Good day, and welcome to the Abeona Therapeutics Second Quarter 2021 Conference Call. [Operator Instructions] As a reminder, today's conference is being recorded. I'll now introduce your host for today's conference, Greg Gin, Vice President of Investor Relations and Corporate Communications at Abeona. Please go ahead.

Thank you, Paul. 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.abeonatherapeutics.com. On the call today with prepared remarks are Michael Amoroso, Chief Executive Officer of Abeona; 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 Kevany, 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 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 the SEC. These documents are available on our website at www.abeonatherapeutics.com. And with that, I will now turn the call over to Michael. Michael?

Thank you, Greg. Good morning, everyone, and thanks for joining us. We're all excited to be with you today, and I hope this call finds you and your loved ones safe in still uncertain time. I'd like to begin this morning with a review of our 3 strategic priorities from this management team in 2021: first, bolstering our relevant operational experience, first and foremost for our management team, but also for our Board members; second, 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 towards the clinic, starting with a focus that we discussed on 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 1, 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 4 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 EB and MPS. We've added relevant regulatory BLA experience, some of which has been paramount for our successful 2 Type B meetings over the last 6 months. Also, we continue to fortify our quality and technical operations team 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…

Now Michael has rejoined. Go ahead, Michael.

Yes, 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 ARVO 2021 and completed nonhuman primate studies. As a reminder, the NHP results showed that AAV204, one of our in-licensed 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 AAV214D5, 2 wholly owned Abeona 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 it over to Ed our Chief Accounting Officer, to review our financial results. Please Ed. Thank you.

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 3 and 6 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 EB-101 and MPS programs, the manufacturing of the drug products for EB-101 and ABO-102 and our preclinical ophthalmic research activities. Our spend on general and administrative activities was $5.5 million in the second quarter of '21, down significantly from the $6.6 million spent in the first quarter of 2021. General and administrative spend included 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 and 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?

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, are moving towards completing enrollment for EB-101 Phase III VIITAL Study in RDEB. In MPS IIIA, we've aligned with the FDA on Transpher A as the pivotal trial and the primary endpoint, giving us great guidance and clarity on the potential regulatory pathway for EB-102. We are focusing our resources on completing these registration-enabling studies and preparing for the potential of 2 BLA filings. The second quarter was a highly effective and productive quarter for Abeona, 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 for questions and answers. Thank you.

[Operator Instructions] And the first question is coming from Kristen Kluska from Cantor Fitzgerald.

Congrats on the Type B meeting outcome. The first one I have is, could you remind us about the latest efforts and the current database for natural history in MPS IIIB. And given that for MPS IIIA, 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 2, given that these patients are actually receiving a higher dose than MPS IIIA.

Thanks, Kristen. Good to hear your voice. I think what I'll do, Juan Ruiz is actually with us on the phone, my lead clinician and MD from the IIIb program. I think we're asking about the national history of registries that exist or repositories, if you will, that exists for IIIb. And then Kristen, I'll ask you to clarify. Are we also asking about the expectation of the higher dose cohort from IIIB and how if we're expecting similar similarities to IIIA. I just want to clarify the second part of that question before I have Juan answer, please.

Sure. But also the focus was on Cohort 2 for MPS IIIB, just given that the protocol for the MPS IIIB trial includes higher doses relative to what you're studying for MPS IIIA .

Yes. Got you. Okay. So there's this 2 doses in IIIB that are actually the cohort 2 and 3 that are higher than the highest dose in IIIA, obviously, a different drug. And I think we also believe -- the data we showed in February was from Cohort 3 also from IIIB, the highest dose, 1x10^14. 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 IIIB and what we should be looking for from IIIB, which arm we discussed as far as expecting neurocognitive results in 2022. Please, Juan.

Thank you Michael and thank you Kristen, for the question. Regarding MPS IIIB, the Nationwide Children's Hospital conducted a natural history study for IIIA and IIIB. So they used the information to inform the clinical trials. So there is already data rather from Nationwide on IIIB patients. In addition, Chester Whitley at the University of Minnesota, conducted a natural history study on IIIB patients that has been published. So we have access to this information and we are using to compare the children in our trials. And also, BioMarin has released some data on a significant natural history study on IIIB 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 IIIA for our Transpher A program. So we are confident that there will be significant amount of information that is needed in order to make the comparisons between the evolution of the children in Transpher A with natural history data. Regarding doses in Transpher B versus Transpher A, I would like to remind first that the product that we are using in both trials, although based on AAV9, both of them, have some differences. The Transpher A, I mean, the product for the IIIB program is a self-complementary AAV9 versus the single stranded AAV9 vector for the Transpher B. And this has implications regarding the speed of the transduction and also the amount of gene expression. So although the doses are different and 3x10^13 in Transpher A versus onetime 1x10^14 in Transpher B. This is somehow compensated with the higher expression derived for self complementary AAVs. In that regard, yes, the Cohort 2 that is using 5x10^13 in the Transpher B program would be kind of -- I mean, similar to the dose higher dosing cohort 3 in Transpher A, but it's difficult to compare this explanation. We are going to -- we are continually collecting data from these children, and we will have data around the year, and they will complete 2 years follow up before the end of the year, and we'll be ready for beginning of 2022.

Thank you, Juan. Thanks for the excellent explanation.

Yes. And then moving on to ABO-102. Is there a specific time line to 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?

Yes, Kristen. Great question. I'll take that one. So I think the time line 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, that 2-year time point, knowing that neuro cognition and development and those comparisons versus the Scale of Bayley and ultimately, hopefully, Kauffman and Vish speak about that, I'm sure coming up in another question as Bayley turns to Kauffman as the child gains a certain level of acceptable cognitive age, which is obviously a good news if you're turning to that survey. But the bottom line here is 2 years, Kristen, 2 years of 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, 3-year time frame we've talked about, Kristen. So we want to make sure we've got at least 2 years post follow-up of a treated patient. Again, that was based on the youngest patient at the time being treated about 12 months. It could be lesser data, for example, if you're treating a patient at baseline who is 2 years old. Now at 2 years, they're going to be 4, you should see a real clear delineation. So we think 2 years is a minimum follow-up is really important. Kristen, by the fall of next year, with the majority of all the cohort 3, the 3x10^13 from ABO-102 from Transpher A. We'll have almost all patients -- almost all patients will be past 2 years by the fall, and we'll have some patients up to about 5 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 it, will it 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 2-year mark and around the fall of next year for almost all of the patients, and we think we can have a valuable package that early. So we'll have between 2 and 5 years on those patients.

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 3 patients in good detail now that you have some neurocognitive finding biomarkers in this data as well. Could you talk about how all of these endpoints are correlating with each other?

Yes. Sure. I'm going to turn that back over to Juan because he can do a better justice for that than I can. Juan, do you want to take that one, please?

Yes. Thank you, and this is a very important question. Yes, indeed, we see a very good correlation between the biomarker data. So in a sustained decrease 2 years after the treatment in CSF heparan sulfate. Brain MRI data, what do we see that compared to the brain atrophy that is progressing in children without treatment. The 3 children for which we have 2 years follow-up have shown this increase in gray matter volume, amygdala volume and also corpus callosum volume. To mention just 3 areas of the brain. There are other vectors showing the same variation. So we are deviating from the -- I mean brain atrophy and loss of TCA in the trial, and this correlates with the cognitive evolution of this children that has shown over 2 years, and in fact, 30 months and 36 months in them because we have 2.5 years and also 3 years data, have some continuous gain in cognitive skills going beyond the ceiling of natural history and deviating clearly from what is expected according to natural history data.

And the next question is coming from Maury Raycroft from Jefferies.

Congrats on the progress and I'll start off sticking with the MPS IIIA program. So for the neurocog time point, you mentioned both Bayley and Kauffman are used sequentially, and it sounds like Kauffman is used after Bayley. 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 2 endpoints will be weighted in FDA's review? I guess will a patient have to improve on both measures or 1 or the other in order to succeed.

Maury, 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 Bayley and Kauffman kind of work together when the handle off the curves, and it will be really one seamless test, not co-primary in any way.

Sure. Thanks, Michael, and thanks, Maury, 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 Bayley to continue the evaluation of children. So in the natural history studies in MPS IIIA 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 31 months. So in Transpher 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, Maury, your question.

Yes, 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 the right way to think about it?

That's correct. That's correct. There's not very much natural history data for Kauffman. It will be descriptive for us.

Got it. Okay. And then the other question was on EB-101. And so -- you said you dosed more than half of the target, 35 wounds in 5 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 I/II experience. And then you've mentioned potential to complete enrollment in 2021. At this point, can you put any more, I guess, finer points or clarity on time lines?

Yes, Maury, thank you. I'll take that. It's Michael. First and foremost, yes, past the halfway point on wounds, large and chronic wounds, remember, guys. Different types EB out there, just a quick reminder, RDEB is the worst, unfortunately, the worst prognosis of all EB right now, morbidity and mortality. The 2 different types of wounds that occur within RDEB are kind of, if you will, early 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 will be super complementary and we're rooting very hard for patients and our partner companies out there. And then where EB-101 kicks in, Abeona's work has been focused more, if you will, on kind of that last line of defense. The other half of the RDEB wounds, which is when those wounds are no longer recurrent small open close 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, 100s of centimeters of wounds at times. And chronic, this is an important term. Chronic means the wound has now been open for 6 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 EB-101 and the surgical transplantation. So those are the wounds that we are focusing on in VIITAL in the RDEB 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 has been positive. I think the -- what we're trying to replicate, and I think the consistency we'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 6 years. So this is really important, right? We know it's not a topical gel. We know there's -- you've got to take some biopsies from patients, you've got to make these grafts and you 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 Maury, that's what we're looking for. I 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?

Just based on -- if you have more clarity on timing at this point. You've already 30 or got greater than half...

Yes. Thanks, Maury. So far, we're not changing our kind of -- I always said it was -- we said the terms was in guidance, but a bold goal we were putting for the team. Frankly, I joke 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 5. 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 2 sites on the East and West Coast. So we've got to see how that plays out. We can treat up to 2 patients a month in our facility right now, while we're still in that 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 at the end of the year. Later this year, probably on our next call more, I can give you a better idea if it might spill into Q1 at all to get to our accrual because it is tough to predict when patients kind of come in the queue for the trial. But we're very, very pleased with what we're seeing. We think we're getting past the halfway point is very important. And now we've got 2 sites. If you just think about it that could expedite and we could double the amount of volume. I think we could be getting towards the end really close. Just a reminder to the group, once we accrue, why that's so important, is from the last patient plus 6 months, that will be when we have top line data to say if it's a positive pivotal Phase III 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.

And the next question is coming from Mani Foroohar from SVB Leerink.

I'm going to a little more of a practical commercial one. We talk a lot about capacity and manufacturing as it is number of patients, but I want to narrow in on more of a volume -- I guess to earlier question. When you're talking about large wounds, you are talking that sometimes can scale, as you said, the entire backs, large parts of the chest, a very high percentage of the body surface area. Can you help scale for us the absolute area of graft you could manufacture on an annualized basis 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-acquired manufacturing, volume, et cetera?

Yes, Mani. Good question, and thanks. Good to hear your voice. I'll take that one. So it's a great question. The practical now really -- the fact that we having practical conversations is good news, right? As we get closer to patients, that's a really important point. So let's talk about that a little bit. Let me remind you in one product of EB-101 is. They are 6 sheets, 1 product with 640 centimeters squared, a little bit bigger than maybe the largest business card you've seen, 40-centimeter square sheets times 6 for 240 centimeters will be what 1 product delivery is, 1 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. Go head to toe or double the size of the grafts. 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 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 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 RDEB in the U.S. specifically. It's not a concentrated disease. You'd see similar, for example, you could expect similar in the E5 and so on. So it's diffuse across the world. But if you just think about 2,000, 2,500 patients with RDEB, about 50% of their wound burden at any given time is large…

Thanks. that's really helpful.

And there are no more questions in queue. I will hand the call back to the management team for any closing remarks.

Operator, I thank you for your help today. I thank our investment community, about your interest, about you guys writing the analysis. 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 3 management team priorities: talent, operational excellence, and then, of course, first and foremost, in our in-clinic programs, 2 of which now we're in pivotal and we're looking and intended to bring to registration. We could have a valuable packages as early as next year for both and patients super progress that's been made in Brian's domain and Neena's domain and research under Vish and of bringing really prioritizing first our core preclinical 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.

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.