All right. Good morning, everyone. Thanks for joining us for the next half hour. My name is DaeGon Ho, one of the biotech analysts here. Joining me for the next half hour, we've got Abeona Therapeutics. From Abeona, we have Dr. Vishwas Seshadri, the CEO of the company, and we also have Dr. Madhav Vasanthavada from the company as well, Chief Commercial Officer and Head of BD. That's a mouthful, so I hope I didn't butcher those names. But thanks again for spending half an hour with us, guys. I'll turn it over to you, Vish. Just briefly introduce us to Abeona for those of us that are less familiar with the story, and we'll dive right into Q&A.
First of all, thank you so much. Good morning, and thanks for having us here, DaeGon. It's a pleasure to be part of this virtual conference. Before I get into what Abeona is all about, I just wanted to remind our audience that our forward-looking statements that we have issued, both as SEC documents as well as our press releases, detail out the risks associated with all the statements that we'll be making today, whether it's regarding regulatory or commercialization. But that notwithstanding, we've never been more excited about Abeona. We are a late-stage BLA stage biotech in the cell and gene therapy space for serious diseases, and we're looking to soon transition from being an R&D stage company to a commercial stage company, and we see a clear path to profitability. This is something that we're seeing for the first time in our company.
Our lead program, prademagene zamikeracel, or pz-cel, it's an autologous engineered cell therapy for a disease called recessive dystrophic epidermolysis bullosa, or RDEB in short, where patients have a monogenic underlying mutation where they don't have functional collagen VII produced in their body. What that leads to is a connective tissue disorder. Skin cannot remain intact, blisters, wounds, and leads to other complications like squamous cell carcinomas over the course of the disease. Patients seldom see beyond the ages of 30s and 40s. The leading cause of death in these patients is squamous cell carcinoma. The cumulative risk of that happening is above 95% once you hit the age of 25. You can see how debilitating the disease is. In clinical studies, our lead product, pz-cel, has demonstrated a coverage of large wound areas, of the most tough-to-treat wounds.
We'll describe that more in detail as we talk about it, which is large and chronic wounds, and shown sustained wound healing and pain reduction over many months and years after a one-time application of this therapy. So that's something that we're looking to bring forward to patients upon approval by the FDA of our BLA. And beyond pz-cel, we also have the in vivo gene therapy platform. We have AAV-based therapies in preclinical stages for ophthalmology monogenic diseases. And we also have partnerships, partnered programs with our AAV asset with Taysha Gene Therapies as well as with Ultragenyx. So we're at a very exciting juncture at Abeona and really excited to talk about it today.
Yeah, great, great. Let's dive into a little bit more on the pz-cel component you introduced us to addressing RDEB, which is a proportion of the dystrophic epidermolysis bullosa. I guess if you can maybe remind us, what exactly is the underlying mechanism that you're pursuing with pz-cel? And there is a drug approved already in the market from Krystal called Vyjuvek. How is pz-cel different? Can you talk to us a little bit about the trial, the size of the wound you were going after, and what you saw?
Sure. So pz-cel is autologous ex vivo engineered cell therapy. It is essentially epidermal sheets that are created from patients' own keratinocytes, which are from their own epidermis. And we culture these keratinocytes and correct the collagen seven missing gene situation by introducing that collagen seven gene and integrating that into the patient's own host genome. So these sheets that we create express the functional collagen seven, and they are sutured back onto the patient's wounded areas. And that produces the collagen seven and helps promote the wound healing and sustain that. Because it's an integrated vector, it's the basis, underlying basis for durability, because at cell divide, you do not dilute out the vector because the vector also divides as part of the genome. But that is why we have sustained collagen expression.
So in our Phase 1/2a clinical studies, we've seen biopsies of the treated sites from patients, even as late as 2 years or 3 years after it's been applied and the wound has healed, and we're able to see through IIF, which is an immunofluorescent technique that specifically looks for the collagen VII expression, and we're able to see that expression. Basically, that is the proof for the sustained expression of the transgene that we put in. So the only logical explanation that we have, which is hypothesis, is that there are some progenitor-type cells that may be dividing and maintaining the transgene expression over these years. So that's kind of the underlying mechanism of how pz-cel works. But in terms of the clinical data, we have 2 clinical studies that currently give the body of evidence for our approval.
One is a phase I to VIII study where patients have been followed for a mean of nearly six years and a maximum of about eight years. And we are seeing that the clinical wound healing as well as pain reduction are sustained over the follow-up period from a one-time application. And we also have a randomized study, which is a pivotal phase III study, the VIITAL study, where wounds were randomized between treated and untreated wounds, and we have seen statistically significant wound healing that is between the treated and the untreated arms. Now, something significant to note is the types of wounds that are included in our studies are distinct. These are the most challenging wounds to treat. If you take the dimension of size, which is a minimum of 40 cm, a wound was required to be included in our study. And the second aspect is chronicity.
How long have these wounds been open without the ability to self-heal? We had to have at least 6 months open for admission into the study. In reality, if you look at the average chronicity, these wounds have been open for about six years. That is the duration to which these wounds could not heal at all. It is because of that challenging nature of these wounds that you see that the control arm, untreated arm, the complete wound healing rate was 0. This is very much in contrast to if you look at the spontaneous complete wound healing rate in other studies. For example, the product that you mentioned, it's about 23%, if I'm not misquoting that, 23% of the wounds which were not treated healed completely. Basically, that shows you how difficult to treat these wounds were.
But it's important to note that the fact that we have treated in our clinical evidence the toughest to treat wounds does not mean the label needs to be restricted to just those wounds, because benefit could be extended to many other types of wounds. And interesting to note also is we've been able to treat multiple different anatomical locations in the body. You're looking at torso, extremities, front, back, and there are examples of wound healing in every which anatomical location that we've considered. That's also something that we will be discussing in scientific congresses very soon. So given the ability to achieve coverage and from a single treatment to provide durability for especially these chronic wounds, and if you look at the published literature, these chronic wounds had the highest risk of developing squamous cell carcinomas.
So we have a clear differentiated product, which we believe, and we not just believe, we're hearing the thought leaders tell us that you're going to need this product in addition to what you already have in the marketplace. So we are quite committed to bringing this product to patients. And as I said, we'll also continue to review literature on why we see the kind of durability that we see. And we will publish some science around what types of cells may have a progenitor phenotype in the sheets that we manufacture, and all that is coming.
Okay. On that point, a lot to unpack there, but if you can just remind us, given the durability element on the efficacy side, the treatment that you're administering is a retrovirus gene therapy, which I guess sort of at a high level people have associated with nonspecific integration and therefore some kind of a safety implication down the line. Remind us what you have seen on the safety front as you kind of follow these patients out long term. How should we feel about that retroviral element to this therapy?
No, great question. We do have a gamma-retroviral vector that does integrate into the host genome, as I mentioned, which is the basis for the durability that we see. There are two types of studying risk with these sets of vectors. It's true for retroviral vectors and to a great extent also with lentiviral vectors that have been used in CAR-T products, as you know, they're also integrating viruses. We have first, we do not inadvertently introduce a replication-competent retrovirus. That's important. And we just presented data from our clinical experience that in none of our manufacturing experience as well as patient follow-ups, there's about 120 data sample points that we've monitored. There's never been an instance of replication-competent retrovirus happening.
This is true of literature that's been published from various clinical trials testing more than 1,500 patients to date that RCR does not happen with these types of technologies, right? And so we are, and that's one of the things that the FDA had asked us to show beyond doubt, and we validate those assays and things like that. So RCR risk is something that we can put behind us. The second kind of risk that people talk about is insertional oncogenesis, because if you have in euchromatin areas of the host genome where there is a viral integration happening in a random way, is there, first of all, is there any additional risk or propensity for these types of vectors to integrate into a proto-oncogene locus? That is something that we have to demonstrate in our preclinical data through experimentation that there is not that additional probability.
It's what randomly happens. We have very strict limits on what the pro-viral genome copy number. That adds another layer of minimizing the chances that such events would happen. Finally, if you look at clinical data with integrating viruses, even on the CAR-T side, you've seen about 30,000 patients treated. You can count in double digits the number of patients who had secondary malignancies. Within that, there is a subset where a clone of the autologous ex vivo engineered cell was detectable in that secondary malignancy. Within that, we still have not seen hard evidence that there was an integration event in a proto-oncogene locus or something that is driving an oncogenesis there. So it's still kind of, there's literature to say this could happen, but the chances or probability of such events happening is going to be infinitesimally small.
Why that is important to note is we're looking at a disease whereby the age of 25, the cumulative risk of a patient developing a squamous cell carcinoma is almost certain, 95% in the disease space. When you put those two things side by side, I could say in layman's terms, yes, we do believe in doing no harm, but doing nothing may be the most harmful thing you would do. I think if you put it in that context, the risk-benefit profile for pz-cel is very favorable. That's why in our CRL, there's no question about the clinical data. It's all about CMCs.
Can I just quickly on that point? I do want to go into the CRL element, which is the bulk of the debate that's going on right now for your stock. The squamous cell carcinoma element, now that you are prepping to refile your BLA here, is there anything that you can add to demonstrate proven efficacy as to prevention of squamous cell carcinoma from your trials, or is that still going to be borne out over the longer term and not necessarily with the BLA?
It's the latter. What I would say is as part of our protocols, we have to analyze any squamous cell carcinoma that happens in these patients. We have seen the occurrence of squamous cell carcinomas, but never in treated sites, which is a great sign to see because chronic wounds are where squamous cell carcinomas commonly occur, but they have occurred in untreated wound sites and never on the treated wound sites. But that is not statistically robust enough for data set to make the claim, but it's trending in the right direction for us. Now, as we launch pz-c el, because we're a gene therapy, we're going to have registry data that is obligatory to collect. And this is where the source of the data will be, and we'll be monitoring these patients.
And so we'll build upon what we've already had with those 18 patients in our current clinical studies.
Okay, sounds good. Pivoting over to the CRL, I know that's more recent of an occurrence. You had kind of made some projections around when things could be complete as well as the guidance for second half BLA resubmission. So I wanted to kind of go through a laundry list, if you will. So starting with sterility assay validation, replication-competent retrovirus assay, sterile filter validation, and cell-based identity assay. Of those, how many were raised from the prior Form 483 that just became more of a repeat, as in how many of those assay development or amelioration technologies were already in place by the time CRL was issued?
So yeah, I think a lot of these questions that came up as CRL items started to be discussed as part of our late review cycle meeting, which happened around late, I think March, late March. And the sterile filtration validation is something that we had already seen in the 483. But the important point is, regardless of whether it came from a PLI or the inspection, or it came through just review of our submission as part of the IR process, it is all captured comprehensively in the list of CRL items, right? So that is what is important. And even more important, we are on track for getting all these data in place very soon. There is no showstoppers. Everything is on track and asked for how we had, exactly how we had predicted or forecasted will happen.
I would say approximately 80% of those items we already have generated the data. So report writing is what's going on. The remaining 20% is due course of time because these were new equipment or assets that were implemented in our premises, in our facility, and feasibility data has been generated. We feel comfortable that we're ready for the validation. The protocols have been finalized. It's just going through those runs to show that they're working within robust parameters. So we feel pretty good about where we are at this stage. So we're still on track for a second half submission.
Okay. Just to be clear, we are now in the third quarter. The RCR, the replication-competent retrovirus and the sterile filter validation, I think in our prior conversation in the first quarter earnings, you mentioned that those would be slated for completion in the second quarter. Again, we are officially in third quarter. Can you speak to whether they are confirmed complete, or is this under the CRO's timeline and therefore somewhat independent of what you had envisioned?
Yeah, no, the RCR had been completed, I think even as early as May. We compiled those data. We sent it to the FDA. We've heard responses that this looks good. So that is behind us. With the sterile filter validation, it's almost complete. I think the results are looking good. It's just a matter of CROs writing up validation reports and things like that. So until that is done, we don't have it in our hands, but we haven't heard anything that the data suggests that there is a showstopper. So if not already done, it's coming in weeks.
Okay, okay. The sterile filter validation is a work in progress. I guess pivoting over to the guidance you provided for the 3Q anticipated timelines, I think there is the sterility assay validation, cell-based identity assay, both of which were slated for 3Q. You mentioned earlier on that about 20% is still a work in progress. I mean, are these complete or are these part of that 20% that has yet to be completed as part of the 3 Q?
These are all part of the 20% because a vast majority of what we have to deliver in the CRL items list are completed. But what we are doing is we are requesting the agency for a Type A meeting, which will happen sometime in the first half of August. And we want to make sure that in our view, this has been completed and this is locked and loaded. Do you agree? Because we do not want to be in a position where there is misalignment and surprises. So that's why we're taking that extra effort to package everything, get the agency to review those, and state that, yes, this looks good to go for resubmission. So there may be one or two items where the data may not exist at the time we propose this briefing book to the agency.
For those types of items, at least we will have a validation protocol approved by the agency. That way, the goalpost is set and the protocol is set. All we're doing is enacting that protocol and showing that the results are within the goalpost. So that's just formality.
Vish, are you able to disclose what those one or two assays that won't be complete by your Type A meeting are?
That may not be. I'm not even sure that it won't be. It could be complete just around or before the Type A meeting, but because we have to give the briefing book 30 days in advance for the Type A meeting, those data may not have been included. That's the nuance here. So the things that are in that bucket, the sterility assay, right? Because we've done all the feasibility studies, we asked the agency some questions about how we've designed the protocol. We wanted them to be okay with that. We got that response. So we've been having a lot of informal back and forth with the FDA. So that work is ongoing right now. Obviously, the data are not ready to be packaged into a briefing book, but the validation protocols are. So that's one example.
Okay, okay. The Type A meeting has been penciled in for the first half of August. Aside from the one or two assays, including the sterility assay, the bulk of the data will be included in that briefing book and will be part of that Type A meeting.
Correct. Just to clarify that we don't have an exact date of the Type A meeting, but we're estimating that to be in the first half of August because we need the agency to confirm a date.
I see, I see. Okay, okay. What's the potential for that being delayed to like the second half of August, if not September? I mean, is that completely out of the question?
For the resubmission?
No, for the Type A meeting.
For the Type A meeting given summer. Well, as per the guidance from the FDA, when you get a CRL, the sponsor has a certain amount of time to make a request for a Type A meeting. I think that is 90 days. And once the request is made, the Type A meeting is provided in a 30-day window, within the 30-day window of that request. I can tell you that we made the request. So that's why we're anticipating that it's likely first half of August. And obviously, once we get a date, we will be able to communicate further.
Okay. Let's suppose the meeting does happen in the first half of August, given that the 1-2 assays that won't be fully included in the briefing docs. I mean, second half resubmission, I understand there's a little bit of flexibility baked in, but what are you guys internally thinking is realistically possible, right? Because you are on track to completing those 1-2 assays near term, right? Is this something that you can envision filing before the end of the third quarter, if you will? Or do you really envision this dragging out into, say, October or even November?
Yeah, we think it's a very strong possibility that we could do the submission by third quarter. The reason for not being that granular is simply because we haven't been through the Type A meeting yet. This is a very potential meaty meeting. It's going to involve a lot of topics. I think that it behooves us to go through that meeting and then come out and say, yes, we're making the submission. What if there's something that they say you need in addition to that, some bolt-on, and that creates another month of work? Those types of things can happen. I think the important big picture here is whether we submitted in quarter three or quarter four, which is still the first half 2025 approval timeframe, the unmet need and the opportunity for pz-cel does not change. That's definitely going to be there.
We do not see the unmet need being eradicated or something drastic in a couple of months. So I think if you look at that opportunity size and the valuation, we believe it's still a very significant opportunity for us to serve here.
Vish, another positive element to this whole story is that the CRL did not raise any issue on the efficacy or the safety component of the submission package. So if you were to refile this BLA in the second half of this year, would this fall under class one and therefore like approval timeline within two months of acceptance of the BLA, or would it be more like a class two where it's more of a six-month review?
Yeah, we anticipate this will be more like a class two where the PDUFA is going to be six months out. But what the FDA communicated to us is it's not necessary that we may take this entire six months to review, given the finite number of items that we have to review in your resubmission, because the delta between what is approvable and what is not is very clear now. And so the review can be shorter than the six months, but they will reserve their right to take the six months. So that's how the PDUFA is going to be defined.
Sure. Okay, okay. So base case six months, but it could potentially be shorter than that. Madhav, maybe I'll bring you in. I know it's only five minutes left. You've been patiently waiting, but I want to ask you a little bit more on the commercial prep, right? So as the CRL has delayed the launch timeline, it obviously gives you more time to get the ground or the foundations up and running. So can you maybe talk to us a little bit about how many QTCs you already have activated or are ready for launch as of now? How many more are you planning on activating if we assume first half 2025 approval?
Yeah, I mean, I think our plan is to have 5-7 centers at the time of launch. We want to stick to that plan because this is where really most of the patients are. We're working with these centers to get them fully trained and ready to go as soon as approval. As you said, I mean, we have this time advantage. It's working well. We're learning a lot more about the market. The interest for pz-cel just continues to grow strong. Even with Vyjuvek on the market, as more patients get on this therapy, we're actually identifying more patients, more payer insurance and clearance is happening. So we can be better positioned as a second mover in this particular space. The centers we're working with are the high-volume centers. So they have the bolus of these patients.
We're talking to these centers to identify what that number is in a couple of dozens at least for each center. So we have that kind of initial interest. And that's why we're working with these centers. And over time, we are also, of course, going to be working with the community physicians so that more patients get funneled into the QTCs.
Sounds good. And what's your current thinking in terms of pricing strategy? I know in the past we kind of talked about maybe bundling this with the entire procedure and the hospitalization cost or drug prices being separate. I mean, should we be looking at Vyjuvek pricing as a benchmark or any other in vivo as a benchmark for that?
Yeah, no, I think from a reimbursement perspective, we are hearing more and more carve out of the bundle, which is really good news because that means the gene therapy is going to be priced and reimbursed separately from the bundle. So that means hospitals can bill separately for the cost of procedure and the cost of therapy is different. So that's one point. With regards to the pricing, the gene therapy alone, yeah, we started with benchmarking versus Vyjuvek, but we heard initial research, multiple of Vyjuvek premium over Vyjuvek is something that payers could give. But given the recent precedents in the marketplace and just the transformational outcome with pz-cel, we have been able to show plus Vyjuvek's lifetime cost, we think we can have comfortably at a recently launched gene therapy kind of a pricing, $1.5 million as a floor.
We are looking to see as to where we can go north of that, making sure that patients have the most access to it and that there are no severe restrictions in place. Pricing is looking strong and the perception is also looking good from payers.
Okay, okay. And then when you talk to these centers, the 5-7 centers you're prepping, I mean, do you get a sense that there is some kind of a warehousing effect going on of patients who might be waiting for pz-cel? Or do you think this is really going to be your work when you launch to get these patients?
There is some warehousing. I think it's a mix of both. There is some warehousing and there will be some work that will be needed because it is multi-step process, right, to get pz-cel versus go to CVS Pharmacy and get your pills. So because of that, I think if you look at the warehousing effect and the unmet need, at least when we talk to the community physician, 100% of the community physicians that we spoke with said they are willing to refer the patients in. It's just the ability to have long-term durable benefit with a single round of treatment gets that excitement going. Now, when you ask about what percent, there is a big chunk of Vyjuvek patients that physicians think that can be pz-cel candidates and de novo patients also that they feel could be pz-cel candidates. So I think it's a mix.
We believe we can draw patients from both these sources, but overall, it's a complementary treatment. So from that standpoint, I think right now patients have had no other option. So if I were a patient, I would use Vyjuvek. Once you have another alternate on the marketplace and an FDA-approved product, then this is definitely going to gain some traction.
Cool. Okay. Well, let's close out the discussion with a cash and runway question, which everyone loves. So you guys recently done a financing. So Vish, can you just remind us where you stand on the financial stability?
Sure. With the $75 million raise that we did recently in quarter two, we are funded. So our cash runway extends into 2026. And if you actually layer in the PRV that we will have with the pz-cel approval, we are potentially funded through profitability. So we'll talk more about that in the coming quarterly calls, but essentially that's where we stand. And we're very excited that our investors have shared the same conviction for this product.
Okay. Well, with that, Vish and Madhav, thank you very much for the time and everyone. You can now disconnect. Thank you.
Thank you so much.