Thank you for standing by, and welcome to the Krystal Biotech KB801 first patient dose update call. At this time, all participants are on a listen-only mode. Following the presentation, there will be a question-and-answer session. As a reminder, today's conference is being recorded. I would now like to hand the conference over to your host, Stéphane Paquette, Vice President of Corporate Development. Please begin.
Good morning, and thank you all for joining today's call. Earlier today, we announced dosing of the first patient in Emerald-1 , our ongoing Phase I-II study evaluating redosable eye drop genetic medicine KB801 for the treatment of neurotrophic keratitis. The press release and today's presentation are available on our website at www.krystalbio.com. Both the press release and today's presentation have also been filed with the SEC as exhibits to a Form 8-K. Joining me today will be Krish Krishnan, Chairman and Chief Executive Officer; Suma Krishnan, President of Research and Development; Trevor Perry, Vice President of Product Development; and David Sweet, Director of Clinical Development. This presentation will, and our responses to questions may, contain forward-looking statements.
You are cautioned not to rely on these forward-looking statements, which are based on current expectations using the information available as of the date of this webcast, and are subject to certain risks and uncertainties that may cause the company's actual results to differ materially from those projected. A description of these risks, uncertainties, and other factors can be found in our SEC filings. The agenda for today's call is outlined here. Krish will open the call with an introduction to neurotrophic keratitis and the limitations of currently available therapy. Suma will then discuss the platform opportunity for Krystal in the front of the eye, and together with our R&D team, present an overview of our KB801 program, including key preclinical data and the design of our now ongoing Emerald-1 Phase I-II study.
Suma and Krish will close the call providing their perspectives on the longer-term development path for KB801 and upcoming pipeline milestones. With that, I will turn the call over to Krish.
Thank you, Stéphane. Good morning, everyone, and thank you for joining us. We're excited to announce an important milestone for Krystal. We dosed our first patient with KB801, which is a redoable eye drop genetic medicine for the treatment of neurotrophic keratitis, or NK. As you will hear on today's call, KB801 is not only well-positioned to deliver significant benefit for patients with NK, but also is a strong showcase of the versatility of our HSV-1-based gene delivery platform, which we are now advancing at full speed in three tissues: the skin, the lung, and the eye. The therapeutic goal of our 801 program is the treatment of NK, a serious degenerative and vision-threatening disease of the front of the eye. NK is caused by damage or loss of function in the neurons innervating the eye that, in turn, compromise their roles in maintaining a healthy corneal epithelium.
The disease is heterogeneous, ranging in severity from punctate lesions to recurrent or persistent epithelial defects and ulcers that lead to stromal melting and corneal perforation. Vision impairment is frequently reported, and unfortunately, severe cases can lead to blindness. NK is a rare disease, but awareness and diagnosis rates have increased dramatically in recent years, and based on available claims data and third-party analyses, the estimated number of U.S. patients with an NK claim in 2024 was 68,000, up over 115% compared to 2020. As of now, there is only one specific therapy approved by the FDA for the treatment of NK. This therapy, approved in 2018 and branded as Oxervate, is an eye drop formulation of recombinant human nerve growth factor. Oxervate targets the underlying nerve defect in NK patients and has been shown to improve lesion healing in NK patients.
However, rapid protein clearance requires intensive dosing six times per day, dosed every two hours for eight weeks, which is both highly burdensome and may lead to suboptimal outcomes. This problem is further compounded by frequent reports of eye pain with this treatment, as well as concerns about corneal deposit formation. Despite these limitations, Oxervate is on a blockbuster trajectory in the United States. Based on public CMS data, the combined spend of Medicare and Medicaid on Oxervate in 2023 was over $540 million, rising sequentially each year since launch, and based on third-party claims analysis, estimated days of reimbursement for Oxervate therapy in 2024 were over $410,000. We believe 801 is well-suited to overcome the limitations of Oxervate, ensuring more consistent nerve growth factor exposure in the front of the eye while dramatically reducing treatment burden, all using an easy-to-use and recognizable eye drop dose format.
I'll now hand it off to Suma and the team to share more detail on our platform and KB801.
Thank you, Krish. As Krish shared, this is an exciting time for Krystal and our pipeline. With KB801 in the clinic, we now have two clinical-stage ophthalmology programs under active evaluation, showcasing the potential of our platform in the front of the eye. The front of the eye presents unique challenges to therapeutic development. Rapid protein clearance has severely limited the utility of biologic therapies, and high cell turnover has prevented the development of gene therapies using traditional vectors like AAV or lentivirus. Our redosable HSV-1 platform is particularly well-suited to overcome those challenges. HSV-1 exhibits a natural tropism for epithelial cells of the eye and is compatible with eye drop formulation. More importantly, the safety and efficacy of repeat administration of our vectors to the eye have been already clinically validated by our initial experience with B-VEC eye drops in a DEB patient under compassionate use.
The large cargo capacity of HSV-1 also allows for delivery of a wide variety of biological payloads or combinations, providing additional flexibility. With these attributes, we see multiple exciting opportunities to leverage our platform and improve front-of-the-eye outcomes for patients. This includes targeting rare genetic diseases, as we are doing with KB803 for the treatment of corneal abrasions in DEB patients, as well as diseases where a biologic therapy would be beneficial but is not feasible given the eye clearance rates. By encoding these biologic therapies in our vector platform, as we're doing with KB801, we can transduce local cell populations to drive sustained expressions with low-frequency dosing in order of once or twice a week. Before moving to KB801, I wanted to briefly touch on our other clinical-stage ophthalmology program, KB803, which is already under evaluation in an ongoing Phase III study.
Our excitement for KB803 is driven by the profound improvements realized by the DEB patient treated with B-VEC eye drops under compassionate use. As reported previously, repeat administration of B-VEC eye drops was well-tolerated and associated with full corneal healing, as well as significant visual acuity improvement, which critically was maintained with regular therapy. Based on this data, we recently initiated our Phase III to evaluate an eye drop formulation of B-VEC, KB803, for the treatment of corneal abrasion in DEB patients. We are excited to be progressing this program as we endeavor to treat DEB patients as comprehensively as possible. We also expect our KB801 development program to benefit from key learnings and FDA interactions as KB803 advances towards a potential registration.
Turning now to KB801, our second clinical-stage ophthalmology program, KB801 is designed to leverage many of the features of our HSV-1 platform to enable superior and sustained nerve growth factor exposure in the cornea when compared to recombinant protein approaches, all while significantly reducing dosing frequency. We believe this is a high-value proposition with the potential to drastically simplify administration for patients and drive superior outcomes. KB801 is built using a proprietary, non-replicating HSV-1 vector platform and encodes two NGF transgene copies. Studies conducted during preclinical development are summarized here and collectively demonstrated that KB801 is able to effectively transduce corneal epithelial cells in vitro and in vivo, leading to sustained NGF production in front of the eye. I will now hand it off to Trevor to walk you through some of our preclinical data that supports the clinical development of KB801. Trevor?
Thank you, Suma. We first set out to construct a vector encoding human NGF and to demonstrate that this product was capable of expressing and secreting its human cargo from clinically relevant cells without toxicity. On the left, we can see that KB801 efficiently transduced primary human corneal epithelial cells in vitro and expressed its transgene in a dose-dependent manner. As demonstrated by the ELISA and Western Blot seen on the right, transduction also led to dose-dependent secretion of mature human NGF, a critical step for protein processing as NGF exerts its function extracellularly. Importantly, no cytotoxicity was observed in treated corneal epithelial cells, even at the highest doses tested. We then conducted our first in vivo proof-of-concept study to examine transgene distribution in the eye after topical application of KB801 to wounded mouse corneas.
In this study, we included an animal-equivalent dose of recombinant human NGF protein, adjusted for eye surface area, to mimic a single topical dose of Oxervate. As can be seen here, we observed uniform longitudinal deposition of human NGF protein across the entirety of the murine corneal surface that looked similar to what was achieved with the topical recombinant protein itself. This study also included a histological assessment of all major structures in the eye to ensure that KB801 did not induce any adverse effects in these sensitive tissues. Eyes collected 24 hours after KB801 dosing appeared indistinguishable from vehicle controls, showing no immune cell infiltrate, tissue damage, necrosis, or other obvious histological changes that might otherwise be suggestive of poor tolerability to topical ocular KB801. Similar findings were seen after a longer-term safety study involving eight weeks of KB801 dosing.
Here we see results of a short-term pharmacokinetic study we performed to quantitatively compare human NGF protein kinetics in wounded mouse eyes following topical ocular administration of a single dose of KB801 or a single dose of recombinant human NGF. In this study, a 20-nanogram-per-eye dose of recombinant human NGF was employed to represent 1/30 the human Oxervate dose, as the KB801 dose administered here is approximately 1/30 the intended human dose. Whole eyes from each treatment group were assessed by ELISA at the indicated time points post-dosing to determine if KB801 treatment resulted in a higher total human NGF exposure than recombinant protein therapy.
A higher peak level of NGF in the eye and a longer total NGF exposure time was seen in the KB801 treated group as compared to the recombinant protein control, with NGF remaining at detectable levels in two-thirds of the dosed eyes at seven days post-treatment. Finally, a study was conducted to quantitatively compare human NGF protein kinetics in wounded corneas following a single dose of KB801 or six doses of recombinant human NGF, given at two-hour intervals to mimic the daily clinical regimen of Oxervate. The total amount of human NGF present in treated whole mouse eyes was assessed by ELISA at 10 hours and 15 minutes, 24, and 34 hours post-KB801 or first recombinant human NGF dosing, equating to 15 minutes, 14, and 24 hours, respectively, after the sixth recombinant human NGF dose.
The 10-hour-15-minute time point was included here to capture the expected peak of recombinant human NGF within the mouse eye, as it was the earliest feasible sampling time point following the full recombinant protein dosing regimen. As shown here, we found that a single KB801 topical treatment resulted in higher eye NGF levels as compared to six doses of recombinant human NGF at all time points tested. Again, KB801 resulted in both higher peak level of NGF in the eye and a higher total NGF exposure, even in comparison to the animal-equivalent of the sixth-dose commercial Oxervate regimen. Altogether, results from these studies provided sufficient data to file and clear an IND supporting the development of KB801 as a potential ocular topical therapy capable of achieving robust and sustained NGF delivery to the corneas of NK patients.
I will now turn it over to David to discuss our ongoing clinical program.
Thank you, Trevor. I have the pleasure of introducing the KB801 clinical program today. KB801 is currently under evaluation in our first-in-human Phase I-II study, Emerald I. Emerald I is a double-masked, randomized, placebo-controlled study in patients with moderate to severe neurotrophic keratitis. Up to 27 adult subjects with Stage II or Stage III NK, as defined by the Mackie criteria, will be enrolled and randomized two-to-one to receive either KB801 or placebo topically to the study eye twice weekly for eight weeks. To enroll in the study, subjects will need to demonstrate persistence of a corneal epithelial defect as well as reduced corneal sensation of the affected study eye. The primary focus of Emerald I is evaluation of safety and tolerability of topically applied KB801. The study will also assess efficacy of KB801 in treating the hallmark of NK, persistent corneal epithelial defects.
Images of fluorescein-stained corneas will be read by independent masked readers to evaluate defect closure at various time points. Additional efficacy endpoints include change in corneal sensitivity by Cochet-Bonnet aesthesiometry and change in ocular symptom severity as reported by subjects. Durability of effect will be evaluated two and 12 weeks after completing the treatment period, where defect closure and corneal sensation will again be assessed. I will now hand the call back to Suma to discuss the outlook for KB801 and the broader pipeline. Suma?
Thank you, David. One of the many exciting aspects of the KB801 program is the possibility of expedited development, shortening the time to registration and patient impact. The prior experience with Oxervate is one key advantage. With Oxervate approved in 2018 and on market now for five years, there is extensive clinical and commercial experience that significantly de-risks the safety of our KB801 payload. We also have the benefit of known endpoints with a short time to read out. Taken together with the agency's experience with our platform and the fact that NK is a rare disease, we see opportunities for efficient registrational study designs primarily focused on efficacy evaluation. We're also pursuing the platform technology designation with the FDA, which could provide additional timing advantage and codify some of the efficiencies we are already seeing with the FDA review of programs on our HSV-1 platform.
Potential advantages could include earlier expanded or accelerated FDA interactions, opportunities to leverage previous preclinical and clinical data, possibility of FDA referencing prior CMC validation of the manufacturing process, release testing assays, and stability for future marketing authorizations. Collectively, these have the potential to make the clinical development of KB801 relatively short and cost-effective, with the additional benefits of safety, efficacy, and manufacturing all being significantly de-risked. With these tailwinds, we see an opportunity to rapidly progress both of our ophthalmology programs, KB803 and KB801, with potential for registration in 2026 and 2027. I will now hand the call over to Krish.
Thank you, Suma. With KB801 now in the clinic, we have built out a broad and diversified pipeline poised to deliver multiple readouts in the months and years ahead. In the lung, we're on track to deliver KB407 molecular data readout later this summer and expect to provide additional updates on KB408, which is now in repeat dosing later this year, and with patients dosed with both KB803 and 801, we're excited to drive enrollment to completion and report data on relatively expedited timelines. This is all in addition to our ongoing programs in oncology, aesthetics, and skin, each of which addresses urgent unmet needs and collectively demonstrate the breadth that we believe exists in our HSV-1-based technology platform. As you heard today, we are very excited about the future of the pipeline at Krystal.
With our HSV-1-based technology, we have the ability to efficiently deliver genetic cargo to high-turnover tissues repeatedly and non-invasively. The skin, lung, and eye are all great tissues for us that have simultaneously proven intractable to other gene therapy modalities, setting up durable value creation opportunities. Today's announcement is an important step on what we see as a clear path to building long-term shareholder value. The Vyjuvek franchise, soon to be bolstered with EU and Japan launches, is poised for growth for years to come. The addition of KB803, if approved, would be highly synergistic with Vyjuvek and drive further top-line and bottom growth. Our pipeline efforts in the lung and the eye are then springboards to take Krystal to the next level. Success in either would be a step jump for our organization, opening up multi-product opportunities in blockbuster markets.
We're excited about what's to come and the opportunity to build a true portfolio of diversified, high-value genetic medicines for patients in need. Thank you, and I'm going to turn over to Q&A.
Thank you. The floor is now open for questions. If you have a question at this time and would like to join the queue, please press Star 1 on your telephone keypad. We do ask if listening on speakerphone this morning that you take up your handset while asking your question to provide optimal sound quality. Once again, please press Star 1 on your telephone keypad at this time. If you wish to join the queue to ask a question, please hold a moment while we pull for questions, and our first question this morning is coming from Alec Stranahan from Bank of America. Alec, your line is live. Please go ahead.
Hey, guys. Thanks for taking our questions, and I appreciate you holding the call this morning. Two from us. First, on NGF expression, do you think peak NGF or duration of NGF expression is maybe more important from your preclinical work? And I guess, how did this influence dosing frequency selection in the Phase I? And then I've got a follow-up.
Thanks, Alec. Trevor, do you want to take that?
Sure. Thank you. I think probably peak exposure is important, but we think a duration of exposure is really important to keep a consistent level of NGF in the eye in these patients. I think one of the issues that we've seen with Oxervate is the protein turns over so quickly, and they spend so much of their day without NGF exposure to the eye just from the clearance rate of the protein itself. We expect durable expression of the protein will be critical for demonstrating success of the program. In determining dosing interval, if you look at the PK profile of the single-dose study that we did, we see a favorable duration of exposure to NGF at levels equating to Oxervate for three to four days.
So our thought was, by inducing twice-weekly dosing, we could keep that level at or above Oxervate's kind of peak level throughout the duration of a week of dosing.
Okay. That's helpful. And then maybe just one quick one for Krish. I guess, given the turnover at the FDA and the fact that there's an approved medicine for this population, I guess, what sort of feeds into your confidence that maybe an accelerated pathway could be available to you guys and also around sort of what you would expect would be an approvable endpoint? Obviously, there's precedent there, but I wonder if that maybe changes given there's an approved medicine. Any thoughts there would be great. Thank you.
Yeah. There's a combination of thoughts, but I'll let Suma answer this one on the FDA interaction.
I think we are pretty confident that we will get the accelerated pathway because, again, if you look at KB801 versus Oxervate, there's substantial advantage because, again, we have to dose hopefully once or twice a week versus six times a day. So we're going to see some benefits. I mean, clearly, there's a dosing benefit because these are mostly older patients, and they really cannot basically, it is adherence to the therapy with Oxervate. That's what we hear when we speak with the KOLs that these patients cannot I mean, they are not able to adhere to the five or six-day dosing, so they're not seeing the benefit or the effect in real commercial setting. I think this is something we can overcome, and the data is pretty evident.
So I think from an accelerated pathway, we feel pretty confident that the FDA should still give us that path forward. And in addition, also because we are in the process of applying for a platform technology, keep in mind that CMC is the biggest challenge. I mean, this is something we went through with Vyjuvek and also with all of the process improvements and validation. So we believe with the platform approach, having the same manufacturing process and 90% of common assays for releasing and some of the stability that we have on the vector itself can be applied to this product. So it's basically doing the clinical study. We know we have many sites opened up. We feel pretty confident that we can enroll these patients.
So it's basically just for us, it's just finishing the clinical trial, and the rest is very much doable. So I really see this as a very fast to Phase III and a process to filing a BLA or a registration because of just the platform technology in general and the patient population and the advantage of the dosing regimen for these patients.
Makes sense. Congrats on the progress. Thank you.
Thank you. Your next question is coming from Roger Song from Jefferies. Roger, your line is live. Please go ahead.
Great. Congrats for dosing the first patient for this indication in NK. And then thanks for taking our question. A couple from us. Maybe start with the addressable market. Understanding the claims data is doubling for the past couple of years, and then the epidemiology team have a range. So what's your current estimate for the addressable market? And specifically, what's the percentage of the Stage II and III among the entire NK population? And I have a follow-up. Thank you.
Stéphane.
Yeah. Thanks for the question, Roger. Obviously, we're doing some of that work now to scope out further the size of the NK patient population and get to the moderate and severes. I mean, right now, we're getting the numbers that we've reported today, the 68,000 or so. That's all patients with an NK claim, and we're trying to get a sense of how many are on Oxervate, which may be in the high thousands kind of ballpark. So at this point, it's hard to say definitively on exactly what the moderate to severe looks like. It could be from other countries, something like a third, roughly. We expect to continue to drill down on that as we progress here. I mean, either way, for us, considering the size of populations we're typically targeting, it's quite sizable and a meaningful opportunity for Krystal.
Got it. Yeah. Thank you. And then understanding you're pursuing the more accelerated pathway, just curious about this Phase I-II data timing, and then what is your expectation to see the efficacy tolerability compared to Oxervate given different modality and then different dosing regimen? Thank you.
Roger on timing. Look, it's an eight-week study, and we thought we would provide further guidance on timing once enrollment is complete. As you know, we're looking for some 27, 30 patients to enroll, so stay tuned in terms of data update in terms of timing update on data announcement. On the second question on what we expect coming out of the Phase I, so obviously, it's a safety study, and we actually, if the clinical data mimics some of the preclinical data that you've seen on the first of the presentation, that would be really useful to us, and one of the things we'll be looking for is frequency of dosing, right? We're starting with twice a week based on the PK. It's an opportunity to go to once a week, and also durability.
If you look at our clinical study, we're measuring, while the endpoint is eight weeks, we're measuring at four and six and eight and ten and twenty. That'll give us an idea of how quickly the drug works and how long the durability of the drug is. So I know it's a long-winded question to what do you expect success, but I think we feel really optimistic based on the preclinical data and the platform and the corneal and the turnover and the HSV. But Suma, do you want to?
Yeah. I'll just add this is an efficacy trial too. It's both safety and efficacy. So it is a placebo-controlled trial. So obviously, if you see, we're going to compare it to the placebo and see the benefits. So we will get very strong efficacy and safety data from this trial. So I mean, that will help us design our Phase III as far as what the effect size is and how many number of patients do we need for a pivotal single Phase III study.
Yep. Got it. Yeah. You just started. And then we definitely understand. And then we'll stay tuned. Thank you.
Thank you. Your next question is from Ritu Baral from TD Cowen. Ritu, your line is live. Please go ahead.
Thanks for taking the question, guys. Krish, at the very beginning, you mentioned that one of the issues with Oxervate was deposits you mentioned. Is that a function of the payload, and is that something that you guys are watching as well, or is it an excipient thing? And then I wanted to talk a little bit about endpoints. Looking at the Oxervate label and per our previous discussions, Krish, you mentioned that complete corneal healing at week eight was the pivotal endpoint. Is that what you're also considering for accelerated approval? And how does the mean corneal sensitivity, which is also in the Oxervate label, how does that factor into how FDA evaluated that drug and could evaluate your drug?
David, do you want to start on that one?
Yeah. I can take the deposition question. So although the exact mechanism of those corneal depositions is not clear, what is, I think, thought to be the driving mechanism is the formulation itself and salt contents and that sort of thing. There isn't a biology necessarily that suggests that NGF for any reason would be causing those depositions. And so because of that, we're relatively confident that that wouldn't be an issue, at least from the mechanism of NGF standpoint.
In terms of endpoints eight and 10, Suma, do you have any?
You want to start with endpoints?
Yeah. Yeah. So I can continue with that. So the main endpoint and efficacy is obviously going to be the healing of these corneal epithelial defects. The increased corneal sensation that was shown by Oxervate and has been shown in kind of post-hoc studies as well is certainly a benefit and shows that the mechanism of NGF is what we think it is. And so demonstrating that in this study would be an added benefit, but we're really focusing on closure of these defects because that's what is ultimately going to create the most benefit for these patients in the long run and prevent some of the complications that are seen with NK.
Got it. And then it seems like go ahead, Suma. Sorry.
Yeah. Also, as Krish earlier mentioned, if you look at our clinical design, we are evaluating wound closure at many different time points. So we could be sooner, again, because of the mechanism, right? Because we have continuous expression of NGF versus trough and peak in these patients, and there could be an extended period of time where these patients don't have exposure to NGF, which could be different with KB801. So we believe that hopefully we look time to wound closure, durability of the wound closure. So this particular study will really give us a window into all of those different factors that will really help us then design our Phase III pivotal trial and position us for the exact success and how we can be superior to Oxervate.
Understood. And Oxervate also had in their studies, they had two Phase IIIs. One was in unilateral disease, and the other was in patients with bilateral disease. Will you have to look at both? And if so, how different are these patients for management? Thanks.
Yeah. I can take that one too. So our current study does not make a distinction between these two patient populations. And just looking at the epidemiology, bilateral disease is probably 10%-20% of Stage II and Stage III NK patients. So we don't necessarily have a plan to separate that out necessarily because the mechanism is all going to be the same from our standpoint. And so for our current study, we are even in individuals with bilateral disease, given that it's a Phase I-II, only treating one of those study eyes, but it's certainly in the future we could see inclusion of both eyes once we establish the safety profile.
Understood. Thanks.
Thank you. Your next question is coming from Gavin Clark-Gartner from Evercore ISI. Gavin, your line is live. Please go ahead.
Hi. Thank you. This is Gautam on for Gavin. Congrats on the update. So we have two quick questions. One is on dosing volume and formulation for 801 and how it compares to 803 for DEB. And how much will the upcoming ocular data de-risk 801 safety and tolerability? And the second question is for the registrational, would this be a placebo-controlled or an Oxervate-controlled trial?
Look, in terms of safety, our vector and we've seen that one compassionate use on 803 where a patient has been on the drug for like a year and a half or two and continues to be on drug. So we feel that with respect to 801, the 803 kind of points in the direction like we're not overly concerned about any change in formulation. The approach is the same. What's encoded is different. And so we don't and even the titer levels are very similar. And so we're not expecting anything on safety. On the design of the registrational trial, Gautam, we're not ready to make a comment yet on whether it will be blinded or head-to-head. But Suma, if you want to add.
I mean, from an FDA approval process, they will not mandate a head-to-head study unless you want a superiority or something on the label. So again, this is a discussion, I mean, with the agency. I mean, a placebo-controlled study will be plenty for getting approval, even as an accelerated path. And obviously, even with the placebo, it's going to tell you, I mean, we will have differences in label, right? I mean, if it's once a week, single administration, we may have faster wound-to-closure durability. All of those will be studied against the placebo in our Phase I-II study. And we'll see what we see. And if that's pretty strong, then we may not, I mean, the placebo-controlled study is plenty to get approval.
As Krish said, our Phase I and Phase II will then help us decide what kind of a path we want to take with our Phase III.
Gotcha. Thank you. Makes sense.
Thank you. Your next question is coming from Sami Corwin from William Blair. Sami, your line is live. Please go ahead.
Good morning, guys. Congrats on the update, and thanks for taking our questions. I got two. The first is I was really struck by the rapid time from IND clearance to the first patient being treated. And so I guess I was curious if that's reflective of the overall demand and just how you were thinking about how quickly you could fully enroll this Phase I-II trial. And then there's been some mention about that KB801 could potentially lead to faster wound closure. So I guess, do you still expect to use the eight-week course like Oxervate, or could this potentially be a four-week course? And I heard Suma kind of mention the potential to use once-a-week dosing. So when exactly will that be evaluated? Thank you.
Hey, look, Sami, I don't think we necessarily announced when the IND was cleared. So yes, it was really fast, but I was just trying to clarify that point. We hadn't previously announced the IND clearance. But Suma, maybe you can talk about enrollment speed.
Absolutely. I mean, we were excited about this program, so we engaged many of the KOLs with the academic sites much earlier on, even before we filed the IND. So that gave us an advantage. I mean, obviously, sharing the preclinical data, and again, we are so good. I mean, we have a platform technology. We have a good relationship with the division. They understand our HSV product. They know the safety of the product. So I think the bar for very minimal preclinical studies are required to support our IND based on the existing bolus of data that's already on file with the agency. So that really accelerates not just IND, but I think we have the advantage for our consecutive products to accelerate quicker, as I mentioned, through a platform technology and agencies' comfort with our product and safety of our product. So again, we were pretty diligent.
We engaged with a lot of sites. We've got a lot of private sites engaged much earlier on, and our team has spoken with all these sites, and they gave us some feedback on why there's still an end-to-end need for these patient populations. There's a lot of patients. There are a lot of patients out there, and Oxervate is not something that we want to even get on because of the dosing regimen, so I mean, our operations and clinical team is, again, very aggressively working with all these sites, and we have opened quite a few sites, so hopefully, that'll help us.
Any comment on the four-week versus eight-week?
Again, our data will direct us in that direction, right? I mean, many of these patients have different severity levels of wounding. So there's a little bit of understanding how severe, what kind of these patients, and I think our Phase I, P hase II data with, as I said, there's very frequent evaluations will really help us understand all of that, so I mean, based on the data, then we have to decide how we want to design the study and endpoints from a timing perspective.
Sami, right now, based on the PK data that you saw, we're going towards a twice-a-week application. If there is something very different we see at the end of the Phase I-II, we'll at that point think about once a week. But for now, we stick to twice-a-week administration.
And I think I just want to add because with Vyjuvek, we've worked with the agency, not only the U.S., but global regulators to administer this product at home. So I think there'll be advantages. I mean, hopefully, that's going to be a big thing with this product. So home administration. So even if it's twice a week, it makes life easy for these patients compared to six times a day.
Very helpful. Thank you.
Thank you. Your next question is coming from Andrea Newkirk from Goldman Sachs. Andrea, your line is live. Please go ahead.
Good morning. Thanks for taking the question. Suma, can you just remind us what proportion of patients are able to achieve complete durable healing of the epithelium with Oxervate? And how do you anticipate this to compare to KB801 given the profile you are seeing and the idea that it does offer more consistent NGF levels in the eye?
Do you want to take that, David?
Yeah. So Oxervate was seeing around anywhere from, depending on the study, 50%-70% of patients achieving complete closure at the eight-week time point. It's obviously too early for us to predict what our percentage or proportion of patients with complete closure is. Obviously, we're very excited about the mechanism of our drug and the ability to hopefully, at the very least, meet that threshold. But I'll just kind of leave it at we'll see how the data points us what direction, yeah.
Thank you. And as a reminder, if you would like to ask a question at this time, you may press star one on your telephone keypad to join the queue. Once again, as a reminder, it'll be star one, join the queue to ask a question at this time. Your next question this morning is coming from Yigal Nochomovitz from Citigroup. Yigal, your line is live. Please go ahead.
Hi. Can you hear me?
Yes, Yigal. Your line is coming through.
Oh, great. Hi. This is Joanne Wu coming on for Yigal Nochomovitz. Thanks for taking our question and congrats on the progress. Maybe just two quick clarifying questions. In terms of the twice-a-week regimen currently, I just want to clarify. Is that every three days, or are there certain pre-specified days that the patients are currently utilizing the KB801? And in terms of enrollment for patients for the trial, are these patients that had never had been on Oxervate previously?
Yeah. Thanks for the question. So for the first part, we are leaving some flexibility for the dosing, for the twice-a-week dosing, anywhere between three to four days for that second dose in a week. And we're seeing that's going to be pretty consistent throughout our study and giving a little bit of wiggle room there. For the second question, you asked something like.
Wait, so the previous.
Oh, yes, yes, yes. So our current study is not restricting patients who have previously been on Oxervate. Currently, we have just a 14-day washout period if an individual had previously been on Oxervate. This is almost like 100 times the half-life of Oxervate just to ensure proper clearance. But yeah, there's no restriction, nor are we obviously limiting to those who have "failed Oxervate" in the past. So we're leaving it pretty open from an enrollment system.
Gotcha. And maybe just one quick follow-up. In your research, how long do these Oxervate patients typically stick with the six times administration per day? I guess just wondering the average time of therapy commercially on your discussions with physicians?
Yeah. So that's going to be highly variable, unfortunately. So I don't have a great answer for you. It's going to be patient-dependent, and so unfortunately, I just don't have those numbers.
But again, when we speak with the KOLs of experience, I mean, who treat any of these patients, they said compliance is one of the biggest issues with these patients because these are older patients. So many of them don't comply, and they don't heal. So there is an issue. There are patients that then get off Oxervate, and there is an unmet need. So that's what consistently we hear from speaking with all of these different KOLs. And they're really excited about the product because I think this infrequent dosing, once or maybe twice a week, is going to make a huge difference for this patient population.
Got it. Thanks so much.
Thank you. Your next question is coming from Bill Maughn from Canaccord Genuity. Bill, your line is live. Please go ahead.
Hi. Good morning, and thanks. I have two. Just looking at the decision to go forward into this study with a single dosing regimen, just wondering what gives you the confidence to forego dose finding initially out of the gate and the confidence that the FDA might not require some more extensive dose finding before a pivotal study. And my other question is just for a little more color on the difference between a Stage II and a Stage III patient. Are these generally, do you consider them more similar than different, or are there significant differences between Stage II and Stage III that might lead to different treatment penetrations? Thank you.
Okay. I can address the FDA question. Obviously, you saw the preclinical data that Trevor presented. We have clear indications when you give Oxervate versus KB801. You can see the pharmacokinetics. So the title that we give in the animal studies that's extrapolated to the humans, we feel confident it's human dose converted from Oxervate to our product. So we can see from the pharmacokinetic and expressions of NGF that gives us the confidence of the levels that we would see that Oxervate's pharmacokinetics with us match for the clinical trial. And that's what we justified to the agency. The agency seems to be satisfied. We had interactions with them. We had pre-IND meetings. We sent them the protocol design. They commented on it. And so whatever we have designed is with extensive input from the agencies and concurrence and agreement.
So whatever we have done is in agreement with the agency because, again, they understand our vector. They know the profile from all our pipeline products. So I think, again, the study is in agreement with the agency. So we're pretty confident that this dose is acceptable for evaluation for both safety and efficacy.
I can comment on the Stage II and Stage III. Yeah. I think Stage II and three NK are much more similar to one another than to Stage I. Obviously, there is a spectrum even between Stage II and three, but I would not expect there to be vast differences in response necessarily between those two severities. And I think a similar kind of trend was seen in Oxervate studies as well. If anything, the more severe disease allows for more obvious wound closure. And so in short, I don't think we will need to change our dosing regimen or anything clinically to distinguish between those two populations.
Thank you.
Thank you. This does conclude today's question and answer session, and it will now also conclude our call. Thank you for your participation. You may disconnect at this time and have a wonderful day.