What changed in this filing

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Item 1. Business

2024-03-18 compared with 2023-03-29 · 416 added, 356 removed, 893 unchanged (46% of the section changed)

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or the “Company”), is a clinical-stage biopharmaceutical company developing cell and gene therapies for life-threatening

Our lead clinical program is EB-101, an autologous, engineered cell therapy currently in development for recessive dystrophic

epidermolysis bullosa (“RDEB”).

EB-101 has been granted Orphan Drug and Rare Pediatric Disease (“RPD”) designations

Food and Drug Administration (“FDA”) and Orphan Drug Designation by the European Medicines Agency (“EMA”).

plan to continue development of AAV-based gene therapies designed to treat ophthalmic diseases with high unmet medical need using

the novel AIM™ capsid platform that we have exclusively licensed from the University of North Carolina at Chapel Hill

(“UNC”), and internal AAV vector research programs.

Abeona’s novel, next-generation AAV capsids are being evaluated to improve tropism profiles for a variety of

devastating diseases.

Our lead clinical program is for prademagene zamikeracel (“pz-cel”), our investigational autologous, COL7A1 gene-corrected

epidermal sheets currently in development for recessive dystrophic epidermolysis bullosa (“RDEB”).

Pz-cel has been granted

Orphan Drug and Rare Pediatric Disease (“RPD”) designations by the U.S.

Food and Drug Administration (“FDA”)

and Orphan Drug Designation by the European Medicines Agency (“EMA”).

plan to continue development of adeno-associated virus (“AAV”) based gene therapies designed to treat ophthalmic diseases

with high unmet medical need using the novel AIM™ capsid platform that we have exclusively licensed from the University of North

Carolina at Chapel Hill (“UNC”), and internal AAV vector research programs.

Abeona’s novel, next-generation AAV capsids

are being evaluated to improve tropism profiles for a variety of devastating diseases.

Mission and Strategy

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the promise of genetic medicine and redefining the standard of care through cell and gene therapies.

In November 2022, we announced positive

topline data from the VIITAL™ Phase 3 study evaluating the efficacy, safety and tolerability of EB-101.

In September 2023, we submitted

a Biologics License Application (“BLA”) for pz-cel to the FDA.

In November 2023, the FDA accepted and granted priority review

for our BLA for pz-cel.

Under the Prescription Drug User Fee Act (“PDUFA”), the FDA has set a target action date of May 25,

partner with leading academic researchers, patient advocacy organizations, caregivers and other biotechnology companies to develop therapies

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We plan to continue to develop our chimeric AAV capsids capable of improved tissue targeting

for various indications and potentially evading immunity to wildtype AAV vectors.

for various indications and potentially evading immunity to wild-type AAV vectors.

our Leadership Position in Commercial-Scale Cell and Gene Therapy Manufacturing.

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Additional Cell and Gene Therapy Franchises and Adjacencies through In-Licensing and Strategic Partnerships.

seek to be the partner of choice in cell and gene therapy treatment and have closely collaborated with leading academic institutions,

seek to be the partner of choice in cell and gene therapy treatments and have closely collaborated with leading academic institutions,

key opinion leaders, patient foundations, and industry partners to accelerate research and development, understand the needs of patients

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Patients with RDEB have a defect in the COL7A1 gene,

resulting in the inability to produce Type VII collagen, which plays a vital role in anchoring the skin’s dermal and epidermal

a result of the genetic defect, RDEB patients have fragile skin, which can easily damage to produce open and blistering wounds, disfiguring

scars throughout the body, fused fingers and toes, limits in range of motion at joints (e.g., arms and legs), and an abnormal narrowing

of the esophagus.

Long-term RDEB patients can suffer from anemia, are at high risk of developing aggressive squamous cell carcinomas,

infections, and premature death.

The most severe patients are approximately 20 times more likely to die by 30 years of age than the general

resulting in the inability to produce Type VII collagen, which plays a vital role in skin functioning by anchoring the skin’s dermal

and epidermal layers to one another.

a result of the genetic defect, RDEB patients have fragile skin, which can easily damage to produce open and blistering wounds,

disfiguring scars throughout the body, fused fingers and toes, limits in range of motion at joints (e.g., arms and legs), corneal

abrasions, and an abnormal narrowing of the esophagus.

Long-term RDEB patients can suffer from anemia, are at high risk of

developing aggressive squamous cell carcinomas, infections, and premature death.

The most severe patients are approximately 20 times

more likely to die by 30 years of age than the general population.

to other rare diseases, the incidence and prevalence of RDEB are not well defined.

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of COL7A1 variants, which is believed to cause RDEB, Stanford University estimated the incidence of RDEB to be approximately 63 per million

births, and prevalence could be up to 3,850 patients in the U.S., whose wounds may benefit from COL7A1-mediated treatments such as EB-101.

patients have, on average, 11 active wounds on their bodies, with the majority > 20 cm 2 (Stanford University;

et al., 2017).

births, and prevalence could be up to 3,850 patients in the U.S., whose wounds may benefit from COL7A1-mediated treatments such as pz-cel.

patients have an active disease with the majority of the wounds typically > 20 cm 2 (Stanford University;

Solis, D., et

In 2020, a survey of RDEB patients reported that approximately 60% have active wounds covering greater than 30% of their

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Nature Research, 2017).

expect EB-101 could be a treatment option for toughest to treat RDEB wounds.

EB-101 has shown durable healing and associated pain reduction

in our VIITAL™ phase 3 trial in large and/or chronic wounds that carry the highest burden, including the need for frequent dressing

changes, pain, pruritus, risk of infection, and developing skin cancer.

our VIITAL TM phase 3 and phase 1/2a clinical trials, pz-cel was applied as a one-time surgical procedure onto RDEB wounds

and has shown up to 8 years of durable wound healing and associated pain reduction even in the toughest-to-treat in RDEB wounds.

evaluated in the VIITAL TM phase 3 trial had large wounds (> 20cm 2 ) and, on average, had wounds remained open

for 6.2 years, and in some cases up to 21 years, prior to pz-cel treatment.

Most RDEB patients have large and chronic wounds that carry

the highest burden, including the need for frequent dressing changes, pain, pruritus, risk of infection, and developing skin cancer.

Management of RDEB

present, there are no approved treatments for RDEB in the U.S.

management currently consists of time and labor-intensive supportive care to limit contamination and infection, and reduction in mechanical

forces that produce new blisters.

Care usually includes treatment of new blisters by lancing and draining.

Wounds are then dressed with

a non-adherent material, covered with padding for stability and protection, and secured with an elastic wrap for integrity.

costs of wound dressings alone for an RDEB patient can amount to as high as $996,000 per year.

of care in RDEB wound management currently consists of time and labor-intensive supportive care to limit contamination and

infection, and reduction in mechanical forces that produce new blisters.

Care usually includes treatment of new blisters by lancing

and draining.

Wounds are then dressed with a non-adherent material, covered with padding for stability and protection, and secured

with an elastic wrap for integrity.

In a cost analysis conducted by Debra of America, based on 3,274 patient’s health insurance

claims from private insurance the annual cost of dystrophic epidermolysis bullosa (DEB) was identified to be 465% greater than the

annual cost to the healthcare system from all people.

The cost of wound care supplies could be as high as

$996,000 per year.

patients also have periodic surgeries to relieve disease related issues such as narrowing of their esophagus, fusing of fingers, and

corneal abrasions.

Status and Positive Topline Data

is an autologous, engineered cell therapy in which a functioning COL7A1 gene is inserted into a patient’s own skin cells (keratinocytes)

using a retrovirus.

The keratinocytes are then transplanted back to the patient to restore Type VII collagen expression and skin function.

from a completed Phase ½ study that enrolled 7 patients with large and chronic RDEB wounds at Stanford University showed that

EB-101 was well-tolerated and resulted in significant and durable wound healing (Siprashvili, Z., et al., 2016), with up to eight years

2023, Vyjuvek ® and Filsuvez ® were approved by the FDA for treatment of wounds associated with DEB and

wounds associated with Junctional (JEB) and DEB, respectively.

The introduction of these drugs may further increase the total cost of care.

is our investigational autologous epidermal sheets in which a functioning COL7A1 gene is inserted into a patient’s own skin cells

(keratinocytes) using a retrovirus.

The keratinocytes are then grown into credit card sized sheets and surgically applied to the patient to restore Type VII collagen expression

and skin function.

from a completed Phase 1/2a study that enrolled seven patients with large and chronic RDEB wounds at Stanford University showed that

pz-cel was well-tolerated and resulted in significant and durable wound healing (Siprashvili, Z., et al., 2016), with up to eight years

of follow-up (So.

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To date, there have been no reported serious adverse events.

November 3, 2022, we announced positive topline data from VIITAL™ study.

November 2022, we announced positive topline data from our VIITAL™ study.

The pivotal phase 3 VIITAL™ study evaluated the

efficacy, safety and tolerability of EB-101 in 43 large chronic wound pairs in 11 subjects with RDEB.

efficacy, safety, and tolerability of pz-cel in 43 large chronic wound pairs in 11 subjects with RDEB.

The large chronic wounds randomized

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and (2) pain reduction associated with wound dressing change assessed by

the mean differences in scores of the Wong-Baker FACES scale between randomized treated and matched untreated (control) wounds at the

six-month timepoint.

the mean differences in scores of the Wong-Baker FACES ® Pain Rating Scale between randomized treated and matched untreated

(control) wounds at the six-month timepoint.

VIITAL™ study met its two co-primary efficacy endpoints demonstrating statistically significant, clinically meaningful improvements

in wound healing and pain reduction in large chronic RDEB wounds.

EB-101 was shown to be well-tolerated with no serious treatment-related

Pz-cel was shown to be well-tolerated with no serious treatment-related

adverse events observed, consistent with past clinical experience.

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retrovirus results, and no systemic immunologic responses were reported during the study, as well as no squamous cell carcinoma at treatment

sites after application of EB-101.

Two subjects reported at least one serious adverse event unrelated to EB-101.

sites after application of pz-cel.

Two subjects reported at least one serious adverse event unrelated to pz-cel.

Four subjects reported

related treatment emergent adverse events, including procedural pain, muscle spasms and pruritis.

Infections unrelated to EB-101 were

Infections unrelated to pz-cel were

observed in eight patients.

on these positive topline results, we intend to submit a Biologics License Application (“BLA”) for EB-101 to the FDA by mid-2023.

EB-101 has been granted Regenerative Medicine Advanced Therapy (“RMAT”), Breakthrough Therapy, Orphan Drug and RPD designations

by the by the FDA as well as Orphan Drug designation by the EMA.

September 2023, we submitted a BLA for pz-cel to the FDA.

In November 2023, the FDA accepted for filing and granted priority review

for our BLA for pz-cel.

Under the PDUFA, the FDA has set a target action date of May 25, 2024.

Pz-cel has been granted Regenerative

Medicine Advanced Therapy (“RMAT”), Breakthrough Therapy, Orphan Drug and RPD designations by the by the FDA as well as

Orphan Drug designation by the EMA.

the potential benefits of Orphan Drug designation are a potential seven years of market exclusivity following FDA approval, potentially

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A PRV may be used to receive expedited review of a subsequent marketing application for a different product or sold to another

have continued to prepare our cGMP commercial facility in Cleveland for manufacturing EB-101 to support our planned BLA filing.

have continued to prepare our cGMP commercial facility in Cleveland for manufacturing pz-cel to support our planned BLA filing.

study drug product for all our VIITAL™ study participants has been manufactured at our Cleveland facility.

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Overview and Program Overview

XLRS is a rare, monogenic retinal disease that results in the irreversible

loss of photoreceptor cells and severe visual impairment.

XLRS is caused by mutations in the RS1 protein, which is normally secreted by

retinal photoreceptors and bipolar neurons and functions to mediate cell-cell adhesion.

XLRS is characterized by abnormal splitting of

the layers of the retina, resulting in poor visual acuity, which can progress to legal blindness.

The incidence of XLRS is estimated to

be between 1 in 5,000 and 1 in 20,000 in males, with an estimated prevalence of 35,000 in the United States and Europe combined.

are currently no disease modifying therapies approved for XLRS, but because the genetics of the disease are well understood, early intervention

via gene therapy has significant potential to reverse or stabilize disease progression at early stages and prevent vision loss.

ABO-503, composed of a functional human RS1 packaged

in the novel AIM™ capsid AAV204, has shown preclinical efficacy following delivery to the retina in a mouse model of XLRS.

studies have demonstrated robust RS1 expression in the retina, improved cone photoreceptor density and overall photoreceptor cell survival,

as well as a restoration of outer retina architecture.

We submitted a pre-IND meeting request with the FDA in March 2023.

is a rare, monogenic retinal disease that results in the irreversible loss of photoreceptor cells and severe visual impairment.

is caused by mutations in the RS1 protein, which is normally secreted by retinal photoreceptors and bipolar neurons and functions to

mediate cell-cell adhesion.

XLRS is characterized by abnormal splitting of the layers of the retina, resulting in poor visual acuity,

which can progress to legal blindness.

The incidence of XLRS is estimated to be between 1 in 5,000 and 1 in 20,000 in males, with an

estimated prevalence of 35,000 in the United States and Europe combined.

There are currently no disease modifying therapies approved

for XLRS, but because the genetics of the disease are well understood, early intervention via gene therapy has significant potential

to reverse or stabilize disease progression at early stages and prevent vision loss.

composed of a functional human RS1 packaged in the novel AIM™ capsid AAV204, has shown preclinical efficacy following delivery

to the retina in a mouse model of XLRS.

Preclinical studies have demonstrated robust RS1 expression in the retina, improved cone photoreceptor

density and overall photoreceptor cell survival, as well as a restoration of outer retina architecture.

Results of these studies were

presented at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting in May 2023.

A pre-IND meeting for ABO-503 was conducted

with the FDA in April 2023 and provided Abeona with comprehensive feedback to support a future IND submission.

for the Treatment of Stargardt Disease

Overview and Program Overview

Autosomal recessive Stargardt disease, the most common form of juvenile

macular degeneration with estimated incidence of 1 in 8,000 to 10,000 people, causes vision loss in children and young adults.

common form of Stargardt disease is caused by mutations in the ABCA4 gene, which prevent removal of toxic compounds from photoreceptor

cells that results in photoreceptor cell death and progressive vision loss.

There are currently no FDA approved treatments available,

and to date, development of investigational gene modifying therapies has remained challenging in part due to the large size of the ABCA4

gene, which exceeds the encapsidation capacity of a single AAV vector.

Abeona’s internal research and development team developed ABO-504,

which is designed to efficiently reconstitute the full-length ABCA4 gene by implementing a dual AAV vector strategy using the Cre-LoxP

recombinase system.

In May 2021, at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, Abeona reported preclinical

data demonstrating the ability of the dual AAV vector system to produce full length ABCA4 protein in cell culture.

Recent proof-of-concept

studies have extended these findings by showing expression of ABCA4 mRNA and full-length ABCA4 protein in the retina of subretinally dosed

abca4-/- knockout mice, at levels similar to endogenous ABCA4 in wild-type animals.

recessive Stargardt disease, the most common form of juvenile macular degeneration with estimated incidence of 1 in 8,000 to 10,000 people,

causes vision loss in children and young adults.

The most common form of Stargardt disease is caused by mutations in the ABCA4 gene,

which prevent removal of toxic compounds from photoreceptor cells that results in photoreceptor cell death and progressive vision loss.

There are currently no FDA approved treatments available, and to date, development of investigational gene modifying therapies has remained

challenging in part due to the large size of the ABCA4 gene, which exceeds the encapsidation capacity of a single AAV vector.

internal research and development team developed ABO-504, which is designed to efficiently reconstitute the full-length ABCA4 gene by

implementing a dual AAV vector strategy using the Cre-LoxP recombinase system.

Abeona previously reported preclinical data demonstrating

the ability of the dual AAV vector system to produce full length ABCA4 protein in cell culture.

Recent proof-of-concept studies, presented

at the 2023 ASGCT Annual Meeting, have extended these findings by showing expression of ABCA4 mRNA and full-length ABCA4 protein in the

retina of subretinally dosed abca4-/- knockout mice, at levels similar to endogenous ABCA4 in wild-type animals.

A pre-IND meeting for

ABO-504 was conducted with the FDA in June 2023 and provided Abeona with comprehensive feedback to support a future IND submission.

for the Treatment of Autosomal Dominant Optic Atrophy (“ADOA”)

Overview and Program Overview

ADOA, a form of hereditary vision loss associated with RGC death, is predominantly

caused by mutations in the Opa1 gene.

Opa1, a dynamin-related GTPase, acts to stabilize the inner mitochondrial membrane and acts in mitochondrial

fusion and inner membrane remodeling.

Mutant phenotypes present with a progressive loss of RGCs that results in optic nerve degeneration

and legal blindness with a loss of visual acuity, optic disc pallor, and color vision deficits.

ADOA affects approximately 1 in 30,000

people worldwide.

a form of hereditary vision loss associated with retinal ganglion cell (“RGC”) death, is predominantly caused by mutations

in the Opa1 gene.

Opa1, a dynamin-related GTPase, acts to stabilize the inner mitochondrial membrane and acts in mitochondrial fusion

and inner membrane remodeling.

Mutant phenotypes present with a progressive loss of RGCs that results in optic nerve degeneration and

legal blindness with a loss of visual acuity, optic disc pallor, and color vision deficits.

ADOA affects approximately 1 in 30,000 people

Currently, there is no approved treatment for people living with ADOA.

ABO-505 is designed to express a functional copy of human Opa1 in the retina

following para-retinal injection.

ABO-505 aims to take advantage of the robust optic nerve and retinal ganglion cell (RGC) transduction

ability of AAV204 to deliver its genetic payload to the cells most affected by ADOA.

Preclinical studies have confirmed expression of

Opa1 in both cell culture and the retinas of dosed wild-type and disease model animals.

Initial efficacy results suggest an improvement

in retinal signaling to the brain, and improved visual acuity in treated mutant mice.

preclinical data with ABO-503, ABO-504 and ABO-505 have been submitted for presentation at a future medical meeting in the second quarter of 2023.

is designed to express a functional copy of human Opa1 in the retina following para-retinal injection.

ABO-505 aims to take advantage

of the robust optic nerve and RGC transduction ability of AAV204 to deliver its genetic payload to the cells most affected by ADOA.

studies have confirmed expression of Opa1 in both cell culture and the retinas of dosed wild-type and disease model animals.

efficacy results suggest an improvement in retinal signaling to the brain and improved visual acuity in treated mutant mice.

These studies

were presented at the ASGCT Annual Meeting in May 2023.

Therapy Treatments anchored in AIM™ Vector Platform

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for clinical trials related to our product candidates and ensure commercial demand is met in the event our therapies receive marketing

Our facility is led by a team of highly-skilled production, process/assay development and QC scientists with expertise in cell

and gene therapy, particularly in cell culture, upstream manufacturing, downstream purification, assay development and wet lab techniques.

Our facility is led by a team of highly skilled production, process/assay development and quality control scientists with expertise

in cell and gene therapy, particularly in cell culture, upstream manufacturing, downstream purification, assay development and wet lab

have completed our 16,000+ square foot manufacturing build-out in Cleveland, Ohio.

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The facility is designed to initially

manufacture clinical drug products with later intent of manufacturing commercial grade cGMP drug product.

The second phase, completed

in 2019, was the completion of an additional 8,000 square feet of state-of-the-art laboratory space to support our expanding quality

control, process development, and assay development teams.

The second phase also included nearly 2,000 square feet of cGMP Inventory

Control space.

have advanced our in-house manufacturing capabilities for EB-101.

manufacture clinical drug products with intent of manufacturing commercial grade cGMP drug product.

The second phase, completed in 2019,

was the completion of an additional 8,000 square feet of state-of-the-art laboratory space to support our expanding quality control,

process development, and assay development teams.

The second phase also included nearly 2,000 square feet of cGMP Inventory Control space.

have advanced our in-house manufacturing capabilities for pz-cel.

The product is manufactured as a multilayer cellular sheet containing

corrected keratinocytes that is fastened to a petrolatum gauze backing with surgical hemoclips.

Engineered sheets are applied over wound

areas, where they are expected to produce keratinocytes with functioning Type VII collagen, providing immediate wound coverage and allowing

corrected keratinocytes that is fastened to a petrolatum gauze backing with surgical titanium ligating clips.

Engineered sheets are applied

over wound areas, where they provide keratinocytes with functional Type VII collagen, providing immediate wound coverage and allowing

for long-term wound healing.

A key component to the EB-101 drug product manufacturing process is the retroviral vector, which delivers

A key component to the pz-cel drug product manufacturing process is the retroviral vector, which delivers

the functional copy of the Collagen VII Alpha 1 cDNA to the autologous patient cells.

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Production Facility, we have transferred the cGMP manufacturing process for the LZRSE-Col7A1 retroviral vector to our Cleveland facility

and have produced three cGMP lots for analytical and clinical comparability.

We have also created and characterized a cGMP master cell

bank and a working cell bank to support the cGMP production of the retroviral vector.

and have demonstrated analytical comparability between IUVPF and Abeona-produced retroviral vector.

In order to support licensure, we

have produced three cGMP process validation lots and have also created and characterized a cGMP master cell bank and a working cell bank

to support the cGMP production of the retroviral vector.

have established AAV vector manufacturing capabilities that use the triple plasmid transient transfection method.

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At the end of the

incubation period, the newly generated AAV vectors are harvested, purified and filtered in a multi-step process.

We continue to maintain

focus on cGMP compliance and ensuring adequate supply to support our future clinical activity.

incubation period, the newly generated AAV vectors are harvested, filtered, and purified in a multi-step process.

have established and maintained strong and collaborative relationships with third-party companies specializing in the testing of cell

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have made significant investments in developing optimized manufacturing processes and believe that our processes and methods developed

to date provide a comprehensive manufacturing process for EB-101 and AAV-based vector therapies, including:

scale to support commercial manufacturing requirements for EB-101

related to biopsy, cell collection, storage and transportation as part of manufacturing for EB-101

related to product release testing for EB-101

related to the manufacture and release testing of retroviral supernatant

transportation and packaging processes and materials for finished EB-101 product

AAV vector manufacturing processes and techniques that produce a highly purified product candidate

serum-free suspension technology that is readily scalable

assays to accurately characterize our process and the AAV vectors we produce

series of purification processes, which may be adapted and customized for multiple different AAV capsids, with a goal of higher concentrations

of active vectors, and that are essentially free of empty capsids.

to date provide a comprehensive manufacturing process for pz-cel and AAV-based vector therapies, including:

sufficient scale to support

commercial manufacturing requirements for pz-cel

processes related to biopsy,

cell collection, storage and transportation as part of manufacturing for pz-cel

processes related to product

release testing for pz-cel

processes related to the

manufacture and release testing of retroviral vector

establishing transportation

and packaging processes and materials for finished pz-cel product

proprietary AAV vector

manufacturing processes and techniques that produce a highly purified product candidate

AAV serum-free suspension

technology that is readily scalable

multiple assays to accurately

characterize our process and the AAV vectors we produce

a series of purification

processes, which may be adapted and customized for multiple different AAV capsids, with a goal of higher concentrations of active

vectors, and that are essentially free of empty capsids.

believe that these improvements will enable us to develop best-in-class, next-generation cell and gene therapy products.

As we look to

commercialize EB-101 (subject to FDA approval), we are working towards filing a BLA to support commercial manufacturing of EB-101 from

our Cleveland facility.

Based on feedback from the FDA, we believe that we have alignment with the FDA on the CMC requirements for EB-101,

including characterization and validation plans.

commercialize pz-cel (subject to FDA approval), we have filed our BLA to support commercial manufacturing of pz-cel from our Cleveland

Strong Intellectual Property Protection

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term extensions, where applicable.

success may depend in part on our ability to obtain and maintain patent and other protections for commercially important technology,

success may depend in part on our ability to obtain and maintain patents and other protections for commercially important technology,

inventions, and know-how related to our business;

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preserve the confidentiality of our trade secrets;

operate without infringing the valid enforceable patents and intellectual property rights of third parties.

Our ability to stop third

parties from making, having made, using, selling, offering to sell, or importing our products may depend on the extent to which we have

rights under valid and enforceable licenses, patents or trade secrets that cover these activities.

In some cases, these rights may need

to be enforced by third-party licensors.

With respect to both licensed and company-owned intellectual property, we may not be granted

patents with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future,

nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful

in protecting our commercial products and methods of manufacturing the same.

and operate without infringing the valid enforceable patents and other intellectual property rights of third parties.

Our ability to

stop third parties from making, having made, using, selling, offering to sell, or importing our products may depend on the extent to

which we have rights under valid and enforceable licenses, patents, or trade secrets that cover these activities.

In some cases, these

rights may need to be enforced by third-party licensors.

With respect to both licensed and company-owned intellectual property, we may

not be granted patents with respect to any of our pending patent applications or with respect to any patent applications filed by us

in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially

useful in protecting our commercial products and methods of manufacturing the same.

are actively seeking U.S.

and international patent protection for a variety of technologies, including the following:

research tools

and methods, methods for transferring genetic material into cells, AAV-based biological products, methods of designing novel AAV constructs,

methods for treating diseases of interest and methods for manufacturing, packaging, and transporting our product candidates.

intend to seek patent protection or rely upon trade secret rights to protect other technologies that may be used to discover and validate

targets and that may be used to identify and develop novel biological products.

We seek protection, in part, through confidentiality

and proprietary information agreements.

We are a party to various license agreements that give us rights to use specific technologies

in our research and development, and future commercialization.

and international patent protection, together with our licensors, for a variety of technologies, including

AAV capsids, AAV-based biological products, methods of designing novel AAV constructs, methods for treating diseases of interest, including

RDEB, and methods for manufacturing, packaging, and transporting our product candidates.

We also intend to seek patent protection or

rely upon trade secret rights to protect other technologies that may be used to discover and validate targets and that may be used to

identify and develop novel biological products.

We seek protection, in part, through confidentiality and proprietary information agreements.

We are a party to various license agreements that give us rights to use specific technologies in our research and development, and future

commercialization.

Technologies and Intellectual Property

Dystrophic Epidermolysis Bullosa

support our EB franchise, we have licensed a patent family from Stanford University covering EB-101 and its use in the treatment of RDEB.

Patents covering our investigational EB-101 product have been granted by the European Patent Office (EP3400287B1) and in other geographical

Recessive Dystrophic

Epidermolysis Bullosa

support our EB franchise, we have licensed a patent family from Stanford University covering pz-cel and its use in the treatment of RDEB.

Patents covering our investigational pz-cel product have been granted by the European Patent Office (EP3400287B1) and in other geographical

regions, and are expected to expire in early 2037.

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expected to expire in 2037.

We have also filed United States patent applications directed to the packaging and transport of EB-101, which,

if granted, are not expected to expire before 2040.

may also rely on the additional protection afforded by data exclusivity (currently 12 years for biologics like EB-101), other market

exclusivity such as orphan drug exclusivity, and patent term extensions, where applicable.

have an exclusive license to an international patent family from UNC covering novel AAV capsids (“AIM™ capsids”) that

may potentially be used to deliver a wide variety of therapeutic transgenes to human cells to treat genetic diseases.

National stage

applications directed to the AIM™ capsids have been filed in the United States, Europe and other geographical regions.

We have also filed United States and Canadian patent applications directed to the packaging and transport

of pz-cel, which, if granted, are not expected to expire before 2040.

may also rely on the additional protection afforded by data exclusivity (currently 12 years for biologics like pz-cel), other market

exclusivity such as orphan drug exclusivity (currently seven years), and patent term extensions, where applicable.

have an exclusive license to an international patent family from The University of North Carolina at Chapel Hill (“UNC”)

covering novel AAV capsids (“AIM™ capsids”) that may potentially be used to deliver a wide variety of therapeutic transgenes

to human cells to treat genetic diseases.

National stage applications directed to the AIM™ capsids have been filed in the United

States, Europe and other geographical regions.

The first U.S.

patent in this patent family, U.S.

10,532,110 (the “’110 Patent”), was issued to UNC on January 14,

The ’110 Patent is entitled to 352 days of patent term adjustment, making its projected expiration date November 6, 2036.

10,532,110 (the “‘110

Patent”), was issued to UNC on January 14, 2020.

The ‘110 Patent is entitled to 352 days of patent term adjustment, making

its projected expiration date November 6, 2036.

The second U.S.

patent in this patent family, U.S.

10,561,743 (the “’743 Patent”), was issued to UNC on

February 18, 2020.

10,561,743 (the “‘743

Patent”), was issued to UNC on February 18, 2020.

The ‘743 Patent is expected to expire on November 20, 2035.

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11,491,242 (the “‘242 Patent”) issued on November 8, 2022.

The ‘242 Patent is entitled to 429 days

of patent term adjustment and will not expire before January 22, 2037.

We have exclusive rights to these patents under our license with

Patent is entitled to 429 days of patent term adjustment and will not expire before January 22, 2037.

Patents have also been granted

in Australia (AU2015349759B2), Israel (IL252072), and Russia (RU2727015).

We have exclusive rights to these patents under our license

also own a second patent family directed to certain AAV capsids and have filed national stage applications in the United States, Europe

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Patents issuing from these applications are not expected to expire before 2039.

Disease (Infantile Batten Disease)

CLN1 Disease (Infantile

Batten Disease)

have also licensed from UNC rights to two patent families directed to treating CLN1 disease (also known as infantile Batten disease).

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geographical regions.

Patents issuing from applications in the second patent family are not expected to expire before 2040.

We have entered

into agreements exclusively sublicensing these two CLN1 patent families to Taysha Gene Therapies.

have licensed rights to patent families from both UNC and the University of Edinburgh relating to gene therapy for the treatment of Rett

The patent family licensed from UNC at Chapel Hill are directed to viral genomes designed to regulate expression of the MeCP2

gene, which is mutated in patients with Rett Syndrome.

This family has pending applications in the United States, Europe and other geographical

Patents issuing from applications in the second patent family will have a 20-year expiration date of no earlier

We have entered into agreements exclusively sublicensing these two CLN1 patent families to Taysha Gene Therapies, Inc.

Rett Syndrome

have licensed rights to one patent family from UNC and two patent families from The University Court of the University of Edinburgh (“U.

Edinburgh”) and The University Court of the University of Glasgow (“U.

Glasgow”) relating to gene therapy for the treatment

of Rett Syndrome.

The patent family licensed from UNC at Chapel Hill are directed to viral genomes designed to regulate expression of

the MeCP2 gene, which is mutated in patients with Rett Syndrome.

This patent family has pending applications in the United States, Europe

and other geographical regions.

Patents issuing from these applications will have a 20-year expiration date of no earlier than 2039.

The patent families licensed from U.

Edinburgh and U.

Glasgow are directed to expression cassettes for MeCP2 polypeptides and to synthetic

MeCP2 polypeptides.

The patent family directed to MeCP2 expression cassettes has pending applications in the United States, Europe and

other geographical regions.

The patent family directed to synthetic MeCP2 polypeptides has pending applications in the United States

and other geographical regions.

Patents issuing from applications in the Edinburgh patent families will have a 20-year expiration date

of no earlier than 2038.

In October 2020, we entered into an agreement exclusively sublicensing these UNC and University of Edinburgh

patent rights to Taysha Gene Therapies.

Multipartite AAV

Delivery of Large Transgenes

own a patent family directed to multipartite delivery of large transgenes using AAV vectors and have filed national stage applications

in the United States, Europe and other geographical regions.

Patents issuing from these applications are not expected to expire before

The patent families licensed from the University

of Edinburgh are directed to expression cassettes for MeCP2 polypeptides and to synthetic MeCP2 polypeptides.

The patent family directed

to MeCP2 expression cassettes has pending applications in the United States, Europe and other geographical regions.

The patent family

directed to synthetic MeCP2 polypeptides has pending applications in the United States and other geographical regions.

also own a pending U.S.

provisional application directed to multipartite AAV delivery and its use for treating Stargardt disease.

New AAV Capsids and

Ophthalmic Disease Treatment via Para-retinal AAV Administration

own a patent family directed to (i) novel AAV capsid proteins and (ii) treating ophthalmic diseases via para-retinal administration of

AAV vectors, and have filed national stage applications in the United States, Europe, and other geographical regions.

Patents issuing

from applications in the Edinburgh patent families are not expected to expire before 2038.

In October 2020, we entered into an agreement

exclusively sublicensing these UNC and University of Edinburgh patent rights to Taysha Gene Therapies.

AAV Delivery of Large Transgenes

have filed a PCT application (PCT/US2021/041527) directed to multipartite delivery of large transgenes using AAV vectors.

We are filing

national stage applications in the United States, Europe and other geographical regions.

Patents issuing from these applications are

not expected to expire before 2041.

AAV Capsids and Ophthalmic Disease Treatment via Para-retinal AAV Administration

own a pending PCT application (PCT/US2022/029797) directed to (i) novel AAV capsid proteins and (ii) treating ophthalmic diseases via

para-retinal administration of AAV vectors.

Patents issuing from future national stage applications of this PCT application are not expected

to expire before 2042.

of Dominant Optic Atrophy and X-linked Retinoschisis

own a pending U.S.

provisional application directed to compositions and methods for treating dominant optic atrophy and x-linked retinoschisis.

from these applications are not expected to expire before 2042.

Treatment of Dominant

Optic Atrophy and X-linked Retinoschisis

own a pending PCT application (PCT/US2023/065877) directed to compositions and methods for treating dominant optic atrophy and x-linked

retinoschisis.

Patents issuing from future national stage applications of this PCT application are not expected to expire before 2043.

expect to explore in due course strategies to support patent term extensions for all of our patent portfolios.

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process required by the FDA before a biologic product candidate may be marketed in the United States generally involves the following:

of preclinical laboratory tests and in vivo studies in accordance with the FDA’s current Good Laboratory Practice (“GLP”)

regulations and applicable requirements for the humane use of laboratory animals or other applicable regulations;

to the FDA of an application for an IND, which allows human clinical trials to begin unless the FDA objects within 30 days;

by an independent institutional review board (“IRB”), reviewing each clinical site before each clinical trial may be

of adequate and well-controlled human clinical trials according to the FDA’s Good Clinical Practice (“GCP”) regulations,

and any additional requirements for the protection of human research subjects and their health information, to establish the safety

and efficacy of the proposed biologic product candidate for its intended use;

of manufacturing processes to ensure the product candidate’s identity, strength, quality, purity, and potency;

and submission to the FDA of a BLA for marketing approval that includes substantial evidence of safety, purity and potency from results

of nonclinical testing and clinical trials;

completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the biologic product candidate is

produced to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the biologic

product candidate’s identity, safety, strength, quality, potency and purity;

FDA audit of the nonclinical and clinical trial sites that generated the data in support of the BLA;

of user fees and the FDA review and approval, or licensure, of the BLA.

BLA application fees for products designated as orphan drugs

by the FDA are waived.

completion of preclinical

laboratory tests and in vivo studies in accordance with the FDA’s current Good Laboratory Practice (“GLP”) regulations

and applicable requirements for the humane use of laboratory animals or other applicable regulations;

submission to the FDA of

an application for an IND, which allows human clinical trials to begin unless the FDA objects within 30 days;

approval by an independent

institutional review board (“IRB”), reviewing each clinical site before each clinical trial may be initiated;

performance of adequate

and well-controlled human clinical trials according to the FDA’s Good Clinical Practice (“GCP”) regulations, and

any additional requirements for the protection of human research subjects and their health information, to establish the safety and

efficacy of the proposed biologic product candidate for its intended use;

development of manufacturing

processes to ensure the product candidate’s identity, strength, quality, purity, and potency;

preparation and submission

to the FDA of a BLA for marketing approval that includes substantial evidence of safety, purity and potency from results of nonclinical

testing and clinical trials;

satisfactory completion

of an FDA pre-approval inspection of the manufacturing facility or facilities where the biologic product candidate is produced to

assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the biologic product

candidate’s identity, safety, strength, quality, potency and purity;

potential FDA audit of

the nonclinical and clinical trial sites that generated the data in support of the BLA;

payment of user fees and

the FDA review and approval, or licensure, of the BLA.

BLA application fees for products designated as orphan drugs by the FDA are

testing any biologic product candidate on humans, including a gene therapy product candidate, the product candidate must undergo preclinical

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clinical trials typically are conducted in three sequential phases that may overlap or be combined:

The biologic product candidate initially is introduced into healthy human subjects and tested for safety, dosage tolerance, absorption,

metabolism, distribution, excretion and, if possible, to gain an early understanding of its effectiveness.

In the case of some product

candidates for severe or life-threatening diseases, especially when the product candidate may be too inherently toxic to ethically

administer to healthy volunteers, the initial human testing is often conducted in patients.

The biologic product candidate is evaluated in a limited patient population to identify possible adverse effects and safety risks,

to preliminarily evaluate the efficacy of the product candidate for specific targeted diseases and to determine dosage tolerance,

optimal dosage and dosing schedule.

The biologic product candidate is administered to an expanded patient population at geographically dispersed clinical trial sites

in adequate and well-controlled clinical trials to generate sufficient data to statistically confirm the efficacy and safety of the

product for approval.

These clinical trials are intended to establish the overall risk/benefit ratio of the product candidate and

provide an adequate basis for product labeling.

The biologic product

candidate initially is introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution,

excretion and, if possible, to gain an early understanding of its effectiveness.

In the case of some product candidates for severe

or life-threatening diseases, especially when the product candidate may be too inherently toxic to ethically administer to healthy

volunteers, the initial human testing is often conducted in patients.

The biologic product

candidate is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate

the efficacy of the product candidate for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing

The biologic product

candidate is administered to an expanded patient population at geographically dispersed clinical trial sites in adequate and well-controlled

clinical trials to generate sufficient data to statistically confirm the efficacy and safety of the product for approval.

These clinical

trials are intended to establish the overall risk/benefit ratio of the product candidate and provide an adequate basis for product

Typically, two phase 3 trials are required by the FDA for product approval.

some limited circumstances, however, the FDA may approve a BLA based upon a single Phase 3 clinical study plus confirmatory evidence

or a single large multicenter trial without confirmatory evidence.

Under some limited circumstances, however,

the FDA may approve a BLA based upon a single phase 3 clinical study plus confirmatory evidence or a single large multicenter trial

without confirmatory evidence.

kinds of data may also help to support a BLA, such as patient experience data.

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required by regulation, PREA does not apply to any biologic product candidate for an indication for which orphan designation has been

the Prescription Drug User Fee Act , as amended (“PDUFA”), each BLA must be accompanied by a substantial user fee that must

be paid at the time of the first submission of the application, even if the application is being submitted on a rolling basis.

adjusts the PDUFA user fees on an annual basis.

Fee waivers or reductions are available in certain circumstances, including a waiver

of the application fee for the first application filed by a small business.

Additionally, no user fees are assessed on BLAs for product

candidates designated as orphan drugs, unless the product candidate also includes a non-orphan indication.

the PDUFA, each BLA must be accompanied by a substantial user fee that must be paid at the time of the first submission of the application,

even if the application is being submitted on a rolling basis.

The FDA adjusts the PDUFA user fees on an annual basis.

Fee waivers or

reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small

Additionally, no user fees are assessed on BLAs for product candidates designated as orphan drugs, unless the product candidate

also includes a non-orphan indication.

FDA reviews a BLA within 60 days of submission to determine if it is substantially complete before the agency accepts it for filing.

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to expedite development and review, such as breakthrough therapy designation, priority review and accelerated approval.

therapy designation:

To qualify for the breakthrough therapy program, product candidates must be intended to treat a serious

or life-threatening disease or condition and preliminary clinical evidence must indicate that such product candidates may demonstrate

substantial improvement on one or more clinically significant endpoints over existing therapies.

The FDA will seek to ensure the

sponsor of a breakthrough therapy product candidate receives the following:

Breakthrough therapy

To qualify for the breakthrough therapy program, product candidates must be intended to treat a serious or life-threatening

disease or condition and preliminary clinical evidence must indicate that such product candidates may demonstrate substantial improvement

on one or more clinically significant endpoints over existing therapies.

The FDA will seek to ensure the sponsor of a breakthrough

therapy product candidate receives the following:

intensive guidance on an efficient drug development program;

intensive involvement of senior managers and experienced staff on a proactive, collaborative, and cross-disciplinary review;

rolling review.

A product candidate is eligible for priority review if it treats a serious condition and, if approved, it would be a

significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious condition compared

to marketed products.

The FDA aims to complete its review of priority review applications within six months as opposed to 10 months

for standard review.

Drug or biologic products studied for their safety and effectiveness in treating serious or life-threatening illnesses

and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval.

Accelerated approval means

that a product candidate may be approved on the basis of adequate and well-controlled clinical trials establishing that the product

candidate has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect

on a clinical endpoint other than survival or irreversible morbidity or mortality or other clinical benefit, taking into account

the severity, rarity and prevalence of the condition and the availability or lack of alternative treatments.

As a condition of approval,

the FDA may require that a sponsor of a drug or biologic product candidate receiving accelerated approval perform adequate and well-controlled

intensive involvement

of senior managers and experienced staff on a proactive, collaborative, and cross-disciplinary review;

and rolling review.

Priority review:

A product candidate is eligible for priority review if it treats a serious condition and, if approved, it would be a significant

improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious condition compared to marketed

The FDA aims to complete its review of priority review applications within six months as opposed to 10 months for standard

Accelerated approval:

Drug or biologic products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that

provide meaningful therapeutic benefit over existing treatments may receive accelerated approval.

Accelerated approval means that

a product candidate may be approved on the basis of adequate and well-controlled clinical trials establishing that the product candidate

has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a

clinical endpoint other than survival or irreversible morbidity or mortality or other clinical benefit, taking into account the severity,

rarity and prevalence of the condition and the availability or lack of alternative treatments.

As a condition of approval, the FDA

may require that a sponsor of a drug or biologic product candidate receiving accelerated approval perform adequate and well-controlled

post-marketing clinical trials.

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authorization may be granted to a similar medicinal product for the same orphan indication if:

second applicant can establish in its application that its medicinal product, although similar to the orphan medicinal product already

authorized, is safer, more effective or otherwise clinically superior;

holder of the marketing authorization for the original orphan medicinal product consents to a second orphan medicinal product application;

holder of the marketing authorization for the original orphan medicinal product cannot supply sufficient quantities of orphan medicinal

The second applicant can

establish in its application that its medicinal product, although similar to the orphan medicinal product already authorized, is

safer, more effective or otherwise clinically superior;

The holder of the marketing

authorization for the original orphan medicinal product consents to a second orphan medicinal product application;

The holder of the marketing

authorization for the original orphan medicinal product cannot supply sufficient quantities of orphan medicinal product.

orphan product can also obtain an additional two years of market exclusivity in the European Union for the conduct of pediatric trials.

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Such restrictions under applicable federal and state healthcare laws and regulations include the following:

federal Anti-Kickback Statute, which prohibits, among other things, persons, and entities from knowingly and willfully soliciting,

receiving, offering or paying remuneration, directly or indirectly, in cash or kind, in exchange for, or to induce, either the referral

of an individual for, or the purchase, order or recommendation of, any good or service for which payment may be made under federal

healthcare programs such as the Medicare and Medicaid programs.

This statute has been interpreted to apply to arrangements between

pharmaceutical manufacturers, on the one hand, and prescribers, purchasers, and formulary managers on the other.

Although a number

of statutory exemptions and regulatory safe harbors exist to protect certain common activities from falling under the Anti-Kickback

Statute, these are narrow, and practices may not fall under the applicable safe harbors and exemptions.

For example, the United States

Department of Health and Human Services recently promulgated a regulation that is effective in two phases.

First, the regulation

excludes from the definition of “remuneration” limited categories of (a) PBM rebates or other reductions in price to

a plan sponsor under Medicare Part D or a Medicaid Managed Care Organization plan reflected in point-of sale reductions in price

and (b) PBM service fees.

Second, effective January 1, 2023, the regulation expressly provides that rebates to plan sponsors under

Medicare Part D either directly to the plan sponsor under Medicare Part D, or indirectly through a pharmacy benefit manager will

not be protected under the anti-kickback discount safe harbor.

The PPACA amended the intent requirement of the federal Anti-Kickback

A person or entity no longer needs to have actual knowledge of this statute or specific intent to violate it in order to

commit a violation;

federal false claims and civil monetary penalties laws, including the civil False Claims Act (the “FCA”), which prohibit,

among other things, individuals, or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare,

Medicaid or other third-party payors that are false or fraudulent, or making a false statement to avoid, decrease, or conceal an

obligation to pay money to the federal government.

Certain marketing practices, including off-label promotion, also may implicate

FCA claims may be pursued by whistleblowers through qui tam actions, even if the government declines to intervene and civil

liability may be predicated on reckless disregard for the truth.

The PPACA also codified case law that a claim including items or

services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of

Separately, the criminal federal False Claims Act imposes criminal fines or imprisonment against individuals or entities

who make or present a claim to the government knowing such claim to be false, fictitious, or fraudulent;

federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for

which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions,

to report annually to the Centers for Medicare & Medicaid Services (“CMS”), information related to payments and other

transfers of value made to or at the request of covered recipients, such as, but not limited to, physicians, physician assistants,

nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists and teaching hospitals, as well as ownership

and investment interests held by physicians and their immediate family.

Payments made to physicians and certain research institutions

for clinical trials are included within the ambit of this law.

Reported information is made publicly available in searchable formats

federal false statements and fraud and abuse statutes prohibit knowingly and willfully executing, or attempting to execute, a scheme

to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned

by, or under the custody or control of, a healthcare benefit program, regardless of whether the payor is public or private, in connection

with the delivery or payment for health care benefits, knowingly and willfully embezzling or stealing from a health care benefit

program, willfully obstructing a criminal investigation of a health care offense and knowingly and willfully falsifying, concealing,

or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of,

or payment for, healthcare benefits, items, or services relating to healthcare matters.

PPACA amended the intent requirement of certain

of these criminal statutes under the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) so that a

person or entity no longer needs to have actual knowledge of the statute, or the specific intent to violate it, to have committed

and foreign law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items

or services reimbursed by any third-party payor, including commercial insurers;

state laws that require pharmaceutical companies

to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated

by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources;

state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and

other healthcare providers or marketing expenditures;

and European Union and state laws governing the privacy and security of health

information in certain circumstances, many of which differ from each other in significant ways, may be stricter than those applicable

in the US and may not have the same effect, thus complicating compliance efforts.

the federal Anti-Kickback

Statute, which prohibits, among other things, persons, and entities from knowingly and willfully soliciting, receiving, offering

or paying remuneration, directly or indirectly, in cash or kind, in exchange for, or to induce, either the referral of an individual

for, or the purchase, order or recommendation of, any good or service for which payment may be made under federal healthcare programs

such as the Medicare and Medicaid programs.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers,

on the one hand, and prescribers, purchasers, and formulary managers on the other.

Although a number of statutory exemptions and

regulatory safe harbors exist to protect certain common activities from falling under the Anti-Kickback Statute, these are narrow,

and practices may not fall under the applicable safe harbors and exemptions.

For example, the United States Department of Health

and Human Services recently promulgated a regulation that is effective in two phases.

First, the regulation excludes from the definition

of “remuneration” limited categories of (a) PBM rebates or other reductions in price to a plan sponsor under Medicare

Part D or a Medicaid Managed Care Organization plan reflected in point-of sale reductions in price and (b) PBM service fees.

effective January 1, 2023, the regulation expressly provides that rebates to plan sponsors under Medicare Part D either directly

to the plan sponsor under Medicare Part D, or indirectly through a pharmacy benefit manager will not be protected under the anti-kickback

discount safe harbor.

The PPACA amended the intent requirement of the federal Anti-Kickback Statute.

A person or entity no longer

needs to have actual knowledge of this statute or specific intent to violate it in order to commit a violation;

the federal false claims

and civil monetary penalties laws, including the civil False Claims Act (the “FCA”), which prohibit, among other things,

individuals, or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid or other

third-party payors that are false or fraudulent, or making a false statement to avoid, decrease, or conceal an obligation to pay

money to the federal government.

Certain marketing practices, including off-label promotion, also may implicate the FCA.

may be pursued by whistleblowers through qui tam actions, even if the government declines to intervene and civil liability may be

predicated on reckless disregard for the truth.

The PPACA also codified case law that a claim including items or services resulting

from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA.

the criminal federal False Claims Act imposes criminal fines or imprisonment against individuals or entities who make or present

a claim to the government knowing such claim to be false, fictitious, or fraudulent;

the federal Physician Payments

Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available

under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers

for Medicare & Medicaid Services (“CMS”), information related to payments and other transfers of value made to or

at the request of covered recipients, such as, but not limited to, physicians, physician assistants, nurse practitioners, clinical

nurse specialists, certified registered nurse anesthetists and teaching hospitals, as well as ownership and investment interests

held by physicians and their immediate family.

Payments made to physicians and certain research institutions for clinical trials

are included within the ambit of this law.

Reported information is made publicly available in searchable formats by CMS;

additional federal false

statements and fraud and abuse statutes prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud

or to obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under

the custody or control of, a healthcare benefit program, regardless of whether the payor is public or private, in connection with

the delivery or payment for health care benefits, knowingly and willfully embezzling or stealing from a health care benefit program,

willfully obstructing a criminal investigation of a health care offense and knowingly and willfully falsifying, concealing, or covering

up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment

for, healthcare benefits, items, or services relating to healthcare matters.

PPACA amended the intent requirement of certain of these

criminal statutes under the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) so that a person or

entity no longer needs to have actual knowledge of the statute, or the specific intent to violate it, to have committed a violation;

state and foreign law equivalents

of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by

any third-party payor, including commercial insurers;

state laws that require pharmaceutical companies to comply with the pharmaceutical

industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise

restrict payments that may be made to healthcare providers and other potential referral sources;

state laws that require drug manufacturers

to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing

expenditures;

and European Union and state laws governing the privacy and security of health information in certain circumstances,

many of which differ from each other in significant ways, may be stricter than those applicable in the US and may not have the same

effect, thus complicating compliance efforts.

of the laws described above or any other governmental laws and regulations may result in penalties, including civil and criminal penalties,

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Privacy and Security

as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH Act, and similar state laws

impose obligations on certain entities with respect to safeguarding the privacy, security and transmission of protected health information.

HIPAA’s security and certain privacy standards are directly applicable to persons or organizations of covered entities, other

than members of the covered entity’s workforce, that create, receive, maintain or transmit protected health information on

behalf of a covered entity for a function or activity regulated by HIPAA.

The HITECH Act strengthened the civil and criminal penalties

that may be imposed against covered entities, business associates and individuals, and gave state attorneys general new authority

to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees

and costs associated with pursuing federal civil actions.

In addition, other federal and state laws, such as the California Consumer

Privacy Act, may regulate the privacy and security of information that we maintain, many of which may differ from each other in significant

ways and may not be preempted by HIPAA;

General European Data Protection Regulation (“GDPR”), which became applicable May 25, 2018, harmonizes data privacy laws

across Europe.

The GDPR sets forth rules relating to the protection with regard to the processing and transfer of personal data as

well as an individual’s right to the protection of personal data, including medical information and clinical trial related

In addition, there are rules relating to the export of personal data outside the European Union and in particular there are

certain challenges in relation to export to the United States.

HIPAA, as amended by the

Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH Act, and similar state laws impose obligations

on certain entities with respect to safeguarding the privacy, security and transmission of protected health information.

security and certain privacy standards are directly applicable to persons or organizations of covered entities, other than members

of the covered entity’s workforce, that create, receive, maintain or transmit protected health information on behalf of a covered

entity for a function or activity regulated by HIPAA.

The HITECH Act strengthened the civil and criminal penalties that may be imposed

against covered entities, business associates and individuals, and gave state attorneys general new authority to file civil actions

for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated

with pursuing federal civil actions.

In addition, other federal and state laws, such as the California Consumer Privacy Act, may

regulate the privacy and security of information that we maintain, many of which may differ from each other in significant ways and

may not be preempted by HIPAA;

the General European Data

Protection Regulation (“GDPR”), which became applicable May 25, 2018, harmonizes data privacy laws across Europe.

GDPR sets forth rules relating to the protection with regard to the processing and transfer of personal data as well as an individual’s

right to the protection of personal data, including medical information and clinical trial related data.

In addition, there are rules

relating to the export of personal data outside the European Union and in particular there are certain challenges in relation to

export to the United States.

and Reimbursement

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could result in our competitors establishing a strong market position before we are able to enter the market.

principal executive office is located at 1330 Avenue of the Americas, 33 rd Floor, New York, NY 10019.

Our telephone number

in New York is (646) 813-4701.

We also have manufacturing and laboratory facilities and administrative offices in Cleveland, Ohio.

principal executive office as well as our manufacturing and laboratory facilities are located at 6555 Carnegie Ave, 4 th Floor,

Cleveland, OH 44103.

Our telephone number is (646) 813-4701.

were incorporated in Wyoming in 1974 as Chemex Corporation, and in 1983 we changed our name to Chemex Pharmaceuticals, Inc.

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Abeona Therapeutics

c/o Investor Relations, 1330 Avenue of the Americas, 33 rd Floor, New York, NY 10019.

The SEC’s website, www.sec.gov,

contains reports, proxy statements, and other information that we file electronically with the SEC.

The content on any website referred

to in this Form 10-K is not incorporated by reference in this Form 10-K.

c/o Investor Relations, 6555 Carnegie Ave, 4 th Floor, Cleveland, OH 44103.

The SEC’s website, www.sec.gov, contains

reports, proxy statements, and other information that we file electronically with the SEC.

The content on any website referred to in

this Form 10-K is not incorporated by reference in this Form 10-K.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business