Krystal Biotech, Inc. (KRYS) Earnings Call Transcript & Summary

Good morning, everyone, and welcome to the Krystal Biotech call and webcast to review Phase III data from the GEM-3 trial. [Operator Instructions] As a reminder, this conference is being recorded. At this time, I'll turn the call over to Krish Krishnan, Chairman and CEO. Sir, please go ahead.

Good morning, everyone. Thanks for joining us today. to review the more detailed results from the Phase III trial of B-VEC. As you may be aware, these data were presented over the weekend at AAD and concurrently announced via a press release. Next slide, please. As a reminder, this presentation will contain forward-looking statements based on our current expectations and beliefs. We refer you to the SEC filings for further information. Next slide. So the goal of the call today is to discuss these more detailed Phase III results, Hubert Chen, our Senior Vice President of Clinical Development will walk you through the AAD presentation, following which Andy Orth, our Chief Commercial Officer, will talk about the work that he and his team are doing to prepare for commercialization. I'll close very briefly with an overall summary and next steps and milestones but then open the call up for Q&A, which will also include besides Andy and Hubert, Suma Krishnan, who is the President of R&D and the Co-Founder of Krystal Biotech. Next slide, please. I want to remind all of you that Krystal was started like 6 years ago with a goal of being a fully integrated biotechnology company. In the last 6 years, we've advanced B-VEC to pivotal -- to a successful pivotal readout, but at the same time, we've been building on our manufacturing capabilities. We have Ancoris that's up and running ASTRA that is anticipated to be up and running this year from a manufacturing side and from a commercial side, we're building out our commercial capabilities, both in the U.S. and in the EU, all with the goal of being a fully integrated biotechnology company. So we have a lot going on, but we're fortunate to have a strong balance sheet to execute on all this potential with a focus on the work we're doing to prepare for the potential approval and launch of the lead program B-VEC for dystrophic EB. Next slide, please. So B-VEC is a gel that's delivered to the COL7A1 gene directly to DEB wounds, inducing a local expression of COL6 protein and molecularly correct the disease at its source. We're pleased to announce the top line results, which we did in late November and now excited to share further color on the data in this call. We presented this detailed data at AAD this weekend. We're working hard to get the BLA filed in the first half of this year, which we fully anticipate and then filed a marketing authorization with the EMA in the second half of this year so we're on track with our previously discussed time lines on B-VEC. With that, I'll turn it over to Hubert to review this weekend's data presentation.

Thanks, Krish. My name is Hubert Chen. I joined Krystal last year as Senior VP of Clinical Development. I came to Krystal from Genentech, where I spent over 10 years leading programs in the immunology space spanning first-in-human to registration. At Krystal, this is obviously a really exciting time for us, and it's my pleasure to share this data with you today. So moving to Slide 7 to provide some background. As many of you already know, dystrophic EB or DEB is a serious and rare disease of fragile skin caused by mutations in Collagen 7A1. The fragility of the skin leads to skin blistering and wounding. And in the more severe forms of DEB, the wound burden can be body-wide and lead to a host of other medical issues that need to be managed. The current standard of care in this disease is focused on wound care and while there have been improvements in this palliative approach, having these wounds ultimately leads to permanent scarring and in the more severe patients, fatal forms of skin cancer. So in many cases, this is a life-limiting disease. B-VEC is a gel that's applied topically to the open wounds and as Krish mentioned, the goal is to deliver the Collagen 7A1 gene to skin cells locally at the site of application, resulting in the expression of full-length collagen 7 protein. By correcting the underlying molecular defect, collagen 7 can then be produced, which is necessary to anchor the epidermis to the lower dermal layer, allowing the wounds to stay healed. Then as the skin cells and collagen 7 turn over as they normally do or as new wounds form, B-VEC can be reapplied as necessary. B-VEC was evaluated in a Phase III trial known as the GEM-3 trial, which is a multicenter, randomized, double-blind and placebo-controlled trial that is illustrated here. We've previously described the design, so I won't go into too much detail here other than to remind you that this was an intra-patient controlled trial, meaning that each patient had two matched wounds and therefore served as their own control. One wound was randomized to B-VEC and one to placebo. The wounds were dosed once weekly for up to 26 weeks or until wound closure. Wounds were redosed at any point in the study they were deemed to be reopened by the investigator. The focus of today's discussion is on these primary wound pairs, though the patients also had the opportunity to dose additional wounds with open label B-VEC during the study. Those wounds are called secondary wounds and we present some examples of those during our top line announcement in November. In terms of patient disposition, 31 DEB patients enrolled in the trial based on intention to treat all 31 patients randomized were included in efficacy analysis. We were very pleased with the low dropout rate in this trial, particularly given that the trial was conducted during COVID and required weekly office visits. At the time of study completion, we had noted two study dropouts. But upon further exploration, an additional patient was deemed to be a protocol -- protocol dropout given that they didn't make the final 26-week visit. So there were three dropouts in total, none of which were related to study drug. As you'll recall, we enrolled patients across three sites in the U.S. and broadly speaking, the baseline demographics of the enrolled patients were largely as expected based on the epidemiology of the disease. The trial was open to all dystrophic EB patients, including those with dominant and recessive mutations. As expected, the majority of patients enrolled in the trial had recessive mutations. We had one dominant patient enrolled. Interestingly, the results of another patient at the time of enrollment that was believed to have a dominant phenotype, but upon further testing was shown to be recessive, thus highlighting the importance of genetic testing in this disease. In the bottom right table, we show the characteristics of the wounds themselves. The mean wound size was similar in both the B-VEC and placebo-treated wounds. Almost 3/4 of the wounds in each arm were less than 20 centimeters squared at baseline, which is consistent with the literature on the size of wounds in these patients. As previously announced, the study met its primary endpoint defined as complete wound closure for two consecutive weeks at the end of the 6-month period. So wounds that were completely closed at weeks 22 and 24 or weeks 24 and 26. 67% of wounds treated with B-VEC met that endpoint as compared to 22% of wounds treated with placebo. Given this is an intent-to-treat analysis, multiple imputation was used to account for any missing data. Of note, the B-VEC treated wound in the dominant patient did meet the primary endpoint of 6 months while the placebo wound did not. As a secondary endpoint, the study also evaluated a proportion of wounds that were completely healed in 3 months. About 70% of the B-VEC wounds met that endpoint as compared to 20% of placebo treated wounds. Both those endpoints met statistical significance with a p-value of less than 0.005. As many of you know, the statistical test was the [ McNemar test ]. Response rates within wound pair are assessed and those that have different treatment outcomes, meaning one wound was closed, and the other was open are called discordant pairs. In the primary endpoint analysis, there were 17 discordant pairs of which 15 favored B-VEC. Here, we're showing a few representative images of those discordant pairs on various body parts. On the left are the B-VEC wounds and on the right are the placebo-treated wounds in the same patient. As you can see, complete wound closure is achieved in the B-VEC treated wounds compared to placebo wounds, which remain open. Moving on to durability of wound closure. I want to provide some color on how we're thinking about this or how there are different ways to think about this. From a regulatory perspective, the issue of durability is less about the duration of closure, which is really a function of the half-life of the protein and the cells we're transducing and more about the durability of effect with re-administration meaning the ability to provide consistent benefit over time with retreatment. This was part of the rationale for us running a 6-month study as compared to the 3-month study, which we did in the Phase II. When we examined the wounds that met both the primary and the key secondary endpoint that is closed at both the 3 and 6-month time points, 49.7% were closed at both those points compared to only 7.1% for placebo treated wounds. There's also a more granular view of durability, meaning how long a wound stays closed after a given treatment cycle. We're still gathering data on that. However, one way to start looking at that is to look at wounds that were closed for 3 consecutive weeks at the end of the 3 and 6-month periods. And here again, we see robust differences with almost half of the B-VEC wounds being closed at all previous 3 time points as compared to only 16.5% of the placebo wounds at 3 months and 6.5% of placebo wounds at 6 months. Another way to slice the data is to look specifically at the primary wounds that were closed by the 3-month time point and reexamine their status at 6 months. Here, we see that the wounds that were -- of the wounds that were closed at 3 months, 66.7% of B-VEC-treated wounds were also closed at 6 months as compared to only 33% of placebo wounds. Moving on to some of the subgroup analyses of the primary end point. You can see in the force plot on the left here that the treatment response favored B-VEC regardless of gender or age. The table on the right breaks down response rates by baseline wound size. And again, here, you can see that the response rate is higher in the B-VEC wounds in all wound size categories. Diving into the secondary endpoints in a bit more detail, two that were presented for the first time in AAD were pain and PRO endpoints. On pain, which is challenging in the context of clinical trials, particularly in the setting of DEB, where these patients suffer from significant pain at baseline, we were pleased to see a consistent impact on pain in B-VEC-treated wounds as compared to placebo. And to clarify, this is pain associated with wound-dressing changes assessed at each time point listed. And in particular, among patients who are 6 and older. In addition to these clear trends on improvement in pain. We also looked at 2 patient reported outcomes, the EQ-5D and Skindex-29 assessed before and after treatment with B-VEC. And again, we saw a directional improvement across multiple domains consistent with the wound healing response. And last but certainly not least, B-VEC was generally well-tolerated. As we previously disclosed, there were no AEs leading to discontinuations or death. There were 5 SAEs observed in the trial, none of which were considered to be related to study drug. The one mild AE that was considered possibly related to study drug was characterized as mild erythema. From an immunogenicity perspective, there were no clinically significant immunologic reactions reported during the study. The treatment response to B-VEC was not associated with HSV-1 status at baseline or with the development of COL7 antibodies. We plan to share more detail on safety, particularly on the immunogenicity side at the upcoming SID conference in May. So stay tuned for that. With that, I'll hand it over to Andy.

Thanks, Hubert. Let's start with a view of the global patient population and the potential B-VEC market opportunity. As we've shared in the past, we believe there are approximately 9,000 dystrophic EB patients globally across the U.S., Europe and other additional reimbursable markets such as Japan and Brazil. In the U.S., our current views of diagnosed patients via claims and EHR analytics yields just over 1,000 dystrophic EB patients diagnosed and studies in the major global markets lead us to believe there are over 2,500 patients diagnosed worldwide. We expect the U.S. payer mix to be approximately 80% commercial with the remaining portion largely Medicaid given the devastating nature of the disease. Today, we estimate these patients consume between $200,000 and $400,000 of care and supplies for palliative care alone. Based on the detailed data we've talked about today, our view of the benefit that B-VEC could provide for DEB patients is only strengthened. And as we think about DEB patients, we know there is a lot of variability in how the disease presents and even more variability in how a topical molecular corrective therapy like B-VEC would be used from patient to patient. A more severe patient will likely use more vials per year than a less severe patient and older patients with larger body surface area will consume more than a smaller pediatric patient. In addition to this patient-to-patient variability, we also expect within patient variability over time, as we expect the patient would likely use less B-VEC later in the course of treatment as the regimen reaches steady state. Those variables are important to consider from a reimbursement perspective, and we will work to price B-VEC based upon the average annual steady-state use of the product. We are proactively working with payers to educate them on the disease, our technology and the impressive GEM-3 data. We've been encouraged by the collaborative tone of these discussions so far. Our goal is to partner with these payers to deliver budget predictability as well as engage in a value construct to protect them from annual overruns in the case of a patient or patients with exceptionally high utilization in a given year. I'm pleased to share that launch preparations for the U.S. are well underway and on track. We have individuals in the field educating HCPs, patients and their families and the largest U.S. payers. We continue to build the Krystal commercial and medical teams with a focus on targeted interactions with known EB treaters and profiling sites of care to enable treatment as close to a patient's home as possible. The initial focus of the launch will be the known patient population, which, again, in the U.S., we believe, is around 1,000 patients and ensuring access to treatment. As we work through those patients, the focus will shift more heavily to the more traditional patient finding activities for the missed or underdiagnosed DEB populations. An important piece of both the prelaunch and launch is our in-house patient services hub called Krystal Connect. We're excited to report this program is already up and running to receive and respond to educational requests. And within the hub, we are also building the case management capabilities that will be important to enable reimbursement and site of care coordination. An important aspect of the ongoing patient finding and characterization work is KDB, or Krystal Decode DEB. This sponsored genetic testing program is available in the United States and is a diagnostic resource for patients and physicians and is critically important as genetic testing is frequently cited as a barrier to a correct EB or dystrophic EB diagnosis. The program launched in October of last year and continues to be well-received by the EB community. We are thrilled with the uptake to date and the number of correct diagnoses we've been able to assist with. A foundational piece of our disease awareness activities, DEB Facts launched earlier this year. There are distinct patient and HCP sites focused on the importance of accurate diagnosis, utilizing genetic testing, the absence of COL7 as the core driver of the disease and the importance of treating all wounds given the heightened risk of infection. We're pleased with the traffic of the sites to date, and we'll be making investments in search optimizations and other traffic drivers in Q2. For any of you on the ground here in Boston at AAD, you might have seen us around. We're currently participating in the 2022 Annual Meeting of the American Academy of Dermatology. We're excited to be in person at this congress, which is conveniently right in our backyard in the Seaport where we've had the opportunity to proactively engage with the broader dermatology community. We're leveraging our core disease awareness platform and materials and also taking the opportunity to gain insights from a broad range of HCPs regarding diagnosing and treating EB. Raising awareness and educating key stakeholders is critical, but we also need to be able to meet the expected global demand for B-VEC, and we continue to be well positioned on that front. We remain on track to launch B-VEC with material from Ancoris, our first in-house manufacturing facility, which was purpose-built to supply the global demand for B-VEC. As many of you will recall, Krystal invested early in building out this manufacturing footprint as well as developing a robust and reproducible process to manufacture B-VEC at a commercially relevant scale. The B-VEC material used in Phase III was made in the Ancoris facility using that process and there have been no meaningful process changes as we prepare for a potential launch. Additionally, I'm happy to report that our process validation batches are now complete. We're also making a tremendous amount of progress on our second much larger facility known as ASTRA, which is on track to be completed and validated this year. This facility adds a significant amount of space for both scale up and scale out as well as the ability to bring in automation. Given those advantages over the long term, we intend to transition B-VEC commercial production to that facility.

Thanks, Andy. We covered a lot today, but I hope you'll leave the call with a few key takeaways in mind. First, the top line data on B-VEC was really strong and the continued analysis of the data set only strengthens our confidence in the future potential of B-VEC. Second, Suma and the team are really busy trying to get the B-VEC -- the BLA filed in the first half of this year and working towards the marketing authorization in the second half of this year. Third, Andy and his team have been in parallel working really hard to bring B-VEC to patients. We have several external facing educational efforts underway to raise awareness of the disease among patients, caregivers, HCPs. More detailed patient finding work is ongoing. But I'm happy to say that the early -- the detailed patient finding work has supported our initial estimates of the number of patients living with DEB worldwide. Also, as Hubert mentioned in his talk, we will be presenting more detailed analysis of the safety data from the GEM-3 trial at SIP in May, and we'll continue to have a presence at medical congresses throughout the year to educate the community on the GEM-3 data. To that end, we're also working towards a future peer-to-peer publication. And lastly, we have made tremendous progress with B-VEC, but I'd like to highlight the broader platform. We're close to initiating a Phase I trial of KB407 for the treatment of cystic fibrosis. We're looking to resume the KB105 study for the Ichthyosis in the second -- in 2022. We're looking to file an IND for Netherton Syndrome later in the year. So a very active strong pipeline, both in skin and the emerging pulmonary platform. We continue to invest in the technology itself, which we believe has broad potential in rare and prevalent conditions alike. On this last slide, I want to leave you with a view of the upcoming events and deliverables for 2022. We're on track from a timing perspective, and we hope to add even more to the list as the year progresses. Thank you, and we can now open the call up for Q&A.

[Operator Instructions] Our first questions come from the line of Ritu Baral with Cowen.

Krish, I wanted to ask you about your thoughts on the label and specifically the breadth of the label given that the controlled portion of the study only has one -- at the end of the day, one dominant patient. What other, I guess, data from dominant patients would be included in the BLA? And then would data from Decode actually be included? Have you been finding misdiagnosis of dominant patients as recessive that might factor into arguing for a broad label?

Thanks, Ritu, for the question. Our conversations with the agency have always been about dystrophic EB from the very beginning. If you recall, the RMAT was based on dystrophic EB, the prime was based on dystrophic EB. In our pre-Phase III meeting, there was no real conversations besides a request by the agency for us to try and enroll as many dominant patients as possible in the study. Look, this is a rare disease. And the recessive ones, it's much easier and faster to get recessive patients enrolled. So yes, so to answer your question directly, yes, we had one patient. It is important to note that, that patient was a responder in the study, as we mentioned in the presentation. We are enrolling dominant patients in the OLE. We haven't decided what exactly body of evidence on dominant will go into the BLA, given that the OLE study is just ongoing presently. But our expectation right now, Ritu, is that the label will be broad to include both forms of EB recessive and dominant. On the question of Krystal Decode playing a part in the BLA, we don't expect that to happen presently. Suma, is there anything...

Yes. I mean, with regards to your question was, are you finding people that were misdiagnosed? Yes, I think that's a correct answer because, again, there could be patients that are recessive and are mild. We are seeing that in our OLE study because there was one patient who was absolutely -- to look at the patient, the investigator, just looking at it, assume the patient was dystrophic. But once the generics came back, it was clear that the patient was recessive. So there is misdiagnosis that we see even in our OLE and even with our Decode. So again, there are mild recessive patients, and there are severe dominant patients.

Got it. And then a very quick follow-up on the Q&A as part of Saturday's presentation. Somebody had asked about basically collagen 7 antibodies and it was -- I guess the discussion wasn't perfectly clear about what sort of baseline levels in sort of recessive mild patients collagen 7 antibodies exist in, whether they might interfere with treatment even if they did exist in baseline.

This is Hubert Chen. I'd be happy to take that question. We did measure anti-COL7 antibodies at baseline and we only had one patient who was positive and it was only a borderline positive patient. And with respect to treatment response, it was very similar between the independent [ series ] status.

Yes. And I will just add one more point. Remember, many of these subjects have been in prior therapies. So there are these subjects that are recycled from other studies that they may have participated in the GRASS study or in the protein therapy. So these patients, you will see that maybe because of the result of that, they may have existing antibodies to collagen 7 when they come into the study. But the good part is the levels of antibodies don't increase in our study. And they, again, with time, they tend to -- again, they're pretty much bottom line and they stay there.

Our next questions come from the line of Debjit Chattopadhyay with Guggenheim.

This is Ry Forseth on for Debjit. Could you frame the regulatory implications given the number of discordant pairs achieved in the GEM-3 study relative to criteria in your statistical analysis plan? Per the SAP, at what point would there be too few discordant pairs to have a meaningful primary endpoint?

Can you restate your question again? I'm sorry.

Could you frame the sort of regulatory implications given the number of discordant payers relative to the criteria you have in your statistical analysis plan? And per the SAP, at what point would there be too few discordant payers to have a meaningful primary endpoint?

So the study was powered for 24 patients, and we had more than 24 patients. So we should have been adequately powered.

I mean, yes, go ahead.

So -- and at that point, once we've had adequate power, we we're able to demonstrate statistical [indiscernible] based on the prespecified test. So there is no concern about there being inadequate number of discordant pairs, if that's the concern.

Yes. And because if you didn't have enough doscordant pairs, clearly, the numbers have to be tight to meet the statistical significance. So clearly, we did -- I mean, considering the p value that you see at less than 0.005, we have enough discordant pairs. If you look at it, it's like 60% to 70% were discordant pairs from the total number of payers. So that's pretty good. Again, when we designed the study and the came up on the sample size, it was based on our Phase I, Phase II studies where we clearly looked at the intra-patient discordant and concordant pairs, and we know the placebos can close and open. So the of analysis the sample size calculations for our Phase III was based on this Phase I, Phase II. So again, that is why if you look at our endpoint, it was just three end points, 22, 24, 26 because you can catch the placebo because -- and clearly, we see that in our Phase III study. So we have enough discordant pairs to give us the robust p-value.

And Debjit, just to close the loop. There are no regulatory implications. We feel super comfortable we're going to get the BLA filed in the first half.

Our next questions come from the line of Joe Pantginis with H.C. Wainright.

Thanks for all the details. So two questions. First, when you look at the data, I want to focus on the wound closure, phenotypic and/or physical attributes of the wound closure, especially when you're talking about the durability earlier. So can you make any sort of anecdotal or observational views with regard to the physical attributes of wound closure and the durability with regard to maybe how the skin sort of appears, how it might be different from the original skin, how the wounds might be feeling different later on as durability might subside?

I mean when you talk about the phenotype of the wounds, I mean, again, clearly, the instructions were given in the protocol that they would pick similar wounds with regards to how the wounds look, the size, the chronicity of the wound. So the guidance was the wounds would be open for a period of time similar to both those wounds. So they were on the same level playing field. I mean, again, of the nature to the wound's healing, obviously, there are some information that investigators have recorded with regards to the type of the skin texture. And I can only tell you from some of the comments that we received based on our database [ block ] and the comments that we receive. They do say that they see a better improvement in the texture of the skin, the thickness of the skin. And these are all just -- these are just comments that we received -- see in our -- from our data collected. So they are observing that, and those are the kinds of comments made again, but this is not something we systematically collected.

No, of course. That's helpful. And then just going early -- to your earlier comments regarding the early commercialization efforts that you're currently doing and some earlier comments made on the call. I guess, what would be the general reasons that you see delayed diagnosis in patients?

Andy?

Yes, I'm happy to take that one. This is when we get into a more traditional rare disease, either the severity isn't there that a local position knows to flag it and either send it to a [ peak ] derm or a derm specialist who knows more about EB at that point in time or they're just in a location, right, that health care isn't helping. So there are more -- this is the classic Zebra stripes argument. They're there. They're just a little bit more hidden. And in general, their disease severity is less.

And just to add to Andy's point, again, I'll give you for my clinical experience. In the OLE that the subject that came in was very mild, has very few wounds, but still wanted to participate but never genetically tested. And came into the study because he had a distant cousin that was identified as a severe recessive patient. So when they came in, again, as I said, is the investigator looked at the patient and didn't even know if he had EB, but assume that even if he did, it would be dominant because it was so mild and genetic testing came up and it was recessive. So again, I think there are many, many such patients that are not identified because they're so mild. And you can just say because they're mild, they're dominant. They are recessive, that's something we learned, and we are seeing that in not just one but two patients in our small clinical studies. So I expect there could be more milder recessive patients.

Our next question is come from the line of Madhu Kumar with Goldman Sachs.

This is Rob on for Madhu. I was just wondering how should we be thinking about redosing of B-VEC for treated wounds that close and then reopen. In broad shows, could you speak to B-VEC's efficacy profile in that setting? And do you plan to present data on that at a later date?

Thanks, Madhu. There's a lot. And I think a few of us are going to answer different pieces of your question. First point I'd like to make, there were a certain number of wounds that showed that met both the, I think Hubert mentioned it, met both the primary endpoint and the secondary endpoint. A certain percentage of them probably opened in that duration and a certain stayed closed. We plan to share that data at some point in the future, but it speaks both to some extent, the durability of the treatment and to some extent, towards redosability of the treatment. Both these redosability and durability have commercial implications. I'll let Andy briefly talk about what that means and how we're thinking about bringing the medicine to market and then have Suma add any other comments that she's observed not just in the clinical study, but in the open-label extension, where if you think about durability as is just how long does the wound stay closed, we start to gather more information on that in the OLE than specifically in the Phase III study.

Great. And given a few of the knowns such as a weekly max dose as well as right disease severity, et cetera, what we expect is that as the wound burden decreases, over time, and the durability comes into play, these patients will consume less drug in a steady state than they are in the beginning as they're working. And again, this is quite variable in the disease state as the severity and/or patient age changes. But in general, that dynamic will come to play as they get their disease -- wound burden under control.

Yes. I mean I'll just add, again, EB is a complex disease. It's not -- these wounds are not like your burn wounds are diabetic ulcer wounds which are static wounds. These wounds are -- they move around there across different areas of the body. I mean, obviously, there was two goals. The primary goal of our Phase III study was to show, "Hey, these two -- pick two wounds." That's what they want with the need patient and show that two levels playing fields, you're giving the same treatment placebo is there your drug? Is -- does the drug work over placebo? So that was the main goal of the study, and we achieved that. Obviously, that does not satisfy treating these patients. And the reason some of the patients did participate in our trial is because we offered them the opportunity to treat the so-called secondary wounds so they could get overall benefit in these patients. And obviously, we captured that benefit in some of our PRO rated scales, and you can see that we had a trend improvement in those -- in overall -- in the patient's quality of life. And that's what we have to look at. So in the OLE study, we are treating wounds. I mean all the secondary wounds and many wounds, they're all open label. They're also capturing some of the primary wounds that we treated and to see how long does that durability persist than some of the -- and some of the secondary words that we treated. And again, some of these secondary wounds have different. Some are huge, some are small, some are very chronic. And all of this data is going to be as we collect. I mean, obviously, OLE is going to be a little challenging collecting all the data that we are doing to our path knowledge a best capability we are capturing the data. And so we'll see that some of the wounds closed and they go treat another wound. So there will be a good bolus of data that comes out, but we know that these -- that the wounds are closing and they are treating newer wounds and overall, hopefully, we will see the improvement in these patients as we finish the OLE.

Okay. And one quick follow-up question. Do you plan to present OLE data at SID?

We haven't made that decision yet, Madhu. But at some point, in general, our thinking has been the OLE is an ongoing study. We're happy with the way the OLE study is progressing both from a patient experience and from a physician experience. At some -- the general expectation should be that the OLE data will come much more closer to launch than ahead of it because we're because it's kind of cumulative data, but that's the expectation.

Yes. It's -- specifically, collecting the data are going to take time. And we want sites to finish up and collect robust data. So it's time consuming.

Our next questions come from the line of Raju Prasad with William Blair.

I just want to get a sense of clinically how B-VEC might be used. As far as selecting wound size or the wounds to treat first in a patient, is it usually size of wound or where it is or the depth of the wound? And then how many vials do you think doctors would be able to use in one visit. Just trying to kind of understand how clinically this could be dispersed and utilized.

Raju, thanks for the question. The general position of Krystal is the type of wound selected, where to treat first, what to treat second is a conversation between the physician and the patient. And we're not going to be part of that conversation, we're going to let the patient and physician decide. We've noticed how patients sometimes tell the physician about, I'd like a particular wound treated first and something second and gets individual depending on what they do, where they feel pain, et cetera. With respect to vials, which is the second part of your question, we have a max dose per week. So it's one vial a week. And as Andy mentioned, depending on the number of wounds in the patient and the size of these wounds, the consumption would vary patient to patient especially as we go into the launch. At some point in the evolution of [indiscernible], this is a longer-term conversation. There our conversations internally about increasing the max dose per week based on the safety data we're collecting in the OLE. So things like being able to treat many more wounds in the first setting could potentially be an option further down the line. But for now, it's one vial a week at I believe the dose is like 3.2E9 PFU.

Great. Any update on the home administration path that you discussed previously?

So we have -- again, worked with the agency for over two years, finalizing the home dosing protocol. We have finished the study, we should be hearing with regards to what their feedback on the clinical setting. But in our discussions with the FDA in the commercial setting, I mean, they are assuming that -- I mean, we have not had a direct discussion, but all of the assumptions, the way they make, when we talk about packaging distribution, they are leaning towards allowing home dosing. I mean we are able to achieve that in the clinical setting. So again, but we have not had those commercial settings, but all communications we've been getting from the agency is directionally towards home dosing.

But Raju, I just want to point out that we're not sure right now if we're going to get home dosing at launch, we hope to get it maybe at launch or shortly thereafter. But from a commercial strategy perspective, we're planning to get the drug as close to a patient as possible either to a local physician office or and at some point into their homes. So Andy's strategy is not -- is very spread out in terms of getting the vials as close to a patient as possible.

Our next question has come from the line of David Hoang with SMBC.

So I just wanted to ask on pricing. I guess, first, is that something we should be expecting close to launch or at time of launch? And then obviously, you haven't disclosed price per vial. But just in terms of some of the comments around setting an upper ceiling with payers in terms of max vial usage and price. And then given the current standard of care, can you just give a little bit color about sort of how you're approaching that and how the payers are thinking about it in terms of their, just, receptiveness to different price points you may have tested in your payer research.

Sure, sure. So on the first part, with when will we disclose that will clearly be post approval immediately what that vial price will be as well possibly at that point, right, what some of the constructs we have gotten into with these payers on the second part of your question. And the root of the discussions we're having right now is how do we get ourselves into a position where Krystal is fairly rewarded for what we're in the marketplace with, with this efficacy and a safety profile at steady state. And if payers are burdened with a high vile utilization in the first year for a more severe patients, et cetera, to protect them from that, right? Lots of therapies come to market with either a high first year one loading dose. Hemophilia has -- these inhibitor patients, which will -- many firms will protect against, it's going to be a similar construct on that front. The research we have done with payers to date, importantly, is they understand the disease, the pediatric nature and the severity of it. And we think we're going to be able to find a fair price for it here with them. So all positive on that front to date.

Great. Really helpful. And then just in terms of at launch, how many sites, academic centers of excellence and prescribers. How many would you expect to have at the time of launch?

Yes. And it's the right question in general because these patients have been funneled to these academic centers over the last two decades because, frankly, there was nothing else to do. However, what we should really be talking about here is getting these patients treated in their own zip codes. So we know all the COEs, right? Suma has been in this world deeply for a long time. So these doctors are -- and frankly, we've had great opportunity to interact with them this week at AAD, it's really going to be working with that doctor. And the local doctors we are already in partnership with for creates patient in order to get B-VEC administered as close to home for that patient.

Our next questions come from the line of Josh Schimmer with Evercore.

Taking the questions, just a couple of clarifying ones. First, for the potential for at-home delivery at or after launch. Are there any outstanding clinical items or studies that need to be completed to enable that?

No, there's no clinical studies. I think we have already finished the studies that are required for home dosing with regarding to training and you bring in 25 independent HCPs and show them and when they show that they can administer the drug property. All of that is already completed. So hopefully, we can just reference that and we may have to do additional human factor studies specific to a commercial setting. So again, very -- these are just exercises. They're not clinical trials, but they are human factor protocol studies. So all of that can be executed within the time frame needed.

Okay. So what has been completed and what has yet to be completed in terms of the human factor protocols?

What has been completed is right now for the -- in a clinical setting, the drug is going to be mixed at the clinical site at the pharmacy of the institution or at the clinical site. It will be picked up by HCP and they will have taken it to the patient's home. The human factor protocol covers the part of taking it from the clinical side to the patient's home and then administering at the patient's home. So instructions, how do you take the drug, how do you apply the drug, which wound, how do you close the drug. So all of the application aspect is completed. So that's what we submitted. So that's the study is acceptable that the agency clears home dosing. The procedure that I just explained is going to be feasible in our OLE study. For the commercial setting, we don't have to repeat that aspect, picking the drug, taking to the patient's home, if that's an option and taking it application because that's already covered. So the new portion of the human factor for commercial setting will be training the physicians, the physician sites for mixing the drug. So it's mixing and handling the drug, that portion will be needed to be done for a commercial setting. For example, the kit comes to the patient to the physician's office or the patient's home, then what happens from there on, how does the mixing happen. So that's the portion that we need to conduct for commercial selling.

Got it. And then for the vials, can you remind us exactly what a vial comprises? What kind of body surface area a single vial may be able to cover and whether you ultimately plan to have a range of SKUs and a range of vile sizes?

So we can only tell you from our open-label studies that's ongoing. So you have one vial of the gel, which consists of 1 ml, which has the 49 PFU per ml and then you get the gel, which is a 1 ml gel. And you mix the two to create a volume of 2 ml, extractable volume of 2 ml that consists of the total maximum weekly dose. And from what we have seen in our studies, it depends, again, it's the way we have done our human factor protocol studies is the drop of the mixed gel that can be applied across the wound. So we have seen that we can cover up different sizes. If you look at 20-centimeter square wound, you could treat like 8 or 9 rounds of 20-centimeter square. It's larger. What we have seen is you can treat one large wound and a couple of the 20-centimeter square wound for that week.

Josh, just one comment. The unit dose was consistent between Phase I/II and the Phase III study. That kind of talks to you about per centimeter squared what the amount of PFU is so you can kind of multiply and figure out. How much centimeter square of body surface a vial treat.

Our next questions come from the line of Alec Stranahan with Bank of America.

This is John on for Alec. Just a quick one from us. So in terms of the durability of response, we understand that we have the data for the 3 months and 6 months. It would be great if you can shed some light on what would the FDA think -- what they would kind of want to see for approval in terms of that? And also any post-marketing follow-up for duration?

From an FDA perspective, durability of response for -- is defined as a primary endpoint that's met at a point in time and subsequently two weeks later. That is by FDA regulation, which is why you see the primary endpoint in our pivotal study being weeks 22 and 24 or 24 and 26. So that's the regulatory definition of durability of response. And so there is no further expectation the agency on how long a wound stays closed. Those are much more for us to glean and figure out commercial, how many vials a patient would use, et cetera, but do not have the need regulatory implications. Being met by definition, by the durability of response definition based on the agency.

Our next questions come from the line of Ritu Baral with Cowen.

One quick question on the data. Just on the pain data presented. The slide says there was a trend over placebo. Can you just talk to what placebo showed and what FDA had either asked for or at least asked to look at as part of the BLA? And then just a little more color on Decode DEB. Andy, can you talk to the number of diagnoses of RDEB and DDEB that have been made since last October? And then is there any special targeting or rollout of the program given -- based on our halo conversations that a lot of the misdiagnosis is patients older than 10 or 15 versus the younger patients who are born during cheap genotyping days?

Hubert, do you want to...

Absolutely. So with respect to pain, it was a prespecified endpoint in the statistical analysis plan. Honestly, showing differences in pain is very challenging because there's a lot of variance in these measures. And the fact that we're able to show it in such a small number of patients is actually -- we found we were actually quite surprised to be able to show this. And the difference that you're seeing are obviously between the two wounds. And so it didn't [ hurt them ] directly, but there's obviously distribution different responses. But the fact that we can show something and we see the same direction of effect across multiple endpoints, I think make it convincing that this is something that's real.

Yes. I will just add to you, but this point again, pain was measured at bandage change. So we are hoping that it's a direct effect of wound closure. So as you know, is with bandage change, if there are underlying wounds, and opening this bandage in the clinic can be pretty painful and sticky. So I'm hoping that's what we were able to capture. That maybe with the treated wounds, it was closed so the bandage is -- the pain associated with that [ planned ]. But also keep in mind that most of these patients have -- are on underlying pain medication. So either they are on opioids or other kind of pain control. So -- and they have a higher threshold for pain. So you will see, in general, their baseline pain levels are lower than in any other real pain studies. So again, to capture the difference, Hubert said with bandage change could be interpreted as direct correlation with wound closure.

And then, Ritu, on the Krystal Decode DEB, just to reiterate, right, it's hitting the mark in terms of getting the job done with the right diagnosis and the broader community here is pretty excited that HCPs, that advocacy, et cetera. In terms of how we're getting the word out about it, and we have been doing a ton of targeted literally personal interactions with physicians and others across the country, as we start to ramp up investment in search optimization, the two websites I showed earlier as well will also take you to Krystal Decode DEB resources. And then lastly, there's nothing better than when others start to chat about these programs, and we saw tons of unsolicited slides at AAD this weekend with Krystal Decode DEB on them. So the community is pushing us forward on their own as well.

Our next questions come from the line of Debjit Chattopadhyay with Guggenheim.

The follow-up. How many patients from the Phase III enrolled in the OLE?

A very high percent. If you took out -- there were 31 patients in the pivotal study and as you heard Hubert, there are a couple of dropouts. But if you took out people who had moved closer to the clinical site for the pivotal study, people whom we helped relocate from other cities, they obviously, for personal reasons, had to go back pretty much more than 90% of the rest. And I'm hesitating because I don't know the...

This is correct. We have a good chunk of patients who are -- who lived close and can commute are continuing to participate in the study. And we are hoping if we can get home dosing in, then we can get the remaining. They all want to get on the study. But again, we, as Krish mentioned, we relocated a few families for 6 months. That's something that is doable more than that became difficult for everybody. So hopefully, with home dosing, we can get some of those patients back on the trial.

But to answer it a slightly different way, just to close out, there's not a single, local patient who was in the Phase III study, who is not part of the open-label extension study.

We have reached the end of our question-and-answer session. And with that, this does conclude today's teleconference. We do appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.