Great. You guys ready?
Yep.
Yep.
Okay, let's go for it. Hi, my name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome Vish Seshadri, CEO, and Madhav Vasanthavada, the COO of Abeona. We're gonna do a fireside chat format. Thanks so much for joining us today.
Thank you for having us, Maury.
For those who are new to the story, maybe give a brief intro to Abeona and your, your lead program.
My pleasure. Good morning, and I'm Vish Seshadri, CEO of Abeona Therapeutics. We are a cell and gene therapy company based in Cleveland, Ohio. Small but mighty team of 80-plus people here, and we manufacture our lead product fully integrated into the Cleveland site. So that's where we do all our cGMP manufacturing. And our lead therapeutic is an engineered cell therapy for a disease named recessive dystrophic epidermolysis bullosa. This is the worst disease that you never heard of. Patients have a lack of functional Collagen VII, and their connective tissue is compromised due to that. And these patients live almost all their lives with a lot of wounds that cover their entire body, and this significantly impacts their quality of life.
They live in pain and itch and blistering all through their lives, and this leads to infection and other complications like squamous cell carcinomas, and they rarely see beyond their fortieth birthday. So the mortality associated with the disease is also very high. And in addition to the clinical burden, the disease also has a lot of economic and humanistic burden. So our therapy, EB-101, aims to deliver long-lasting, both wound healing as well as pain reduction. And this is a great time to be here because we just submitted the BLA for this drug.
Great. Yeah, much congrats on submitting the BLA. A big milestone for the company. Is there anything new you're saying about what was included in the BLA? I guess, what did that final, BLA package look like?
Yeah, the final BLA package, very much in line with all the points that we've discussed. As you can recollect, this entire year, since we had even last year in November, we publicly disclosed the top-line results from the phase III study. Since then, we've been in touch with the agency, many informal meetings, and we also had a pre-BLA meeting recently. And the purpose was to really align on all the critical elements of both CMC as well as clinical. And we've taken all the efforts to make sure that all those critical issues that the agency has discussed with us are all addressed the way we aligned, and that's what is included in the BLA package.
Of course, the clinical evidence that is the basis for this application comes from the two studies, the phase I/II-A that was conducted by Stanford, as well as the phase III study that Abeona just completed last year.
Got it. And with everything that's included in there, you're confident that the BLA should be accepted, and that would probably happen in about 60 days, some sort of an update?
Correct, correct. So there is a typical 60-day window by which they, the FDA, you know, comes back and does the BLA acceptance. But the important point to note here is the reason why we took so long, this is atypical between top line and submission time, and the reason why we've taken this long is to make sure that comprehensively, we've addressed all the CMC as well as clinical aspects of our submission. You would have probably caught from our, you know, press release that we did after the pre-BLA meeting itself, that there were some things that the agency asked us to include in the BLA package. Two of those that we specifically addressed were the identity testing and the potency testing.
What we proposed for the identity testing was agreed upon at the Pre-BLA meeting. It's pretty plain vanilla. It's a validated assay that we already have. In terms of potency, this is something that many of you will appreciate in autologous cell therapy products, especially ours. We have a very limited shelf life. Once we manufacture the product, it has to get to the patient within hours or days, and we don't have a lot of ability to do days of testing. So we have a test for potency that is upstream of the final release of the drug product. The agency's question was: Does that potency live through the end of the drug product? And we've done a lot of characterization studies that do show that evidence, and the agency said, "Okay, then include those in the BLA package. We wanna definitely review that as well.
Got it. Interesting. How does this regulatory milestone change or advance your regulatory work in other geographies, such as the EU? Do you basically use a lot of the same information for your EU filing?
We have had interactions with the EMEA, but it's been a little while since we did that. The primary clinical evidence that will be the basis for application for approval in other geographies will still be the same studies that we've done here, but manufacturing is something that we will need to set locally because this is a product that has a finite shelf life, and operating out of the U.S. manufacturing site to supply to the rest of the world is a challenging proposition. So for that purpose, we will need to set up manufacturing in a European site, but we've been very laser-focused on the U.S. launch. Once this BLA is accepted and review is underway, we will be able to resume some of the conversations that we've had with other health authorities.
What we may not need to repeat the endpoints from a clinical study, but we'll have to demonstrate that in a local manufacturing setting, we're able to make product for those patients.
Got it. That makes sense. And for your lead program, EB-101, can you give a recap of the clinical data? And you said FDA wanted to pool the data from the two clinical studies. Is there anything worth noting about the pool data set as a whole?
... So there were two clinical studies, the phase I/II-A that was conducted by Stanford, and that study was not a randomized controlled study. And we have a pivotal study, which is VIITAL, that we just completed, and that is a randomized controlled study where wounds are randomized intra-patient between a control wound and a treated wound in pairs, right? For the phase I/II-A data, the evidence basically supports the fact that EB-101 promotes wound healing and pain reduction for many years after a single application. And we have the most mature follow-up we have for a patient is eight years, and the mean follow-up is 5.9 years. So the durability really comes from the phase I/II-A experience because it was started a while ago.
Now, the phase III study is important for regulatory decision-making because it shows, it teases out the treatment effect between every pair of treated and control wounds within the same patients. And that, the primary, co-primary endpoints of, the, wound healing and pain reduction, were measured at the sixth-month time point. But this is more statistically robust because it was set up to, to demonstrate that. Now, to your other part of the question to do with the pooling, strategy, for efficacy, it is challenging to pool two studies that were conducted with a slightly different experimental setup. One is a single-arm study, one is meant for actually looking at treated versus control. One is following patients for so many several years, and one is looking at a six-month endpoint.
So for those reasons, the agency actually looks at each of those efficacy data sets as separate entities, and that's how we anticipate the label to also call it out. However, from a safety perspective, pooling makes sense, and so far, you know, the safety profile looks very encouraging, and we will be presenting the safety profile as a consolidated across the two studies, and also broken out for treated wounds, control wounds, and non-study wounds as well. That way, you're able to see what is the baseline level of AEs that happen in these patients naturally, and if there's some signal that's above and beyond that, and we haven't seen anything that's not expected for these EB patients. So that's also encouraging.
Got it. Makes sense. And even though you can't directly compare efficacy between those two studies in the filing, I think some of the efficacy trends you're seeing with wound healing are similar between both studies.
Yes.
When could you have some additional follow-up from those studies? And one of the things I think the treatment does is you don't see the squamous cell carcinoma, which is really bad for these patients. Maybe talk a little bit about that.
Yeah, no, a great question because the long-term follow-up has the two goals of both efficacy and safety. In terms of efficacy, I'll first address that question, which is, Stanford published in the journal Orphanet Journal of Rare Diseases in December 2022 the follow-up that I just mentioned from the phase I/II-A study. That's as much as you're gonna see efficacy follow-up with the same methodology, because for having patients come again and again to travel to Stanford and investigator doing these assessments is gonna be challenging. So you're more dependent on talking with the patient remotely, and that is the nature of follow-up that you're gonna see.
But the squamous cell carcinoma question that you asked is a very relevant one because so far, in the 18 patients that have been treated in the phase I/II-A and VIITAL studies, we've never seen occurrence of a squamous cell carcinoma in a treated site, and that's a very encouraging result. And, we are monitoring every patient for a total of 15 years. So, every year, you can imagine that there will be a safety data cut, that will be updated. And especially we want to monitor for squamous cell carcinomas because if we're seeing that none of the treated sites develop squamous cell carcinomas, that's an encouraging result in itself, and we want to see what's the durability of that.
Got it. Makes sense. What would you expect with natural history with squamous cell carcinoma, I guess?
With natural history, what we've learned is the chronic wounding and inflammatory processes that happen alongside the body trying to heal these wounds have some natural propensity to eventually lead to these types of complications like squamous cell carcinomas. That's kind of the existing wisdom and theory, if you may, and this is where what we're hoping to one day, you know, provide evidence that if you're able to promote wound healing, you're able to avert these kinds of but that level of clinical evidence doesn't exist today. That's our goal, to get there.
Got it. Okay, and for the BLA filing, you talked about the potency and identity assays. I think in the pre-BLA meeting, FDA also asked for supplemental data pertaining to certain chemistry, manufacturing, and controls and clinical topics. Anything else on that point that's worth mentioning that was included?
It's what we would have anyway included in the BLA package. It's challenging to have pre-BLA feedback from the FDA be comprehensive, that it's already reviewed the entire BLA, right? We're gonna focus on those areas where we think there could be two, three different ways of approaching, and we want the agency to provide a preference, right? For that reason, they take a very comprehensive view of, "Okay, we've discussed these, let's say, 10 topics. There are 90 other things we haven't touched on, so do A, B, C, D, E." And if you look at that list, it's what we would have naturally put in the BLA anyway. So there's nothing that is out, you know, surprising that we've seen there.
Got it... Okay. Why don't you get into the commercial landscape a little bit? Can you talk about the criteria or characteristics of the wounds that you think will be treated in the commercial setting? For smaller recurring wounds, are there wounds of interest that may be worth treating with 101, even if the wound is not the typical large chronic wound, but could make sense with 101's benefits?
Sure. I'll start off the answer. I also have Madhav chime in here, as he's deeply looking into our commercial launch activities. But the wound characteristics that we have treated in VIITAL, as well as the phase I/II-A studies, basically tell us that these are the toughest to treat wounds. What does large and chronic means? These are not wounds that can self-heal easily, so we're treating the toughest to treat wounds. The primary reason we highlight that is to add context to the clinical efficacy that we're seeing with the EB-101 drug product. It is not to mean that if you're able to heal toughest to treat wounds, it doesn't mean the drug won't work in other types of wounds. If you've really dealt with... it's a battle-tested drug.
So, we don't anticipate that the label is gonna restrict what type of wound is gonna be treated for these patients. It's gonna be for RDEB wounds, basically. But if you created, let's say, eight grafts for a patient, and you covered the large chronic wounds, and then there is more grafts available, and you can treat other wounds, you're not gonna restrict, you know, the patient from getting access to that therapy. So we believe that it's gonna be agnostic of wound type, how the label would read. Now, where clinical practice is going and how we position, I think that's something that, you know, we want to offer patients the immediate wound closure.
If there's urgency and pain reduction, that's the goal. We have an option that could be prioritized, and that's where our positioning is. And so Madhav, please feel free to.
think you've captured it well on that one.
Yeah, that's really helpful, and I think the discussion around the label is helpful as well. For us to better understand the logistics of a patient getting treated with EB-101, can you walk us through the patient experience there, and just how long it takes for them to go through the process of getting the graft?
Yeah, I think, I mean, it's a high level, as we already know, it's an autologous process, where biopsy samples from the patient is taken, and epidermal sheets are developed with functional collagen gene in it, and then they are placed back onto the patient. Site of care-wise, this is going to be a hospital, in-hospital procedure. And the patient, just step by step to your question, Maury, the patient is either referred in to the hospital, or these are the patients who are already at these centers. And the reason these people go to these hospitals is because they have long and chronic wounds. They want to make sure what their infection progress is like. We talked about squamous cell carcinoma. So every three months, six months, it's a periodic as part of the follow-up.
So these people are at these hospitals, and once a patient is identified as someone who can benefit from EB-101 graft, then there is a coordination of clearing the insurance process and verification that happens, and then the first coordination will happen with Abeona, where we will provide them the kit to get their punch biopsy taken. And so this is less than a centimeter, two punch biopsies that are taken from a non-wounded area, which is then sent back to our facility in Cleveland, which is where manufacturing happens. So these skin cells are expanded, and they are grown in epidermal sheets. It takes about 23 days, and we have this really under control. The last 10 runs that we did for VIITAL, pretty much very tight standard deviation.
We had almost 100% manufacturing success rate, so we have this process under control. At day nine, prior to harvesting, is when we look to coordinate with the treatment center so that an operating theater can be coordinated, and these grafts are then sent back to the patient, where EB-101 grafts will be applied. Patient stays as part of the post-procedure for seven days, is where in VIITAL study we needed to have the patient in so that these grafts remain, you know, adherent, and after that, the patient is discharged. So all the clinical trial results that we are talking about, including years of durable healing, is with one-time application.
I think that is so important to just underscore because this is where we differentiate, in that the collagen-producing gene that we have incorporated in these epidermal sheets have the ability to continuously produce collagen because they are multiplying, because the retrovirus that is integrated, and as the cells divide, they keep multiplying and are making carbon copies of the functional gene, right? And collagen is being constantly produced. So think of it like a manufacturing unit, so to speak, which is on top of the patient's wound, which is producing collagen and leading... And we have seen this collagen expression for six months, 12 months, 24 months, even 36 months, with immunofluorescence image of collagen being produced in the healed wound. So that's the one-time application. Patient stays and is discharged, and, you know, we are beginning to hear these stories from patients.
Got it. Makes sense. And you've mentioned some patients in your study are getting a second treatment. In the commercial setting, how could a second treatment work, and how would the economics and pricing be?
Yeah. I mean, so second treatment, right? The patients who have received our second treatment, they are getting a second treatment for the control arm of the VIITAL study. So it just shows the testament again, the patient wants to come back to get their other non-treated wounds healed. We've had so far three patients out of the four who have received the second treatment. With regards to the pricing, we have discussed this with payers. Our pricing model is going to be pretty simple, which is per biopsy procedure and application of these grafts. The initial discussions we had with payers, there was no pushback with regards to having a different pricing model for the second, you know, round of application, so to speak.
So it'll be the pricing will be per biopsy to application, and if a patient requires a second one or a third one, you know, that's essentially the similar pricing. But this is something we will, you know, continue to discuss with payers and see, especially as we get closer to launch.
Got it. Makes sense. And that, that kind of leads into the next question, just, commercially, if, if you treat a patient and maybe the patient gets a second treatment, but at some point, other parts of their body become disrupted, and they have to come back, you'd be able to retreat that patient again, there's-
Right. Yeah. Yeah, we should be able to retreat. You know, we had one patient, an 80-year-old, who got a second round, and. You know, this is just an anecdote with speaking with the physician. Two-thirds of her body is covered, there's still a third that is remaining, and even after a second round application, the patient is looking to getting a day where, you know, she can get her other wounds treated. And as she grows, it's—that's the unfortunate part of this disease is because there's no collagen in their skin, and it is susceptible for wounding and, you know, for infections to happen. So that's our, that's our hope.
Makes sense. And now that you've got the BLA part done, what's the next priority? Are you gonna be talking to payers, working with the supply chain, and identifying patients? Maybe talk a little bit about that.
Yeah, we have, we've started off actually, in fact, with some of the most critical activities, which is working with the high-volume treatment centers and discussing with these physicians. We have a good team already in place. In fact, we have hired Heather Stitley, who is from Bristol Myers Squibb, and she is stellar in having set up hospital centers for autologous cell therapy processes. So we have a strong person there. We have an advisory board coming up, where with really the movers and shakers in terms of thought leaders coming in, and for the very first time, we'll be showing these wound images to these physicians. So as we have the engagement with the hospital centers, that's going to be taking up our, you know, immediate focus.
In parallel, we'll continue to put together, you know, value proposition and engage with payers. So that's our, sort of, I would say, categorize as the two main important, you know, focus areas from a launch pre-planning standpoint.
For sales team, how many people do you think you'd need in place at the time of launch?
Yeah.
Have you identified a list of patients who would be ideal first patients for the commercial?
As we've discussed, I mean, the commercial footprint sales team is going to be pretty tight and, you know, much smaller, maybe a dozen, including medical science liaisons, sales, and key account manager people. And the reason for that is, because this is going to be a center of excellence model with a tight-knit patient community. We believe patients will find us, and as we ramp up, then, you know, we will look into expanding if need be. But it's going to be pretty nimble. To your question, we haven't, like, identified yet in terms of the number of patients, but again, we are seeing how patients are being identified, you know, through Krystal Biotech, and we are very well positioned as a second mover in this marketplace.
That is going to help us, you know, with our identified patients. As we do the site onboarding exercise, the large volume centers, physicians are already thinking about, you know, who would be a good patient candidate.
Got it. And for the capacity to treat patients and the cadence of treatment, how many patients do you think you'd be able to treat in the first year and potentially second year is that?
As we've discussed in the past, at launch, our capacity is gonna be capped at about 120 manufacturing cycles in a year, and that's as much we can do in the current facility that's available. What that translates into is about 10 patients in a year, which is why we believe that going with 5-7 centers of excellence as our, you know, out of the gates for launch to be onboarded is a fairly decent number that will already take up our manufacturing capacity. We do plan upon launch to, you know, increase that capacity as patients start to get treated, and we're, we have a better grasp of how the demand is trending, so we'll know how much to go above that. There will be a lead time of about 18 months once we make that decision for that higher capacity to be fully operational.
Got it. And, maybe talk about payer coverage and, any updated thoughts on pricing.
Payer coverage, we have received no pushback when we first presented the profile of EB-101 versus Vyjuvek, including, this research was done before the launch of B-VEC. In terms of just because of the ultra-rare disease nature and the strong value proposition, right, of one-time ability to treat and heal the wound for multiple years, the pricing also, they put value, a premium. Payers do put premium on EB-101, and we have communicated a potential for a seven-digit price point, and we will continue to pressure test this. Now that we have these wound-healing images, what does it mean in terms of 75% of complete wound healing?
All the locations where EB-101 was applied, we have compiled the data, not only, you know, sort of the anterior, but the posterior, the above the body, the below. So you have the ability to heal multiple areas, large areas. I think that proposition, because you in one go, you can go, ... excuse me. As much as 450-480 square centimeters, versus the existing product, you have a limitation in terms of the area that you can cover.
Yep.
It's gonna be very valuable there.
Yeah, and I think we have not come out and shown these images because the top-line results talk about one consolidated number, or the proportion of wounds that show 75% plus wound healing is so much. But just having that visually, at what kind of locations in the body, how comprehensive that is, I think this is all gonna be additional, you know, value that we'll be bringing forward. And that's why we're excited about this ad board, where the top leaders who are at the top of the helm of this space-
Mm
-are going to actually look at those types of data.
Makes sense. Yeah, makes sense. And, with the Krystal launch, they reported in their second quarter update that they had 121 patient start forms in six weeks. We estimate that about 90 of those were potentially RDEB. What percentage of Vyjuvek-treated patients would be good candidates for 101? I guess, are these patients more or less likely to use 101?
We think a big chunk of these patients will be eligible for, you know, EB-101. And that's what we've heard from KOLs, as an ad board that we had done last year. Physicians look at this as completely different modalities for different wound sizes, right? And as we discussed earlier, about even practically how much you can apply Vyjuvek on a patient on a weekly basis, week after week after week, you have to be able to, you know, apply these. So there is a clear unmet need for these large patients, where both therapies can coexist. In terms of your question of, will these patients be willing to try? I think it's a matter of time, as to how the clinical trial results translate into real world for Vyjuvek, right?
Because some wounds were larger, some wounds smaller in GEM- 3, but the average was 10.6 centimeters squared. Now, you are going to be applying it to larger, you know, areas of body. So how is that gonna translate and just overall practical aspects, but overall, we think that, you know, there is room for both therapies.
The bottom line is that the amount of wound surface area patients have on average is way more than what can be covered, as per label for B-VEC. So patients are going to need both therapies there.
Got it. Makes sense, and I wanted to ask, getting at the label a little bit again, the commercial opportunity for the dominant form of DEB, relative to the recessive DEB, so DDEB versus RDEB. Could you potentially treat those, the DDEB patients? And, if you had any discussions with FDA on this.
We have not had discussions with the FDA, and we don't have clinical evidence for DDEB, and so we really don't know how our therapy will work. But in terms of disease severity, we hear from physicians that there is a small proportion of DDEB patients that may have RDEB-like disease, in terms of symptom and how grave it is. And so there has been some inquiries from thought leaders that, "Can we treat these patients with EB-101?" But in our viewpoint, this is still gonna be an investigative effort because we have never treated a DDEB patient in either of our clinical studies. So it's evidence to be generated.
Got it. Makes sense. And we've talked a lot about EB-101 and RDEB, but you've got the eye therapy gene therapy programs in the works as well. Maybe provide some of the key highlights for those programs.
Yeah. What we are excited about with the AAV-based ocular programs, we have—we've announced three diseases. We have two approaches: one, where our differentiation is about being able to, you cannot package the ABCA4 gene. It's too large for one AAV vector, and we've been able to show through our recombination system. And that full-length ABCA4 can be expressed in certain compartments of the eye, which is very encouraging. The second is, we have proprietary AAV serotypes, the AAV204, that's able to transduce with very high efficiency, tissues like macula and optic nerve. And these are gonna have some tremendous applications in X-linked retinoschisis and autosomal dominant optic atrophy, and we're excited, and we've got our pre-IND feedback from the FDA.
It's very encouraging to see that we don't have to conduct non-human primate studies for toxicology. That will also help us accelerate some of the IND-enabling studies. So we do want to aim to advance at least one of those three programs into clinic by second half of 2024.
Great! Well, Madhav, Vish, thanks so much for joining us today.
Thank you very much.
Thank you.
Thanks for having us.