INmune Bio Inc. (INMB) Earnings Call Transcript & Summary

Good morning, and welcome to the INmune Bio investor event. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be available on the INmune Bio website following the conclusion of the event. I'd now like to turn the call over to Mark Lowdell, Chief Scientific Officer and Chief Manufacturing Officer of INmune Bio. Please go ahead, Mark.

Good morning, everyone, and welcome to our webinar to announce the pivotal study in refractory dystrophic epidermolysis bullosa with CORDStrom. I'm Dr. Mark Lowdell, CSO of INmune Bio and inventor of CORDStrom. CORDStrom is a unique mesenchymal stem, stromal cell product or MSC, which is in clinical development. Today's webinar will begin with a recorded presentation by Dr. Anna Martinez, who is unable to join us because of her clinical duties. Anna is the lead of the U.K. National Epidermolysis Bullosa Service, an initiator and principal investigator of a randomized trial of CORDStrom in pediatric EB. She will share with you some of the data from the trial, which have led to the orphan drug designation and RPD Designation given to us recently by USFDA. We will then return to the live webinar, and I will give some more detail about CORDStrom platform and describe how we plan to take this through regulatory filings in the U.S., U.K. and Europe over the next year before opening the floor for questions at the end. Before we begin, I remind you of our forward-looking statements, which can be found in our SEC filings and encourage you to read them before making any decisions in response to the data we're about to share with you. Epidermolysis bullosa or EB is a horribly debilitating condition, which manifests shortly after birth and in the worst recessive dystrophic form, or RDEB, is due to the lack of collagen protein anchoring the dermis to the epidermis. This is a condition which manifests all over the body, including inside the mouth, down the esophagus, even behind the eyes. The slightest abrasion leads to sort of wounds you will see here. Over 5 years ago, Dr. Martinez, who is an internationally recognized expert in the management of EB and the service lead at Great Ormond Street Children's Hospital in London, conceived the MissionEB trial, which she's about to present, principally funded by the U.K. National Institute of Health Research and NHS England, this was the first-ever randomized placebo-controlled, double-blind, crossover multicenter trial of an MSC drug in the world and was delivered by Anna and her team at GOSH alongside colleagues at Birmingham Children's Hospital and with INmune Bio. Anna, thank you for joining us, and please share your data.

Great. I'm delighted to be here, and thank you for the introduction, and I'm really thrilled to present the results of MissionEB. So this -- first of all, EB is really rare inherited blistering disorder where the skin and wounds develop blisters following very minor trauma. There are 4 main forms, and I'm focusing on recessive dystrophic EB. And that's due to either a complete lack or dramatically reduced protein in the skin, collagen VII, which is critical to anchor the epidermis to the dermis. Now EB is a multi-systemic disease. And you can see from the pictures, most organs are affected, and the disease is progressive. The only organ spared really is the brain. And we've described this in a recent publication, just highlighting the progression that happens naturally in children and patients that are untreated. There's a real sort of cutoff around the age of 10, where we see the inflammation is so great that it's really hard then to get on top of this huge systemic burden of disease, which progresses, eventually leading to death by squamous cell carcinoma. So MissionEB is a study that we set up giving intravenous mesenchymal stromal stem cells umbilically derived for children with recessive dystrophic EB in the U.K. So the aim of the study was to see if repeated infusions of CORDStrom, these umbilically derived MSCs, were safe and could help children with recessive dystrophic EB. So our primary objective was first to assess safety and then to see how these cells helped the efficacy as well as the safety of repeated infusions of these cells. We also wanted to assess the patients' and parents' views of the effectiveness of the treatment. So this was a double-blinded randomized placebo-controlled crossover study. All patients were randomized to receive 2 consecutive doses intravenously 14 days apart of either cells or placebo. There was a 9-month washout period between the 2 infusions. Now if this study is successful, we hope to go to a 12-month open-label study, where all patients will be given 2 infusions every 4 months of CORDStrom. Now this is a diagram of the study. And in the blue line in the middle, you can see the dates. So there's 2 groups. The first group is allocated 2 infusions of cells. There's a 9-month washout period and then the opposite, placebo. And then the other arm had the placebo first washout and then the cells. We collected lots of different evaluations at the time points at 3 months and at 6 months, and this is a data that I'm about to present. So in summary of the trial, the first patient was recruited October 2021, and we were delighted that we saw no significant toxicity events throughout the whole study. I'm presenting results of 30 children that completed a total of 124 infusions throughout the study, and we'll be looking at the primary and secondary outcome data. Now just a quick mention about the scoring systems that we have this naturally progressive disease. We only have 2 validated scoring systems, EBDASI, which is a disease activity and scarring index. And although this score is helpful and measures activity, it also includes damage element such as fibrosis and contractures that we know are not reversible with this sort of treatment. So it had a disadvantage. The other validated scoring system that we use was iscorEB, which is an instrument for scoring clinical outcomes for research in EB. There are 2 components. There's a clinician's component that looks at the skin, and there's the patient aspect that looks at several aspects of the disease, pain and itch, but a recall over the preceding 4 weeks, which, again, had some limitations. So the results from the study at 3 months showed overall all children that had CORDStrom showed benefits that were observed throughout the study for Itch Man, iscor, clinician's element and the iscorEB skin involvement. So that was across the whole study, all 30 patients showing benefits in these scales compared to no benefits from the placebo. We also saw overall a 20% reduction in itch. We did not see changes in EBDASI and iscorEB overall, but we think this is limitations of the scoring systems without breaking down the population. So if we're looking now at the under the age of 10, and this includes the severe and intermediate children, in fact, this is 21 of the 30 children that took part in the study. 12 of these, 57%, had the severe type of recessive dystrophic EB. And what we're seeing here is a mild improvement in the iscorEB clinician scores, with an 8.4% improvement of their iscorEB skin involvement and a 20.2% improvement in the Itch Man Scale. So this is across 21 of the 30 children in this group. Now if we look at over the age of 10, here, we're seeing clinically relevant pain reduction. And this pain reduction is measured in the FACES score by the children themselves and in the visual analog score, VAS, by the parents. What this showed in over the age of 10 was an 8.3% reduction in pain reported by the patient and 7.3% average pain by the parent, and the worst pain was reduced by the patient 2.8% but by the parents recording 12.5%. We didn't see improvements in the skin scores in this group, and there was insufficient Leuven Itch data. Now if we look at the RDEB EB intermediate group, this group saw across the study the greatest and most consistent benefits. They saw -- we saw a large effect and improvement in the iscorEB clinician score of 6%, and the iscorEB skin score improved by 9.1% in favor of the cells. We also now saw a mild improvement in the EBDASI activity score and in the skin component. We're seeing very clinically benefits in pain and itch reduction in this group. The average pain recorded by the children in FACES themselves improved by 22.2% and the worst pain by patients was reduced by 27.8%. Parents reported an average pain reduction by 0.7%, but the worst pain was reduced by 19.1% Overall, we saw an itch reduction in this age group of 16.4%. The independent photography reviewers concurred with these positive results. Now if we look at the RDEB severe cohort across the whole study, this group saw the largest improvement in itch at 23.7%. Now at 3 months in this severe cohort, we didn't see improvements in the skin assessment scores. Now if we look at the month 6 results across the study, if we focus on the under 10s, we see, again, this is the largest representative cohort of 21 out of 30 children, 57%, 12 children had RDEB severe. And here at 6 months, the Itch Man Scale showed the largest reduction across the study now of 26.7%. It was 20.2% at 3 months. And this itch reduction has been maintained over the 6-month study period. And now we're starting to see iscorEB scores showing great improvement, which were not observed at 3 months. We're seeing at 6 months now an improvement in all of the iscorEB scores, including the clinician score of 4.8%. The skin score was reduced by 8.1%. The overall improved by 4.3%, and the patient's reported scores improved by 3.9%. We didn't see these improvements at 3 months. And these improvements are in keeping with qualitative analysis data and the interviews, which I'll present shortly. Over the age of 10, at 6 months, we had 9 children in this group. And as we saw at 3 months, there were improvements in pain scores, but there was a further reduction in pain compared to 3 months with the worst pain now falling from 2.8% to 8.3%. This is an 8.3% reduction from baseline. The EBDASI activity score has also shown an improvement of 3.4%, which was not seen at month 3. Again, there was insufficient data for itch in this age group. When you're looking at the month 6 results from the RDEB intermediate, this is results from 16 children. What we're seeing at 6 months post-CORDStrom infusions that many of the positive results have disappeared, but there are still few outcomes that are favoring the cells even 6 months after the infusions. And that includes an improvement in the iscorEB clinicians, in the iscorEB skin component and the EBDASI activity. And importantly, itch reduction as per the Itch Man Scale is still reduced at 6 months by 14.6%. Now in the RDEB severe cohort at 6 months post infusions with CORDStrom, we're seeing a maintained reduction, even further reduction from 3 months of 27.5% across the whole cohort of RDEB severe patients. This sustained reduction of itch is likely to lead an improvement in wound and reducing the disease severity because now the iscorEB scores, which were not detected at all at 3 months, are showing an overall improvement of 9.3%, a patient score improvement of 9.6%, the clinician score improved by 6.4% and the skin score by 2.8%. Looking at the safety across the study. In terms of adverse events across the whole study, there were 211. 111 were on cells and 100 on the placebo. 22 were minor, 13 possibly related to cells, but these resolved spontaneously. 8 of the 9 were related to headaches. Again, these resolved spontaneously within 24 hours. In terms of serious adverse events across the study, across 124 infusions, no serious adverse events were documented with the study with cells or placebo. There were 28 SAEs reported, 14 in each arm, but none were related to treatment. So what about the qualitative results? 13 participants, 8 parents and 5 children completed interviews at 2 time points, 3 months post infusion and then 3 months post the second infusion, so either placebo or cells. 10 of the 13 interviews noticed a clear difference in favor of the cells compared to placebo. There was a strong feeling that people, patients, parents knew when they had received cells by the impact on the patient's symptoms and the improvement in quality of life. In fact, all intermediate patients in children and one severe reported that the cells had a positive impact on their quality of life. And this impact was positive generally for the intermediate patients more than the severe. Some parents reported difficulty when the symptoms were coming back and the comments of the short duration of some of the effects and benefits from the treatment. This is an example of some of the interviews. This is an under 6 patient. After the cells, the parent described that wound healing was faster and that they changed the frequency of dressings. After the placebo, they still found there were some positive benefits with healing, and they talked generally about improvements since starting the study. This is a young patient under the age of 1 that received cells first, and we're likely seeing a long-term benefit of cells in the very young children that have this treatment. The second interview was an under 6 patient with RDEB intermediate. So the parent was interviewed, and after the cells, they reported a huge benefit all around, improvement in energy, eating, wound healing and recovery time. After the placebo, and remember, this is a blinded process, both interviewee and [ interviewer ] did not know which order they'd had the treatment. But after placebo, they reported no change this time compared to the first infusion, where there was a great improvement. Patient 3, C. After the cells, the family reported that they felt there was a significant positive change since the infusion. The skin was less sensitive. Wound was healing, was quicker. There was less itch, less pain. The patient, this is a 10 year old, reported significant decrease in wounds, in blisters. There's less pain. Wounds were healing faster. There was improvement in sleep, and general activities became easier to do. After placebo, the child said there was no impact of this infusion compared to the first when they thought that it had helped. And the parent said that eye pain and itch was worse after this infusion compared to last time, where the first infusion was much better. And so it goes on. So the conclusion from this powerful qualitative blinded analysis, 10 out of the 13 interviews knew when they had cells because they could feel the benefits which they did not feel from the placebo. In the 3 that was less clear, I've mentioned the first, which was a very young child who had cells first, and we suspect that the effect of this treatment continued. The other patient was a severe 10 year old who reported minimal change with both cells and placebo. And the third was an intermediate patient who felt that there was benefit from both periods, but the parents strongly felt that they knew that the cells had benefit and the placebo did not help. So when we're drawing conclusions and drawing the results of this study together, conclusion from the 3-month data showed benefit across all patients receiving CORDStrom. And these benefits were seen in the Itch Man Scale, in the iscorEB clinician score and in the iscorEB skin involvement. Under the age of 10 patients, including severe and intermediate, showed mild improvements in their iscorEB and skin scores, but the Itch Man Scale had a large response with approximately 20% improvement. Now the intermediate and the younger patients under the age of 10 saw the greatest effect with improvements of their skin with iscorEB reduced by approximately 10%, pain reduction by 20% and itch score reduced by 16%. Patients over the age of 10 saw a large reduction in their 4 pain scales but not in their skin. Severe patients across all the study at 3 months didn't show an improvement in their skin scores at this stage, but after the cells, they reported the largest impact of itch with approximately 25% reduction. Qualitative interviews showed positive effects in favor of the treatment overall, and the largest benefits were reported in the intermediate and under 10. The severe and older patients over 10 didn't show changes at this point in their skin scales, but the itch and pain improved greatly. From the 6 months data, we can conclude that CORDStrom have proven to be beneficial treatment with no safety signals in patients with recessive dystrophic EB from the age of 6 months over the whole study. The overall improvement of outcome measures were seen with the largest effects in the younger and intermediate patients. Itch reduction is maintained 6 months post infusion across the whole Itch Man Scale cohort with the largest itch reduction seen in the RDEB severe group, in fact, at 6 months post infusions at 27.5%. With this itch reduction over time, we're seeing improvement in the iscorEB scores, which have improved in both the severe and intermediate cohort. But the large improvements in iscorEB in the RDEB severe cohort was not seen at 3 months, and now we're seeing improvements in all aspects of the iscorEB, including the overall score, the patient, clinicians and the skin score. Now these observed skin improvements and this wound closure is likely, in my opinion, to be disease modifying, improving pain and quality of life in these children and families and likely to reduce the long-term risk of squamous cell carcinoma. So thank you for listening. And now I'll hand over back to INmune Bio.

Thanks, Anna. That was excellent. So as Dr. Martinez has shown you, epidermolysis, and particularly RDEB, is a horribly debilitating condition. But most importantly, it's a multisystem disorder. While Krystal Biotech's topical drug has had an impact, it remains a very considerable problem for these children. Indeed, it's a side effect of VYJUVEK treatment. And this requires a systemic rather than a simply topical solution. CORDStrom may be used stand alone or possibly indeed as an adjunctive therapy in the 4,500 potential RDEB patients in the United States, the U.K. and Europe. As you've heard, Dr. Martinez concluded the randomized placebo-controlled double-blind crossover multicenter trial alongside colleagues at Birmingham Children's Hospital and with INmune Bio, and over 120 infusions were delivered as day case procedures with no serious adverse events related to CORDStrom. The formulation and packaging were designed for ease of use in a routine clinical setting with drug transported on dry ice and stored in conventional pharmacy freezers prior to administration. The reported benefits that you've seen were significant clinical improvements in itch scores and skin involvement. So a previously published trial using umbilical cord MSCs from single donors in RDEB showed clinically important reduction in itch and wound healing in recipients of 3 fortnightly infusions. We're seeking to confirm the effects on wound healing in an open-label extension of MissionEB, which will test 3 repeat cycles of the fortnightly treatment. This will run in the U.K. initially while we submit an IND in the U.S. for U.S. patients. But while this extension trial is ongoing, we'll use the data you've just seen presented by Dr. Martinez to submit a BLA in the U.S. later this year, followed by applications in the United Kingdom and European Union. Following the launch in the U.S., the product may be eligible for a PRV by September 2026. So having shown you the efficacy and safety of CORDStrom in RDEB, we wanted to share with you why it's a drug delivery platform and not just a single treatment. I'm sure you're seasoned followers of the cell and gene therapy space and are well aware of the somewhat inglorious history of mesenchymal stromal cells. And from the early description of these cells almost 50 years ago, it took a further 30 years for the first steps towards commercialization of their potential with the founding of Osiris Therapeutics in the U.S. This was somewhat prescient since it was a full 10 years before human cells became developable as medicines in the U.S. But it was a paper from the Karolinska in Sweden in 2008, which gave full validation of the potential of MSCs to treat serious diseases, in this case, steroid-refractory graft-versus-host disease in recipients of allogeneic hematopoietic stem cell transplants. And this paper justified Osiris Therapeutics' attempts to commercialize that specific indication. However, the basic research showing MSC abilities to enhance wound healing, suppress T cells and differentiate into cells of different lineages led to an explosion of clinical trials, most of which failed. Nonetheless, Osiris pressed ahead and obtained a BLA in Canada in 2013 for use in steroid-refractory graft-versus-host disease and sold the drug to Mesoblast, which then went on to achieve FDA BLA as remestemcel-L in December 2024. Meanwhile, the nomenclature for these cells remains controversial with the International Society of Cell & Gene Therapy requiring the term mesenchymal stromal cell, whilst many journals still publish papers describing these cells as stem cells. But after 3 days of discussion at the NIH with the FDA and other regulatory agencies in 2015, the FDA host rather tongue-in-cheek described them as magic sticky cells. We've chosen to use the name CORDStrom since these are mesenchymal stromal cells isolated and expanded from umbilical cord tissue from 4 or more donors. So why has there been such a dismal success rate? Well, we think there are 4 primary problems, and we've solved all of those with CORDStrom. First, the source. There are multiple sources of MSCs. Most of these are adult sources, and there's great heterogeneity of adult donors. Umbilical cord tissue is actually a much more controlled source, and the donors are obviously neonatal. Secondly, the identity of the cells. The international identity of MSC is based upon 3 simple surface markers, proteins expressed on the surface of the cells, but there are many, many subsets of MSCs. In fact, many of them are probably unknown. Therefore, what happens is that individuals develop or companies develop products with a lack of a well-understood mechanism of action. As I said, there's great donor-to-donor heterogeneity, and that's even more significant in adult donors. There's source-to-source heterogeneity. But equally, when you expand these cells in vitro to produce a drug substance, the number of what are called cumulative population doublings, the number of times the cells double, can change the effectiveness of the cells or indeed their potency. And I'll show you those data later. And of course, when you grow these cells out to very large numbers, as Osiris was doing in the 2010s, many of them become senescent. Also, most of these trials that have been published that have been partially successful or failures have been investigator-led trials with a naive assumption that all MSCs are the same cell, and therefore, there's no need for isolation of the product. And what we end up with is a product, which is not truly a mesenchymal stromal cell. In other words, people have done these trials but failed to plan to develop the MSC product as a drug. In contrast, CORDStrom comes from a single source, umbilical cord tissue from multiple donors. The identity is not just based upon CD73, 90 and 105, but we have many other markers. And each of these are linked to potential efficacy of the drug, and therefore, we can provide -- produce a mechanism of action for each indication. The heterogeneity is overcome indeed by pooling the donors. So we can select donors, as you'll see in a minute, with specific characteristics and therefore, tune the product to be -- to target a particular mechanism of action. We only use umbilical cord MSCs, and these cells are known to have a very delayed senescence. In fact, in the indication of EB, we've taken these cells out to more than 50 population doublings, and they still retain their potency. Finally, in terms of clinical development, we've chosen EB to be our first indication, but the other indications we will move towards will only be those from which we can see data from randomized controlled trials or indeed meta-analysis of randomized controlled trials in the published literature. As you can see, CORDStrom was always developed to be provided as a drug. Our manufacturing techniques and our delivery techniques into hospitals as well as targeting the right disease means that we've taken this development as a commercial drug from the start. So what is CORDStrom? Well, as I've said, it's pooled. It's allogeneic, umbilical cord-derived mesenchymal stromal cells available off the shelf. The benefits are that it's extremely reproducible. But as you'll see, we can tune this so that the final product is different depending upon which disease we want to target. We've already shown it's extremely scalable in existing bioreactors, and we're currently working at 15-liter bioreactor scale, and we can take that to 80-liter bioreactors. But more importantly, because we have complete control of the manufacturing process in closed systems, we can operate multiple manufacturing lines in a single Grade D or ISO 7 cleanroom, which controls costs enormously. We already have qualified release assays in the case of EB but in -- being developed in the case of other indications, and these are ready for validation for a BLA submission. The product has been shown to be very stable in long-term storage many years currently. And we believe it's the lowest cost of any MSC product that's being developed or is indeed likely to be developed. And as I've said, it's a platform for spin-offs. We have an intranasal-administered product in animal studies at the moment. That product came from a genetically modified version of CORDStrom carrying TRAIL, and we can genetically modify the cell to carry a number of different payloads. So why is it so good? Well, one of the great advantages is its reproducibility. And if you look at the slide on the left-hand side, we know that the optimum product for EB is a product that's been through between 25 and 30 population doublings. And so if we look at here at 30 population doublings, the time it takes for those cells in culture to divide 30x, we look at singles, individual donor products in the red line, you can see they grow more -- they grow at the same rate, but they start off at a slower rate. And the heterogeneity of the time in which it comes to each population doubling is more variable. Now this matters because in terms of deciding your manufacturing strategy, using expensive cleanroom space and getting staff available, you look at the proportion of the delivery with the product, the CORDStrom product, you can see that it's much more reproducible in terms of the number of days it takes to get to an individual passage. But equally well to get to 30 population doublings, it gets there 8 days faster than the single cords from the same cultures. This is a substantial saving in manufacturing costs. But more importantly, if we look at the data in the middle table, you can see that CORDStrom, these are 3 different versions of CORDStrom with different 4 cord donors. The donors are listed down the left-hand side. And looking at a single parameter of MSC function, the secretion of vascular endothelial growth factor, you can see that some cords like UC-1 fails to secrete VEGF at all, and indeed, the 2 CORDStrom products it's in, P4A and P4B, it still doesn't secrete VEGF. Whereas umbilical cord 3 is a high secreter of VEGF. And indeed, the CORDStrom batch in which it was included, P4C, it continued to secrete a lot of VEGF. So by selecting the right cords to make up our quads, we can select products that are high secreters of VEGF or indeed good wound healers or other individual characteristics. Also, the fact that when we pool cells we can change their potency is shown as an example on the right-hand side, where the secretion of IDO, which is an immunosuppressive cytokine involved in suppressing Th2 responses in RDEB and improving wound healing and reducing itch, you can see here that the amount of IDO secreted in the stimulated CORDStrom is significantly greater than the IDO from matched umbilical cords in -- that haven't been pooled. Finally, we've defined that the best characteristics for CORDStrom in EB are from cells that have been grown to between 25 and 30 population doublings, with 4 umbilical cords pooled to make a single batch of the working cell stock. One working cell stock, the one that's been used for the children you've seen treated in the current MissionEB trial, actually generates enough for 80 million annual treatments. There are 1,000 -- 12,500 total EB cases in the U.S., of which 3,500 are DEB cases. So one optimized working cell stock pool will actually treat over -- all the patients in the U.S. for over 6,000 years. So in summary, CORDStrom is actually a revolutionary MSC drug. It's very unlike the others that have been developed previously. We have patents and manufacturing IP owned by INmune Bio. It grew out of work that was done in my lab, leveraging skills and manufacturing techniques developed for INKmune. It's highly reproducible. And as I've shown you a little bit of data, it's very tunable, so we can select it for different disease indications. It's highly cost effective because of the scale at which we can manufacture. And we have established mechanism of action and potency assays for a number of different indications. More importantly, it's truly off the shelf with local near patient storage and conventional minus 80 freezers that every pharmacy has. There's no post-thaw washing of the product, and it can be thawed in automated thawers at the patient bedside. It's safe, as you've seen already from the data Anna presented, and it's formulated for day clinic use, much like INKmune has been. Epidermolysis bullosa is a perfect initial indication for this drug because of the efficacy in the double-blind, placebo-controlled crossover trial you've just seen and the fact that we have ODD and RPD granted by the FDA already and has potential eligibility to receive a PRV. There is an urgent unmet need in this disease, particularly for the treatment of itch, and the open-label trial to take this into more additional administrations is already approved in the U.K. and ready to go. As you can see, there's a rapid route to BLA, particularly using itch as the indicator, and a large market opportunity with an estimated 2,000 people in the U.S., U.K. and EU suffering from RDEB. So thank you very much for listening. If you have any questions, please, I'm very happy to take them.

Thank you, Mark. [Operator Instructions] Our first question comes from George Farmer at Scotiabank.

Very interesting presentation. Just wanted to -- maybe you could give us some clarification on how INmune got here. I think a lot of people may be surprised to see this all of a sudden at the top of your pipeline portfolio slide. And then also maybe you could talk about the discussions you've had with FDA and as to whether itch is a meaningful end point to grant approval for this product. And what is the threshold that the agency would be looking for?

Thanks very much for the question. Yes, how is a very interesting scenario. Many of you may know that I am still a part-time full professor at University College London. And so I have some responsibilities outside the company. And this product, the CORDStrom product was an invention that I came up with academically to support a trial in non-small cell lung cancer, where we transduced the cells to express TRAIL. Subsequently, we developed this academically. And in 2019, Anna Martinez approached me together with NIHR, the funding body, to provide these cells into the MissionEB trial. But the requirement from NIHR was that they had to be provided by a company. Now many of the techniques that we'd used to develop INKmune within the company were identical to those that we had been working on for CORDStrom. So we bought the drug into the company on the grounds that we were solving a problem for a clinical trial, and it was revenue generating and supported the INKmune program. So this has been going on as a trial funded academically with no input from INmune Bio financially. And what came out of it were data that made us realize that we had a moral obligation to develop this drug for the children and obviously, a great opportunity for the company. So we've been able to modify the IP so that we own it. It's independent of the original work from the university, and we have a really very promising drug. In terms of the FDA, we went to them asking them whether itch was a registrational end point, and they supported that. What we also wanted to know is whether the manufacturing in the U.K. using U.K. donor cords was appropriate, and they gave us clear indications how that would be eligible for the BLA submission. So yes, we came back from that with a clear route to delivering a BLA by the end of the year.

And do you think you've hit those -- the thresholds that the agency would be looking for as far as impact on itch?

Yes, I believe we have. And we need to look at the data that we've just got access to from that trial to interrogate it more deeply in terms of the -- as Anna alluded to, the breakdown of the patients in terms of their disease severity and age to pull out the particular data that will be most useful in our submission of the BLA. But yes, I believe we have hit those targets.

Our next question comes from Gary Nachman at Raymond James.

All right. Great. Thanks also for the presentation and very interesting data. So yes, I just want to follow up. In your meeting with FDA, was there any talk of a potential confirmatory study that might be needed before filing since it was only in 30 patients studied in the Phase II and in the U.K. And it seems there were different outcomes for different subsets of patients, so like you just mentioned, whether in terms of age or severity. So there are a lot of different ways to cut that data. And then also just how clinically meaningful is a 27% reduction in itch and the likelihood that, that translates to skin healing for this condition?

Okay. Well, the discussion with the FDA was a written response. So we didn't have a one to one to answer individual questions, and they came back to us with just clear indications of -- and answers to the questions that we had raised, which was, was itch a meaningful end point that was fit -- suitable for a BLA submission. And they didn't question that. The question about numbers of patients is very interesting. 30 patients in a randomized controlled crossover trial is actually a very significant number in a disease as rare as RDEB. And indeed, the VYJUVEK skin cream reported was given a BLA on the basis of a smaller number of patients, I believe. So I don't think the patient numbers are an issue here. I think what we're talking about is the degree of improvement. Yes, 27% doesn't seem very significant, but the itch score only has 5 scales on it and scale 0 is perfectly normal [ like URI ]. Scale 1 is tolerable with not affecting your quality of life. So it's 2, 3, 4 and 5 that are really important. And what -- a 27% reduction is a whole number, a whole score change. So if you imagine a child going from score 3 to score 2, they've gone from something that's interfering with their quality of life to something that actually is -- removes any degree of patient pathology. So once again, those data will come out from a more in-depth analysis of the data. But yes, 27% reduction in itch, as I think Anna alluded to in her -- presented very nicely in her presentation, is a significant change clinically for these children and for the carers, their parents and other carers that have to look after them.

Our next question comes from Joel Beatty at Baird.

I'm still trying to sort out exactly what data comes from like comparison of a baseline versus from the placebo-controlled portion of the trial. Could you characterize the magnitude of benefit from the placebo-controlled portion of the trial and if there's any p-values to share there?

So the p-value has become somewhat meaningless in such a small patient population. It's very difficult to get a p-value. And indeed, what it means statistically is questionable as well. The change that -- the way in which the change has been calculated has been done on a patient-per-patient basis comparing pre and posttreatment, so -- in an unblinded fashion. So we haven't seen these data. They've been handled by NIHR statistical unit in the U.K. So I can't tell you in terms of how the data were analyzed pre and post but that they are percentage changes for the patient population between the pre and the posttreatment. I guess it's difficult to do it without a slide and -- a slide to present the data, I'm afraid.

Our next question comes from Elemer Piros at Rodman & Renshaw.

So I don't know if I missed this. But was there a report on complete wound closure rates from the cohort?

No. So there have been -- the wounds are based upon a scoring system that Anna presented earlier. So there were no complete wound closures. As I said, these children only had 2 doses, and the clinical trials showing MSCs affecting wound closure have come from children and adults treated with 3 or more doses, and that's the open label. We hope we'll lead to that. But what we're -- we do know from other studies that children where itch is managed by physically preventing them from scratching do get improved wound healing. And indeed, we know from our in vitro data that the MSC products we produce secrete the right cytokines for promoting wound healing. And indeed, in the release assay for the drug, one of them is the demonstration of enhanced wound healing in an in vitro assay. So we do -- although in this study, the wound healing was notable, but there were no complete wound closures as far as I'm aware. We do expect to see with, a, with larger numbers of interventions, but b, with longer follow-up that we will see effects on wound healing. But the BLA submission, the indication will be itch.

Yes. And Mark, you also alluded to potentially using the product in conjunction with the Krystal Biotech, I think VYJUVEK. Now looking at the prescription information there, there is only about 10% rate or 10% identified as itch as a side effect. Do you think it's maybe a reflection of their ability to close the wounds? So if the treatment is not as successful, then the itch remains a concern there or in this population.

So as I understand the Krystal data, the itch is a side effect of the condition. In other words, this is a worsening or an appearance of itch that had not -- that does not occur in the placebo-controlled or non-treated individuals. So I would -- if a child is being treated with the Krystal product, I would imagine that a child with itch, whether it be a stand-alone itch or it's induced by the VYJUVEK, it would be amenable to treatment with CORDStrom. But you have to realize that, as Anna said, that this is a systemic disease. And so treating topical wounds with a cream, whether that be genetically modified or not, treating the topical wounds is only one element of the disease. These children have a systemic problem. And this is the only systemic treatment that is being developed at the moment.

Our next question comes from Jason McCarthy at Maxim.

How does the therapy compare in terms of its reduction to corticosteroids or anything else these kids might be being treated with [indiscernible].

That's a very good question.

And also, just on -- after that, 30 patients or so, it's comparable to the Krystal Phase III, and Abeona had 11, but there are 140. It was all about wound closure. But when you're talking about something -- I don't want to mischaracterize it as qualitative more in nature, not a lot -- no p-values here or anything, and itch and pain, do you need more than 30 patients for approval, do you think? Is the FDA going to come back and ask for more data?

So I'll answer the second one first. The FDA knows what the data are, and they didn't -- that wasn't something they put into their Type B response. So I can't speak for the FDA about how much data they would want, but that wasn't something that they highlighted as a problem. They knew that these data were from 30 patients. What they did insist upon was a randomized controlled, placebo-controlled trial, and that's what this trial is. And additionally, it's a crossover trial and it's multicenter. In terms of other ways of managing itch, if you -- it's a shame Anna is too busy with clinical activity to join us here. But one of the things that she initiated is, is that there is no satisfactory treatment for itch. Corticosteroids are counter indicated in these children. So they -- although they do get corticosteroid treatment, it's extremely difficult to manage. So the whole point of this study and the prior study in adults that Anna was part, too, but was not actually sponsored by Great Ormond Street, another U.K. trial, both of those have shown a significant improvement in itch in patients for whom there is no alternative.

So we have one more question coming from the webcast, Mark. What are the approval end points for EU and U.K. approval? And are there any other clinical trials in human underway with CORDStrom?

So I can't answer the first one, I'm afraid, and that may be something we can get to in a subsequent follow-up. But approval end points will need to be discussed further. But the data, as I said, that we presented to the FDA were based upon the data that you've just seen, and they didn't suggest that those were not approvable end points. In terms of EU, and I can't comment about the EU, I can say that in the design of this study, it's funded by the National Institute of Health Research in the U.K., which is part of the U.K. NHS, and there were extensive discussions with the MHRA about the design of the study and whether it will be approvable. I wasn't party to those because we are a contractor rather than a sponsor. But the -- on the basis of those, NIHR went ahead and funded this trial. So I can only interpret that their interactions with the MHRA were such that the end points that the trial was designed to achieve or to investigate would be adequate for licensing. But I'd say those are discussions that we are yet to have with the MHRA and the EMA. What was the other question, sorry?

The other question was are there other clinical trials in human underway with CORDStrom.

So there is a trial -- the precursor of CORDStrom, which we genetically modified the academic study, that trial is complete and is subject to a paper at the moment, but that's another one that showed safety and delivery of a drug to the clinical site. But apart from that, no, INmune Bio certainly doesn't have any other trials in planning or underway at present.

Great. Thank you, Mark. So this concludes our Q&A session. I'll turn it back to you for closing remarks.

Well, I hope everybody was suitably impressed by Anna's presentation. This is a very, very severe unmet need and something which seems trivial like itch actually has a major impact on these children's lives and indeed is, in many ways, the initiating fact that causes the severe skin wounds that you've seen. INKmune is the only planned systemic treatment for these children. And I think you'll agree that the qualitative data showed how important it is for us to get this out to the patient populations. We're looking very much forward to the open-label study in the U.K. and to opening its sister study in the U.S. and getting U.S. data. But thank you all for participating. Thank you very much for the very intelligent and probing questions that you gave us, and feel free to follow up with us at any time. Thank you very much indeed.