Abeona Therapeutics - Q1 2023

Transcript

Operator (participant)

Greetings. Welcome to the Abeona Therapeutics Q1 2023 portfolio update conference call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the conference over to your host, Greg Gin, Vice President of Investor Relations and Corporate Communications. You may begin.

Greg Gin (VP of Investor Relations and Corporate Communications)

Thank you, Holly. Good morning, everyone. I would like to welcome and thank everyone for joining us on our portfolio update conference call. Our objective today is to share additional new positive data from our EB-101 and AAV ophthalmology programs recently presented at scientific congresses. The press releases announcing the data at the ISID and ASGCT meetings are available on our website at www.abeonatherapeutics.com. Before we start, I would like to note that remarks made during today's call may contain projections and forward-looking statements. Forward-looking statements are made pursuant to the safe harbor provisions of the Federal Securities laws. These forward-looking statements are based on current expectations and are subject to change, and actual results may differ materially from those expressed or implied in the forward-looking statements.

Various factors that could cause actual results to differ include, but are not limited to, those identified under the Risk Factors section in our Form 10-K and periodic reports filed with the SEC. These documents are available on our website at www.abeonatherapeutics.com. On the call today are Dr. Vishwas Seshadri, Chief Executive Officer, who will give some opening remarks. Dr. Dmitriy Grachev, Chief Medical Officer, who will review the new VIITAL study data that were presented at ISID. Dr. Brian Kevany, Chief Technical Officer, who will review the animal proof-of-concept data from our AAV ophthalmology program presented at ASGCT last week. After the prepared remarks, joining us for the Q&A session will be Joe Vazzano, Chief Financial Officer, and Dr. Madhav Vasanthavada, Vice President, Business Development. With that, I will now turn the call over to Vishwas Seshadri to lead us off. Vish?

Vishwas Seshadri (Prseident and CEO)

Thank you, Greg. Good morning, everybody, and thank you for joining us this morning. I want to start today by saying last week was a great advancement for the Epidermolysis Bullosa, or EB, community. I want to congratulate Krystal Biotech, the EB patient community, researchers, and regulators for bringing the first genetic therapeutic option to tackle this debilitating disease. As more therapies come to market, we anticipate increased awareness about therapeutic options in the EB space and also improved diagnosis and genotyping for this painful disease. Recessive dystrophic EB, or RDEB, is a connective tissue disorder in which both copies of the genes for collagen VII are mutated and dysfunctional, resulting in the lack of connectivity between the outer and inner layers of the skin.

Patients with RDEB face a lifelong struggle with fragile skin that easily tears and blisters, with most patients developing large, painful wounds that remain unhealed, often covering a significant proportion of their body. Recently published natural history data in RDEB analyzing 251 RDEB wounds described the two distinct types of RDEB wounds. On the top are chronic open RDEB wounds, while on the bottom are the recurrent wounds. On the right, the spider plots show chronic wounds rarely show 50% or greater wound healing, while the recurrent wounds frequently heal even completely and open again. Furthermore, at ISID this year, a prospective study was presented by the team at Stanford that further corroborated this distinction between large chronic wounds and recurrent wounds.

We are excited to advance EB-101 as a potential therapy that could deliver years of sustained wound healing and proven pain relief after a one-time treatment cycle for large chronic RDEB wounds. These are pictures of a patient in our VIITAL study with large chronic wound on the upper left side. You can see the large area coverage and wound healing that were achieved with three EB-101 sheets applied in a quilt-like fashion. On the far right, tattooed wounds were scored as greater than 75% healed. Although the wound looks nearly completely healed to the naked eye, they were scored at 75%+ healed because without picking the crust, the yellow crust that you see there, the physician is unable to confirm complete healing. That speaks to the stringent criteria in our scoring for complete wound closure.

Over the next two slides, I'll discuss the molecular basis for how EB101 delivers wound healing in a sustained fashion. EB101 works by durably restoring functional collagen VII expression to RDEB keratocytes. Keratocytes are sourced from patient skin biopsy, grown in cell culture, and transduced with a corrected copy of the COL7A1 gene through a retroviral vector. The transduced keratocytes are further cultured into epidermal sheets that are transplanted onto open wounds of patients to secure instantaneous closure. The scientific rationale for EB101 durable benefit is that the transgene encoding functional collagen 7A1 integrates into the host genome and is therefore maintained stably as cells divide and form epidermal sheets in our manufacturing process. Furthermore, immunohistochemistry of skin biopsies from EB101-treated sites demonstrate sustained collagen expression for up to 24 months, and in fact, we have unpublished data for up to 36 months.

Those green lines that you see indicate collagen VIIA1 staining, and the white arrows point to the dermal-epidermal junction. This is the rationale for the compelling durability with EB-101, as observed in our Phase I, 2A study at a mean follow-up of 5.9 years and a maximum of eight years. The results show that majority of EB-101-treated wounds showed sustained healing and pain reduction after a one time treatment. I'd now like to turn the call over to our Chief Medical Officer, Dr. Dmitriy Grachev, who will review the results that were presented at ISID.

Dmitriy Grachev (Chief Medical Officer)

Thank you, Vish. I would like to express my excitement about data presented at the International Societies for Investigative Dermatology meetings or ISID. Dr. Jean Tang, professor of dermatology at Stanford and principal instigator of the VIITAL study, presented the data during oral session at ISID, data were also featured in separate poster presentation. The results presented at ISID show that EB-101 improved wound healing and pain reduction at 6, 12, and 24 weeks compared to control wounds following one-time application of EB-101. EB-101 demonstrated improvement in patient-reported and caregiver-reported outcomes for itch and blistering severity. Before reviewing the results, I want to provide a brief summary of the trial design for VIITAL. VIITAL was designed to investigate the efficacy, safety, and tolerability of EB-101 in approximately 36 large chronic wound pairs in 10 to 15 patients with a minimum age of 6 years.

Our study was randomized and controlled. Each patient had a minimum two large chronic wounds selected, with each randomized treated wound being paired with a control wound similar in size, years that wound remained chronically open, and anatomical location to the extent possible with the same patient. In VIITAL, we define large chronic wounds as wounds that have greater than 20 square centimeters of surface area and remain open for a minimum of 6 months, although many were open for years. We align with FDA on the study endpoints and statistical analysis plan. Given that EB-101 is targeting large chronic wounds, remember, the hardest to treat wounds that remain open for years because they cannot self-heal. We align on the co-primary endpoint of greater than or equal to 50% wound healing and the second co-primary endpoint of pain reduction as additional measure of clinical benefit.

Specifically, the co-primary endpoints were, first, the proportion of RDEB wound size was greater than or equal to 50% of healing from baseline, comparing randomized treated with match-controlled wound size at six months time point, as determined by direct investigator assessment. Second, pain reduction associated with wound dressing change assessed by the mean difference in score of the Wong-Baker FACES Pain Rating Scale between randomized treated and match-controlled wounds at six months time point as reported by the patient. This is the first pivotal study with patient-reported pain as a co-primary endpoint. The secondary endpoint was the proportion of RDEB wound size with complete wound healing from baseline comparing randomized treated with match-controlled wound size at weeks 12 and 24. Exploratory endpoints included additional assessment for wound healing and pain reduction, as well as assessment for itch severity and blistering.

We reviewed the baseline characteristics during the VIITAL top-line results call and won't go into details here. I'm just remind you of the large size and severe pain associated with the wounds included in VIITAL. Median body surface area of randomized wounds treated with EB-101 per patient was 160 square centimeters with a range of 80-200 square centimeters. To clarify, every treated wound is 40 square centimeters, exactly the size of the graft. For large chronic areas that exceed 40 square centimeters, multiple grafts could be applied to quilt-like fashion, in which case the area covered by the each graft is considered a distinct wound. In a wound area with less than 40 square centimeters, debridement was required to prepare the wound bed to fit the graft. On the contrary, control wounds were not debrided.

Median wound duration of randomized treated wounds, that is months that the wound had remained chronically open, was 60 months or 5 years. The control wounds had very similar wound duration. We can turn to the results. To help you follow the charts and graphs, EB-101 treatment treated wounds are in blue and control wounds in gray. Wound healing was observed at the earliest time point assessed, which was 6 weeks, and was sustained at all subsequent time points, including 24 weeks. Consistent with wound healing, statistically significant pain reduction was seen in earliest time point assessed, which was 6 weeks, and sustained at all subsequent time points, including 24 weeks.

Pain assessment by caregivers showed greater improvement in pain scores for EB-101 treated wounds, with 46% of caregivers categorizing wounds as much improved or very much improved at week 24 from baseline for EB-101 treated wounds, compared to 0% for the control wounds. In addition, at home pain severity assessment using Wong-Baker FACES Pain Rating Scale showed significant pain reduction with EB-101 treatment as early as week three. Pain was also assessed using Patient-Reported Outcomes Measurement Information System called PROMIS, with a significantly greater improvement in pain quality sensory score achieved with EB-101 treatment. In addition to significantly reducing pain, patient-reported and caregiver-reported outcomes related to itch and blistering showed significantly greater improvement with EB-101 treatment. As a reminder, itch for RDEB patient is a significant factor that impacts quality of life and increases risk of trauma, blistering, and infection. Let's review safety and tolerability.

EB-101 was shown to be safe and well-tolerated, with no serious treatment-related adverse events observed in VIITAL, consistent with past clinical trial experience. In conclusion, VIITAL demonstrated positive pivotal study results and a favorable risk-benefit profile for EB-101 in patients with RDEB. Back to you, Vish.

Vishwas Seshadri (Prseident and CEO)

Thank you, Dmitriy. We've made significant progress toward BLA submission and are marching toward commercialization. We had previously mentioned one of the key milestones was to complete 3 consecutive Process Performance Qualification or PPQ runs to demonstrate our validated process and readiness for commercial production. We're excited to share that today we have completed this important step for both the retroviral vector manufacturing and EB-101 drug product manufacturing, which was the last critical piece of data we had to generate to complete the CMC module for the BLA submission. We announced in our Q1 2023 results press release that we had submitted a pre-BLA meeting request to the FDA. The FDA has since accepted our request, the pre-BLA meeting is scheduled on July 10th, 2023, to discuss the format, content, and acceptability of the anticipated BLA application.

Based on this meeting date, we are on track for the anticipated BLA submission in early third quarter of 2023. Based on the anticipated timing of BLA submission, we expect potential BLA approval in late Q1 or early Q2 of 2024. If the BLA is approved, we anticipate being granted the priority review voucher, which can be used to receive expedited review by the FDA of a subsequent marketing application for a different product or sold to another company. Prior PRVs have been sold to other biopharma companies for approximately $100 million. As part of our commercial planning for EB-101, we continue to engage with stakeholders across the healthcare system, including public and private payers and healthcare providers, to better understand market access and pricing for EB-101.

We are encouraged by the initial feedback from these stakeholders and feedback that we have received from patients advocates and organizations which collectively support positive coverage decisions and pricing in line with the value of a one-time treatment that delivers wound healing and pain reduction for years. Based on our initial discussion, payers view RDEB as a disease with very high unmet need and believe EB-101 has a well-differentiated profile with durable clinical benefit for the treated wounds. Also, given the ultra-rare prevalence of RDEB, payers view EB-101 will have a limited overall budget impact and have indicated high willingness to cover EB-101 with favorable access policies, giving us confidence in its potential. Now let's turn to our preclinical ophthalmology programs. We presented animal proof-of-concept data at ASGCT for investigative AAV-based gene therapies for Stargardt disease, X-linked retinoschisis, and autosomal dominant optic atrophy.

The preclinical proof-of-concept data provides early evidence of the potential of our proprietary AAV capsid and gene constructs to express the recombinant protein in target tissues and rescue mutant phenotypes in mouse disease models. I'd now like to turn the call over to our Chief Technical Officer, Dr. Brian Kevany, who will review the results presented at ASGCT.

Brian Kevany (Chief Technical Officer or Chief Scientific Officer)

Thank you, Vish. We are excited by the broad potential for treating serious eye diseases with the new AAV-based therapies using novel AAV capsids from our in-licensed AIM Capsid Library and internal research. At ASGCT, we presented three posters highlighting encouraging findings from animal proof-of-concept experiments from our AAV ophthalmology program. The first poster presented featured ABO-504, a novel approach to treating Stargardt disease, the most common form of juvenile inherited macular dystrophy. Autosomal recessive Stargardt disease is caused by mutations in the ABCA4 gene, preventing the removal of toxic substances from photoreceptor cells that result in photoreceptor cell death and progressive vision loss. Our proprietary strategy is designed to efficiently reconstitute the full-length ABCA4 gene, which is too large to fit in a standard AAV genome, by implementing a dual AAV vector strategy utilizing the Cre-LoxP recombinase system.

The data at ASGCT provides compelling evidence that two independent AAV vectors utilizing Cre recombinase can efficiently reconstitute the ABCA4 gene, leading to full-length ABCA4 protein expression. Key conclusions presented include in vivo Cre-mediated recombination yields full-length ABCA4 using our dual AAV vector system. Recombination, recombinant human ABCA4 is detected and properly localized to photoreceptor outer segments within one month of treatment. Our results show that Cre-mediated recombination of dual AAV vectors is safe and effective in delivering an expression of full-length human ABCA4 in a knockout mouse model, paving the way for a novel therapeutic approach for treating Stargardt disease. Further studies will evaluate ABCA4 expression on accumulation of lipofuscin in a mouse model of Stargardt disease. We believe our dual vector approach using Cre-Lox can also be adapted for other therapies in which AAV-based delivery of large genes is desired.

Our second poster presented at ASGCT featured ABO-503, a novel gene therapy approach for the treatment of X-linked retinoschisis or XLRS, the most common form of inherited macular dystrophy in males. XLRS patients present in the first decade of life with cavities developing between retinal layers, leading to discontinuity within the retinal circuitry, photoreceptor degeneration, and vision loss. ABO-503 is composed of a functional human RS1 packaged in the novel AIM capsid AAV204 that effectively targets photoreceptors and restores RS1 expression. ABO-503 will be administered via a para-retinal injection that will provide an improved safety profile for treatment of XLRS, in which targeting of photoreceptors is desired but where disease renders the retina susceptible to damage from more invasive approaches.

The data presented at ASGCT demonstrated robust RS1 expression in the retina, improved cone photoreceptor density, and overall photoreceptor cell survival, as well as a restoration of the outer retina architecture. Treatment with ABO-503 in mutant mice was associated with photoreceptor preservation and improved retinal function. These results support further development of ABO-503 for the treatment of XLRS. Our third poster presentation at ASGCT featured an investigative AAV gene therapy for autosomal dominant optic atrophy, or ADOA, a form of vision loss associated with loss of retinal ganglion cells, or RGCs, residing in the inner retina caused by mutations in the OPA1 gene. The candidate vector is composed of the human OPA1 gene packaged in the AIM capsid AAV204 discussed previously. The proximity of RGCs to the vitreous cavity make them an attractive target for gene therapy delivered via a pararetinal dosing route.

The data presented confirmed expression of OPA1 in both cell culture and retinas of dosed wild type and disease model animals. Improvements in photoreceptor outer nuclear layer thickness and optokinetic responses were observed with our OPA1 gene therapy candidate in a 10-month proof-of-concept study designed to test the functional consequences of OPA1 restoration in mouse retinas following an intravitreal injection. Initial efficacy results suggest an improvement in retinal signaling to the brain and improved visual acuity in treated mutant mice. These benefits support further development of our OPA1 gene therapy candidate. Back to you, Vish.

Vishwas Seshadri (Prseident and CEO)

Thank you, Brian. We're looking forward to pre-IND meetings with the FDA for two of our programs taking place this quarter. With that, I'll turn the call back over to Holly for the Q&A section.

Operator (participant)

At this time, we will be conducting a question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment while we poll for questions. Your first question for today is coming from Maury Raycroft at Jefferies.

Maury Raycroft (Equity Research Analyst at Biotechnology)

Hi. Good morning, congrats on the updates, thanks for the presentation today. We saw Krystal's VYJUVEK was approved with a relatively broad label. Do you expect the same based on your conversations with the agency, including patient profile, type of wounds, et cetera? Maybe if you can talk a little bit about what you're expecting in the label.

Vishwas Seshadri (Prseident and CEO)

Thank you, Maury, for the question, and good morning. Regarding the indication and the patient types, I want to reiterate that VIITAL, our pivotal study, has treated RDEB patients, recessive dystrophic EB. We have inclusion criteria that focus on large and chronic wounds. It's very early in the BLA process to comment on how broad or restrictive the label would be given of course, the high unmet need, and this is an ongoing dialogue that's gonna be there with the agency. Unfortunately, I cannot give you a definitive answer, but what I can assure is the types of wounds that we have generated evidence for.

Maury Raycroft (Equity Research Analyst at Biotechnology)

Got it. That makes sense. You mentioned that initial feedback from stakeholders across the healthcare system has been positive. Maybe if you can talk a little bit about how you're anticipating pricing could work out with VYJUVEK having a list price of about $630,000. I guess, how does that inform how you're thinking about pricing?

Vishwas Seshadri (Prseident and CEO)

Certainly can talk about that. I will turn the call over to Madhav Vasanthavada, who is leading a lot of our discussions with important stakeholders like both payers as well as hospital administrators, where there's a clear appreciation for the value proposition of a one-time treatment that can give you years of benefit without having to treat the same wound again. Madhav, if you can, you know, throw light on the differentiation and how we have discussed about pricing, please.

Madhav Vasanthavada (SVP, Chief Commercial Officer and Head of Business Development)

Sure, Vish. Hey, Maury. Thanks for the question. Yeah, we find VYJUVEK's launch price now to be very insightful in how we will go about with pricing. Earlier in the year, we had conducted payer research, mostly blinded research, with nearly a dozen payer groups across commercial Medicare, Medicaid. And it was very encouraging to hear when we discussed the clinical profiles of both, all the investigational therapies, including VYJUVEK, as well as for EB-101, that the payers really find the clinical profile for EB-101 to be very transformational given the wound healing profiles, pain reduction, and durable. And at that time, we had placed a few different scenarios as to what if the entry price for VYJUVEK would be and how would that compare with potential price and price elasticity for EB-101, which is all very encouraging.

Now that we have learned what the pricing for VYJUVEK is, we will be in a much better position to be able to place pricing for EB-101, to making sure that there is no access hurdles to patients, but at the same time, we are also capturing the value for the innovation and the, you know, the durable effect that EB-101 will be able to bring. All in all, I think the price elasticity maintains. Given the profile that we now have, we'll be in a better position to be able to, you know, place a price for a launch price for EB-101.

Maury Raycroft (Equity Research Analyst at Biotechnology)

Got it.

Madhav Vasanthavada (SVP, Chief Commercial Officer and Head of Business Development)

Help, Shed?

Maury Raycroft (Equity Research Analyst at Biotechnology)

Yep. Yeah, that's helpful. Makes sense with understanding the value proposition. Maybe last question, then I'll hop back in the queue. The gene therapy data from ASGCT looks good. Just wondering if you could talk a little bit more about how you're prioritizing those three different opportunities. Should we think of Stargardt with the 504 program as being the lead? Or how should we think about that?

Vishwas Seshadri (Prseident and CEO)

Sure, I can talk a little bit about it and then turn it over to Brian for any additional thoughts. Right now we have compelling preclinical data from these disease models in mind that show the expression of gene that's, you may be aware. There's high unmet need in all three of those indications. We have chosen those indications specifically based on how many other investigational therapies are able to make inroads and have hit some challenges along the way. We're encouraged to see that Stargardt, of course, the most talked about among the three, we're able to uniquely address the size of the ABCA4 gene and produce that in the correct tissue. In terms of prioritization and how we resource these programs, Maury, we have a lot of dialogue going on.

We're looking at various different sources of funding, non-dilutive as well, and even, you know, some potential government funds. These are programs that are all equally high in unmet need. It's not really going to be an either/or. It's just going to be a matter of when. Such events will be further discussed in our upcoming calls as we make more progress and also get a little bit more clarity on other nuances from our dialogue with the agency because that tells us, I mean, are we gonna be held to having NHP data or can we have other types of animal studies which will make it much quicker to develop this, these drugs? There's a lot of other pieces to the equation which will further inform our prioritization.

Maury Raycroft (Equity Research Analyst at Biotechnology)

Got it. That makes sense. Thanks for taking my questions. I'll hop back in the queue.

Vishwas Seshadri (Prseident and CEO)

Thank you, Maury.

Operator (participant)

Your next question is coming from Kristen Kluska at Cantor Fitzgerald.

Kristen Kluska (Managing Director and Biotechnology Equity Research)

Hi, good morning, everybody. Congrats on both of these recent data sets. The first question I had was related to the ophthalmology portfolio. We haven't seen as many dual AAV vector strategies yet in gene therapy. I know it's something that others have talked about for some time. Maybe the first part of the question is just.

Understanding what you think is differentiated about your construct that led to the successful findings at this preclinical stage. The latter half of that question is just, you know, frankly, looking at the dual AAV vector landscape, what are the expectations on how you would expect this to translate into human studies? The key things to look out for, given the difference between the models.

Vishwas Seshadri (Prseident and CEO)

Hi, Kristen. Thanks and thanks for the question. I'm going to turn it over to the expert on AAV and ophthalmology, which will be Dr. Brian Kevany. I think before that, I'd just say that Thank you for this question specifically because there are certain mechanistic elements of why we think we can be successful, where some other approaches of getting full length ABCA4 or other methods failed in the past. Brian, can you please throw some light on our unique gene constructs and the dual AAV system, please?

Brian Kevany (Chief Technical Officer or Chief Scientific Officer)

Of course. Yeah. Thanks, Kristen. Yeah. I think, you know, there have been a number of strategies that have been tried both in dual AAV vectors as well as mini genes for ABCA4. While those programs have been going on for a number of years, we haven't seen a lot of movement. I think we were encouraged by our ability to do this and push into a field that is still struggling to get a construct that provides full length ABCA4. You know, as far as how we differentiate from others, the Cre recombinase system is one of the most efficient recombination systems known in nature. We're trying to take advantage of that as part of developing this therapy.

I think that is the one place where we differentiate from others, where they're using things like homologous recombination and inteins, where the efficiency of recombination may not be as high as what we're seeing with the Cre-recombinase system. I think the major differentiating point for us is less about the dual AAVs and more about the actual mechanistic aspects of the therapy that we're trying to develop here. Kristen, could you repeat your second part of your question?

Kristen Kluska (Managing Director and Biotechnology Equity Research)

The second part of the question was just essentially on how you think it's gonna translate into human studies, and I guess what are the key things to, you know, consider the risks, of course, going from the different models outside of what you would normally expect.

Brian Kevany (Chief Technical Officer or Chief Scientific Officer)

Sure. Yeah. I mean, I don't anticipate any significant differences. I mean, the advantage here is we're approaching this with a subretinal delivery for the Stargardt program. For those that aren't aware, this is a relatively very specific injection that occurs between the photoreceptors and the retinal pigment epithelium. This directed injection keeps the vector very close to the site of action and does not get diluted out as if you were providing it as an intravenous or other types of injections. I think the aspects of that keep it somewhat similar to as we're moving between, say, mouse to a larger animal model during IND-enabling studies and then beyond into the human studies.

I think the translation from, say, the large animal to the human studies is going to be relatively smooth because of the injection volume will be exactly the same between the large animal model and the human. We'll be using a lot of the exactly the same type of dosing. I think that sort of translation from large to humans is gonna be relatively seamless. Yeah.

Kristen Kluska (Managing Director and Biotechnology Equity Research)

Thank you. For the autosomal dominant optic atrophy study that you presented on, you have the bullet here that says that visual acuity assessments demonstrate function recovery. I think with a lot of the AAV ophthalmology gene therapy trials, the goal essentially is to show slowing down of disease progression rather than reversal. I guess I'm just kinda interested in the context of that comment and maybe how you think about this clinically. Understand a lot of it is going to have to do with age of intervention and as these different diseases progress at different rates, but what the underlying goal you're essentially looking at will be.

Brian Kevany (Chief Technical Officer or Chief Scientific Officer)

Visual acuity in mice is, you know, is something that we've studied with this animal study and looking at preservation or improvement of visual acuity over time. These animals, as they age, the mutant animals age, they start to lose their ability to have high acuity vision. This treatment was provided very early on in the disease progression prior to any degradation of that visual acuity. It really was a prevention of that development. You know, and visual acuity is a difficult thing to study in humans because it's something that takes a long time to develop. We've seen a number of failures in the industry where visual acuity was the primary endpoint for their trial.

Because of the slow progression of these diseases and specifically visual acuity, it tends to be a bit of a blunt instrument for looking at therapeutic benefit. I think as part of our discussions with the agency, we're gonna be looking at understanding how primary endpoint decisions are made to better capture a therapeutic benefit. This was a very hot topic at ASGCT last week, specifically in ocular, but in general over the rare disease space, about understanding meaningful endpoints that capture therapeutic benefit that may not be the ones that are available right now. I think as we start to talk to regulators, we'll have a better sense of how we wanna approach endpoints and make sure that we're capturing that benefit that is probably there but may not be captured by something like visual acuity.

Vishwas Seshadri (Prseident and CEO)

Yeah. If I may just add to that, Kristen, also what we're gonna be looking at is for any monogenic disease where we have a gene therapy, our goal is to treat early enough that the disease symptoms don't appear or you preserve your eye function, right? In terms of clinical development, it's going to be the first priority would be prevention or cessation of deterioration of visual acuity. Of course, the bigger goal is also to see can you reverse disease that's already happened because it's a prevalent pool of patients with foregone disease. We're gonna be looking to test all types of populations, maybe those that start at around 20 to 60 level of vision and maybe for those subjects where, you know, visual function may have deteriorated even more, can you reverse that? Right?

We're gonna be investigating clinically for all those signals. Of course, the long-term goal is to prevent such deterioration from happening in the first place.

Kristen Kluska (Managing Director and Biotechnology Equity Research)

Great, thanks. Last question for me related to RDEB at ISID, two of the two key new findings were just understanding the effects at an earlier point of evaluation and then also around some of these other secondary endpoints. Since you've presented these data, wanted to hear as you have all these discussions with thought leaders, how important these two components are. I know in the past we've talked about looking at understanding pain reductions correlated with wound healing, but now you have a number of other data points to support these notions. Thank you again.

Vishwas Seshadri (Prseident and CEO)

Thanks for that. I'll take that, Kristen. Just to kind of highlight what the delta of data that we presented at ISID, which wasn't in the top line, right. The top line focused on the 6-month endpoint because that's the regulatory endpoint timing. What we presented at ISID is number one, how quickly do we see these effects, right. You saw that 6 weeks, 12 weeks, 24 weeks. Even 3 weeks where there wasn't a patient visit to do a physician's assessment where they are reporting they're maintaining their diaries and writing down the pain levels and itch levels and things like that, and caregivers are scoring as well.

We're seeing that the clinical benefit sets in early, and we've seen an example of even three weeks, which is pretty much soon, like a couple of weeks after they discharged and went home, right? At every time point, you can see the same kind of benefit between treated wounds and untreated wounds that effect has sustained. That's key, and that's important to note. The second is also we've previously presented the correlation between the wound healing level and pain reduction. That's also very encouraging to see that it's not a one time point that's showing that it's very consistent over the time course post-treatment. Those are the some of the new data points that were discussed, and we've had a lot of discussions with KOLs.

This is going to be very important in, you know, further building on the value proposition. As Dr. Dmitriy Grachev presented, we had itch data that's also showing a dramatic improvement for treated versus untreated. As you heard, itch can also be a risk factor for further blistering and trauma, and that's something that we're encouraged to see. This is going to be a holistic view of what is the benefit to patients.

Beyond all what the KOLs opine and what we see as data points, what's encouraging to us is those patients who went through VIITAL are coming back in our current ongoing study, which is a source for our manufacturing runs that we conduct at PPQ, and they've all lined up, and they're asking for their control wounds to be treated and things like that. That's for us, the ultimate source of, you know, confidence and conviction that this is something that, you know, patients really value. I hope that answered your question, Kristen.

Operator (participant)

Once again, if you would like to ask a question, please press star one. Your next question for today is coming from James Molloy at Alliance Global Partners.

James Molloy (Managing Director and Senior Biotechnology and Specialty Pharmaceuticals Equity Analyst)

Hey, guys. Good morning. Thank you for taking my questions. I just want to follow up on a question earlier, obviously competitive VYJUVEK approval. I think on their call, they're talking about the $630,000 a year, about $485,000 a year after US government discounts. I think they're saying about 1,100 target patients. Not to hold you to a competitor's numbers, how do those change up or down your guys' estimates for where you think pricing can come in and size of the market, given sort of their, what they've put out there publicly as their estimates?

Vishwas Seshadri (Prseident and CEO)

Thank you for the question, Jim. We did take note of what their pricing is, Jim, but you know, at this point in time, as Madhav mentioned, we're encouraged by the value that, you know, the various stakeholders are placing in these types of gene therapies. I would reiterate that what we thought a year ago, maybe in terms of what pricing we were considering and then post-VIITAL results, clearly having seen the results in the best-case scenario of clinical profile play out, we're definitely, you know, relooking at pricing in a different way. Now, what we don't know is many details about the label for VYJUVEK is number 1 very broad. It includes all of Dystrophic EB.

Whereas we're currently looking at our clinical evidence is focused on Recessive Dystrophic EB, which is half of DEB. It's really an apples to oranges comparison because our DEB is a smaller, it's a relatively rarer, narrower disease space, and the value proposition is different as well. I mean, it is one on the one hand, you have a redosable gene therapy, on the other hand, we have for a given wound, a one-time treatment that gives you years of benefit and not having to retreat soon enough, right? That's something we will definitely take into account. I don't want to comment anything about exact price points and things like that because we have to do our homework on how the estimated pricing per year works out and what happens in the real world.

Sometimes we make these estimates and then the real world, turns out. There is some time and homework for us to do before we come up. I want to reassure that we will be responsible corporate citizens and make sure that patients will get access to our therapies because that's our guiding principle here.

James Molloy (Managing Director and Senior Biotechnology and Specialty Pharmaceuticals Equity Analyst)

Outstanding. Thank you. On the pre-BLA, anything that we should anticipate potentially coming out of the pre-BLA? I imagine it should be a fairly straightforward meeting then right into a BLA. A follow-up would be, again, given the competitor's approval, has this changed your thinking on going on self-launch or potentially partnering?

Vishwas Seshadri (Prseident and CEO)

Thanks, Jim. The first question that you asked on the pre-BLA, it's every BLA submission, given the complexity of our therapies, the therapeutic space, limited experience that we have in these disease areas, it behooves us to have the pre-BLA meeting to make sure that we have everything that warrants a submission, there's no deficiencies. That's kind of but the pre-BLA meeting itself is that formal step that you have. However, I just want to assure that it's not like we have complete silence with the agency and suddenly appearing for one meeting on July 10th. We've been having a lot of interaction with the agency even as we speak. There's also series of informal meetings and exchange. This will be like the final culmination step, saying we scored everything that we needed to.

We're gonna make, put this dossier in front of you, right? That is what the pre-BLA meeting is, and we're confident we should be in time, because as I mentioned, that the biggest piece of work that we had to finish was the PPQ run, and we completed those 3 consecutive manufacturing runs successfully. What's significant about that is it's not just that we had to meet the release criteria for EB-101 drug products, but also all the various process parameters have to fall within the pre-specified range to show the robustness of our process. We're happy to report that all those parameters met the goal and we have everything we need to pull together the package. That's for the pre-BLA and the submission work stream itself. Your second question was about partnering and commercialization.

This is a rare disease. You know, we have, the focus for us is more on the delivery of our therapy in the centers where we're gonna administer this and lesser on, sales and marketing and pool demand, because we're gonna be working closely with the advocacy groups, the patient communities. There's, you know, atypical launch scenario here that the focus where is gonna be on how do we deliver, what's the patient services that's gonna be needed. Given that, the profile of a partner, if we get a partner, is gonna be a very different profile than a typical large pharma kind of, partnership. We're open to that.

At the same time, we're also looking at how do we retain the value we've created, and is there options where, you know, we should be ready because we don't want to wait forever to, well, you know, make a partnership deal. While those types of conversations are still ongoing, we want to score certain pieces of launch readiness in our hands already, which is why we started to do the payer research and start to talk to the stakeholders and get ready one step at a time. Of course, that is only gonna pick up more steam once we're through with the BLA submission, which is kind of the 800 pound gorilla in the room right now. I hope that gives you some sense to how we're looking at commercialization as a next step.

The H2 of the year is gonna have a lot of that conversation coming up to limelight.

James Molloy (Managing Director and Senior Biotechnology and Specialty Pharmaceuticals Equity Analyst)

Great. Thank you for taking the questions.

Vishwas Seshadri (Prseident and CEO)

Of course. Thank you.

Operator (participant)

We have reached the end of the question and answer session, and I will now turn the call over to Vishwas for closing remarks.

Vishwas Seshadri (Prseident and CEO)

Thank you. In closing, I want to thank our shareholders and other stakeholders who have listened to this call, and we will talk to you again soon. Thank you.

Operator (participant)

This concludes today's conference, and you may disconnect your lines at this time. Thank you for your participation.