing the stem cells sufficient time to let them secrete all the biofactors, again, that they do to maintain their growth and viability.
We then remove the cells, and we have an aqueous solution that contains this mixture of important human biomolecules. We then process that in a simple fashion to a topical ocular formulation for the patients. We think this offers many of the benefits of cell therapy, but may avoid some of the safety and logistic issues with standard cell therapy today. Secretomes have been published. A great deal of data has been published in the literature about the ability of secretomes to impact corneal and ocular diseases, particularly wound healing, inflammation, and tissue repair, which is what we're focused on with our first product. These secretomes have multiple potential applications in the eye, all in the rare disease state.
The two most prominent are persistent corneal epithelial defects that we are currently running a trial in, and secondly, limbal stem cell deficiency, which we're planning to initiate a trial. And we'll talk a bit about those in a little bit. So our current pipeline includes the PCED, as we call it, trial, that's reading out the end of this year. Our limbal stem cell program, which we're designing a study to initiate, as well as a research program looking at the effect of different secretomes on the retina and the ability to treat inherited retinal diseases. A little bit about KPI-012. Again, it's composed of the biomolecules that these human mesenchymal stem cells secrete. And as I said, we are able to formulate that as a topical ocular formulation.
The product contains key classes of molecules, proteins, growth factors that are involved in corneal wound healing, and so we think it provides a multifactorial mechanism of action for treating conditions and diseases that are caused by impaired healing of the cornea... our phase IIb pivotal trial that I'll touch on in a minute, our goal is to demonstrate complete healing of these lesions, and as we talk about the issues associated with these, that will be obvious. We have orphan drug and Fast Track designation. So persistent corneal epithelial defects, or as we call them, PCEDs, basically a persistent non-healing defect on the surface of the eye. It's typically described as one that doesn't heal with conventional therapy for 10-14 days.
As you can imagine, the cornea is one of the, or probably the most highly innervated tissue in the body, and it's protected by the epithelium. So when you get a defect or a denuding of that epithelium, as you would expect, there's a significant amount of pain, and other issues that patients experience. If this defect is in the center of the cornea, then you've got a significant amount of vision loss. As importantly, if these are not healed in appropriate amount of time, you can get risk of infection, which is a significant, can often lead to losing the eye. You get further degradation of the cornea, where you can get skinning, thinning of the stroma.
You can actually get perforation of the cornea that usually requires a corneal transplant and often results in vision loss. These defects can be caused by a number of underlying etiologies. Common ones are trauma, burns to the eye, neurotrophic keratitis is a common one, diabetic keratopathy is quite common, herpes keratitis is a very common, and patients often have more than one underlying etiology. For example, a diabetic patient who goes into surgery or may have a herpetic lesion is probably more likely to develop this because they have more than one underlying etiology. We estimate the epidemiology, about 100,000 patients in the U.S., and if you add U.S. and Japan, over 200,000 patients.
and we have conducted, and we'll talk about a phase Ib trial in this condition where we had some excellent data. It's an underserved market today. There's only one product on the market, Oxervate, which is indicated for the treatment of PCEDs secondary to neurotrophic keratitis. So we estimate that is about a third of all the incidences of these lesions. So Oxervate will cover about a third of them all, but still it's approaching $1 billion in sales in 2023. So we think there is a great need for a product that will treat PCEDs of all etiologies, rather than just neurotrophic keratitis.
So the unmet needs here, we think, are a single agent, single product that can treat PCEDs of a variety of different etiologies, one that gets robust wound healing, and one that has a patient-friendly approach. The current treatment, Oxervate, is administered six times a day and has to be formulated by the patient at home. It's a 19-step process. And as we said, based on the data we're hearing from other sources and published data, Oxervate is approximately approaching $1 billion in sales, so a significant potential here for this product. Our goal is to seek approval for a broad PCED indication. Our discussions with FDA have been fruitful in that respect, and we think if this trial is positive, ongoing trial, we'll need one additional phase III trial to for a BLA submission.
So a little bit about how KPI-012 works and our focus here are on diseases involving impaired corneal healing. And we know there's a lot of literature about what drives healing of the cornea, and a lot of pathways involved. Amongst those, you have to have, because it involves sloughing of epithelium and denuded cornea, you have to have epithelial cells that are produced, differentiate, and migrate to the site of action. In many of these cases, you have enhanced proteolysis associated with inflammation, and you have to knock down those proteases. In addition, you've got an impaired basement membrane in many of these etiologies that even if you have epithelial cells that are produced and migrate, they don't have a scaffold to adhere to.
So amongst the biomolecules that are in our product, we have growth factors such as hepatocyte growth factor, PEDF, that promote epithelial proliferation and migration, also promote innervation of the cornea, which plays a critical role in healing. We have a protease inhibitors such as TIMP-1, that can knock down the proteases and slow or stop the proteolysis. And then we have matrix proteins such as fibronectin and collagen that can provide the scaffold to improve adherence of the epithelial cells to the underlying wound. And we think that this combination of biofactors provide a multifactorial mechanism of action that should be able to address PCEDs of multiple etiologies. We've conducted a phase Ib clinical trial.
It started out with a 3-patient safety cohort where we saw no issues. This is conducted at what is now the 1 unit dose. We're going into the... Our current trial is 1 and 3 units. And there were 8 patients then, where they moved into the efficacy cohort of the trial. All 8 of those patients improved, and 6 of 8 of those showed complete healing, and that means complete re-epithelialization. So that 75% number is similar to what Oxervate saw in their trial with just neurotrophic keratitis, so we think that, at least on our initial results, have very promising efficacy. This rather complicated graph, table shows really the duration by which patients were treated.
The green spots or the blue spots are when they healed, and then the line beyond that is how long we followed them up. None of the patients saw recurrence of the PCED during the follow-up. As I said, six of eight completely healed, and that was measured by corneal fluorescein staining, which is a very common technique used by ophthalmologists, which we are using for our current clinical trial. It's also the endpoint that FDA has indicated they want to see for proof of efficacy. We also, in this trial, saw significant relief of pain in these patients, and six of the eight patients in the trial had significant pain. As you see here, within three weeks, we were able to completely resolve that pain.
That's likely a surrogate for the fact that the lesions are healing. We're progressing, as I said, toward a phase IIb readout by the end of this year. We've had significant progress. Our pre-IND meeting, FDA indicated that they were open to a broad PCED indication if we enrolled these defects of a variety of different etiologies, which we're currently doing. They provided input on our CMC, on key elements of the study design. We also have Orphan Drug and Fast Track designation. We filed our IND in November of 2022, and it got accepted in December, and we were able to initiate our phase IIb study.
FDA did ask for us to do a small safety cohort, which we did with no significant issues, and then moved into the efficacy cohort of the trial in Q2 of last year. We recently had a Type C meeting with FDA concerning CMC and our potency assay approach. That's a common question that's asked. It was a very productive meeting, and basically, FDA agreed with what we are doing. The plans that we have, the tests that we are running, they're sufficient for entering phase III and likely sufficient for BLA filing. So that was a significant milestone for us to do that. We also, because KPI-012, we have an IND, we're able to conduct other indications with that under the current IND or file a new IND and reference the previous one.
As I said again, if the Phase IIb trials are positive based on our interactions with the FDA, it's to be sufficient for the first of 2 pivotal trials needed for our BLA submission. A little bit about the trial. I touched on the 2-patient open label cohort that we did to demonstrate safety, and we saw no problems there. The current efficacy portion of the trial involves 90 patients. It's a randomized, placebo-controlled trial using 3 doses, a 1-unit dose, a 3-unit dose, and vehicle, and a 1-to-1 randomization, 30 patients per arm.
And that trial was based—the powering of that trial was based on the Oxervate results, and if we assume a similar effect that Oxervate had and that we had in our phase Ib, we have a 98+% power to show a statistically significant effect. It's an 8-week treatment arm, a treatment period, and then follow-up 2 weeks to look again to see if the lesion, if the lesion is still healed, and then a 6-month safety check for the patients. We're using about 40 sites, a mix of academic and non-academic sites from the U.S., and we're in the process of initiating sites in Latin America as well, because Oxervate's not available there, so we think that would be a fruitful place to do some of the studies.
The primary endpoint, as I said, is complete healing of the lesion, as measured by corneal fluorescein staining, which is a common technique that shows the area of denuded cornea. And we do it using photographs. The investigators or a certified photographer takes photographs of the fluorescein staining. That goes to a central reading center that, in a mass fashion, then makes a determination if it's healed or not healed. So it's a binary endpoint, healed or not healed. And, our current trial, the primary endpoint, is at 8 and 10 weeks, 8 weeks for healing and then 2 additional weeks to show that it hasn't, it hasn't reopened or that the lesion is still gone. And so, as I said, those top-line data, the study's progressing well.
We're looking at the end of 2024 for our top-line data for that. The other indication we're planning on is called limbal stem cell deficiency. As you know, as with other epithelial layers, the corneal epithelium is continuing to slough and regenerate. So the limbal stem cells that are between the cornea and the limbus are the stem cells responsible for producing epithelial cells. And so if you have a deficiency or a loss of the limbal stem cell niche, then you're not making epithelial cells that can replenish those that are sloughed. And it comes with a number of different sequelae, a great deal of patient-reported symptoms. You also get recurrent breakdown of the epithelium with the problems that it has, a lot of neovascularization and inflammation as well.
One of the most common causes of limbal stem cell deficiency is overuse of contact lenses. So this often presents to an optometrist or an ophthalmologist, where a patient thinks, "I need a new prescription because the current one's not working." And when they examine, they find out that it's not your contact lens, it is this disease, and they usually refer them directly to a corneal specialist that has an armamentarium that can treat this. But there are few treatment options today, and there are no approved Rx products that can treat the disease. So there's a significant unmet need here, and particularly the fact that it's underdiagnosed, and we'll probably see more and more as it becomes more prevalent or more diagnosed.
There's about 100,000 patients in the U.S., similar to the size of the PCED, so we see a significant market potential as well. So, to wrap up a little bit, you know, in addition to the 12 years of exclusivity, we will get, as the first biologic product in the BLA, we have a pretty robust patent portfolio that should take us out to 2040 or longer. So again, we're looking forward to our top-line results at the end of this year, and we look forward to presenting them at the next conference. And again, I want to thank the Jefferies team for inviting us and being great hosts. So thank you.