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

Good morning, everyone, and welcome to the Krystal Biotech call and webcast discussing top line data from the Phase III GEM-3 trial of topical VYJUVEK and dystrophic EB. [Operator Instructions] Today's call is being recorded. At this time, I'll turn the call over to Whitney Ijem. Please go ahead.

Thank you very much, and good morning, everyone. Thank you for joining us today for our conference call to review the positive top line results from our pivotal GEM-3 study of topical B-VEC in patients with dystrophic Epidermolysis Bullosa or dystrophic EB, which we announced in a press release earlier this morning. As you may have also seen in the release this morning, we have received approval in the U.S. and EU for the brand named VYJUVEK, which is another important update for this program. Before we begin, I'll remind you all that this presentation will contain forward-looking statements based on our current expectations and beliefs. Such statements are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those presented. We refer you to our SEC filings for further information. On the call today will be Krish Krishnan, Chairman and CEO, who will provide some opening remarks. We're also joined by Dr. Peter Marinkovich, assistant professor at Stanford University and the principal investigator in the GEM-3 study, who will provide some background on dystrophic EB. Then Suma Krishnan, Founder and COO at Krystal, will review the GEM-3 trial results and discuss next steps from a regulatory perspective. And finally, Andy Orth, Krystal's Chief Commercial Officer, will provide an overview of the commercial readiness activities that are already underway. Krish will then provide some closing remarks, and all mentioned here will be available for the subsequent Q&A. With that, I'll turn it over to Krish.

Thanks, Whitney, and thank you, everyone, for joining us this morning. This is a great day for the dystrophic EB community and for the field of gene therapy. We could not be more pleased with the results of this study that we are sharing with you today, which brings us one step closer to bringing VYJUVEK to patients. Before we get into the Phase III study, it was not that long ago when we founded Krystal Biotech based on Suma's idea of developing a painless patient-friendly therapy for the treatment of dystrophic EB, sometimes referred to as the worst disease you've never heard of. Our approach was different. We were looking for the best technology to fulfill her vision as opposed to having a technology, and looking for a problem to solve. We had to think outside of the box when it came to gene therapy technologies, given the nature of this disease. We needed a new type of viral gene delivery technology, one that can be applied in vivo directly to the skin in a topical formulation, and one that can be reapplied over time as needed to provide continued clinical benefit to these patients. Something that no other gene therapy company to date has been able to accomplish. The foundation of our technology platform is the engineered herpes simplex virus vector, which our scientists have engineered to be replication and competent, which prevents the virus from multiplying and spreading. They have been modified in a way that leaves the immune invasive properties of the vector intact while allowing the vector to consistently and repeatedly deliver corrected copies of the missing unmutated gene to the patient. In other words, allowing the patient to get redosed as required. The Krystal team developed this novel vector technology specifically to help people living with dystrophic EB. In the process of doing that, we realized that our redoseable gene therapy technology has potential to help people living with other rare diseases as well. Rare skin diseases where we use the same topical approach to treating the disease, and then expanding into other organ systems next into the lung where local inhaled formulations of our vectors can replace mutated genes. Starting with the CFTR gene for the treatment of cystic fibrosis. As we've continued to explore the potential of our engineered vectors, we've uncovered other areas where they may be uniquely suited to provide benefit, and we will be talking more about that in the coming months. Suffice it to say, we believe the power of this platform is vast. And this morning's positive pivotal data for VYJUVEK provides important clinical validation. I will now turn the call over to Dr. Peter Marinkovich, the GEM-3 principal investigator from Stanford University to provide more clinical background on DEB. Peter?

Thank you, Krish. Good morning, everyone. It's great to be with you on such a happy day for the dystrophic EB community. Before discussing dystrophic EB, I'd like to provide you with important context around our clinic. Stanford has been a national EB center in the United States for decades, and we consult hundreds to patients with various types of EB every year, and have extensive clinical experience caring for the array of needs in this community. Our clinic incorporates multidisciplinary specialists and experts who collaborate together as the team to address a whole array of medical and health issues for our patients. We are really proud of this holistic, multidisciplinary approach in the care of our patients. As a disclosure, I'd like to declare that I'm an investigator on the Krystal GEM-3 study. To ground us all, EB is a serious chronic and rare disease that causes skin blistering and wounding with the most serious form, typically diagnosed right after a child is born. Dystrophic EB is a unique form of EB and is associated with very fragile skin blistering and wounding permanent debilitated scarring, and a specific type of cancer, which can be fatal. And while we've improved wound care and therefore, are seeing patients surviving into their 20s and 30s, some of these patients do develop fatal forms of cancer like squamous cell carcinoma. So it's incredibly frustrating as physicians for us to work in this field since there are no currently approved corrective treatment. This is a truly devastating disease that in the more severe forms and [indiscernible] Early on, given the severe and recurring blisters. And typically, the diagnosis is made through skin biopsies though the gold standard here as with any genetic disease is genetic testing. However, one of the problems here in the United States is that only about half of the patients with EB has been properly diagnosed at the DNA level. So even in the most severe cases of dystrophic EB, there are patients who have a biopsy-based diagnosis that haven't been genetically tested to confirm. And in less severe cases, it can take patient years to even get a diagnosis, and it's often incorrect either with a different form of EB or another blistering condition because of this lack of genetic testing. This is often the result of a lack of insurance coverage. So I was really encouraged that Krystal launched the Decode DEB program, which offers no-charge genetic testing for all types of EB. So genetic testing for what you might be asking, because you haven't heard the full story of dystrophic EB yet, which is that it is a monogenetic disease or disease caused by mutations in a single gene, the gene that codes for the protein called type VII collagen or COL7 for short. The field has been working to get a better grasp within this disease for nearly half a century. And my mentor made a seminal discovery back in the '80s, which led us to better understand more about the epidermis thermal connection and type VII collagen role. Essentially, when you're exposed to disruptive external forces, for example, when you scratch a niche, there are structural anchors that ensure the dermis and the epidermis stay together, essentially a special adhesive structure, which is type VII collagen. Mutations in the gene lead to dysfunctional missing [ types of collagen ]. Without it, the skin layers separate upon the slightest of friction, creating the characteristic blisters and ultimately open wounds. With this discovery, it was now clear that dystrophic EB is caused by a single missing protein, and the field began to work to figure out how to add that protein back in, which is exactly what B-VEC was designed to do. Let's look now at the current treatment options, which are largely palleted in nature, and do not address the underlying protein deficiency. And so they fall short. The current treatment process is the painstaking one that affects the whole family as parents or caregivers have to spend hours daily with wound dressing changes, which is very painful for the patients to go through. We've tried everything to help these patients. And certainly, wound care has improved over the years with more elegant nonstick bandages, creams and ointment. And soaking solutions such as dilute bleach or vinegar and other things to disinfect skin. We focus on preventing skin infections, providing better wound care and ultimately try [ to stay off ] the skin cancers, which in severe patients are almost inevitable because of the constant wounding and rehealing and inflammation in the skin. And these cancers can be fatal. So today is an important day as we learn more about the potential of topical B-VEC, which does what current therapies cannot. Via application of this topical gel provides a patient's own selves with a given wound, the [ template ] to make COL7 to correct the protein deficiency, to add back those structural anchors so that the wounds heal that the skin is stronger, and it will resist blistering as new wound healing forms. Before I turn it over to Suma who is going to share with you the data the company released earlier today. I just want to say as a physician researcher who's been treating these patients and focused on the community for 25 years, I really believe that we're approaching a new era in the treatment of dystrophic EB. We spent the last 4 decades building a foundation and that foundation is firmly in place. And now we're beginning to see where we can go. Suma?

Thanks, Dr. Marinkovich, as you've pointed out, this is an exciting day for dystrophic EB community, but also for the entire Krystal Biotech team. And personally, as a founder of the company, it's extremely gratifying to reflect that we started with one goal in mind, which was to develop a noninvasive solution for dystrophic EB. And now, today with these data, it appears we have achieved this goal. The GEM-3 Phase III trial top line results showed strong efficacy in the dystrophy EB patient population with a good safety profile. These data represent a number of important firsts. This was the first ever placebo-controlled double-blinded study that evaluated a genetic therapy in dystrophic EB. These data positioned VYJUVEK to potentially become the first ever topical gene therapy. This data also position VYJUVEK to become the first ever redoseable in vivo gene replacement therapy. Now to the trial. GEM-3 was a randomized, double-blind, placebo-controlled trial evaluating topical VYJUVEK and dystrophic EB patients. Each enrolled patients had 2 wounds selected that was similar in size, anatomic location and Chronicity or the time they have been an open wound. One of these wounds were randomized to receive topical VYJUVEK and the other placebo. The dose assigned was a function of the size of the wound at baseline and was fixed throughout the study. VYJUVEK or placebo were applied once weekly in the doctor's office and that continued until complete wound closure. If at any point during the study, wound were not completely closed, the weekly dosing resumed again until wound closure. Overall, 31 patients enrolled in the study across 3 trial sites. All enrolled patients have been diagnosed with dystrophic EB biogenetic testing. The majority of enrolled patients [ adverse ] of the disease or death, with less than 10% having dominant type, DDEB. Nearly 2/3 of the enrolled patients were younger than 18, for the youngest patient being 1, and the oldest been 44 at the time of enrollment. Primary wound pairs fell into each of the 3 size categories. First, let's look at the safety data. Once weekly VYJUVEK was very well tolerated with a safety profile consistent with prior studies. There were no treatment-related assays or discontinuation due to VYJUVEK treatment. There was only 1 drug-related adverse event observed in the trial, which is classified as mild. Importantly, the immunogenicity profile as measured by anti-HSV-1 or anti-COL7 antibodies, was also as expected and consistent with the results in our previous studies. Now let's move to efficacy. The primary endpoint of the trial was investigator assessed wound healing at end of the study, looking for wounds that remain closed for 2 weeks at the end of the 6-month study. The wound that were completely closed at weeks 22 and 24 or weeks 24 and 26. 67% of VYJUVEK wounds met the endpoint as compared to 22% of placebo wounds. That difference was statistically significant with the p-value of P less than 0.005. As a secondary endpoint, the study also evaluated the proportion of wounds that were completely healed after about 3 months. The wounds that were completely closed at weeks 8 or 10 or week 10 and 12. This endpoint was also met with P of less than 0.005. We also looked at the proportion of wounds that were closed at both the 3- and 6-month time point. And again, we saw a statistically significant benefit relative to placebo with the P less than 0.005. We are planning to present more detailed top line results at a medical conference in the first half of 2022. One other aspect of the study was the ability for patients to treat additional wounds, called secondary wound. With topical VYJUVEK on an open-label basis. This is driven by the concept of a maximum weekly dose of VYJUVEK that is defined based on the maximum dosing we reached in the earlier studies. In a real-world setting, this would allow patients to treat very large and all multiple wounds with the weekly dose. In the Phase III trial, this meant that after the doses were assigned to the primary wound. There, at baseline, the remainder was calculated and fixed throughout the study. That amount will then available for patients to use on an open-label basis to address these so-called secondary wound, which were exploratory in nature and were not monitored for endpoint analysis. On the next slide, we will walk through a couple of case studies involving the secondary wound dose in the study. So to orient you, this is a patient back, and this wound, as you can see, is a very large wound, greater than 100-centimeter square and very severe at baseline. The patients supported that this [ wound ] have been open for over 10 years, and at the time VYJUVEK treatment was initiated. After 1 weekly VYJUVEK for 6 weeks, approximately 50% of the wound had healed, and continue to heal throughout the study. As you can see, by the end of the study, the wound image is truly remarkable. And from a quality of life perspective, this patient who had been previously unable to take a shower stated that following wound healing after treatment is now able to do so. The other secondary wound or wound, we show here, are on both the right and left foot in an area of significant mechanical strength in a 34-year-old patient. These are recurring wounds, wounds that did demonstrate healing on their own, but easily rewounded or opened back up when the patient put on shoes and walked around. After 1 weekly VYJUVEK, the foot wound closed in 6 weeks. At the end of this study, we observed that these wounds continue to stay close and this patient noted they were able to walk without pain or discomfort. These images and stories are truly remarkable. This speaks to the potential of VYJUVEK to not only to treat the full spectrum of wounds that a dystrophic EB patient may have, but also to the significant impact that wound yielding driven by a genetically targeted therapy has on the day-to-day life of patients who are living with dystrophic EB. We are learning a lot from these additional wounds, that were treated and plan to present more of these learnings at future medical conferences as well. On to the e Open Label Extension study, which is now up and running. This study enables patients who have completed the Phase III trial to roll over and continue to receive VYJUVEK on a weekly basis. We have been pleased with the rate of enrollment into the study. We are also opening up enrollment at 3 additional sites to enable new patients who met the enrollment criteria in the Phase III study to participate in the e Open Label Extension as well. We are actively working towards next steps, which are outlined here. We are working quickly to get the BLA complete and file in the U.S. in the first half of 2022. VYJUVEK has already been granted regenerative medicine advanced therapy or RMAT designation and Fast Track designation and rare pediatric designation by the U.S. FDA. So should VYJUVEK ultimately be approved in the U.S., Krystal will be eligible to receive a priority review voucher or PRV. We have also been granted prime designation by the EMA, which has enabled early conversations in Europe. Our most recent conversation has solidified our plan to move forward with an MAA filing on the basis of the GEM-3 data, and we expect to complete this filing shortly after the BLA. We are also in discussions with the PMDA in Japan to get a better understanding of what a potential path forward might be there. I would like to thank everyone that participated in this clinical trial, health care providers, and patients, and our team, and our collaborators. In less than 6 years, we have taken our founding mission from preclinical lab work to a successful Phase III study. We are gratified that we are now on the cusp of potentially bringing VYJUVEK to patients, and we'll continue to work tirelessly until our goal is achieved. I'll now turn it over to Andy for an update on how the team is preparing to do just that. Andy?

Thank you, Suma. Exciting times for the dystrophic EB community indeed, and I'm excited about the work we're doing in preparation to get VYJUVEK to patients in need around the globe. Let's now turn to the dystrophic EB patient population. We believe there are approximately 3,000 patients in the U.S., another 3,000 patients in Europe, and about 3,000 in other locations around the world. These numbers are based on a detailed review of the epidemiologic data as well as our interactions with EB experts worldwide. While many of these patients are readily diagnosed given the severity of the disease, we believe there is a significant number of patients around the world struggling to get the appropriate diagnosis. We are conducting additional ground-up research to put a finer point on some of these numbers and plan to provide more details next year. Our team has been digging in across multiple fronts, including physicians and patient-focused disease awareness activities, focusing on the genetic nature of the disease. And we recently launched the Krystal Decode DEB program. A sponsored genetic testing program in the United States as a diagnostic resource for patients and physicians. Genetic testing is frequently cited as a barrier to correct EB or dystrophic EB diagnosis, which is important, as you heard from Dr. Marinkovich to ensure patients are receiving the appropriate therapy for their specific EB subtype. Additionally, we have medical personnel and patient-facing community liaisons in the field engaging with the dystrophic EB community. In parallel, we're having initial discussions with U.S. payers to help educate them on the disease, its impact on patients, caregivers in the health care system, and VYJUVEK. And I can say early feedback on the concept of a redoseable gene therapy has been positive from the U.S. payer lens. On the CMC front, we've been making VYJUVEK clinical material at commercial scale for the Phase III study at our in-house manufacturing facility ANCORIS near our company headquarters in Pittsburgh. If approved, we expect to launch VYJUVEK out of this facility, which was designed for this purpose. Our second larger ASTRA facility is also under construction, also in Pittsburgh, and we expect that to be complete and come online in 2022. ASTRA will add greater capacity as we think about global demand for VYJUVEK as well as supporting our growing pipeline of other therapeutic candidates. The key takeaway here is should VYJUVEK be approved, we will be ready to serve patients. Krish, I'll now hand it back to you.

Thanks, Andy. Our commitment to patients living with dystrophic EB and other diseases does not stop here. We'll continue to push ourselves to develop patient-friendly redoseable gene therapies to address other rare diseases. We look forward to advancing our rare dermatological disease pipeline, including KB105 for TGM1 deficient necrosis, a disorder characterized by dry, scaly, or thicken skin, which is currently in Phase II, initiating a Phase I trial with KB104 for the Netherton syndrome, a rare hereditary disorder characterized by scaling skin next year, and continue our early-stage discovery efforts. Outside of the skin, we're in the process of getting our first pulmonary clinical trial started for KB 407 for the treatment of cystic fibrosis and growing the pipeline of treatments focused on the lungs. We're also exploring the potential of our platform to address more prevalent conditions first of which are in aesthetics under our wholly-owned subsidiary Jeune Aesthetics. We look forward to Jeune's upcoming announcement of initial Phase I proof-of-concept efficacy data for KB301, in aesthetic skin conditions early next year. As the company has evolved and the promise of our novel vectors has become clearer, we have and will continue to think creatively and work diligently to apply our technology in other diseases where there is a clear patient need. As our pipeline grows, we'll remain focused on our original mission to help dystrophic EB patients. I want to thank everyone who's played a part in the VYJUVEK development program and especially in this pivotal study, which we started and completed during a very challenging time to the patients and caregivers specific particularly. Thank you for your time and commitment to this important study. Operator, we can now open the lines for questions.

[Operator Instructions] Our first question comes from the line of Josh Schimmer from Evercore ISI.

Congrats on the exciting results. For the patients who did not have a complete response noted. Was there a meaningful reduction in their wound size that would merit applying the therapy even if they're not achieving a full wound closure? And then were there any predictors of which patients did or did not respond to?

Thanks, Josh. Thanks for your question. I'll let Suma answer the question.

Josh, thank you for the question. Yes, I mean, we can clearly see from our secondary wounds. Obviously, we have not fully analyze the primary wounds because they were blinded in nature. But clearly, from our secondary wounds, we see a great benefit. We see these wounds, as you saw, even large wound size that we showed on our slide, I mean, the wounds were clearly reducing. And as you continue to treat them, the wounds continue to keep closing, and then you see wound closure. So we do see benefit. And even it may not be 100%, in secondary wounds we do see reduction in wound size. And the second question was...

Predictors of response or lack of response?

No. Again, we have not analyzed the data completely to really dive into that. But I think as we mentioned in the future, we will look at -- we'll complete more of these analysis and maybe present this data maybe at some conference or in the future.

Our next question comes from the line of Ritu Baral with Cowen and Company.

Congratulations on the data. I wanted to ask on gating factors to filing. What's -- what if any CMC issues remain and also what preclinical or clinical tox package issues might still be needed to be generated before the filing? And then I have a quick follow-up on home administration.

Thanks, Ritu, for the question. I'll cover the toxicology first. From a preclinical talks, we have got an agreement with the agency that all of the studies we have completed to date is sufficient to file the BLA. So there's no additional preclinical tox requirements for the BLA filing. With regards to CMC, I mean, as you guys know, we have the RMAT designation. With the RMAT designation, we have the ability to have very frequent communication and guidance from the agency. And we were very, very fortunate that from the very beginning, because of the RMAT status, we have had many, many and several meetings with the FDA specifically focused on the CMC. And this is the very reason that we were able to even initiate our Phase III studies. As you know that CMC is very critical for us to start a Phase III trial because all of your assays have to be qualified, your potency assays have been in place. Your comparability studies has to be completed, and all of those were met. So I think from a CMC perspective, we feel like we are in a good position towards the BLA filing.

Great. And then on home administration, can you tell us where you are on incorporating that into the ongoing Open Label? And what your expectations are for the ability to home administer at the time of approval and launch?

So with regards to home, human factor for home dosing, we were -- we -- again, this is a 2-year effort with the agency. The human factor protocol was approved by the agency, which was, I think, was a big event considering this is a home dosing viral vector. So this was a couple of months ago. The protocol was signed off. We have completed the human factor studies. We are in the process of putting the study report together. We expect to file that study report shortly. It's a 60-day review. Once the agency is satisfied, I think based on our [ CSR ], we feel pretty confident that we have met all of the requirements that the agency wants. I think once that's cleared, the first quarter of next year, we intend to implement -- we are hoping to implement home dosing in our OLE studies with our ongoing clinical trials. So with regards to commercial...

And Ritu, I'll add to that. This is Andy. That speed to access here is going to be critical for the potential launch, and we'll be prepared for every eventuality. And that means in-office administration, in-hospital administration and/or in-home administration is available, and we're currently working with partners on the specialty distribution, specialty pharmacy side, et cetera, to set those up. Importantly, as close to the patient's home as possible. So we'll be ready for any eventuality here.

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

Really congratulations. Hopefully, this is a really great day for DEB patients everywhere. So our 2 questions are, first, what can you say on the durability of wound closure on VYJUVEK? And then secondly, what can you say on the wound closure dynamics of wounds that closed on VYJUVEK subsequently reopened and were then redosed with VYJUVEK after the reopening?

Madhu, thanks for the question. Look, we presented top line data. We feel we'll be able to glean more information on durability. The question of how long a wound stays closed from the data under pivotal and also from the ongoing OLE study as we continue to follow patients over a longer-term period, which I think will be more representative of a top line situation. With regard to your question on the dynamics of wound opening, look, it's fair to say a certain percentage of wounds, if you just think about the Phase III trial, a certain percentage of wounds probably opened between the 3 and 6 months, and a certain percentage stays closed, one speaks to the redosability of the platform, while the other speaks to the durability of the drug. But to get a more precise answer to your question, I think we will continue to analyze the current data and the future data on the OLE, and hopefully share that at our congress in the future.

And I guess a question for Andy on that front is when we think about the wound closure dynamic that you'll see in GEM-3. How does that influence how you guys think about the pricing of this drug? So this is a drug that is used, say, once and the wound stay close and don't really reopen. How does it affect the pricing dynamic as compared to one where there is a kind of steady state of wounds opening and closing and kind of readministration of the drug? Like how are you guys thinking about that dynamic?

Yes. Yes. It's a good question, and it's actually a little bit of a complicated one. And we'll certainly share more details on price as we get closer to launch on how we're thinking about it. But at the end of the day, simply, we're going to need to understand the ongoing run rate of the average dose per patient over time. That's the simplest I can put this to it and then design a place around that and work with payers to construct a way to do that so that all sides are protected from any variability there, et cetera. So we'll be able to share more about that as we get closer to launch.

Our next question comes from the line of Debjit Chattopadhyay with Guggenheim Securities.

This is Robert on for Debjit. Congratulations on the great data. Two questions from our side. 29 completed the study, those were primary analysis based on 29 or 31 patients. And then the same thing, could you specify the number of discordant patients? And the number of concordant drop from analysis? And then our second question is, do you have full agreement with the FDA to file with the current data set once again to that and thank you?

I'm going to start -- thanks for the question, Robert. I'm going to start answering a couple and I'll turn it over to Suma to talk about what's any gating factors of the data -- with respect to the data set and filing the BLA. Look, the analysis is imputed. And so as we've said in the Phase III trial, we analyzed across 31 patients. So while we did announce there were 2 dropouts in the study, their data depending on when they dropped out was imputed on to the study. So the answer is 31. We're presently -- we're still working. We've not gotten to the level of detail of completely disclosing how many concordant discordant pairs yet, something we'll definitely look to announce at a congress in 2022. And then -- so that said, I'll turn it over to Suma to start with some of the gating factors on filing?

Absolutely. I mean, look, the design of the Phase III study was absolutely done with the guidance we received from the FDA based on our end of Phase II meeting. So we basically followed the guidance from the FDA. The statistical analysis of the study or the plan was again based on discussions with the FDA, the SAP plan was submitted to the FDA. The FDA agreed upon the plan. So all of that -- everything we've been doing on this clinical study is based on clear communication and guidance from the FDA. So we believe to date, both on our CMC and our clinical because of our interactions and frequent communications with the FDA. I believe we are truly aligned with the requirements from the FDA. So I don't see any sort of risk factors at the moment. So the next process is obviously going to be -- we're going to request a pre-BLA meeting with the FDA, and it's going to be more -- just letting them aware of the data, so they know that this is coming. And we, again, get the attention and the guidance from the agency and also administratively make sure that all of the pieces that needs to go into the application is all in the right order. So when we're ready to file, we are complete and good with it. So hopefully, that addresses your question.

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

Congrats on the data. I reiterate my thanks in that regards. Yes. So a couple of questions just on the primary endpoint analysis. I know that FDA had given you guidance to use a specific statistical test, I think it was the McNemar. Can you just confirm that, that was the test you executed here?

David, thanks. Yes, we can confirm McNemar.

Okay. Great. That's pretty clear. And then just in terms of the RDEB versus DDEB patients. Is there anything you can talk about qualitatively in that regard, where we feeling trends similar for both subgroups?

Yes. So the first point I'll make on that is, look, our agreement with the agency is that this study is targeting dystrophic EB patients. We have previously announced that we anticipate, and it turned out to be true that less than 10% of the overall enrollment would be the dominant patients in the study. But in terms of further granularity on that, I ask you to be patient for an upcoming congress. It's a kind of fresh, and we definitely want to talk more about it. But our expectation right now as a company is that, should the drug get approved, we expect to get a Label to [ serve ] dystrophic EB patients.

Our next question comes from the line of Raju Prasad with William Blair.

Congrats on the data. I was a kind of curious to the recurrent versus chronic wound treatment. Could you give us a sense of how those wounds responded? And then on a kind of wondering the exact number or a kind of a sense of the number of patients that were retreated within the study?

Look, I'm going to a kind of repeat what I said previously. The indication of the study was not designed to show any kind of distinction between a recurrent and a chronic wound. What the requirement was that we found the wound pair -- wound pairs that were anatomically similar in a patient, same size, same location, preferably same chronicity. And even with the agency, we did not ever get into any kind of sub cohort analysis with respect to recurrent and chronic. That said, as we analyze and produce more detailed data on later congresses, I think one can expect more visibility into that question. And with respect to your second question, on how many were redosed. Look, one of the things we announced based on the ad hoc analysis was that a lot of wounds that were close to the 3-month time point were also closed at the 6-month time point. And my only comment, which I'm repeating myself, is you could assume a certain percentage of them stay closed through the link and a certain percent probably opened and were redosed. Both speak to positive things in our opinion, one speaking on redosing and one that speaks to durability. So with that said, give us some time to look through the data, and we'll also be definitely want to talk about publishing and congresses. So we're trying to be a little guarded about -- the expectation on this call is just top line data, so I'm trying to stick to that.

Great. And then maybe just one quick one on commercial. If -- how important was the home dosing be for the commercial launch of the product, just given you obviously had a really low dropout rate in the study and patients are fairly compliant.

Yes, let me -- I'll take that one. So optionality for home dosing is what we are working towards. That said, when you take a look at any time a home dosing is upward in these types of diseases, some patients take it and some do not. So it is something we want as optionality for the entire patient population, but we don't expect it to be the vast majority, frankly, of where the administrations occur. And hence, we're going to work diligently to provide sites of access and sites of care as close as possible to the patient's homes.

Just 1 question here. I forgot to do this -- But on your question on recurring versus chronic. Since Peter is on the line, there are 2 things, Peter, I'd like you to talk about, one on that point. And the second, just provide some overall color or experience on the study, if you can, please?

Yes, sure. As far as the recurrent or chronic wounds, we did get the history of the patient's wounds prior to treating. And some of these wounds were many years chronic. And so we certainly were treating both the chronic as well as the recurrent wounds. And so the efficacy you've see reflects both of those wounds. Is there another question? Wanted to be -- anybody wanted to address?

No, Peter. I think that addresses the question. I should have looked better, look to you even earlier.

Our next question comes from the line of Joe Pantginis with H.C. Wainwright.

Congratulations as well and definitely fantastic news for patients. So Krish, I know, obviously, you're going to be presenting much more data, today is just top line, but there was an intriguing age range in this study. I mean up to 44 years old. So I was just curious if you have even any anecdotal observations ahead of the more detailed set of data regarding age impacts on the results?

Yes. I mean, we -- I think previous -- thanks, Joe, appreciate the question. Previously, we announced at 61% of the patients were pediatric, if I'm remembering the number right. Look, the only color we want to talk about today is on the secondary wounds, right? And as Suma said in her presentation, look, it's pretty powerful when you think about somebody who says that they've not been able -- I mean, you see the picture before and after, who have not been able to shower, and now is so excited to be able to do very basic things from a quality of life. It speaks to the improvement of the quality of life, being able to walk, not able to walk or dance because of the hurting shoes to being able to do walking and dancing are powerful. And just as a broad comment to your question, the pre values are so robust that across age ranges, across type of wounds, we feel the results are really robust without hesitation. So like, look, if we are able to file the BLA and get the drug approved, we really hope to bring a drug to treat the DEB patients broadly across all age groups.

Got it. I appreciate that. And then with regard to manufacturing, you guys really did a lot of the heavy lifting ahead of time regarding putting your facilities in place. And I'm glad Andy mentioned that obviously ANCORIS is already at commercial scale. So if you fast forward today, we certainly live an interesting time. So as you're looking to expand ASTRA and get it online, for example, are you experiencing or are you planning ahead for any issues regarding all the various global supply chain constraints?

Suma?

That's a good question. Again, I think we were very prepared. We knew with what is coming with COVID, both from a clinical perspective and supply chain issues. And we knew exactly how many batches that we needed to make at ANCORIS and ASTRA that's coming online. So we started planning back a year, 1.5 years ago. from a supply chain perspective, we have all of the raw materials, especially single-use bioreactors are commodity these days with COVID and all of the stuff. And we -- I mean, we were very fortunate. We have planned with all our vendors, and we make sure that we are completely stocked all the way up to 2020 -- end of 2023. So we don't anticipate any issues with supply chain with regarding to manufacturing or even with our pipeline products. As Krish mentioned, we will be very rapidly getting into IND for 407. We will be continuing our 105 program into the clinic, 104, and all of this the limitation is manufacturing. And I think with our supply chain and our positioning of ASTRA, we feel we are in a good place to get all of these programs from a CMC perspective to get it up and running. So we're pretty excited about 2022 and onwards. I mean B-VEC, of course, is a big milestone and a big project for us. But as Krish mentioned, we are equally excited to bring other therapies, for example, KB105 with ichthyosis, our patients are desperate. They keep e-mailing us saying, when are we going to kick start that program. So we are very, very excited to get those programs up and running, first half of next year.

Our next question is a follow-up from the line of Ritu Baral with Cowen and Company.

Could you elaborate a little bit just on what that mild treatment emergent AEs was? And does this have any impact on what you think will be required for the clinical tox package or exposure package or retreatment data set required for filing?

As you can see Ritu, we had a very favorable adverse event profile with B-VEC. I mean, obviously, this is an interpatient study because the placebo and the B-VEC was treated in the same patients. I mean, obviously, these patients have a lot of the preexisting conditions. I mean in spite of the precondition and existing conditions and chronic infection, as you can see from B-VEC treating these patients with B-VEC, we really did not adversely affect the patients from an AE perspective. So we only reported a single adverse event that was related to B-VEC to VYJUVEK, and that was reported as a mild adverse event.

Got it. And then clear with me. I've got a follow-up question on the numbers reported. Given, you did the McNemar and you reported 67% of VYJUVEK' wounds closed, and 20% of wounds closed. Are those numbers on the absolute number of wounds assessed in this study? Or are those percentages reflected -- reflective of just the discordant wound pairs that went into the McNemar analysis?

It's absolute. Ritu.

Thank you. Ladies and gentlemen, that concludes our question-and-answer session. I'll turn the floor back to Mr. Krishnan for any final comments.

Thank you. Thanks for joining the call. We have a lot of work to do to get the BLA filed and work towards bringing this drug to patients and appreciate your time.

Thank you. This concludes today's conference. You may now disconnect your lines. Have a wonderful day.