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spk04: morning ladies and gentlemen thank you for holding your conference call will begin in just a couple of minutes once again thank you for holding your conference call will begin in just a couple of minutes Thank you. Thank you. Thank you. Good day and welcome to the Abiona Therapeutics second quarter 2021 conference call. There will be a Q&A session after the presentation and instructions will follow. As a reminder, today's conference is being recorded. I'll now introduce your host for today's conference, Greg Ginn, Vice President of Investor Relations and Corporate Communications at Abiona. Please go ahead. Thank you, Paul.
spk02: Good morning, everyone. I would like to welcome and thank you for joining us on our second quarter 2021 conference call. The press release announcing the second quarter results and recent operational progress is available on our website at www.abionatherapeutics.com. On the call today with prepared remarks are Michael Amoroso, Chief Executive Officer of Abiona, and Ed Carr, Chief Accounting Officer. After the prepared remarks, we will host the Q&A session. We are also joined by Dr. Vish Seshadri, Head of Research and Clinical Development, and Dr. Brian Kavaney, a lead research scientist working on our preclinical eye programs. Before we start, I will review our safe harbor statement. Remarks made during today's call may contain projections and forward-looking statements regarding future events. Forward-looking statements are made pursuant to the safe harbor provisions of the federal securities laws. These forward-looking statements are based on current expectations and are subject to change and actual results excuse me, actual results may differ materially from those expressed or implied in the forward-looking statements. Various factors that could cause actual results to differ include, but are not limited to, those identified under the section entitled Risk Factors in the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed by the company with DSCC. These documents are available on our website at www.abionatherapeutics.com. And with that, I will now turn the call over to Michael. Michael?
spk11: Thank you, Greg. Good morning, everyone, and thanks for joining us. We are excited to be with you today, and I hope this call finds you and your loved ones safe in this still uncertain time. I'd like to begin this morning with a review of our three strategic priorities for this management team in 2021. First, bolstering our relevant operational experience, first and foremost for our management team, but also for our board members. delivering operational excellence, both timely and fiscally disciplined, to make sure we advance our clinical programs with meaningful data toward regulatory milestones. Third, prioritizing, executing, and advancing our preclinical pipeline toward the clinic, starting with a focus that we've discussed in our last call on the eye or ophthalmic gene therapy programs. Now that it's the midpoint of 2021, let's assess how we're doing. Priority one, accomplished. We have added specific operational experience to our management team and our board of directors. As noted on our Q1 call, we enhanced our board with the appointment of four new members. And most importantly, we strengthened our management team with the appointment of Dr. Vishwas Seshadri, who joined us from a senior level position at BMS to be our head of research and clinical development. In addition, we've added even more strength and experience to our clinical development program teams under Vish for ED and MPS. We've added relevant regulatory BLA experience, some of which has been paramount for our successful two Type B meetings over the last six months. Also, we continue to fortify our quality and technical operations teams in Cleveland as we move closer to the BLA readiness skill sets. All of these teams have been strengthened in 2021 thus far, and we will continue to be opportunistic about adding the best talent in the marketplace. Priority two, on target. We are delivering and have delivered operational excellence in achieving significant clinical milestones in a fiscally disciplined and timely manner. Let's start with our pivotal program in RDEM, EV101. I'm excited to tell you about the progress we made in patient enrollment, opening a second site for completing our registration trial, and ultimately all driving towards a BLA in 2022. I'm also excited to tell you about the progress made on our MPS3A program, which we had a successful and collaborative Type B meeting with the FDA last month, confirming that TRANSFER-A is the pivotal study for ABO102 in MPS3A. Our third clinical program, MPS3B, we are at the conclusion of enrollment at the high-dose cohort 3 level and will be closing the TRANSFER-B study for further accrual. We'll continue to follow these patients to assess long-term safety and efficacy, specifically neurocognitive development over time. And then priority three, also on target, we are advancing our preclinical eye programs toward the clinic with great speed and precision. During Q2, we reported the results of two non-human primate studies. We are on track to begin proof of concept studies in the second half of this year, and this will be toxicology study enabling into 2022 with some select ophthalmic indications. Now, let's take a deeper dive into the progress of our clinical programs and preclinical programs. Starting DB101, our lead pivotal phase three vital study for recessive dystrophic epidermolysis pilosa, or RDEM, we continue to build enrollment momentum in vital. There continues to be high and growing level of interest among patients and health care professionals, and we are very pleased to have recently activated a second clinical trial site at UMass Memorial Medical Center in Worcester, Mass., under principal investigator and world-renowned EB expert, Dr. Karen Wiss. Dr. Wiss is a professor of dermatology and pediatrics at UMass Medical School, and she's the director of pediatric dermatology. We are excited to have the UMass team join Aviona's mission of pursuing a standard of care for large and chronic R-dead wounds. This is a significant and major milestone, and I want to congratulate the team on this timely execution and thank the staff and team at UMass. Now, in addition to our lead trial site at Stanford Medical Center in Palo Alto, California, we can provide convenient treatment locations for study participants on both the West and East Coast, making travel logistics easier for patients and family. I'll remind our investment community, this was one of the major challenges we heard from the community in 2020 and thus far, In 21, it seems to be opening up with our pandemic. This second site is paramount to our success. At the same time, we're expanding necessary physician experience with EB101 as we plan for potential commercial launch in the U.S. We look forward to collaborating closely with the clinical team at UMass to screen and enroll subjects in vital as soon as possible. They are ready to go. Next, we continue our progress toward completing patient enrollment in the vital study. We have successfully administered EB101 to patient number five. As you may recall from our last call, this is the patient who opted to re-biopsy and make new product. We are extremely happy to report that the re-biopsy and manufacturing of EB101 product was successful for this patient and they have received their EB101 administration. The patient will be followed as per our vital protocol Additional patients continue to be identified and prescreened at both Stanford and now UMass to determine their eligibility for vital. As a reminder, the target for the pivotal trial is the treatment of approximately 35 large chronic wounds across 10 to 15 patients. Today, I'm excited to report that we have treated more than half of the target number of randomized pairs of wounds thus far. Next, let's turn our attention to our AAV platform, our second in-clinic program, ABO102 for San Felipe syndrome type A or MPS3A disease. Yesterday, we announced some very exciting news about our type B meeting with the FDA for the MPS3A program. We had a successful collaborative type B meeting and aligned with the FDA that the current single-arm transfer A study will serve as the pivotal study for ABO102. and potentially support a biologic license application, of course, depending on the data set. Since 2016, we have now treated 21 patients in the TRANSFER-A trial. We're excited about the safety and the magnitude of benefit seen with our investigational ABO102 product in the younger children from the higher-dose cohort, as we reported at the World Symposium earlier this year. We remain hopeful that if the more recently dosed children in cohort three displayed similar treatment effects as those already presented, we could have an invaluable data set in 2022. The patients we serve have tremendous unmet need. They cannot wait. And we remain fully focused on operational excellence with the intent of now delivering two pivotal data packages in 2022, one for EB101 and one now for ABO102. At the Type B meeting, we also aligned with the FDA on the definition of the primary endpoint for Transfer A, which is neurocognitive assessment using the raw score from the Bailey Scales of Infant and Toddler Development and the CalcMint Assessment Battery for Children. These scales will be used in sequence. This is data we're already collecting as secondary endpoints. They will move to primary in Transfer A and Vish will tell you a little bit more about that shortly. We are grateful to the FDA for their guidance, and we look forward to continuing to work closely with the agency toward our goal of bringing potentially life-saving therapy to patients afflicted with MPS3A. In the near future, we intend to share the Type B meeting feedback with the EMA, followed by potentially other regulatory authorities around the world, to guide our development plans for NAA in ex-US markets. Of course, the United States is our first focus. In addition to the guidance and clarity from the FDA on the regulatory front, we also shared some very encouraging new clinical data from TransferA that had not before been published this past weekend during an oral presentation at the 16th International Symposium on MPS and Related Diseases, our new MRI data. The data indicates that ABL-102 increases gray matter, corpus callosum, and amygdala volumes in the brain in three young patients with MPS3A at 24 months post-treatment compared to an afflicted patient without treatment. Now, let's talk about this for a moment. Brain volume loss is characteristic in children with MPS3A, and it's associated with long-term cognitive and physical disabilities. Specifically, gray matter is important for cognitive development. Corpus callosum for motor function, and amygdala for fear learning, as well as social and emotional development. We're excited about the MRI data, as are our clinicians, and it's consistent with previously reported results of preservation of neurocognitive development in the three younger children from cohort three that we have presented from Transfer A earlier this year with the longest follow-up. Moving onward to our last in-clinic program, ABL101 in the Transfer B study for MPS3B. As noted on the last quarterly call, we reported results from Transfer B at the World Symposium in February. The results to date, Transfer B high-dose cohort, like the high-dose cohort from Transfer A, show the drug is safe and well-tolerated, eliciting a dose-dependent sustained reduction in disease-specific biomarkers, denoting clear biologic effects. As I've reminded you in the past, we absolutely want to see biomarkers moving in the right direction, but the gold standard will be the collection of neurocognitive development data, and we need to let that mature into 2022. Previously, we shared the accrual in Transfer B was paused after dosing four patients in the higher cohort because the drug product, again supplied by Nationwide Children's Hospital in Ohio, had reached its two-year shelf life expiration. Some of our additional stability testing results showed specifications were not met for all parameters of transfer B protocol. However, specifically physical titer. However, after reviewing the test results based on equivalent potency, infectious titer, as well as the purity profile of the drug, the German Health Regulatory Authority, along with our DSMB, deemed that the benefit of the drug outweighed the risk and endorsed the use of the product for those remaining patients with highest unmet need through the German Named Patient Program. The NPP is a compassionate use program in Germany that allows individuals to be treated at the request of the retrieving physician and families. We're thankful for the authority and the DSMB actions acting quickly to get drug to these patients. To date, three patients have been dosed in the German NPP and a fourth is pre-screened and getting ready for treatment. The total number of patients treated now at the higher dose, one times 10 to the 14th vector genome per kilogram, between transfer B cohort three and now the MPP program will soon be eight children collectively. In parallel, we're in the process of closing enrollment in the transfer B study, and patients from both the transfer B and the main patient use program will be monitored with the same rigor for ongoing safety and efficacy of the high-dose AB101 product as they would have been within the Transfer B study. While early biomarker data are promising, neurocognitive preservation and development is the gold standard as we've discussed. We look forward to seeing two-year neurocognitive data beginning in the first half of 22 for some of the first patients dosed in the higher-dose cohort from Transfer B. And subsequently, we'll determine next steps for the program once we have some of these important and essential data points. As we await these data, I'll remind you that out of our wholly owned Cleveland non-CDMO dependent manufacturing facility, AB0102 for NPS3A commercial grade product is being made. Our experience in AAV production from our fully owned Eliza Litton Center will be highly transferable if and when we decide to manufacture AB101 for MPS3B program, of course, data-dependent in 22. Finally, I'll give a brief update preclinical, and I'll open it up to the group of questions. As previously noted, we conducted preclinical research with novel AAV capsules, including our Abiona invented and partnered capsules in six undisclosed eye indications. These eye indications represent opportunities in the U.S. alone of about 5,000 to 15,000 patients with the highest unmet need. This continues our ebiona identity as a fully integrated end-to-end gene therapy company focused on high unmet needs.
spk07: Please hold the line while I dial back out to my... Michael has rejoined.
spk04: Go ahead, Michael.
spk11: Yeah, I'm sorry about that to the community. I'll pick up where I left off with the preclinical programs. In the second quarter, we reported preclinical data from Argo 2021 and completed non-human primate studies. As a reminder, the NHP results showed that AAV204, one of our in-license AIM capsid programs, was superior to AAV8 using a recently developed novel route of ocular administration. and Brian will be on the call to tell us about that if you have any questions. In a separate NHP experiment, AAV214 and 214D5, two wholly-owned aviona capsids, demonstrated nearly identical levels of transduction compared with AAV8 of photoreceptor and retinal-pigmented epithelium cells, which are the cell types most frequently affected in inherited retinal diseases. These data are believed to be very important findings, as we'll remind you the gold standard today in ophthalmic subretinal drug delivery is AAV8. So we're enthusiastic about the findings. We're moving, as we speak, to proof of concept studies in the second half of this year, and this will enable toxicology studies in 2022. With that, I'm going to turn over to Ed, our Chief Accounting Officer, to review our financial results. Please, Ed. Thank you.
spk03: Thank you, Michael. I would like to remind everyone that the Form 10-Q is available on our website, which is where you can get additional details on our financial results for the three and six months ended June 30, 2021. While pursuing the key strategic priorities outlined by Michael, we have thoughtfully and carefully managed our spending decisions. Across each function within the organization, there is a balanced approach to not only focusing on moving forward towards our key milestones, but also using our cash resources prudently and on time to deliver results. Looking at research and development activities in the second quarter of 2021, we spent $7.4 million, which is consistent with the $7.2 million spent in the first quarter of 2021. Research and development spend includes the cost of the clinical development of the EB101 and MPS programs, the manufacturing of the drug products for EB101 and AB0102, and our preclinical ophthalmic research activities. Our spend on general and administrative activities was $5.5 million in the second quarter of 2021, down significantly from the 6.6 million spent in the first quarter of 2021. Generally, administrative spending includes the cost of personnel not working directly on clinical and preclinical activities, as well as professional fees, insurance, rent, and office expenses. The decrease in general administrative spend in the second quarter of 2021 results primarily from lower professional fees. Turning to the financial resources on our balance sheet, we had cash, cash equivalents, and short-term investments of $77.6 million as of June 30, 2021, as compared to $86.8 million as of March 31, 2021. The change in cash resulted primarily from $11.5 million of cash used in operating activities, partially offset by $2.3 million of cash from financing activities. Based on our existing cash, cash equivalents, and short-term investments, our ability to access additional financial resources, and our financial flexibility to reduce operating expenses if required, we believe that we have sufficient resources to fund operations through at least the next 12 months. And with that, I'll turn the call back over to Michael. Michael?
spk11: Thank you very much, Ed. We're committed to delivering operational excellence and bringing the gene therapies to patients with no approved treatments. We continue to advance our clinical programs with great operational know-how, many of our pre-existing team and new hire talent, and with fiscal discipline. We've activated a second clinical trial site at UMass. We're moving toward completing enrollment for EB101 Phase 3 Vital Study in RDEV. In MPS3A, we've aligned with the FDA on Transfer A as the pivotal trial and the primary endpoint, giving us great guidance and clarity on the potential regulatory path for AB0102. We are focusing our resources on completing these registration-enabling studies and preparing for the potential of two BLA filings. The second quarter was a highly effective and productive quarter for Abiona, and I want to thank our patients, their families, and our team, including our investors, who make this incredible drug development possible. With that, I turn it over to the operator to open up questions and answers.
spk04: Thank you. Thank you. Ladies and gentlemen, the floor is now open for questions. If you have any questions or comments, please press star 1 on your phone at this time. We ask that while posing your question, you please pick up your handset if listening on speakerphone to provide optimum sound quality. Please hold while we poll for questions. And the first question is coming from Kristen Kluska from Cantor Fitzgerald. Kristen, your line is live.
spk01: Hi, good morning, everyone. Congrats on the type B meaning outcome, and thanks for taking the questions. The first one I have is, could you remind us about the latest efforts and the current database for natural history in MPS3B? And given that for MPS3A, you've achieved the best results when treating early in the high-dose cohort, how should we also be thinking about perhaps the long-term data in cohort two, given that these patients are actually receiving a higher dose than MPS3A?
spk08: Thanks, Kristen. Good to hear your voice.
spk11: I think what I'll do, Juan Ruiz is actually with us on the phone, my lead clinician and MD from the 3B program. I think we're asking about the natural history registries that exist or repositories, if you will, that exist for 3B. And then, Kristen, I'll ask you to clarify, are we also asking about the expectation of a higher dose cohort from 3B and how, if we're expecting similarities to 3A? I just want to clarify the second part of that question before I have Juan answer, please.
spk01: Sure, but also the focus was on cohort 2 for MPS3B, just given that the protocol for the MPS3B trial includes higher doses relative to what you're studying for MPS3A.
spk11: Yeah, gotcha. Okay, so there's two doses in 3B that are actually, cohort 2 and 3, that are higher than the highest dose in 3A, obviously a different drug. And I think we also believe The data we showed in February was from cohort three also from 3B, the highest dose, one times 10 to the 14th. But I'll let Juan address both of those. So Juan, let me open it up to you to please address what natural history data exists for 3B and what we should be looking for from 3B, which arm we discussed as far as expecting neurocognitive results in 2022. Please, Juan.
spk09: Yes, thank you, Michael. Thank you, Christian, for the question. Regarding MPS3B, the nationwide children's hospital conducted a natural history study for 3A and 3B. So they used the information to inform the clinical trials. So there is already data gathered from nationwide on 3B patients. In addition, Ted Whitley at the University of Minnesota conducted a natural history study on 3B patients that has been published. we have access to this information that we are using to compare the children in our science and also Biomarin has released some data on a significant natural history study on 3b patients for their own programs so this information has been collected and it's been used and we are using it in a similar way to the information collected for 3a for our transfer a program so we are confident that there will be amount of information that is needed in order to to make the comparisons between the evolution of the children in transfer B with natural history data. Regarding doses in transfer B versus transfer A, I would like to remind first that the products that we are using in both trials, although based on AB9, both of them have some differences. The transfer A, I mean, the product for the 3A program is a self-complementary AB9, and versus the single-stranded AV9 vector for the transfer B. And this has implications regarding the speed of the gene transduction and also the amount of gene expression. So although the doses are different, and 3 times 10 to the 13 in transfer A versus 1 times 10 to the 14 in transfer B, this is somehow compensated with the higher expression derived for self-complementary AVs. In that regard, yes, the cohort two that is using five times 10 to the 13th in the transfer B program is similar to the higher dose in cohort three in transfer A, but it's difficult to compare because of this explanation. We are continually collecting data from these children, and we will have data along the year and they will complete two years follow-up before the end of the year and will be ready for beginning of 2022.
spk11: Thank you, Juan. Thanks for the excellent explanation.
spk01: Yes, thank you very much. And then moving on to ABO102, is there a specific time length of follow-up that you're looking to collect for the more recently treated patients in Cohort 3? as it relates to your comments about having a potential pivotal package next year?
spk11: Yeah, Kristen, great question. I'll take that one. So I think the timeline that you guys have heard me talk about on post-treatment, not that it's a perfect science, but I'll just remind you, is that two-year time point, knowing that neurocognition and development and those comparisons versus the scale of Bailey and ultimately, hopefully, Kaufman, and Vish will speak about that, I'm sure, coming up in another question, as Bailey turns to Kaufman as a child gains a certain level of acceptable cognitive age, which is obviously good news if you're turning to that survey. But the bottom line here is two years, Kristen. Two years is that time point we've talked about. Now, again, what does that relate to? Basically, our youngest patients are around 12 months. So when you really start to see the separation versus the historical controls out there, the natural history, is that three-year timeframe we've talked about, Kristen. So we want to make sure we've got at least two years post-follow-up of a treated patient. Again, that was based on the youngest patient at the time being treated about 12 months. You know, it could be lesser data. For example, if you're treating a patient at baseline who's two years old, you know, now at two years, they're going to be four. You should see a real clear delineation. So we think two years is a minimum follow-up. It's really important. Kristen, by the fall of next year, with the majority of all the cohort three, the three times 10 to the 13th from Fabio 102, from transfer A, We'll have almost all patients, almost all patients will be past two years by the fall, and we'll have some patients up to about five years. So that's what we say based on the magnitude of effect still being determined in the SAP with the FDA. We talked a little bit about, you know, it'll be a review decision, which is great. That's okay. I think people are very confident in the results we see thus far. But we think we get past that two-year mark and around the fall of next year for almost all of the patients, and we think we can have an invaluable package that early. So we'll have between two and five years on those patients.
spk01: Thanks. Appreciate that. And then the last question on the same program, in regards to the brain MRI data you recently shared, Were there any other measurements conducted at time points besides 24 months? And then just looking across these three patients in good detail now that you have some neurocognitive findings, biomarkers, and this data as well, could you talk about how all of these endpoints are correlating with each other?
spk11: Yeah, sure. I'm going to turn that back over to Juan because he can do better justice to that than I can. Juan, do you want to take that one, please? Thanks.
spk09: Yes, thank you, Kristen, and this is a very important question. Yes, indeed, we see a very good correlation between the biomarker data, showing a sustained decrease two years after treatment in CSF herbal insulfate, brain MRI data, where we see that compared to the brain atrophy that is progressing in children without treatment, the three children for which we have two years follow-up have shown this increase in gray matter volume, amygdala volume, and also corpus callosum volume, to mention just three areas of the brain. There are other data showing the same variation. So we are deviating from the brain atrophy and loss of tissue in the child, and this correlates with the cognitive evolution of these children that has shown over two years And in fact, 30 months and 36 months in them, because we have two years and a half and three years later, have shown continuous gain in cognitive skills, going beyond the ceiling of certain natural history and deviating clearly from what is expected according to natural history data.
spk08: Thank you, Juan. Thanks, Kristen.
spk07: Thanks.
spk04: Thank you, and the next question is coming from Murray Raycroft from Jefferies. Murray, your line is live.
spk05: Hi, good morning, everyone. Congrats on the progress, and thanks for taking my questions. I'll start off sticking with the MPS3A program. So for the neurocog time point, you mentioned both Bailey and Kauffman are used sequentially, and it sounds like Kauffman is used after Bailey. So I'm just wondering if you could talk more about this and the timing, and then separately, Can you provide specifics on how the two endpoints will be weighted in FDA's review? I guess will a patient have to improve on both measures or one or the other in order to succeed?
spk11: Hey, Maury, how you doing? Good questions. I'm going to turn it over to Vish and have him answer. The short answer on the second is no, they're not like co-primary endpoints. They're used in tandem. But, Vish, maybe you can walk the group through how Bailey and Kaufman kind of work together. when the handoff occurs, and it will be really one seamless test and not co-primary in any way. Please go ahead, Dish.
spk06: Sure. Thanks, Michael, and thanks, Marie, for the question. Just to clarify, Bayley and Kauffman are used sequentially, as you pointed out correctly, and not in combination. Bayley is used in children until they reach the upper limit of the scale at about 42 months of the development age. And after that upper limit is reached for Bayley, then Kauffman will replace Bailey to continue the evaluation of children. So in the natural history studies in MPS3A to date, it's important to note that Kauffman was not implemented mainly because the children never achieved a cognitive age close to that 42-month of development age, and that upper limit observed was about 30 to 31 months. So in Transfer A, however, we are already collecting data with Kauffman as children are reaching that 42-month cognitive age time point, which is something that's very interesting and we will continue to follow. So the short answer is they are not going to be combined. They will be measured sequentially. I hope that clarifies, Murray, your question.
spk05: Yes. Yeah, it's really helpful. And so it sounds like any data that you get on Kauffman, there's probably not much natural history data to compare to. And so any data you get on Kauffman will be important and kind of like a bonus for FDA's review. Is that correct? what do you think that's correct that's correct there's not very much natural history data for Kauffman it'll be descriptive for us got it okay thank you and then the other question was on um EB101 and so you said you dosed more than half of the target 35 wounds in five patients and so just wondering if there's anything you can say about the types of wounds you're seeing how they compare to the phase one two experience and then you've mentioned potential to complete enrollment in 2021
spk11: at this point can you put any more uh i guess finer points or clarity on timelines yeah maury thank you i'll take that michael um first and foremost uh yeah past that past the halfway point on wounds um large and chronic wounds remember guys uh different types of eb out there just a quick reminder our deb is the worst unfortunately the worst prognosis of all eb right now morbidity and mortality um The two different types of wounds that occur within R-DEB are kind of, if you will, earlier in the chronology of the disease, small clustering recurrent wounds. Think about a patch of blisters that opens, close, open and close. Some of the other life sciences companies are concentrating on such wounds. So we think that's great. We think that'll be super complimentary and we're rooting very hard for patients and our partner companies out there. And then where EB-101 kicks in, AB-Owner's work's been focused more, if you will, on kind of that last line of defense. The other half of the RDEV wounds, which is when those wounds are no longer recurrent, small, open, closed cluster, they just become one continuous chronic wound. Definition of large in the trial, 20 centimeters or greater. I'll remind everybody, we have entire legs, thighs, entire backs, hundreds of centimeters of wounds at times. And chronic, this is an important term. Chronic means the wound has now been open for six months or longer and can no longer close itself. That's where you need the regeneration of skin that we're obviously doing with the keratinocytes for EB101, and the surgical transplantation. So those are the wounds that we are focusing on in VITAL and the RDEP trial. I think, Maury, what I could tell you, obviously, it's an ongoing pivotal, so we're not looking at data along the way. I could tell you that feedback's been positive. I think what we're trying to replicate, and I think the consistency you'll be looking for here, is what we see from the Phase I-II. I'll remind everybody we just showed you durability data of almost six years. So this is really important, right? We know it's not a topical gel. We know you've got to take some biopsies from patients. You've got to make these grafts, and you've got to put them on. And the reality for this drug product is it's got to be worth it. And we believe the key here is in the worst of the worst wounds that lead to ultimate morbidity and mortality, the durability will be super important. So, Morrie, that's what we're looking for. Can't talk to you too much about results, safety, and efficacy because we are in pivotal. The second part of that, Maury, for EB was, I'm sorry, remind me the second part of that question.
spk05: Just based on if you have more clarity on timing at this point, you've already got greater than half in the five minutes.
spk11: Yeah, thanks, Maury. So, so far we're not changing our kind of, I always said it was, we said the terms wasn't guidance, but a bold goal we were putting for the team. Frankly, I joke, but because the patients really need us. So we're not changing our push to try to hit accrual by the end of this year. We're still on that. It is a bold goal. We truly don't know what the run rate will be monthly now that UMass is onboarded, Maury, right? So really important. We've treated patient five. We've got some candidates in the queue here. I won't say anything about the next patient just yet. It's a little premature. But now we've got two sites on the east and west coast. So we've got to see how that plays out. We can treat up to two patients a month in our facility right now, you know, while we're still in clin-dead stage before we turn on kind of commercial manufacturing size. So that's really important to know. So right now we're still holding to our bold goal of end of year. Later this year, probably on our next call, Maura, I can give you a better idea if it might spill into Q1 at all, if we get to get to our accrual, because it is tough to predict when patients kind of come into queue for the trial. But we're very, very pleased with what we're seeing. We think we're getting past the halfway point. It's very important. And now we've got two sites. If you just think about it, if that could expedite and we could double the amount of volume, I think we could be getting toward the end really close. Just a reminder to the group, once we accrue, why that's so important is from the last patient plus six months, that'll be when we have top-line data to say if it's a positive pivotal phase three at that point in time. So if we accrue at the end of this year, we're looking for positive top-line results mid-next year, Maury.
spk05: Great. That's really helpful. Thanks for taking my questions.
spk11: Thank you.
spk04: Thank you. And the next question is coming from Mani Faruhar from SVB Lyric. Mani, your line is live.
spk10: You guys, thanks for taking the question. I'm going to do a little more of a practical commercial one. We talk a lot about capacity and manufacturing as if it's number of patients, but I want to narrow in on more of a volume, or I guess an area question. When you're talking about large wounds, that sometimes can scale, as you said, the entire back, large parts of the chest, the very high percentage of body surface area. Can you help scale for us the absolute area of graft you could manufacture on an annualized basis um and how to think about that as some of these patients may require tremendous volumes of graft with implications for per patient cost per patient required manufacturing volume etc yeah mike good question and thanks good to hear your voice i'll take that one so it's a great question that the practical now really matt you know the fact of having practical conversations is good news right as we get closer to patients
spk11: That's a really important point. So let's talk about that a little bit. Let me remind you what one product of EV101 is. They are six sheets. One product is six 40 centimeters squared, a little bit bigger than maybe the largest business card you've seen. 40 centimeters squared sheets times six for 240 centimeters will be what one product delivery is, one product transplantation. I'll remind you how we got there. True empiricism, guys. That was how it was done at Stanford. And when we spoke to the FDA before starting the trial, of course, this is an investigational therapy. So it's not something that the FDA felt comfortable going even beyond that of, you know, go head to toe or double the size of the graphs. We truly follow the empiricism of what started at Stanford. So there's no perfect science for that. Of course, our process development teams are looking at, you know, what's the next product follow on? How do we enhance that? But what I will tell you is if you look at the EB-101 typical patient, as we've as we've kind of thought about our forecasting and the capacities we're going to need. About 50% of their wounds, so think about 2,000 to 2,500 patients a year with ARDEV in the U.S. specifically. It's not a concentrated disease, so you'd see similar, for example, you could expect similar in the EU5 and so on, so it's diffuse across the world. But if you just think about 2,000 to 2,500 patients with ARDEV, about 50% of their wound burden at any given time is large chronic wounds. The other 50% are small recurrent. Now again, do we think that small recurrent could be addressed? That's some phase four work we'll do with EB-101. First things first, we want it to be the line of defense for the most problematic and troublesome wounds. That's the positioning of the EB-101 product, durability in the worst of the worst wounds. So if you look at the R-DEB wound distribution of about 50% in these patients at any given time, there's also a range of different afflicted wound surface area, Imani. on these patients. And the best published literature shows about 30% of the body's surface area afflicted with wounds at any given time. So think about half of that being large and chronic. So if you do the math on that, at 240 centimeters squared, this will be a repeat treatment. Very important to understand. This will be a therapy that you're looking at probably a median of four over a lifetime to treat the entire wound surface area of large chronic wounds on the median EB-101 R-DEV patient. Okay, so I kind of walked you through some numbers there. You're thinking about three to four, a little more than three, about four administrations over the lifetime. So you could imagine maybe there's one or two procedures a year. Let's say two years in, you've had your three or four procedures and you've now covered that full body surface area. We think that's super important because we're improving this drug on improvement in quality of life when you really think about pain and the ability to close wounds. mortality is something that we'll have to look at long-term as we follow these patients in a long-term follow-up. How much body surface area do you need to close for how long? And so our goal here is to get to all of the large chronic wounds, and in some of our Phase 4 work, follow-on work, we'll focus on maybe the small recurrent wounds. Okay? So, Mani, I hope that gives you a little bit of a depiction.
spk08: Thanks. That's really helpful.
spk04: Thank you. There are no more questions in the queue. I will hand the call back to the management team for any closing remarks.
spk11: Well, Paul, operator, I thank you for your help today. I thank our investment community. Without your interest, without you guys writing the analyses, without your investments, we would not be able to bring these potentially and hopefully life-saving therapies to these patients. I want to thank the patients and families. And as always, I want to thank my team. I think the AB on the team has really shown a lot of progress over the last you know, nine plus months that I've been with them. And, you know, I'm very privileged to be part of this group. I think we're doing a lot with a small, mighty group of people. We're continuing to bring talent in. And we'll continue to talk to you about our, you know, our three management team priorities, talent, operational excellence, and then, you know, of course, first and foremost, in our in-clinic programs, two of which now we're in pivotal and we're looking and intended to bring to registration. We could have the valuable packages as early as next year for both. And patients really, really need that. So we'll keep you up to date on that. And then again, super progress that's been made in Brian's domain and Linus' domain and research on the Vish and of bringing, really prioritizing first our core pre-clin programs, the eye, and moving them closer to the clinic. So I thank the teams and the patients for all the work. I thank the investment community for their interest. And I know I'll speak to some of you in follow-up. So again, thank you. Please be safe, everybody.
spk04: Thank you, ladies and gentlemen. This does conclude today's conference call. You may disconnect your phone lines at this time and have a wonderful day. Thank you for your participation.
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