All right, welcome back to the Leerink 2025 Global Healthcare Conference. I am Lily Nsongo within the genetic medicine team here at Leerink, and today we have the pleasure of having the Abeona management team with us, and that includes Vish, CEO of Abeona, and we also have Madhav, who is the CCO as well as the Head of Business Development. The floor is yours.
Thank you so much, Lily, and thanks for having us here. I'm Vish Seshadri, the President and CEO of Abeona Therapeutics, and it's my pleasure to talk on behalf of our company. Joining us is Dr. Madhav Vasanthavada, who is the Chief Commercial Officer. Abeona Therapeutics is a cell and gene therapy company based out of Cleveland, Ohio, and if you look at our—there will be a lot of statements that I'll be making through this presentation that are forward-looking in nature. It will contain words like "may anticipate" and "expect," and please keep in mind that our business is a biotech business, as usual, is wrought with these types of risks. I just wanted to introduce what our core capabilities are. As a cell and gene therapy company, we have capabilities in two different types of platforms.
One is the ex- vivo autologous cell therapy platform, which is where we have our lead asset, prademagene zamikeracel, or pz-c el. Most of the talk today is going to focus on this asset because this is the one that is most mature, and we have a PDUFA date with a BLA review that is ongoing April 29th of this year, so it's less than two months away. We're all very excited. This is our first anticipated commercial launch, and this product—we have a rare pediatric designation, and we anticipate a priority review voucher with it. The second platform that we have is AAV-based in vivo gene therapies, and we have assets in the preclinical stage of development for monogenic ophthalmic diseases. I'll touch on that a little bit, but the most, you know, the most advanced one there is X-linked retinoschisis and the RS1 gene.
Other than our fully owned programs that I just mentioned, we also have out-licensed gene therapies. One is UX111, which is an MPS IIIA out-licensed product for Ultragenyx, and there is a PDUFA date of August 18th for that asset as well. Very exciting to see our assets reach these milestones and get to patients quickly. We also have another out-licensed program, our Rett syndrome program with Taysha Gene Therapies, and we're seeing very compelling early clinical data for that asset. Now moving on to our lead asset, which is pz-c el, this is a product for patients with a disease called recessive dystrophic epidermolysis bullosa, or RDEB in short. This is a very rare, ultra-rare and debilitating connective tissue disorder.
Patients with this disease do not have functional collagen seven, which is encoded by the COL7A1 gene, and the product of this gene, really what it does is it's the anchoring mechanism by which the outer layer of the skin is well-crowded onto the inner layer of skin. That's how the intactness and integrity of the skin is maintained. In the absence of that function, skin blisters easily and forms wounds. These patients are covered in large wounds that are quite life-threatening because over time they become very adamant and tough to treat. They do not self-close, and these are the types of wounds that typically become chronic and then lead to cancers like squamous cell carcinoma over the lifetime of these patients.
These patients very rarely see their 40s and 50s of age, so that gives you the gravity of the disease, and they're constantly in need of wound dressing changes two to three times a week. They have to be bandaged again and again and spend about six, seven hours every setting in every, you know, caring for their wounds. From a, you know, humanistic as well as economic perspective, there's a lot of burden on these patients and their families. What we have with pz-c el is to address some of the still outstanding unmet needs for these patients, which is to provide multi-year durable wound healing and also relief from their pain and itch. Hopefully, if you address wound healing, that will reduce the risk of squamous cell carcinomas.
That is really what we're all trying to solve for for these patients, and our first product, pz-c el, or prademagene zamikeracel, is uniquely positioned to address many of these unmet needs that I just articulated. I'll describe the product in a little bit, but before going there, the unique and differentiated factors of, or properties of, pz-c el is delivering long-lasting wound healing as well as pain reduction for especially large and chronic wounds for RDEB patients for years following a one-time therapy. As I mentioned, these wounds become chronic over time, which means that they do not have the property of healing by themselves.
The studies that we have put pz-c el, we have investigated pz-c el, have the toughest to treat wounds in these studies, and we're very happy to see that long-lasting wound reduction, wound healing accompanied by pain reduction and itch relief is something that we've been able to see in our phase I/II clinical studies as well as the phase III study that has been completed to date. With that, I'm just going to talk about the pivotal study that investigated pz-c el in clinical trials, and this is unique in many ways. It's an intrapatient controlled randomized study where every treated wound with pz-c el is paired with an untreated wound, and we're looking at co-primary endpoints that straddle both in terms of physician-assessed wound healing as well as patient-reported pain reduction.
It's a very unique kind of an endpoint construct because usually you have, you don't see patient-reported outcomes in a primary endpoint for clinical studies. Forty-three wound pairs across 11 patients were the primary data set, and across both wound healing and pain reduction, we saw statistically significant results, and wound healing was studied. All of those endpoints were measured at six months post-treatment. Although we see treatment effect as early as six weeks post-treatment, the primary measurement for the regulatory path was a six-month time point, which is very standard for these types of assets. The first co-primary endpoint, as I mentioned, you can see 81% versus 16%, very significant wound healing was observed at six months, and also pain reduction where patient-reported Wong-Baker pain scale, that's what was used. It's a validated tool, and you can see that there's a significant effect there as well.
A picture speaks a thousand words. Just to add a little bit more color and data to that, when we talked about wound healing, we are measuring wound healing at three different levels. What is the proportion of wounds treated with pz-c el show at least 50% wound healing, which is 50% of the area that was treated, and 75% or better, and then 100%, right? We have very stringent criteria for what would qualify as a 100% healed wound. I just wanted to give you a little bit of more detail on that. Here you see a large thigh wound in this picture, and there are three wound areas within that large wound that is just designated because the sheets of pz-c el come as 40 centimeter squared sheets, which are about the size of a credit card each.
In large contiguous wounds, you can see that we can apply pz-c el more than one sheet in that large area. You see three wounds here before and after at week 24, and you can see that the wounds show healing. All these three wounds are scored as greater than 75% wound healing. They're not scored as 100% healed, and the reason is you see some yellow crusting that's visible on these wounds. You cannot pick on those crusts and verify if the skin underneath is healed or not, so the physician will give it a 75% plus and not a 100% wound healing. That is important context for what would qualify for a 100% healed wound.
Here you see an example where the bottom wound is scored as a 100% healed wound, whereas the top wound is scored as a 75% plus because there is a small red speck there in the bottom right, and absent that closure, it's scored as greater than 75%. Here, this example is an upper trunk. Here there's another example that you see, upper back. They're both scored as B3 is a treated wound, it's scored as a greater than 75% wound healed. Again, that's because of the crusting. Another example of the left flank, you can see examples both of greater than 75% healed and 100% healed wounds. Just to give you the idea that there are so many different anatomical areas that have been investigated in our pivotal study for wound healing.
There was also, prior to the pivotal study, there was a phase I/II study that was done. This was a Stanford investigator-led study. We have published the results in 2022 with eight years of max follow-up and 5.9 years of mean follow-up for the study, and you can see both 50% healed status as well as proportion that are greater than or equal to 75% healed reported in the blue and green histograms on the left, and you can see that wound healing is sustained after a one-time application over years.
The pain reduction of these wounds, here the pain reduction was not measured on a Wong-Baker pain scale, but it was a binary yes or a no for pain associated with the wound, and you can see that also significantly reducing and staying that way over time, and that correlates with the wound healing status as well. This is really the durability that we've studied, and some of these wounds that were treated in the phase I to II study were open for an average of like 11 years, which speaks to the chronicity of these wounds. They do not have the ability to self-heal, so that's very important. It was also evident with the fact that if you looked at our pivotal study results, the completely healed wounds were zero. You don't have any control wounds that showed complete wound healing.
That's another distinguishing feature that highlights what types of wounds we've really treated. Here's another example from the phase I/IIa study, back wound treated with pz-c el sheets, upper back, and you can see what it looks like here at year two and also year five. The question always arises, why do you have this kind of durability of pz-c el treatment? When, you know, we are doing some studies to look at progenitor phenotype cells, but at the molecular level, the way the gene is introduced to the patient's cells is through retroviral transduction. What that does is cause stable integration of the transduced COL7A1 gene in the genome of these cells, and as these cells divide and propagate, they are going to be maintained. You don't lose this gene over time.
That is really the reason for long-term gene expression, and what you see here is a biopsy of a patient treated with pz-c el over various time points going all the way to year two, and you can see even at year two, the green lines that you see in the bottom, that is looking for COL7A1 expression. So that's kind of nice correlation to see continuous expression of collagen seven even two years post-application of pz-c el. The safety profile of pz-c el is also very favorable. We see across 21 pz-cel patients, 120 wounds treated. We do not have any serious adverse events that are treatment-related, which is an excellent safety profile in itself, and we've also paid specific attention to squamous cell carcinomas because squamous cell carcinomas are common in these patients.
The cumulative risk of having a squamous cell carcinoma by the age of 55 is more than 95% in these patients, so we're almost definitely getting squamous cell carcinoma over that period of time, and you can see that in our treated sites, we have not seen any occurrence of squamous cell carcinomas. We also routinely check for replication-competent retroviruses because our technology uses a retroviral vector, and we want to make sure that we haven't introduced any replication-competent retrovirus, and we've never seen such instances in any of these patients over more than 120 sample points. With that, I'm going to turn this over to Madhav to take us through our commercial opportunity and preparations for launch.
Thank you, Vish. As we get closer, we are getting excited and getting ready by the prospect of being able to treat many more patients, recessive dead patients.
We have done our homework with regards to finding out how many patients there are in terms of the prevalence pool, and based on our analysis of the claims data set, we estimate there are about 750 patients in the U.S. that are pz-c el eligible. There are about 1,300 dystrophic EB patients, 750 patients that are pz-c el eligible. These are severe to moderately severe RDEB patients, and based on the data that we shared and the natural history study where these patients have on average about 30% of their body is wounded, 30%, each 1% of the body is roughly the size of the palm of the recessive dead patients. That is a significant area of the body that is wounded. We estimate a patient requiring roughly two treatments per their lifetime. Could be more, pediatric patients could be less, but two on average.
That equates roughly 750 patients times two treatments, so you're talking about 1,500, north of 1,500 treatment opportunities. From a pricing standpoint, we have communicated this is going to be priced similar to one-time, recently launched one-time gene therapies. What we have said is a floor price of $1.5 million. It's going to be north of that, but at least $1.5 million. So 1,500 treatment opportunities times $1.5 million per treatment, you're talking about a totally addressable market of north of $2 billion, right? Even if you think that we're going to get 50% of that, that would be accomplished. We are talking about a billion dollar at least, which is a big gap versus where we are right now, Abeona, as a company from a valuation standpoint.
From a gross margin standpoint, we think it's going to be 85%-90% at a steady state when we are able to manufacture consistently, and that is primarily because manufacturing for pz-c el happens within Abeona. We are not relying on a third party to make the vector. We make it ourselves in Cleveland, Ohio, and so based on our pricing potential and our COGS plus the sales general expenses, we think about three to five patients per month, we will be on a path to profitability. That is really where we are looking from a total opportunity standpoint. The question is, how are we approaching? What are we planning to do with regards to our engagement? First off, the commercialization team is in place. We've got a really good group of people experienced in having launched prior cell and gene therapies.
We are very much in active discussions with centers of excellence. There are about five centers of excellence that we look to onboard and make them patient-ready by the end of this year, by the launch year, which is 2025. What we hear from these centers is that if they are able to treat one or two patients a month, that is pretty sufficient for our capacity as to where we are right now. These are really good and long conversations we've been having with these centers, which involves usually the leadership within these institutions.
have had kickoff meetings with these centers, having visited them in person in some of these centers to understand how the patient flow is going to happen, how the product is going to be received, and all of the administrative work, as well as training these centers to be able to treat with the product. The reason to believe that this is going to be met with success is the enthusiasm that we hear not just from the physicians and the payers, but also from the patients themselves. The feedback that really resonates here is the durability of the treatment. Oftentimes, these patients that require continuous application of other treatments are potential to be able to apply a single, although surgical application. It is a procedure. It is a process that the patients have to go through, but the outcome and the durability of the outcome is quite enthusiastic feedback.
That's really what we hear from them. Also, the excitement from the referring physician because our strategy is to get about five centers ready to treat, and then we are also calling on and we will be educating other centers. There are about 23 total centers of excellence within the U.S. that treat recessive DEB patients, so the rest of the centers that are not the qualified treatment centers will be asking them to be able to refer their patients over to the QTCs for treatment. Along with the sites onboarding, we are in active discussions with various payers. The overall payer mix for RDEB, a little over 50% are commercially covered lives, about 30% are Medicaid, and the rest is Medicare patients. Medicare, not because they are 65 and older, but because they are under lifelong disability. The feedback that we hear from commercial payers is very encouraging.
We've had more than 40 clinical presentations to national payers, regional payers, and we are currently under confidential CDA discussions with them discussing what is the price range and what the coverage status would look like. Overall, given the ultra-rare nature of the disease, the durability of the product, and the ability to cover large areas of the body in one surgical application, it's clearly compelling for these payers. Post-approval, we will engage also with Medicaid. We'll plan to apply for the Medicaid drug rebate application, and that'll also incentivize some of these states to carve out the product from the bundle payment, which will potentially make the reimbursement favorable for these sites. As we do that, we are also in the process of ramping up our manufacturing capacity.
We've always been communicating that this is going to be a supply-gated uptake, and especially in the outer years, we look to ramp up significantly. I think in this year, 2025, we should expect the sites to treat one or two patients and get the confidence from a reimbursement and the payer flow, and as these sites begin to feel comfortable, then in 2026 onwards, we should expect a greater uptake of the product, and that syncs up very nicely with the planned ramp-up of the manufacturing capacity. At launch, we will have capacity to treat four patients a month, roughly just one a week, and our goal will be to get to treat 10 patients a month in first quarter or so of 2026.
Now, of course, like any other autologous process, there's going to be certain requirements to shut down and maintenance of the manufacturing plant, so on and so forth that will need to be in place. Even with 10 patients a month, kind of a capacity, we are looking around 80-90 plus patients our ability to treat once we are fully at steady state of manufacturing. We will be supplying with all of the resources we have to make sure that the patient journey is as seamless as possible. As Vish explained earlier, the beauty of our product is that we are actually using patients' own starting materials, and we are gene-modifying the keratinocyte cells, and in exchange, we are giving them a functional version of their own skin that has the ability to produce collagen. With that kind of process, it involves an intake process.
There is a biopsy that is required to collect. The biopsy is collected typically in an outpatient setting in a hospital which is a qualified treatment center. The manufacturing happens in Cleveland, Ohio. It's a 24-day turnaround time. During that time, the patient is back at their own care at their home and residence, and the patient comes back in for the surgical procedure, which the surgical procedure takes typically three to four hours, depending on how many sheets that we have supplied in exchange. The patient stays in the hospital for about a week to allow the wounds or the product to get taken up, and then is discharged. This is the one-time process.
It is a process to get the product, but the outcome that what we are hearing from the patients, we've had patients who have gone through our clinical trials and have come back. We've had six patients who have come back again to go through this process to treat other parts of the body that were not previously treated. We've had one patient who has come back three times to treat different areas of their body. To us, those choices that these patients are making and these centers are making is quite telling in and of itself. Before I give it back to Vish, like I said, we've gone through cellular therapy products before. Both Vish and I, as well as many members on our team, have launched CAR T-cell therapies, and we understand what it takes.
It takes a village to be able to get these patients to treatment, but that's really the beauty of these kinds of durable, long-lasting treatment options where there is a high willingness to pay. We are also there to support these patients through their copay assistance programs. We'll have a patient navigator in place who is going to take care not only on the phone, but even at the site to be able to handle the logistics, the reimbursement support, the transportation support, and whatever it takes to get these patients the treatment because we know that it is going to be game-changing for them. With that, Vish, back to you.
Thank you, Madhav. In closing, I just wanted to also add a note on our financial health.
Without accounting for any PRV proceeds or sales from pz-c el this year, we're still funded into 2026 with the capital that we have currently. That is a very healthy place to be in itself, and Madhav talked about capacity. If you look at pz-c el capacity, even at three to five patients a month, this is going to be a profitable business. We feel very confident that with the current cash and having a PRV in hand, sales starting from the later quarter three, quarter four this year, this gives us a bridge to profitability for Abeona. We did not talk very much about our other platforms, but we do have goals for our AAV platforms, the first asset to get to clinic next year, but you will see that in the coming quarters and other updates, we are going to talk more about those programs. We are very excited.
We just want to pulse it as we get through important milestones with pz-c el first. Thank you. Any questions?
Can you talk about your confidence that CMC is buttoned up this time?
Yes. We have addressed all the CMC items that were noted in the CRL. We have had many meetings with the FDA before we made the resubmission, so we feel we're in a good place. Of course, the review is still ongoing, so I cannot say it's done, but from our perspective, we are not negotiating that we're going to give you 60% or 70%. We're doing all those things that they asked for.
I guess in the time we have left, maybe I'll ask a few questions. The first one being, you mentioned in the U.S., in terms of patients that will be eligible, you estimate that it's 750 patients. Are there any things that can be done in terms of life cycle management to expand this to the rest of the patient population?
Yeah, that's a great question. We're looking at a lot of still unmet needs. For one example, of course, when you look at patient populations, we are focused on RDEB, right? I think there is definitely DEB as a disease we are going to investigate if we can help with pz-c el. Some of these patients have pseudosyndactyles, right? So their digits fuse, and then they undergo hand surgeries. They have to undergo hand surgeries to separate the digits, and then over a period of one or two years, they start fusing again, and they may need additional surgeries after that. We will investigate if pz-c el can be a potential solution to keep those digits separated. These are some of the ideas in the RDEB-related disease or on where we could potentially take our therapy to expand.
I guess in the last minute we have, how should we think about timing of global expansion beyond the U.S.?
We have had a lot of interest come in, inbound interest from third parties in Europe in taking this technology ex-U.S. We just have not had the bandwidth as of yet, but this is an important goal for us. Whether it is through a CDMO or through a partner, once we get the U.S. launch underway, we are going to be entertaining and exploring those avenues as well, so we should have future updates on that.