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Item 1. Business

2023-03-29 compared with 2022-03-31 · 493 added, 638 removed, 756 unchanged (60% of the section changed)

Therapeutics Inc., a Delaware corporation (together with our subsidiaries, “we,” “our,” “Abeona”

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

life-threatening rare genetic diseases.

Our lead clinical program is EB-101, an autologous, gene-corrected cell therapy for

recessive dystrophic epidermolysis bullosa (“RDEB”), which is currently in the pivotal Phase 3 VIITAL™ clinical

Following a comprehensive portfolio review in early 2022, we have decided to focus our research and development resources on

the VIITAL™ readout while actively pursuing a potential commercialization partner for EB-101 with the objective of reducing

operating expenses and extending our cash runway.

As part of this portfolio prioritization, we have intensified our pursuit of a

strategic partnership to take over development activities for our adeno-associated virus (“AAV”)-based gene

therapy ABO-102 for Sanfilippo syndrome type A (“MPS IIIA”) and we have discontinued development of our AAV-based gene

therapy ABO-101 for Sanfilippo syndrome type B (“MPS IIIB”).

plan to continue development of AAV-based gene therapies designed to treat ophthalmic and other diseases and next-generation

AAV-based gene therapies 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.

believe that our current product candidates are eligible for orphan drug designation, breakthrough therapy designation, or other

expedited review processes in the U.S., Europe, Japan, or other world markets.

Our pipeline includes programs for which we hold several

and European Union (“EU”) regulatory designations, and a pipeline of additional earlier stage programs:

Our pipeline features early- and late-stage candidates with the potential to transform the treatment of devastating genetic diseases,

and we are conducting clinical trials in the U.S.

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.

Mission and Strategy

is at the forefront of cell and gene therapy research and development.

We are a fully-integrated company featuring therapies in

clinical development, in-house manufacturing facilities, a robust pipeline, and scientific and clinical leadership.

We see our mission

as working to create, develop, manufacture, and deliver cell and gene therapies for people impacted by serious diseases.

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

therapies that address the underlying cause of a broad spectrum of rare genetic diseases for which no effective treatment options exist

2021, we continued to make progress toward fulfilling our goal of harnessing the promise of genetic medicine to transform the lives of

people impacted by serious diseases and redefining the standard of care through cell and gene therapies.

Our strategy to achieve

this goal consists of:

our Clinical Cell and Gene Therapy Programs and Research and Development with a Focus on Rare and Orphan Diseases.

our cell and gene therapy expertise in research and development, we believe we are positioned to introduce efficacious and safe

therapeutics to transform the standard of care in devastating diseases and establish our leadership position in the field.

Novel Next-Generation AIM™ Capsid Technology to Develop New In-Vivo Gene Therapies.

are researching and developing next-generation AAV-based gene therapy using our novel capsids developed from the AIM™ Capsid Technology

Platform and additional Company-invented AAV capsids.

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

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

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

established current Good Manufacturing Practice (“cGMP”), clinical-scale manufacturing capabilities for gene-corrected cell

therapy and AAV-based gene therapies in our state-of-the-art Cleveland, Ohio facility.

We believe that our platform provides us with

distinct advantages, including flexibility, scale, reliability, and the potential for reduced development risk, reduced cost, and faster

times to market.

We have focused on establishing internal Chemistry, Manufacturing and Controls (“CMC”) capabilities that

drive value for our organization through process development, assay development and manufacturing.

We have also deployed robust quality

systems governing all aspects of product lifecycle from preclinical through commercial stage.

is a fully-integrated cell and gene therapy company featuring research and clinical development programs, in-house manufacturing facilities,

and scientific and clinical leadership.

Our mission is to create, develop, manufacture, and deliver cell and gene therapies to transform

the lives of people impacted by life-threatening diseases.

In 2022, we continued to make progress toward fulfilling our goal of harnessing

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.

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

that address the underlying cause of a broad spectrum of rare genetic diseases for which no effective treatment options exist today.

strategy consists of:

and Commercializing our Late-Stage Clinical Cell and Gene Therapy Programs with a Focus on Life-Threatening Diseases.

our cell and gene therapy expertise in research and development, we believe we are positioned to introduce efficacious and safe therapeutics

to transform the standard of care in devastating diseases and establish our leadership position in the field.

We intend to commercialize

our assets either by ourselves or through strategic partnerships, subject to FDA approval.

Novel In-Vivo Gene Therapies Using AIM™ Capsid Technology.

are researching and developing AAV-based gene therapy using our novel capsids developed from the AIM™ Capsid Technology Platform

and additional Company-invented AAV capsids.

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.

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

established current Good Manufacturing Practice (“cGMP”), clinical-scale manufacturing capabilities for engineered cell therapy

and AAV-based gene therapies in our state-of-the-art Cleveland, Ohio facility.

We believe that our platform provides us with distinct

advantages, including flexibility, scale, reliability, and the potential for reduced development risk, reduced cost, and faster times

We have focused on establishing internal Chemistry, Manufacturing and Controls (“CMC”) capabilities that drive

value for our organization through process development, assay development and manufacturing.

We have also deployed robust quality systems

governing all aspects of product lifecycle from preclinical through commercial stage.

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

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

leaders, patient foundations, and industry partners to generate novel intellectual property, accelerate research and development, and

understand the needs of patients and their families.

and Growing IP Portfolio.

strive to have a leading intellectual property portfolio.

To that end, we seek patent rights for various aspects of our programs, including

vector engineering and construct design, our production process, and all features of our clinical products including composition of matter

and method of administration and delivery.

We expect to continue to expand our intellectual property portfolio by aggressively seeking

patent rights for promising aspects of our product engine and product candidates.

Our pipeline features early- and late-stage candidates with the potential to transform the treatment of devastating genetic diseases.

lead clinical program is EB-101, an autologous, gene-corrected cell therapy for RDEB, which is currently in a Phase 3 clinical

Following a comprehensive portfolio review in early 2022, we have decided to focus our research and development resources on the EB-101

program with the objective of reducing operating expenses and extending our cash runway.

As part of this portfolio prioritization, we have intensified our pursuit

of a strategic partnership to take over development activities for our AAV-based gene therapy ABO-102 for MPS IIIA and we

have discontinued development of our AAV-based gene therapy ABO-101 for MPS IIIB.

We continue to develop

additional AAV-based gene therapies designed to treat ophthalmic and other diseases and next-generation AAV-based gene therapies

using the novel AIM™ capsid platform that we have exclusively licensed from UNC, and internal AAV vector research

seek to be the partner of choice in cell and gene therapy treatment 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

and their families, and generate novel intellectual property.

and Growing our IP Portfolio.

seek patent rights for various aspects of our programs, including vector engineering and construct design, our production process, and

all features of our clinical products including composition of matter and method of administration and delivery.

We expect to continue

to expand our intellectual property portfolio by aggressively seeking patent rights for promising aspects of our product engine and product

Next-Generation Cell and Gene Therapy

for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (“RDEB”)

belongs to a group of genetic skin disorders known more broadly as epidermolysis bullosa.

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

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 population.

for the Treatment of RDEB

belongs to a broad group of genetic skin disorders known as epidermolysis bullosa.

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

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

Incidence of 0.2 to 3.05 per million

births and prevalence of 0.14 to 1.35 per million people have been observed across different geographies, primarily estimated by limited

population analyses of clinical databases or registries (Eichstadt et al.;

Incidence of 0.2 to 3.05 per million births and prevalence

of 0.14 to 1.35 per million people have been observed across different geographies, primarily estimated by limited population analyses

of clinical databases or registries (Eichstadt et al.;

Clinical, Cosmetic and Investigational Dermatology, 2019).

Using genetic modeling 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.

Using genetic modeling

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;

6 unchanged sentences

Nature Research, 2017).

expect EB-101 could be a treatment option for large and chronic RDEB wounds for which EB-101 has shown durable healing

and associated pain reduction in a phase 1/2 clinical trial.

The data from the phase 1/2 clinical trial supports the VIITAL™ phase

These larger and/or chronic wounds carry the highest burden, including the need for frequent dressing changes, pain, pruritus,

risk of infection, and developing skin cancer.

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.

Management of RDEB

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

management currently consists of supportive care to limit contamination and infection, and reduction in mechanical forces that produce

new blisters.

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.

The estimated annual cost of wound

dressings alone for an RDEB patient can range from $245,000 per year to significantly higher in more severe cases.

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.

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

corneal abrasions.

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

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.

has been granted Regenerative Medicine Advanced Therapy (“RMAT”), Breakthrough Therapy, Rare Pediatric Disease, and Orphan

Drug designations by the U.S.

Food and Drug Administration (“FDA”);

as well as Orphan Drug designation by the European Medicines

Agency (“EMA”).

from a completed Phase 1/2 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 seven years of follow-up

(Eichstadt, S., et al.

JCI Insight 2019).

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

of follow-up (So.

Y, Nazaraoff, et al., Orphanet Journal Rare Disease 2022).

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

the past two years, we have been conducting a pivotal Phase 3 clinical trial, referred to as VIITAL™, evaluating the potential

of EB-101 for the treatment of RDEB.

VIITAL™ is an ongoing randomized, control-matched Phase 3 clinical trial assessing treatment

with EB-101 in 10 to 15 patients, comprising approximately 36 large chronic wound sites treated in total.

The co-primary endpoints

of VIITAL™ are a) proportion of EB-101 treated wounds with >50% healing from baseline at 24 weeks and b) improvement in pain

at 24 weeks assessed by the Wong-Baker pain scale at time of dressing change versus an untreated control wound.

The FDA has agreed on

the endpoints and other characteristics of the study.

We achieved target enrollment for the VIITAL™ study in the first

quarter of 2022.

Given that the co-primary endpoints are measured at 24 weeks following treatment, we anticipate topline results in the

third quarter of 2022.

We are focusing our research and development resources on the VIITAL™ readout while actively pursuing a potential

commercialization partner.

2021, we continued to prepare our cGMP commercial facility in Cleveland, Ohio for manufacturing EB-101 drug product to support our planned

Biologics License Application (“BLA”) filing.

EB-101 study drug product for all our VIITAL™ study participants has

been manufactured at our Cleveland facility and we have now completed the update to Module 3 of the Investigational New Drug

Application describing the in-house production of both retroviral vector and the final drug product.

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 to support the BLA submission.

and ABO-101 for the treatment of Mucopolysaccharidosis (MPS) III (Sanfilippo syndrome)

III (Sanfilippo syndrome) is a group of four inherited lysosomal storage diseases, described as type A, B, C or D, which result from

enzyme deficiencies responsible for abnormal accumulation of glycosaminoglycans (“GAGs”), which are long, linear polysaccharides

also known as mucopolysaccharides, in body tissues that lead to progressive cell damage, and neurodevelopmental and physical decline.

The incidence of MPS III (all four types combined) is estimated to be 1 in 70,000 births.

are intra-cellular sacs that harbor enzymes for replacing used materials and

breaking them down for disposal.

Children with MPS III are missing a lysosomal enzyme that is essential in breaking down mucopolysaccharides,

specifically heparan sulfate.

The partially broken down heparan sulfate remains stored in cells in the body causing progressive lysosomal

and cell damage and eventually cell death.

Babies may show little sign of the disease early in life, but as neurodevelopment is impaired

and more cells become damaged, symptoms start to appear within the first few years of life.

MPS III, the predominant symptoms are speech/language delay, cognitive decline, behavioral abnormalities, motor dysfunction, and seizures,

eventually leading to premature death.

Most patients with the rapidly progressing form of MPS III do not reach a level of cognitive function

above that of an unaffected three-year-old child.

Accumulation of heparan sulfate and related cell dysfunction also affects other organs,

leading to liver enlargement and soft tissue coarsening.

To date, there is no cure for MPS III and care is only supportive and palliative.

2021, we continued developing AAV-based gene therapies ABO-102 and ABO-101 for MPS IIIA and MPS IIIB (Sanfilippo syndrome Type A and

Sanfilippo syndrome Type B, respectively).

These gene therapies are administered once through intravenous infusion.

ABO-102 and ABO-101

deliver a functioning copy of the defective gene to cells of the central nervous system (“CNS”) and peripheral organs with

the aim of halting the deleterious effects caused by the malfunctioning enzyme and impairment of lysosomal functioning.

Both viral vector

constructs rely on the neurotropism of the AAV9 serotype and its ability to cross the blood brain barrier (“BBB”) and deliver

the functional copy of the gene to the CNS.

in vivo efficacy studies in animals with MPS IIIA showed that a single dose of ABO-102 significantly restored cell and organ function,

corrected neurological deficits, increased motor control, and increased the lifespan by more than 100% one year after treatment compared

with untreated control animals.

In addition, safety studies conducted in animal models of MPS IIIA demonstrated that delivery of ABO-102

was well-tolerated with minimal side effects.

ABO-102 received Fast Track and RMAT designations by the FDA, PRIME designation in the

EU, Orphan Drug designations in the U.S.

and EU, and FDA Rare Pediatric Disease designation.

IIIA is caused by the absence of functional SGSH gene.

In the pivotal gene transfer clinical trial of ABO-102 (scAAV9.U1a.hSGSH) for

patients with MPS IIIA (study ABT-001;

NCT02716246), subjects receive a single intravenous injection of ABO-102 to facilitate systemic

delivery, including to the CNS, of a functional SGSH gene.

Subjects are evaluated at multiple time points post-treatment for safety and signals of biopotency and clinical efficacy.

to-date from the high dose cohort 3 showed evidence of preservation of neurocognitive development with continuous cognitive gains within

normal range of a non-afflicted child, especially for children treated with ABO-102 with DQ higher than 60 around or before 30 months

of age, as well as dose-related and sustained reduction in cerebrospinal fluid (“CSF”) levels of heparan sulfate, denoting

transgene expression in the CNS, and a durable reduction of liver volume.

No treatment related serious adverse events (“SAEs”)

have been reported to date, with follow-up longer than two years post treatment in the majority of patients.

of MPS IIIA ABO-102 Phase 1/2/3 Study Data as of March 2022:

patients treated over three cohorts (including 18 patients in Cohort 3)

dose-response and sustained reduction of heparan sulfate levels in CSF

reduction in liver volume

neurocognitive signals seen in younger, higher functioning patients enrolled in cohort 3

of March 2022, mean follow-up in cohort 1 (62 months);

cohort 2 (57 months);

has been well tolerated to date

infusion-related adverse events

serious drug-related adverse events

negative for the SGSH enzyme

In 2021, we continued recruitment in a second Phase 1/2 clinical trial

with ABO-102 (study ABT-003;

NCT04088734) to treat certain patients who did not qualify for participation in study ABT-001 for MPS IIIA.

A total of 5 patients were treated.

The ABT-003 study was terminated in March 2022 based on a lack of improved neurocognitive ability

in older children with more advanced disease.

part of our portfolio prioritization in early 2022, we have intensified our pursuit of a strategic partnership to take over development

activities for ABO-102.

As part of the FDA’s feedback on the Statistical Analysis Plan in January 2022, the FDA recommended that

all participants be followed to an age of at least 60 months, which would shift timing of the neurocognitive outcomes data readout to

late-2024/early-2025, as compared to our prior projection of the second quarter of 2023.

in vivo efficacy studies in mice with MPS IIIB showed that a single dose of ABO-101 significantly restored cell and organ function,

corrected neurological deficits, increased neuromuscular control, and normalized lifespan compared with untreated control animals.

addition, safety studies conducted in MPS IIIB mice and wildtype mice, and in non-human primates, demonstrated that systemic delivery

of ABO-101 was well tolerated with minimal side effects.

the ABO-101 (rAAV9.CMV.hNAGLU) program for patients with MPS IIIB, subjects in our ongoing Phase 1/2 gene transfer clinical study (study

NCT03315182) receive a single, intravenous infusion of ABO-101, which uses an AAV9 vector to introduce a functional NAGLU gene

to treat patients with MPS IIIB disease.

Subjects are evaluated at multiple time points post-injection for safety assessments and efficacy

2021, we reported updated data from the ABT-002

trial showing dose dependent increases in plasma NAGLU activity, with normalization up to 6 months in cohort 3, accompanied by dose-dependent

reductions of plasma and urinary heparan sulfate and urinary GAGs and decreased CSF levels of heparan sulfate levels sustained up to

Preliminary neurocognitive assessments, brain and liver MRI analyses demonstrate changes in the direction of improvement.

Longer follow-up with patients treated in cohorts 2 and 3 is needed to confirm preliminary cognitive and brain volumetric changes.

was one serious drug-related adverse event of prolonged hospitalization reported in cohort 3 where the patient experienced a grade 2

episode of diarrhea and vomiting after treatment with ABO-101 and was required to stay in the hospital for two additional days for observation.

of MPS IIIB ABO-101 Phase 1/2 Study Data as of March 2022:

patients treated

signals of biologic effect with reduction of disease-specific biomarkers in the CSF, plasma

and urine and reduction in liver volumes

follow-up with patients treated in cohorts 2 and 3 is needed to address cognitive changes

of March 2022, mean follow-up in cohort 1 (32 months), cohort 2 (22 months) and cohort 3

has been well tolerated to date

infusion-related adverse events

serious drug-related adverse event requiring two additional days of hospitalization for observation

due to a grade 2 episode of diarrhea and vomiting

negative for the NAGLU enzyme

In 2021, we discontinued enrollment in our ABO-101 study and in March 2022, we decided to discontinue all further ABO-101 development

Next-Generation

Gene Therapy Treatments anchored in AIM™ Vector Platform

2016, we licensed a library of first-generation novel AAV capsids from UNC.

In partnership with academic institutions, our own scientific

research teams have identified vectors within the AIM™ capsid library showing strong potential to successfully target and reach

the central nervous system as well as ocular, lung, muscle, liver, and other tissues.

Based on continuing research being conducted by

Abeona and our research partners, we observed improvements in gene delivery to specific tissues compared to currently available AAV technology.

We believe AIM™ vectors also have the potential for redosing subjects who previously received certain AAV gene therapy or subjects

who have pre-existing antibodies to naturally occurring AAV serotypes.

for the treatment of genetic eye disorders

research program comprises several vectors being tested for different monogenic retinal disorders.

Eighty percent of genetic eye disorders

affect the photoreceptor or RPE cells, and correction of mutations in the retina has been accomplished by several groups using AAV gene

therapy delivered through subretinal or intravitreal injection.

We are exploring various routes of administration to deliver AAV to the

retina, including subretinal, intravitreal and para-retinal delivery.

We believe intravitreal delivery of small volume gene therapies

is an attractive alternative to deliver gene therapy to the retina in an out-patient setting.

We anticipate para-retinal injection to

be safer as compared to subretinal and may serve programs that currently require subretinal dosing.

AAV-based vectors are currently undergoing lead candidate identification.

Preclinical animal studies are ongoing in indication-specific

disease mouse models with readouts expected in the later part of 2022.

preclinical findings from mouse models identified the novel AIM™ capsid AAV204 as one of three lead candidate capsids that demonstrate

robust transduction of retinal cells.

The data in mice demonstrated that intravitreal administration of AAV204 resulted in broad retinal

expression that penetrated to the photoreceptor and retinal pigmented epithelium layers.

findings were confirmed in non-human primates where we noted that intravitreal administration of AAV204, expressing green fluorescent

protein (GFP), resulted in broad transgene expression in the peripheral retina as well as intense expression in the fovea 25 days post-administration.

Para-retinal administration of AAV204, expressing GFP, also showed transduction of photoreceptor cells in the fovea as well as strong

expression in retinal ganglion cells throughout the retina.

for the treatment of CLN3 disease, also known as juvenile Batten disease (or Juvenile Neuronal Ceroid Lipofuscinosis) (“CLN3 Disease”)

November 3, 2022, we announced positive topline data from 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.

The large chronic wounds randomized

and treated in VIITAL™ measured greater than 20 cm 2 of surface area and had remained open for a minimum of six months

and a maximum of 21 years (mean 6.2 years).

The co-primary endpoints of the study were:

(1) the proportion of RDEB wound sites with greater

than or equal to 50% healing from baseline, comparing randomized treated with matched untreated (control) wound sites at the six-month

timepoint, as determined by direct investigator assessment;

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.

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

adverse events observed, consistent with past clinical experience.

There were no deaths or instances of positive replication-competent

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.

Four subjects reported

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

Infections unrelated to EB-101 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.

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

preventing FDA approval of another product deemed to be the same as the approved product for the same indication, waiver of application

fees, and tax credits for qualified clinical testing expenses conducted after orphan designation is received.

A sponsor who receives

an approval for a BLA with RPD designation may qualify for a Priority Review Voucher (“PRV”), subject to final determination

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.

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

for the treatment of X-linked Retinoschisis (“XLRS”).

Overview and Program Overview

disease is a rare, fatal, autosomal recessive (inherited) disorder of the nervous system that typically begins between 4 and 8 years

Often the first noticeable sign of CLN3 disease is vision impairment, which tends to progress rapidly and eventually result in

As the disease progresses, children experience loss of previously acquired skills (developmental regression).

This regression

usually begins with the loss of the ability to speak in complete sentences.

Children then lose motor skills, such as the ability to walk

They also develop movement abnormalities that include rigidity or stiffness, slow or diminished movements (hypokinesia), and

stooped posture.

Beginning in mid-to-late-childhood, affected children may have recurrent seizures (epilepsy), heart problems, behavioral

problems, and difficulty sleeping.

Normal life expectancy is greatly reduced with most people with juvenile Batten disease only living

into their twenties or thirties.

As of December 31, 2021, no specific treatment is known that can halt or reverse the symptoms of CLN3

(scAAV9.CLN3) is an AAV-based gene therapy that has shown preclinical efficacy following delivery of a functioning copy of the CLN3 gene

in a mouse model of CLN3 disease.

Preclinical studies have previously demonstrated reduced lysosomal storage and decreased astrocyte/microglia

activation in the CNS as well as improved motor function.

for the Treatment of Cystic Fibrosis

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.

for the Treatment of Stargardt Disease

Overview and Program Overview

Fibrosis (“CF”) is a progressive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator

(“CFTR”) gene.

Malfunction of this gene affects cells that produce mucus, sweat and digestive fluids.

In unaffected individuals,

these secreted fluids are normally thin and slippery, but in cystic fibrosis, a defective CFTR gene causes the secretions to become thick

Instead of acting as a lubricant, the secretions plug up tubes, ducts, and passageways, especially in the lungs and pancreas,

and cause repeated lung infections and difficulty breathing, impaired pancreatic function and digestive abnormalities.

preclinical ABO-401 program employs the AAV204 AIM TM capsid.

ABO-401 has shown the ability to deliver the CFTR transgene to

the lungs of gut-corrected delta-F508 mice.

Another study also demonstrated correction of the underlying chloride current deficit in

human CF donor-derived nasal and bronchial epithelium cells treated with ABO-401.

Correction of chloride channel current following ABO-401

administration occurred regardless of underlying mutations of the CFTR gene, including the most common CF mutation, delta-F508.

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.

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.

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.

Therapy Treatments anchored in AIM™ Vector Platform

2016, we licensed a library of novel AAV capsids from UNC.

The AIM™ vector system is a platform of AAV capsids capable of widespread

central nervous system gene transfer and can be used to confer high transduction efficiency for various therapeutic indications.

In partnership

with academic institutions, our own scientific research teams have identified vectors within the AIM™ capsid library showing strong

potential to successfully target and reach the central nervous system as well as ocular, lung, muscle, liver, and other tissues.

on continuing research by Abeona and our research partners, we have observed improvements in gene delivery to specific tissues compared

to currently available AAV technology.

We believe AIM™ vectors also have the potential for redosing subjects who previously received

certain AAV gene therapy or subjects who have pre-existing antibodies to naturally occurring AAV serotypes.

Licensing Agreements

have out-licensed certain clinical and research programs, including for the treatment of Sanfilippo syndrome type A (MPS IIIA) to Ultragenyx

Pharmaceutical Inc.

(“Ultragenyx”), and for CLN1 disease (infantile Batten disease) and Rett syndrome to Taysha Gene Therapies,

Under the terms of our agreement with Ultragenyx, we are eligible to receive payments based on the achievement

of certain sales milestones and royalties on net sales.

Under our agreements with Taysha, we are eligible to receive payments based on

certain clinical, regulatory, and sales milestones and royalties on net sales.

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

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

have completed the first two phases of our 26,000+ square foot manufacturing build-out plans in Cleveland, Ohio.

The first phase, completed

in 2018, was a 6,000 square foot state-of-the-art cGMP production facility for the manufacturing of cell and gene therapies.

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.

In connection with our shift in strategic priorities in 2022, we have ceased the planned build-out

of additional AAV manufacturing space intended for ABO-102.

have advanced our in-house manufacturing capabilities for our autologous cell replacement therapy (EB-101) for the treatment of RDEB.

The product is manufactured as a multilayer cellular sheet containing corrected keratinocytes that is fastened to a petrolatum gauze

backing with surgical hemoclips.

Gene-corrected sheets are applied over wound areas, where they are expected to produce keratinocytes

with functioning Type VII collagen, providing 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 the functional copy of the Collagen VII Alpha 1 cDNA to the

autologous patient cells.

Initially developed at the Indiana University Vector Production Facility, we have transferred the cGMP manufacturing

process for the LZRSE-Col7A1 retroviral vector to our Cleveland, Ohio 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.

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

The first phase, completed in 2018, was a 6,000 square

foot state-of-the-art cGMP production facility for the manufacturing of cell and gene therapies.

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.

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

for long-term wound healing.

A key component to the EB-101 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.

Initially developed at the Indiana University Vector

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.

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

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scale to support commercial manufacturing requirements for EB-101

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

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

● establishing

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

● proprietary

AAV vector manufacturing processes and techniques that produce a highly purified 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.

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

potentially commercialize EB-101, if approved, we are working towards filing a potential 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.

a Strong Intellectual Property Portfolio

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.

Strong Intellectual Property Protection

strive to protect our commercially important proprietary technology, inventions, and know-how, including by seeking, maintaining, and

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to develop, strengthen and maintain our position in the field of cell and gene therapy.

We may also rely on regulatory protection

afforded through data exclusivity, market exclusivity, and patent term extensions where available.

We may also rely on the additional protections

afforded by data exclusivity (currently 12 years for biologics), other market exclusivities such as orphan drug exclusivity, and patent

term extensions, where applicable.

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

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Technologies and Intellectual Property

Mucopolysaccharidosis

(“MPS”) IIIA and IIIB

have secured an exclusive license through Nationwide Children’s Hospital to patent applications for AAV-based treatments for patients

with MPS IIIA and IIIB, including four pending applications in the United States.

United States patent(s) that may be granted from this

family would be expected to expire between approximately late 2029 and mid-2032.

Disease (Juvenile Batten Disease)

have licensed exclusive rights to an international patent family from the University of Nebraska Medical Center and the Ohio State Innovation

Foundation, directed to AAV gene therapy for the treatment of CLN3 disease (also known as juvenile Batten disease).

The licensed patent

family includes pending national stage applications in the United States, Canada, Europe, China, Japan, New Zealand, and Australia, as

10,876,134 (“the ‘134 Patent”), entitled “Gene therapy for juvenile batten disease,”

which was issued on December 29, 2020 and contains claims directed to CLN3-related vectors, methods, and formulations.

Patent is expected to expire in approximately December 2035 absent any future grant of patent term extension.

Dystrophic Epidermolysis Bullosa

support our EB franchise, we have licensed a patent family from Stanford University covering technology for the treatment of RDEB.

covering our investigational EB-101 product have been granted by the European Patent Office (EP3400287B1), in Australia (AU2017205925A),

and in Hong Kong (HK40000104), and are expected to expire in early 2037.

National stage patent applications remain pending in the United

States, Canada, Israel, Japan, South Korea, China, New Zealand, Russia, Mexico, South Africa, and Brazil.

United States patent(s) that

may be granted from this portfolio would be expected to expire in approximately 2037.

We have also filed a United States patent application

directed to packaging and transport of the EB product, which has been published as WO2021011821A1.

have an exclusive license to an international patent family from UNC covering novel adeno-associated virus (“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, Australia,

Brazil, China, Hong Kong, Europe, Canada, Israel, India, Japan, South Korea, Mexico, New Zealand, Russia, and South Africa.

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

regions, and are expected to expire in early 2037.

Patent applications remain pending in the United States which, if granted, would be

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.

patent in this patent family, U.S.

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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.

We have exclusive rights to both the ‘110 Patent and the ‘743

Patent under our license with UNC.

patent in this patent family, U.S.

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

also own a second patent family directed to certain AAV capsids 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 2039.

Disease (Infantile Batten Disease)

have also licensed from UNC rights to a patent portfolio directed to optimized CLN1 genes and expression cassettes for use in treating

CLN1 disease (also known as infantile Batten disease).

Patent applications are pending in the United States, Canada, Europe, Israel,

India, China, Japan, South Korea, Australia, New Zealand, Mexico, Brazil, Russia, and South Africa.

United States patent(s) that may

be granted from this portfolio would be expected to expire in approximately 2037.

In August 2020, we entered into an agreement exclusively

sublicensing the CLN1 patent portfolio to Taysha Gene Therapies.

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

of Rett Syndrome.

The patent applications 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.

The patent applications licensed from the University of Edinburgh

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

National stage applications for the

patent application directed to MeCP2 expression cassettes are now pending in the United States, Canada, Brazil, China, Japan, Australia,

Europe, India, South Korea, and Russia, and national stage applications for the international application directed to synthetic polypeptides

are currently pending in the United States, Canada, Brazil, China, and Japan.

In October 2020, we entered into an agreement exclusively

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

United States patents that may be granted

based on the UNC patent applications or the University of Edinburgh patent applications would be expected to expire in approximately

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

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

The first patent family is directed to optimized CLN1 genes and expression cassettes for use in treating CLN1 disease, which has applications

pending in the United States, Europe, and other geographical regions.

patent in the first patent family, U.S.

(the “’435 Patent”), was issued to UNC on November 22, 2022.

The ’435 Patent is entitled to 578 days of patent

term adjustment, making its projected expiration date January 12, 2039.

The second patent family is directed to treating CLN1 disease

using a combination of intrathecal and intravenous administrations, which has applications pending in the United States, Europe and other

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 these applications are not expected to expire before 2039.

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.

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.

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

Biologic Products Development Process

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experts and consumer representatives, to advise CBER on its reviews.

The FDA has issued a growing body of guidance documents on chemistry,

manufacturing, and control (“CMC”), clinical investigations and other areas of gene therapy development, all of which are

intended to facilitate the industry’s development of gene therapy products.

The FDA has issued a growing body of guidance documents on CMC,

clinical investigations and other areas of gene therapy development, all of which are intended to facilitate the industry’s development

of gene therapy products.

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 Investigational New Drug Application (“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 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;

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

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.

BLA application fees for products designated as orphan drugs

by the FDA are waived.

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.

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.

Typically, two Phase 3 trials

are required by the FDA for product approval.

Under some limited circumstances, however,

the FDA may approve a BLA based upon a single Phase 3 clinical study plus confirmatory evidence

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.

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.

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quality system regulation, medical device reporting, and reporting of corrections and removals requirements.

a policy position that, when safe and effective use of a therapeutic product depends on a diagnostic device, the FDA generally will require

approval or clearance of the diagnostic device at the same time that the FDA approves the therapeutic product.

The type of premarket

submission required for a companion diagnostic device will depend on the FDA classification of the device.

A premarket approval, or PMA,

application is required for high risk devices classified as Class III;

a 510(k) premarket notification is required for moderate risk

devices classified as Class II;

novo request may be used for novel devices not previously classified by the FDA that are

low or moderate risk.

FDA may, however, approve a therapeutic product without the

concurrent approval or clearance of a diagnostic device when the therapeutic product is intended to treat serious and life-threatening

conditions for which no alternative exists and the FDA determines that the benefits from the use of the drug/biologic outweigh the risks

from the lack of an approved/cleared companion diagnostic.

The FDA would also consider whether additional protections, such as risk evaluation

and mitigation strategies, or REMS, or post-approval requirements, are necessary.

At this point, it is unclear how the FDA will apply

this policy to our gene therapy candidates.

Should the FDA deem genetic tests used for selecting appropriate patients for our therapies

to be in vitro companion diagnostics requiring FDA clearance or approval, we may face significant delays or obstacles in obtaining approval

In addition, under the Pediatric Research Equity Act (“PREA”), a BLA or supplement to a BLA must contain data

to assess the safety and effectiveness of the biologic product candidate for the claimed indications in all relevant pediatric subpopulations

and to support dosing and administration for each pediatric subpopulation for which the product candidate is safe and effective.

FDA may grant deferrals for submission of data or full or partial waivers.

Unless otherwise required by regulation, PREA does not apply

to any biologic product candidate for an indication for which orphan designation has been granted.

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

FDA has a policy position that, when safe and effective use of a therapeutic product depends on a diagnostic device, the FDA generally

will require approval or clearance of the diagnostic device at the same time that the FDA approves the therapeutic product.

of premarket submission required for a companion diagnostic device will depend on the FDA classification of the device.

A premarket approval,

or PMA, application is required for high risk devices classified as Class III;

a 510(k) premarket notification is required for moderate

risk devices classified as Class II;

and a de novo request may be used for novel devices not previously classified by the FDA

that are low or moderate risk.

FDA may, however, approve a therapeutic product without the concurrent approval or clearance of a diagnostic device when the therapeutic

product is intended to treat serious and life-threatening conditions for which no alternative exists and the FDA determines that the

benefits from the use of the drug/biologic outweigh the risks from the lack of an approved/cleared companion diagnostic.

The FDA would

also consider whether additional protections, such as risk evaluation and mitigation strategies, or REMS, or post-approval requirements,

are necessary.

At this point, it is unclear how the FDA will apply this policy to our gene therapy candidates.

Should the FDA deem genetic

tests used for selecting appropriate patients for our therapies to be in vitro companion diagnostics requiring FDA clearance or approval,

we may face significant delays or obstacles in obtaining approval for a BLA.

In addition, under the Pediatric Research Equity Act (“PREA”),

a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the biologic product candidate for the claimed

indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which

the product candidate is safe and effective.

The FDA may grant deferrals for submission of data or full or partial waivers.

Unless otherwise

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.

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will not result in a finding that two products are different.

Any FDA sameness determinations could impact our ability to receive

approval for our product candidates and to obtain or retain orphan drug exclusivity.

Competitors additionally may receive approval of

different products for the same indication for which the orphan product has exclusivity or obtain approval for the same product but for

a different indication for which the orphan product has exclusivity.

Orphan medicinal product status in the European Union has similar,

but not identical, benefits.

Any FDA sameness determinations could impact our ability to receive approval

for our product candidates and to obtain or retain orphan drug exclusivity.

Competitors additionally may receive approval of different

products for the same indication for which the orphan product has exclusivity or obtain approval for the same product but for a different

indication for which the orphan product has exclusivity.

Orphan medicinal product status in the European Union has similar, but not identical,

development and review programs

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

● Breakthrough

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.

FDA will seek to ensure the sponsor of a breakthrough therapy product candidate receives

the following:

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

and 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.

● Accelerated

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.

In addition, the FDA currently requires as

a condition for accelerated approval pre-approval of promotional materials.

Failure to conduct

required post-approval studies, or confirm a clinical benefit during post-marketing studies,

will allow the FDA to withdraw the drug or biologic from the market on an expedited basis.

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

post-marketing clinical trials.

In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional

Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, will allow

the FDA to withdraw the drug or biologic from the market on an expedited basis.

Track designation, breakthrough therapy designation, priority review and accelerated approval do not change the standards for approval

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not be shortened.

with passage of the 21st Century Cures Act (the “Cures Act”) in December 2016, Congress authorized the FDA to accelerate

review and approval of products designated as regenerative advanced therapies.

A product is eligible for this designation if it is a

regenerative medicine therapy (which may include a cell or gene therapy) that is intended to treat, modify, reverse, or cure a serious

or life-threatening disease or condition and preliminary clinical evidence indicates that the drug has the potential to address unmet

medical needs for such disease or condition.

The benefits of a regenerative advanced therapy designation include early interactions with

the FDA to expedite development and review, benefits available to breakthrough therapies, potential eligibility for priority review and

accelerated approval based on surrogate or intermediate endpoints.

with passage of the 21 st Century Cures Act (the “Cures Act”) in December 2016, Congress authorized the FDA to

accelerate review and approval of products designated as regenerative advanced therapies.

A product is eligible for this designation

if it is a regenerative medicine therapy (which may include a cell or gene therapy) that is intended to treat, modify, reverse, or cure

a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug has the potential to address

unmet medical needs for such disease or condition.

The benefits of a regenerative advanced therapy designation include early interactions

with the FDA to expedite development and review, benefits available to breakthrough therapies, potential eligibility for priority review

and accelerated approval based on surrogate or intermediate endpoints.

Post-approval

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of human clinical trials.

Save where the Clinical Trial Regulation applies (see below) in relation to cross-border trials, in

the European Union, for example, a request for a Clinical Trial Authorization (“CTA”) must be submitted to the competent

regulatory authorities and the competent Ethics Committees in the European Union Member States in which the clinical trial takes place,

much like the FDA and the IRB, respectively.

Once the CTA request is approved in accordance with the European Union and the European

Union Member State’s requirements, clinical trial development may proceed.

Save where the Clinical Trial Regulation applies (see below) in relation to cross-border trials, in the European

Union, for example, a request for a Clinical Trial Authorization (“CTA”) must be submitted to the competent regulatory authorities

and the competent Ethics Committees in the European Union Member States in which the clinical trial takes place, much like the FDA and

the IRB, respectively.

Once the CTA request is approved in accordance with the European Union and the European Union Member State’s

requirements, clinical trial development may proceed.

requirements and processes governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to

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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 product.

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

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.

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.

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 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;

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.

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.

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

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.

made to physicians and certain research institutions for clinical trials are included within

the ambit of this law.

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 a violation;

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;

that require drug manufacturers to report information related to payments and other transfers

of value to physicians and other healthcare providers or marketing expenditures;

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

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.

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.

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

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 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.

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.

and Reimbursement

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that impose similar obligations.

that are currently engaged in gene therapy or companies not yet focused on developing cell and gene therapies could at any time

decide to develop therapies relevant to our business.

Many of our competitors, either alone or with their strategic partners, may have

substantially greater financial, technical, and human resources than we do and may have significantly greater experience in the discovery

and development of product candidates, obtaining FDA and other regulatory approvals of product candidates and commercializing those product

Accordingly, our competitors may be more successful than us in obtaining approval for product candidates and achieving widespread

market acceptance.

that are currently engaged in gene therapy or companies not yet focused on developing cell and gene therapies could at any time decide

to develop therapies relevant to our business.

Many of our competitors, either alone or with their strategic partners, may have substantially

greater financial, technical, and human resources than we do and may have significantly greater experience in the discovery and development

of product candidates, obtaining FDA and other regulatory approvals of product candidates and commercializing those product candidates.

Accordingly, our competitors may be more successful than us in obtaining approval for product candidates and achieving widespread market

Our competitors’ product candidates may be more effective, or more effectively marketed and sold, than any product

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On May 15, 2015, we acquired Abeona Therapeutics LLC and on June 19, 2015, we changed our name to Abeona Therapeutics Inc.

materials used by us are specialized.

of the materials we use are specialized.

We obtain materials from several suppliers based in different countries around the world.

are unavailable from one supplier, we generally have alternate suppliers available.

materials are unavailable from one supplier, we generally have alternate suppliers available.

Capital Resources

a clinical-stage biopharmaceutical company developing cell and gene therapies for life-threatening rare genetic diseases, we seek

to attract, hire, develop and retain qualified and highly skilled personnel with experience in areas such as research and development

and manufacturing operations.

We compete for such personnel with numerous pharmaceutical and chemical companies, specialized biotechnology

firms and universities.

We strive to support our employees’ well-being through a transparent, inclusive, and collaborative culture

and by providing them with the training, support, and resources to help them succeed professionally.

of March 21, 2022, we had 90 full-time employees.

We have never experienced employment-related work stoppages and believe that

we maintain good relations with our personnel.

a clinical-stage biopharmaceutical company developing cell and gene therapies for life-threatening diseases, we seek to attract, hire,

develop and retain qualified and highly skilled personnel with experience in areas such as research and development and manufacturing

We compete for such personnel with numerous pharmaceutical and chemical companies, specialized biotechnology firms and universities.

We strive to support our employees’ well-being through a transparent, inclusive, and collaborative culture and by providing them

with the training, support, and resources to help them succeed professionally.

of December 31, 2022, we had 57 full-time employees.

We have never experienced employment-related work stoppages and believe that we

maintain good relations with our personnel.

In addition, to complement our internal expertise, we have contracts with scientific consultants,

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clinical development, regulatory affairs, toxicology, process scale-up and preclinical testing.

make available free of charge through our website, www.abeonatherapeutics.com , our annual reports on Form 10-K and other reports

that we file with the Securities and Exchange Commission (“SEC”) as well as certain of our corporate governance policies,

make available free of charge through our website, www.abeonatherapeutics.com , including our annual reports on Form 10-K and other

reports that we file with the Securities and Exchange Commission (“SEC”) as well as certain of our corporate governance policies,

including the charters for the audit, compensation and nominating and corporate governance committees of the Board of Directors (the

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The content on any website referred

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

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