Hi everyone, my name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. I'd like to introduce our guests today: Vishwas Seshadri, or I'm sorry, Brian Kevany, the Chief Scientific Officer, and Madhav Vasanthavada, the Chief Commercial Officer of Abeona. We're going to do fireside chat format. Thanks so much for joining us. Maybe to start off, for investors who are new to the story, if you can give a one-minute intro to Abeona and your lead program. Yeah, so Abeona is a BLA staged cell and gene therapy, developing therapies for serious diseases. Our lead program, pz-cel, is a gene-corrected cell therapy for the treatment of large wounds with patients afflicted with recessive dystrophic epidermolysis bullosa, or RDEB. RDEB is a connective tissue disorder that results in the lack of connection between the epidermis and the dermis layer of the skin. This is due to the lack of a functional copy of the COL7A1 gene. These patients suffer a lifelong burden of open wounds that are extremely painful and ultimately lead to early mortality based on either infection or an aggressive form of squamous cell carcinoma. pz-cel's pivotal trial finished in 2022, meeting both co-primary endpoints of wound closure and reduction in pain. We also continue to collect data on our Phase 1/2A study showing durable wound closure for up to eight years of follow-up, differentiating us from additional therapies in this space and providing long-term wound closure for these patients. In 2023, we filed our BLA with an original PDUFA date of May 2024. In April of this year, we received a CRL that is entirely CMC related. We want to note that there's no clinical efficacy or safety signal data that was called into question as part of the CRL. The deliverables that are associated with the CRL are related to method validations and manufacturing process validations. We anticipate shoring up the items that were identified in the CRL by the third quarter of this year with a resubmission to the FDA in the second half of this year. In addition to pz-cel, we also have a pipeline of AAV-based therapies for inherited retinal dystrophies, leveraging internal programs that are as well as AAV capsids that were developed and verified at Abeona. But we're excited about the future of pz-cel and focus pretty much solely on pz-cel right now. Got it. Yeah, I think that's a great intro. And you're currently working on the resubmission of the BLA for pz-cel. Maybe if you can talk a little bit more about why FDA issued the CRL and it wasn't just like a three-month delay. And also, do you have any new insights into why the FDA issued the CRL ahead of the PDUFA date rather than just waiting for the PDUFA? Yeah, it's a good question. Yeah, I think the biggest thing to realize here is this is a very complex therapy. The BLA, the Module 3 of the BLA, which is the CMC area of the BLA, Module of the BLA, is more than 50% larger than a typical BLA because the agency considers our retrovirus as an additional drug substance. This is a very large module to get through in a 6-month priority review. We believe that the sheer volume of information that was included in the BLA, as well as ongoing discussions with the FDA during the IR process, led to a lack of time to be able to sufficiently review that. We had items that showed up even as late as the late cycle review meeting. We had communicated that we were planning to submit this relevant data in the May timeframe, which would have been running up very close to the PDUFA date. And we believe that it just did not allow enough time for the agency to review that data prior to the PDUFA date and thus initiated the CRL. Got it. Okay. Is there any explanation for why it came before the pseudophida then? No, I don't necessarily think there was any actual communication as to why. I think it just became clear that the amount of data that was going to be coming in was not going to meet in that timeframe. In reality, it allowed us additional time now to get ahead of some of the issues that they noted in the CRL. Got it. And based on historical data, what proportion of CMC-related CRLs get approved in resubmission? And what are the most relevant proxy examples that investors should be thinking about? Yeah, precedent suggests that CMC-related CRLs are more resolvable than clinical-related ones. We've done a number of deep dives in trying to understand this exact question. Ones that involve clinical safety or efficacy or require additional trials tend to be much more difficult to resolve than CMC-related CRLs. In a two-year period that we have reviewed, there were 17 CRLs that were initiated by the FDA. Of those, 12 were CMC-related, and of those 12, 11 were ultimately approved, whereas the five that were clinically related, none of those have actually been approved to this point. Got it. Yeah, it makes sense. You guys don't have to run any additional studies or anything like that, so primarily focused on CMC. I guess one of the concerns that we've heard from investors is that with CMC issues, it could get drawn out just based on the back and forth with FDA and what FDA could be asking for. Can you talk about similarities, differences between Abeona and Iovance as an example, as a company where this process was drawn out longer? And what did you learn from what they went through with their BLA process? Yeah, it's certainly an interesting proxy to compare to ours. We certainly looked into how they resolved theirs. The thing about Iovance's CRL, it was primarily related to questions of potency. This informed our communication strategy with the agency around potency. We discussed this very early and often with them prior to the BLA. As you'll note, there are no questions about potency within our CRL, you know, and so we feel like we have de-risked that aspect of the program. You know, Iovance's TILs program is a relatively complex therapy to address potency, whereas pz-cel, albeit a very complex modality, the actual mechanism of action, which is a replacement of collagen 7 expression, is a relatively straightforward metric to assess. Thus, we believe that we've already squared all of our potency questions with the agency. Got it. Yeah, that makes sense. And maybe if you can explain how pz-cel is manufactured, what's done in-house, and what's contracted out to a CDMO. Yeah, as a reminder, this is an autologous therapy. We take a patient punch biopsy, isolate the epidermal layer of the cells, expand the cells, gene-correct them using a retrovirus that we also manufacture in-house, and then expand the cells into multi-layer sheets that are then harvested and placed on the patient. All of this activity occurs for the retrovirus and the drug product occurs at our facility in Cleveland. This is a site that's already been inspected by the FDA as part of our BLA process. And we are a non-CDMO dependent facility. The only thing we utilize outsourced methods for is around some of our release testing for our retrovirus, but everything else is done in-house. Got it. Okay. Let's walk through some of the key requests that were in the CRL from FDA. One of the issues was the rapid sterility assay for release, which you expect to complete in July. Can you talk about what FDA wants to see and where you're at with addressing this issue? Yeah, so sterility assurance is something that we have always been very on top of for our product. We have had validated methods for both the in-process and drug product stages for our manufacturing process since the beginning of our pivotal trial. The thing to note about our product is it has a relatively short shelf life. There's only 36 hours after the product is harvested that it is required to be on the patient. And thus, the agency wanted us to institute a much more rapid form of sterility testing. As part of our ongoing discussions in the BLA process, we had discussions about what types of appropriate platforms we can use. We took one of the ones that they recommended. The equipment is already in-house and qualified, and the assay validations are ongoing as we speak. As you mentioned, we are on track to complete that by the middle of the third quarter. Got it. Okay. And so the next assay was on retroviral replication competency, expected to be completed in May. What's the deliverable here and what has been completed so far? Yeah, so as part of our drug product or drug substance release for our retrovirus, we have to demonstrate the lack of any replication competent retrovirus that could have occurred during the manufacturing process. This is a routine test that's done at a number of different CROs. As part of our routine testing, we have positive controls in those assays. The request from the agency is really around making sure that our matrix is not somehow masking the presence of an actual replication competent retrovirus. So what they have asked us to do is take our matrix and use that for the positive controls in the assay. We've completed this work, and we believe that the data that we've generated will satisfy the request from the agency. Got it. Okay. And you also mentioned sterile filter validation, which could be completed in June. What's special about the sterile filter and what do you need to show? Yeah, so there's nothing truly special about these filters. These are commercially available. They are validated by the manufacturer. Again, this is another one of those places where the agency is looking for us to use our own matrix to demonstrate the acceptability of these filters. We use them for both our retroviral vector sterile filtration as well as our media prep. They've just asked us to go back and redo the validations that the manufacturer did, but with our specific matrices. This work is ongoing at CROs as we speak and again, is on track to be completed prior to the communicated timeline. Got it. Okay. And for the cell-based identity assay, it's been a focus for investors out of the CRL request. Given the novel nature of pz-cel and lack of precedent, can you talk about what the discussion with FDA has been for this one and whether you've aligned on a final deliverable? Yeah, this is the only one that's within the CRL that is idiosyncratic to our process. It's the one that is the most technically difficult and scientifically challenging. That being said, we had already been discussing this with the agency, and we have utilized an informal meeting process post-CRL to align with the agency on both the timing of the sampling as well as some of the method validation aspects of the method validation. This work is ongoing, and we're actually, I think, in a much stronger position than we were even at the point of the CRL being issued to be very much in line with the late July timeline for when we plan to resubmit. Got it. Okay. That's helpful. And wondering if you can clarify for the identity assay if you need to show any characterization of cells other than keratinocytes? And are there threshold limits for proportion of keratinocytes versus other cell types? Yeah, so a good question. So as a reminder, our skin is primarily composed of keratinocytes, but it is by definition a heterogeneous population of cells. There are a number of other minor populations that are in our own skin. This is the same for our patients. When we isolate the cells as part of the manufacturing process, we do not specifically select for keratinocytes or any other cell type. The process itself encourages the persistence of keratinocytes, but not at the expense of excluding any other cell types. So we anticipate the sheets being heterogeneous as well. None of the discussions with the agency have involved the idea of characterizing the other proportions of cell types, just demonstrating that we have a higher proportion of keratinocytes than the other types of cells. Yeah. Got it. Okay. Just wondering, for these deliverables, are they all being done in-house or what's being done by the CDMO? How are you coordinating and aligning between FDA and the CDMO? Yeah, so it's probably a 70-30 split of in-house to CRO. There are some of these capabilities that we just don't have in-house and just are more appropriate to have at a CRO. All of that work is ongoing. I will mention that the CROs have been very collaborative in their understanding of where our timelines are and helping us meet the FDA's expectations. So I think all of that stuff is on track to meet the published timelines. Yeah. Got it. And you said you're going to have a Type A meeting after all the deliverables are completed. Have you scheduled that meeting? And can you talk about what you're going to discuss with FDA? And do you plan on providing any update to the public after the Type A meeting? We have not submitted for that Type A meeting. We will be having a Type A meeting sometime in July. In reality, what we're anticipating getting out of this is really giving the agency a comfort level around the data package that we're going to be submitting, providing them as much information of the data that we've generated so far and then what our strategies are for the outstanding items that won't be finished by then. And yes, we do anticipate continuing the level of transparency that we've provided up to date about this process. And the Type A meeting will definitely be part of that communication as well. Got it. And for the BLA timeline, you've guided to resubmitting second half of this year, and the FDA will have six months to review. Since there's no clinical deficiency, has FDA communicated they will only focus on the CMC deficiencies at this point? And is there potential for FDA to complete the review early? Yeah, our understanding is that as a complete response, that what they have identified in the CRL is the areas of focus. We will be providing all the data reports that are being generated now as well as redline versions of the BLA. It essentially functions as a very large BLA amendment. During a call after the CRL was issued, the agency was very clear that they would expeditiously review this package in order to get this approved as quickly as possible. They have six months, but we are optimistic that it will not take the full six months. Got it. Just wanted to clarify too, does the CRL cover all of the CMC-related issues that were in the Form 483? In other words, would you have addressed the Form 483 by addressing all of the issues in the CRL? The short answer is yes. All the issues that were identified, they are also being captured within the CRL's resubmission. Got it. Let's shift gears and talk about commercial. What's the hospital onboarding process going to look like for pz-cel? Yeah, so pz-cel is a cell-based gene therapy. So the onboarding process is very similar to other cell therapy onboarding process. And most of the centers that we're working with already have onboarded multiple cell and gene therapies. So there should be no surprise from that standpoint. Got it. You've said that you plan to launch at 5-7 high-volume centers. Have you decided which centers and where are you at with the negotiation with the hospitals? We are happy with the progress we are making. We are already under CDA with these centers. In terms of negotiations, we are educating these centers, talking about biopsy collection protocols, trade policies, and things of that nature in active discussions. We've gained the buy-in from the EB physicians at these centers. In fact, actually, they're acting as faculty champions. We have spoken with the surgeons at these locations. The progress is on track. These centers are going to be geographically dispersed across the U.S., and they have the ability to treat both adult and pediatric patients so that the access is also not that much of a hurdle for these people coming into these qualified treatment sites. Got it. Okay. And it's been a few months since Krystal's VYJUVEK has launched. Have you heard from doctors how VYJUVEK has changed how doctors are managing patients? Yeah, I think VYJUVEK's arrival is definitely, as a first gene therapy, a welcome for these people. We recently, earlier this year, surveyed about 64 physicians nationwide in a quant survey, two-thirds of whom had prescribed VYJUVEK to their patients. We think that one takeaway from this meeting is that there is room for multiple treatment options in this space. Because what we are hearing is really the limitation of dosing with 1.6 milliliters in the vial is just not enough to cover the large areas of the body. Being able to treat week after week, it takes time to close these wounds. So that just really opens the opportunity for durable treatment options. Really, that's the need that is coming out very clearly, especially if you look at the transient efficacy that we have currently with VYJUVEK. I think while we have BVEC, we definitely need other treatment options, and that's really what we are hearing. Got it. Are you hearing any anecdotal stories of doctors treating larger chronic wounds with BVEC now? Or what are some of the insights from the launch that you plan to leverage for your launch? We do hear anecdotal stories. Again, for smaller wounds, being the right place to treat. For larger areas, just the amount of time that it takes and the logistical aspect is something that needs to be factored in. The fact that, especially in the back of the body where you have a runny substance like a gel, to be able to keep that area covered and the months, weeks to months that it takes to close those wounds is something that is coming out, at least from our research. I think physicians want to track for a little longer to see how long it takes to close a wound. Some of the wounds they are seeing in 3-4 months out as opening and the need to retreat. So it's going to be an interesting thing to watch even from a payer reauthorization standpoint as to how that will pan out. But again, everything that underscores to clearly say that, yes, you need durable options for these people given the natural history of the disease. Got it. Interesting. Does that transient, the wounds reopening again, could that show up in the FAERS FDA safety database? Just wondering if that's something that's possible. It may not because wound reopening is part of the thing. So once a wound reopens, then for the prescribing information, the patient needs to, they need to reprioritize treating the open wounds first with ZEVASKYN. So it's part of the natural cycle of treatment. Got it. As you continue to interact with CAWALS to raise awareness and prepare for the launch, what have you heard from doctors about PZCell that they're most excited about? Really, of the multiple things, just ability to treat multiple wounds, large areas in a single application. The biggest of all is having unprecedented durability. We have followed our patients for up to 8 years, on average 5.9 years of follow-up. This is just pretty remarkable for this patient population. That is what they are most excited about. For other areas of the body where pz-cel cannot be applied, such as the elbows or the knees or the flexion areas, you do have the need for other treatment options. Got it. And what can you do before the launch to help educate and raise awareness around pz-cel? And what are your estimates on, or can you estimate on whether there's close to 10 patients on the radar that are waiting for pz-cel in the United States, or is it closer to 50 or 100 patients? We will get closer. As we get closer to launch, we'll have more accurate numbers. But the fact that we're working with high-volume EB centers as our qualified treatment sites, we know that there are anywhere from 20-50 patients per each site that these physicians tend to manage. We believe that the initial level of demand will come from these organic pool of patients. And we also are going to work with other centers of excellence. There are some 23 centers of excellence. We will be educating them so that those patients get funneled in. And this is a very tight-knit patient community, right? I mean, in terms of the awareness that they have a very sophisticated patient pool, they are tracking. And the fact that you will be able to announce what are the centers where we will be launching, that's going to drive self-referral as well. All of these factors come into play as we think about the demand going forward. Got it. Are you saying anything more about patient numbers? I guess, can you bookend a conservative estimate and aggressive numbers for eligible RDEB patients in the U.S.? So in terms of patient numbers, if we take the 1,200 number that Krystal has cited that are severe in these hospital centers, and we assume that because RDEB patients tend to be more severe than dominant, take 80% of that as recessive, which is close to 1,000. And then if you think that even not all of them are so into pz-cel eligible. So we think 750 is a good number as a good base. And if you were to really push me on the lower end, I would say maybe 600 as a really, really conservative number, just because the 64 physicians we surveyed, they've all identified 600 patients. So if you think that they have done magically identified all the RDEB patients out there, that'll be the lowest number. But we think anywhere 750-1,200 RDEB patients are our base. That we think is going to grow over time. Got it. And anything more you're saying about just label expectations at this point? We've talked in the past about whether it would include DEB more broadly rather than just RDEB. How could that impact, and how could that impact the commercial opportunity? Our going in is with recessive dystrophic EB. If we do get dominant, we did ask physicians, they think about a third of their dominant patients are eligible for pz-cel just looking at the profile and the severity of the phenotypic presentation. 3,000 roughly DEB, half of them dominant. 1,500, a third is roughly about 300-500 additional patients. Got it. Okay. That's helpful. And it's a good segue for the next question. If you could talk about pricing. There was a recent publication that's been discussed that talks about the cost of treating a patient with pz-cel. How does the latest cost data influence your thoughts on pricing? And can you provide any insight into what you're hearing from payers? I think you mean recent publication on BVEC, a publication. That JAMA paper came out. Yeah, that was interesting where they extrapolated the lifetime cost, assuming $300,000 per year, lifetime around $15 million. Well, we now know that BVEC is much more than $300,000. I think that pz-cel has a clear clinically meaningful differentiation. I think payers recognize that. We've had multiple payer conversations, preclinical exchange. The durability of treatment, ability to cover large areas is meaningful. We do think that we can price this commensurate with recently launched gene therapies in terms of the pricing expectation. Our pricing will be priced per a treatment cycle. A treatment cycle means you take the punch biopsy, manufacture the product, put it back on the patient. Some patients may need more than one treatment. So we will see over their lifetime, just given the extent of wound coverage that is needed. But our pricing will be more like recently launched gene therapies. Got it. We're pretty much out of time. Maybe to close out, if you want to highlight any key points that I forgot to ask and that you want to mention. I just want to say that commercially and opportunity-wise, overall, this is an attractive, I mean, we are confident of the opportunity. Tight-knit patient community coming in second to market in an area where there is unmet need for multiple treatment options and durability. The recent finance raise that we did, I just want to thank all the investors, and especially the new investors who have come in, who believe and have validated at least the story. We are just focused on executing the next milestone. Great. Thanks so much for joining us today. Thank you so much, Mark.