ABEO US Equity☆

UNITED

STATES

SECURITIES

AND EXCHANGE COMMISSION

WASHINGTON,

DC 20549

FORM

10-K

(Mark One)

For the fiscal year ended December 31, 2023

Or

For the transition period from _______ to _______

Commission

file number 001-15771

ABEONA

THERAPEUTICS INC.

(Exact

name of registrant as specified in its charter)

6555

Carnegie Avenue, 4th

Floor, Cleveland, OH44103

(Address

of principal executive offices, zip code)

(646)813-4701

(Registrant’s

telephone number, including area code)

Securities

registered pursuant to Section 12(b) of the Securities Exchange Act of 1934:

Title of each class Trading Symbol(s) Name of each exchange on which registered

Common Stock, $0.01 par value ABEO Nasdaq Capital Market

Indicate

by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate

by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒

Indicate

by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange

Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)

has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate

by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule

405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant

was required to submit such files). Yes ☒ No ☐

Indicate

by check mark whether the Registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting

company, or an emerging growth company. See definitions of “large accelerated filer,” “accelerated filer,” “smaller

reporting company” and “emerging growth company” in Rule 12b-2 of the Act:

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

Emerging growth company ☐

If

an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying

with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate

by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness

of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered

public accounting firm that prepared or issued its audit report. Yes ☐ No ☒

If

securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant

included in the filing reflect the correction of an error to previously issued financial statements. Yes ☐ No ☒

Indicate

by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation

received by any of the registrant’s executive officers during the relevant recovery period pursuant to § 240.10D-1(b). Yes

☐ No ☒

Indicate

by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

The

aggregate market value of the voting and non-voting common equity held by non-affiliates computed by reference to the average bid and

asked price of such common equity, as of June 30, 2023, was approximately $78,468,000.

The

number of shares outstanding of the registrant’s common stock as of March 6, 2024 was 27,355,037.

ABEONA

THERAPEUTICS INC.

Annual

Report on Form 10-K

Table

of Contents

Page

Part I

Item 1. Business 3

Item 1A. Risk Factors 27

Item 1B. Unresolved Staff Comments 55

Item 1C. Cybersecurity 55

Item 2. Properties 56

Item 3. Legal Proceedings 56

Item 4. Mine Safety Disclosures 56

Part II

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 69

Item 8. Financial Statements and Supplementary Data 69

Item 9A. Controls and Procedures 69

Item 9B. Other Information 70

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 70

Part III

Item 10. Directors, Executive Officers and Corporate Governance 71

Item 11. Executive Compensation 71

Item 14. Principal Accounting Fees and Services 71

Part IV

Item 15. Exhibits, Financial Statement Schedules 72

Signatures 74

FORWARD-LOOKING

STATEMENTS

This

Form 10-K (including information incorporated by reference) contains statements that express management’s opinions, expectations,

beliefs, plans, objectives, assumptions or projections regarding future events or future results and therefore are, or may be deemed

to be, “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section

21E of the Securities Exchange Act of 1934, as amended. Words such as “expects,” “anticipates,” “intends,”

“plans,” “believes,” “could,” “would,” “seeks,” “estimates,”

and variations of such words and similar expressions, and the negatives thereof, are intended to identify such forward-looking statements.

Such “forward-looking statements” speak only as of the date made and are not guarantees of future performance and involve

certain risks, uncertainties, estimates, and assumptions by management that are difficult to predict. Various factors, some of which

are beyond the Company’s control, could cause actual results to differ materially from those expressed in, or implied by, such

forward-looking statements. In addition, we disclaim any obligation to update any forward-looking statements to reflect events or circumstances

after the date of this report, except as may otherwise be required by the federal securities laws.

Forward-looking

statements necessarily involve risks and uncertainties, and our actual results could differ materially from those anticipated in forward-looking

statements due to a number of factors. These statements include statements about: the outcome of our submission of a Biologics License

Application for pz-cel and the timing thereof; our plans to continue development of AAV-based gene therapies designed to treat ophthalmic

and other diseases and next-generation AAV-based gene therapies; the achievement of or expected timing, progress and results of clinical

development, clinical trials and potential regulatory approvals; our pipeline of product candidates; our belief that pz-cel could potentially

benefit patients with RDEB; development of our novel AAV-based gene therapy platform technology; our belief in the adequacy of the clinical

trial data from our VIITALTM clinical trial, together with the data generated in the program to date, to support regulatory approvals;

our dependence upon our third-party customers and vendors and their compliance with regulatory bodies; our estimates regarding expenses,

future revenues, capital requirements, and needs for additional financing; our intellectual property position and our ability to obtain,

maintain and enforce intellectual property protection and exclusivity for our proprietary assets; our estimates regarding the size of

the potential markets for our product candidates, the strength of our commercialization strategies and our ability to serve and supply

those markets; and future economic conditions or performance.

Important

factors that could affect performance and cause results to differ materially from management’s expectations are described in the

sections entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results

of Operations” in this Form 10-K. These factors include: the outcome of our submission of a Biologics License Application for pz-cel

and the timing thereof; our ability to access our existing at-the-market sale agreement; our ability to access additional financial resources

and/or our financial flexibility to reduce operating expenses if required; our ability to obtain additional equity funding from current

or new stockholders; the potential impacts of global healthcare emergencies, such as pandemics, on our business, operations, and financial

condition; our ability to out-license technology and/or other assets, deferring and/or eliminating planned expenditures, restructuring

operations and/or reducing headcount, and sales of assets; the dilutive effect that raising additional funds by selling additional equity

securities would have on the relative equity ownership of our existing investors, including under our existing at-the-market sale agreement;

the outcome of any interactions with the U.S. Food and Drug Administration (“FDA”) or other regulatory agencies relating

to any of our products or product candidates; our ability to continue to secure and maintain regulatory designations for our product

candidates; our ability to develop manufacturing capabilities compliant with current good manufacturing practices for our product candidates;

our ability to manufacture cell and gene therapy products and produce an adequate product supply to support clinical trials and potentially

future commercialization; the rate and degree of market acceptance of our product candidates for any indication once approved; and our

ability to meet our obligations contained in license agreements to which we are party.

PART

I

ITEM

1. BUSINESS

Business

Abeona

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

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

epidermal sheets currently in development for recessive dystrophic epidermolysis bullosa (“RDEB”). Pz-cel has been granted

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

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

We

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

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

Carolina at Chapel Hill (“UNC”), and internal AAV vector research programs. Abeona’s novel, next-generation AAV capsids

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

Our

Mission and Strategy

Abeona

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 2023, 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 September 2023, we submitted

a Biologics License Application (“BLA”) for pz-cel to the FDA. In November 2023, the FDA accepted and granted priority review

for our BLA for pz-cel. Under the Prescription Drug User Fee Act (“PDUFA”), the FDA has set a target action date of May 25,

2024.

We

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.

Our

strategy consists of:

Advancing

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

Through

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.

Developing

Novel In-Vivo Gene Therapies Using AIMTM Capsid Technology.

We

are researching and developing AAV-based gene therapy using our novel capsids developed from the AIMTM 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 wild-type AAV vectors.

Leveraging

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

We

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

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.

Establishing

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

We

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

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

and their families, and generate novel intellectual property.

Maintaining

and Growing our IP Portfolio.

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.

Developing

Next-Generation Cell and Gene Therapy

Pz-cel

for the Treatment of RDEB

Disease

Overview

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 skin functioning by anchoring the skin’s dermal

and epidermal layers to one another.

As

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

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

abrasions, and an abnormal narrowing of the esophagus. Long-term RDEB patients can suffer from anemia, are at high risk of

developing aggressive squamous cell carcinomas, infections, and premature death. The most severe patients are approximately 20 times

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

Similar

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.; 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 pz-cel.

RDEB

patients have an active disease with the majority of the wounds typically > 20 cm2 (Stanford University; Solis, D., et

al., 2017). In 2020, a survey of RDEB patients reported that approximately 60% have active wounds covering greater than 30% of their

bodies (Bruckner et al.; Orphanet Journal of Rare Diseases, 2020). Wounds covering up to approximately 80% of body surface area have

been recorded in some EB patients (Hirsch et al.; Nature Research, 2017).

In

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

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

evaluated in the VIITALTM phase 3 trial had large wounds (> 20cm2) and, on average, had wounds remained open

for 6.2 years, and in some cases up to 21 years, prior to pz-cel treatment. Most RDEB patients have large and chronic wounds that carry

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

Current

Management of RDEB

Standard

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

infection, and reduction in mechanical forces that produce new blisters. Care usually includes treatment of new blisters by lancing

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

with an elastic wrap for integrity. In a cost analysis conducted by Debra of America, based on 3,274 patient’s health insurance

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

annual cost to the healthcare system from all people. The cost of wound care supplies could be as high as

$996,000 per year.

RDEB

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

corneal abrasions.

In

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

wounds associated with Junctional (JEB) and DEB, respectively. The introduction of these drugs may further increase the total cost of care.

Program

Status

Pz-cel

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

(keratinocytes) using a retrovirus. The keratinocytes are then grown into credit card sized sheets and surgically applied to the patient to restore Type VII collagen expression

and skin function.

Results

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

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

of follow-up (So. Y, Nazaraoff, et al., Orphanet Journal Rare Disease 2022). To date, there have been no reported serious adverse events.

In

November 2022, we announced positive topline data from our VIITALTM study. The pivotal phase 3 VIITALTM study evaluated the

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

and treated in VIITALTM measured greater than 20 cm2 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® Pain Rating Scale between randomized treated and matched untreated

(control) wounds at the six-month timepoint.

The

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

related treatment emergent adverse events, including procedural pain, muscle spasms and pruritis. Infections unrelated to pz-cel were

observed in eight patients.

In

September 2023, we submitted a BLA for pz-cel to the FDA. In November 2023, the FDA accepted for filing and granted priority review

for our BLA for pz-cel. Under the PDUFA, the FDA has set a target action date of May 25, 2024. Pz-cel has been granted Regenerative

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

Orphan Drug designation by the EMA.

Among

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

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

company.

We

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

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

ABO-503

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

Disease

Overview and Program Overview

XLRS

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

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

mediate cell-cell adhesion. XLRS is characterized by abnormal splitting of the layers of the retina, resulting in poor visual acuity,

which can progress to legal blindness. The incidence of XLRS is estimated to be between 1 in 5,000 and 1 in 20,000 in males, with an

estimated prevalence of 35,000 in the United States and Europe combined. There are currently no disease modifying therapies approved

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

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

ABO-503,

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

to the retina in a mouse model of XLRS. Preclinical studies have demonstrated robust RS1 expression in the retina, improved cone photoreceptor

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

presented at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting in May 2023. A pre-IND meeting for ABO-503 was conducted

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

ABO-504

for the Treatment of Stargardt Disease

Disease

Overview and Program Overview

Autosomal

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

causes vision loss in children and young adults. The most common form of Stargardt disease is caused by mutations in the ABCA4 gene,

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

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

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

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. Abeona previously reported preclinical data demonstrating

the ability of the dual AAV vector system to produce full length ABCA4 protein in cell culture. Recent proof-of-concept studies, presented

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

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

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

ABO-505

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

Disease

Overview and Program Overview

ADOA,

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

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

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

legal blindness with a loss of visual acuity, optic disc pallor, and color vision deficits. ADOA affects approximately 1 in 30,000 people

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 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. These studies

were presented at the ASGCT Annual Meeting in May 2023.

Gene

Therapy Treatments anchored in AIMTM Vector Platform

In

2016, we licensed a library of novel AAV capsids from UNC. The AIMTM 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 AIMTM 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 by Abeona and our research partners, we have observed improvements in gene delivery to specific tissues compared

to currently available AAV technology. We believe AIMTM 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.

Strategic

Licensing Agreements

We

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,

Inc. (“Taysha”). 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.

Leveraging

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

We

have established a cGMP manufacturing facility, the Elisa Linton Center located in Cleveland, Ohio, which enables us to enhance supply

chain control, establish tighter quality control testing, increase supply capacity, reduce production costs and gain manufacturing efficiency

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

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

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

techniques.

We

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 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.

We

have advanced our in-house manufacturing capabilities for pz-cel. The product is manufactured as a multilayer cellular sheet containing

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

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

for long-term wound healing. A key component to the pz-cel drug product manufacturing process is the retroviral vector, which delivers

the functional copy of the Collagen VII Alpha 1 cDNA to the autologous patient cells. 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 demonstrated analytical comparability between IUVPF and Abeona-produced retroviral vector. In order to support licensure, we

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

to support the cGMP production of the retroviral vector.

We

have established AAV vector manufacturing capabilities that use the triple plasmid transient transfection method. We insert, or transfect,

many copies of three DNA plasmids encoding the specific therapeutic gene sequence, or transgene, the capsid coding sequence, and helper

sequences into AAV-293 cells using a serum-free, suspension-based bioreactor vector production technology. During an incubation period

following transfection, each cell produces AAV vectors through biosynthesis using the cells’ natural machinery. At the end of the

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

We

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

and gene therapy material to complement our process and assay development needs.

We

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

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

● sufficient scale to support commercial manufacturing requirements for pz-cel

● processes related to product release testing for pz-cel

● processes related to the manufacture and release testing of retroviral vector

● AAV serum-free suspension technology that is readily scalable

We

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

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

facility.

Maintain

Strong Intellectual Property Protection

We

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

defending patent rights, both for inventions developed internally and for inventions licensed from third parties. We also rely on trade

secrets and know-how relating to our proprietary technology platforms, continuing technological innovation, and in-licensing opportunities

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

Our

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

inventions, and know-how related to our business; defend and enforce our patents; preserve the confidentiality of our trade secrets;

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

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

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

rights may need to be enforced by third-party licensors. With respect to both licensed and company-owned intellectual property, we may

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

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

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

We

are actively seeking U.S. and international patent protection, together with our licensors, for a variety of technologies, including

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

RDEB, and methods for manufacturing, packaging, and transporting our product candidates. We also intend to seek patent protection or

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

identify and develop novel biological products. We seek protection, in part, through confidentiality and proprietary information agreements.

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

commercialization.

Licensed

Technologies and Intellectual Property

1. Recessive Dystrophic Epidermolysis Bullosa

To

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

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

regions, and are expected to expire in early 2037. Patent applications remain pending in the United States which, if granted, would be

expected to expire in 2037. We have also filed United States and Canadian patent applications directed to the packaging and transport

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

We

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

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

2. AIMTM Capsids

We

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

covering novel AAV capsids (“AIMTM 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 AIMTM capsids have been filed in the United

States, Europe and other geographical regions. The first U.S. patent in this patent family, U.S. Patent No. 10,532,110 (the “‘110

Patent”), was issued to UNC on January 14, 2020. The ‘110 Patent is entitled to 352 days of patent term adjustment, making

its projected expiration date November 6, 2036. The second U.S. patent in this patent family, U.S. Patent No. 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. A third U.S.

patent in this patent family, U.S. Patent No. 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. Patents have also been granted

in Australia (AU2015349759B2), Israel (IL252072), and Russia (RU2727015). We have exclusive rights to these patents under our license

with UNC.

We

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.

3. CLN1 Disease (Infantile Batten Disease)

We

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. One U.S. patent in the first patent family, U.S. Patent No. 11,504,435

(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 will have a 20-year expiration date of no earlier

than 2040. We have entered into agreements exclusively sublicensing these two CLN1 patent families to Taysha Gene Therapies, Inc.

4. Rett Syndrome

We

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

Edinburgh”) and The University Court of the University of Glasgow (“U. Glasgow”) relating to gene therapy for the treatment

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

the MeCP2 gene, which is mutated in patients with Rett Syndrome. This patent family has pending applications in the United States, Europe

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

The patent families licensed from U. Edinburgh and U. Glasgow are directed to expression cassettes for MeCP2 polypeptides and to synthetic

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

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

and other geographical regions. Patents issuing from applications in the Edinburgh patent families will have a 20-year expiration date

of no earlier than 2038. In October 2020, we entered into an agreement exclusively sublicensing these UNC and University of Edinburgh

patent rights to Taysha Gene Therapies.

5. Multipartite AAV Delivery of Large Transgenes

We

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

in the United States, Europe and other geographical regions. Patents issuing from these applications are not expected to expire before

2041.

We

also own a pending U.S. provisional application directed to multipartite AAV delivery and its use for treating Stargardt disease.

We

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

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

from these applications are not expected to expire before 2042.

7. Treatment of Dominant Optic Atrophy and X-linked Retinoschisis

We

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

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

We

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

U.S.

Biologic Products Development Process

In

the United States, the FDA regulates biologic products including gene therapy products under the Federal Food, Drug, and Cosmetic Act

(“FDCA”), the Public Health Service Act (“PHSA”), and regulations implementing these laws. The FDCA, PHSA and

their corresponding regulations govern, among other things, the testing, manufacturing, safety, efficacy, labeling, packaging, storage,

record keeping, distribution, advertising, and promotion of biologic products. Applications to the FDA are required before conducting

human clinical testing of biologic products. FDA approval also must be obtained before marketing of biologic products. Gene therapy studies

may also need to comply with the National Institutes of Health (“NIH”) Guidelines for Research Involving Recombinant or Synthetic

Nucleic Acid Molecules (“NIH Guidelines”), which includes additional requirements, such as the review and approval of the

study by an Institutional Biosafety Committee.

Within

the FDA, the Center for Biologics Evaluation and Research (“CBER”) regulates gene therapy products. Within CBER, the review

of gene therapy and related products is consolidated in the Office of Tissues and Advanced Therapies (“OTAT”) and the FDA

has established the Cellular, Tissue and Gene Therapies Advisory Committee (“CTGTAC”), a panel of medical and scientific

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

The

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

Before

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

testing. Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of product chemistry, toxicity, and

formulation, as well as in vivo studies to assess the potential safety and activity of the product candidate. The conduct of the preclinical

tests must comply with federal regulations and requirements including GLPs.

If

a gene therapy trial is conducted at, or sponsored by, institutions receiving NIH funding for recombinant DNA research, the study must

also comply with the NIH Guidelines. Compliance with the NIH Guidelines is mandatory for investigators at institutions receiving NIH

funds for research involving recombinant DNA. However, many companies and other institutions, not otherwise subject to the NIH Guidelines,

voluntarily follow them.

The

clinical trial sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any

available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. Some preclinical testing may continue

even after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA places the

clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical

trial can begin. The FDA also may impose clinical holds on a biologic product candidate at any time before or during clinical trials

due to safety concerns or non-compliance. If the FDA imposes a clinical hold, trials may not commence or recommence without FDA authorization

and then only under terms authorized by the FDA.

Human

clinical trials under an IND

Clinical

trials involve the administration of the biologic product candidate to healthy volunteers or patients under the supervision of qualified

investigators, which generally are physicians not employed by, or under the control of, the trial sponsor. Investigators must also provide

certain information to the clinical trial sponsors to allow the sponsors to make certain financial disclosures to the FDA. Clinical trials

are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection

and exclusion criteria and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial

will be stopped if certain adverse events should occur. Each protocol and any amendments to the protocol must be submitted to the FDA

as part of the IND. Clinical trials must be conducted and monitored in accordance with the FDA’s regulations comprising the GCP

requirements, including the requirement that all research subjects provide informed consent.

Further,

each clinical trial must be reviewed and approved by an IRB at or servicing each institution at which the clinical trial will be conducted.

An IRB is charged with protecting the welfare and rights of trial participants and considers items such as whether the risks to individuals

participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves communications

to study subjects before a study commences at that site and the form and content of the informed consent that must be signed by each

clinical trial subject, or his or her legal representative, and must monitor the clinical trial until completed. Clinical trials involving

recombinant DNA also must be reviewed by an institutional biosafety committee (“IBC”), a local institutional committee that

reviews and oversees basic and clinical research that utilizes recombinant DNA at that institution. The IBC assesses the safety of the

research and identifies any potential risk to public health or the environment.

Information

about certain clinical trials, including a description of the study and study results, must be submitted within specific timeframes to

NIH for public dissemination on their clinicaltrials.gov website. Sponsors or distributors of investigational products for the diagnosis,

monitoring, or treatment of one or more serious diseases or conditions must also have a publicly available policy on evaluating and responding

to requests for expanded access requests.

Investigational

biologics and therapeutic substances imported into the United States are also subject to regulation by the FDA. Further, the export of

investigational products outside of the United States is subject to regulatory requirements of the receiving country as well as U.S.

export requirements under the FDCA.

Human

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

Additional

kinds of data may also help to support a BLA, such as patient experience data. Real world evidence may also support a BLA, and, for appropriate

indications sought through supplemental BLAs, data summaries may provide marketing application support. For genetically targeted products

and variant protein targeted products intended to address an unmet medical need in one or more patient subgroups with a serious or life

threatening rare disease or condition, the FDA may allow a sponsor to rely upon data and information previously developed by the sponsor

or for which the sponsor has a right of reference, that was submitted previously to support an approved application for a product that

incorporates or utilizes the same or similar genetically targeted technology or a product that is the same or utilizes the same variant

protein targeted drug as the product that is the subject of the application.

Post-approval

clinical trials, sometimes referred to as phase IV clinical trials, may be conducted or may be required by FDA after initial approval.

These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly

for long-term safety follow-up.

During

all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical

data, and clinical trial investigators. Annual progress reports detailing the results of the clinical trials must be submitted to the

FDA.

Written

IND safety reports must be promptly submitted to the FDA, IRBs, IBCs, and the investigators for serious and unexpected adverse events;

any findings from other trials, in vivo laboratory tests or in vitro testing that suggest a significant risk for human subjects; any

clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure,

or other safety information. The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the

information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse

reaction within seven calendar days after the sponsor’s initial receipt of the information.

The