UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
WASHINGTON,
DC 20549
FORM
10-K
(Mark One)
For the fiscal year ended December 31, 2020
Or
For the transition period from _______ to _______
Commission
file number 001-15771
ABEONA
THERAPEUTICS INC.
(Exact
name of registrant as specified in its charter)
1330
Avenue of the Americas, 33rd Floor,
New York,
NY10019
(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 Markets
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☒
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, 2020, was approximately $204,160,000.
The
number of shares outstanding of the registrant’s common stock as of March 19, 2021 was 98,788,933shares.
DOCUMENTS
INCORPORATED BY REFERENCE
Portions
of the registrant’s definitive Proxy Statement relating to our 2021 Annual Meeting of Stockholders are incorporated by reference
into Part III of this Annual Report on Form 10-K where indicated. Such Proxy Statement will be filed with the Securities and Exchange
Commission within 120 days after the end of the fiscal year to which this report relates.
TABLE
OF CONTENTS
Page
Part I
Item 1. Business 3
Item 1A. Risk Factors 30
Item 1B. Unresolved Staff Comments 65
Item 2. Properties 65
Item 3. Legal Proceedings 65
Item 4. Mine Safety Disclosures 65
Part II
Item 6. Selected Financial Data 67
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 76
Item 8. Financial Statements and Supplementary Data 76
Item 9A. Controls and Procedures 77
Item 9B. Other Information 77
Part III
Item 10. Directors, Executive Officers and Corporate Governance 78
Item 11. Executive Compensation 78
Item 14. Principal Accounting Fees and Services 78
Item 15. Exhibits, Financial Statement Schedules 79
Signatures 81
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. We caution readers not to place undue reliance on any such “forward-looking statements,”
which speak only as of the date made, and advise readers that these forward-looking statements 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. All such forward-looking statements, whether written or oral, and whether made
by us or on our behalf, are expressly qualified by these cautionary statements and any other cautionary statements that may accompany
the 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 potential impacts of the COVID-19 pandemic on our business, operations,
and financial condition; the achievement of or expected timing, progress and results of clinical development, clinical trials
and potential regulatory approvals; our Phase 3 clinical trial (VIITALTM) for patients with recessive dystrophic epidermolysis
bullosa (“RDEB”) and our beliefs relating thereto; our ability to identify and enroll patients in the Phase 3 clinical
trial; our pipeline of product candidates; our use of the proceeds from the Paycheck Protection Program loan and our eligibility
for loan forgiveness under the Coronavirus Aid, Relief and Economic Security Act, as amended; our belief that we have sufficient
resources to fund operations for at least the next 12 months from the date of filing of this report; the ongoing arbitration proceeding
with REGENXBIO; the dilutive effect that raising additional funds by selling additional equity securities would have on the relative
equity ownership of our existing investors; our belief that EB-101 could potentially benefit patients with RDEB; our belief that
adeno-associated virus (“AAV”) gene therapy could potentially benefit patients with Sanfilippo syndrome type A (“MPS
IIIA”) and Sanfilippo syndrome type B (“MPS IIIB”); our ability to develop our novel AAV-based gene therapy
platform technology; our belief in the adequacy of the data from clinical trials, including VIITALTM and our Phase 1/2 clinical
trials in ABO-102 (AAV-SGSH) for MPS IIIA and ABO-101 (AAV-NAGLU) for MPS IIIB, together with the data generated in the program
to date, to support regulatory approvals; the existence of intellectual property, a license to which might be required to market
MPS IIIA and MPS IIIB; our dependence upon our third-party and related-party customers and vendors and their compliance with regulatory
bodies; 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 impact of the COVID-19 pandemic on our business,
operations (including our clinical trials), and financial condition, and on our ability to access the capital markets; our ability
to access our existing at-the-market sale agreement and any dilution that may result from accessing such sales agreement; our
estimates regarding expenses, future revenues, capital requirements, and needs for additional financing; our ability to raise
capital; our ability to fund our operating expenses and capital expenditure requirements for at least the next 12 months with
our existing cash and cash equivalents; our ability to obtain additional equity funding from current or new stockholders, out-licensing
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; our ability to
continue to develop our novel AAV-based gene therapy platform technology; 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 execute a Phase 3 clinical trial for patients with RDEB; our ability to complete enrollment of patients into clinical
trials to secure sufficient data to assess efficacy and safety; our ability to identify additional patients for our Phase 1/2
clinical trial for patients with MPS IIIA and MPS IIIB; our ability to continue to secure and maintain regulatory designations
for our product candidates; our ability to develop manufacturing capability compliant with current good manufacturing practices
for our product candidates; our ability to manufacture gene and cell 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 gene and cell therapies for life-threatening
rare genetic diseases. Our lead clinical programs consist of: (i) EB-101, an autologous, gene-corrected cell therapy for recessive
dystrophic epidermolysis bullosa (“RDEB”), (ii) ABO-102, an adeno-associated virus (“AAV”)-based gene
therapy for Sanfilippo syndrome type A (“MPS IIIA”), and (iii) ABO-101, an AAV-based gene therapy for Sanfilippo syndrome
type B (“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 AIMTM capsid platform that we have exclusively licensed
from the University of North Carolina at Chapel Hill, and internal AAV vector research programs. Our 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 three programs in clinical development—EB-101, ABO-101 and ABO-102—
for which we hold several U.S. and European Union (“EU”) regulatory designations, and a pipeline of additional earlier
stage programs:
Our
robust 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. and abroad.
Our
Mission and Strategy
Abeona
is at the forefront of gene and cell 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 gene and cell therapies for people impacted by serious diseases.
We partner with leading academic researchers, patient advocacy organizations and caregivers to develop therapies that address
the underlying cause of a broad spectrum of rare genetic diseases for which no effective treatment options exist today.
Since
our last fiscal year, we have 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 gene and cell therapies.
Our strategy to achieve this goal consists of:
Advancing
our Clinical Gene and Cell Therapy Programs and Research and Development with a Focus on Rare and Orphan Diseases.
We
have three programs in clinical development—EB-101, ABO-101 and ABO-102—and a pipeline of additional earlier stage
programs. Through our gene and cell 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.
Applying
Novel Next-Generation AIMTM Capsid Technology to Develop New In-Vivo Gene Therapies.
We
are researching and developing next-generation 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 chimeric AAV capsids capable
of improved tissue targeting for various indications and potentially evading immunity to wildtype AAV vectors.
Establishing
Leadership Position in Commercial-Scale Gene and Cell Therapy Manufacturing.
We
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, OH 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 Gene and Cell Therapy Franchises and Adjacencies through In-Licensing and Strategic Partnerships.
We
seek to be the partner of choice in gene therapy disease 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.
Maintaining
and Growing IP Portfolio.
We
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
Our
robust 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. and abroad.
Our
lead clinical programs consist of: (i) EB-101, an autologous, gene-corrected cell therapy for RDEB, (ii) ABO-102, an AAV-based
gene therapy for MPS IIIA and (iii) ABO-101, an AAV-based gene therapy 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 AIMTM
capsid platform that we have exclusively licensed from the University of North Carolina at Chapel Hill, and internal AAV vector
research programs.
Developing
Next Generation Gene and Cell Therapy
EB-101
for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (“RDEB”)
Disease
Overview
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 layers.
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
population.
Similar to most ultra-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 EB-101.
RDEB patients have, on average, 11 active
wounds on their bodies, with the majority > 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).
We
expect EB-101 could be a treatment option for all RDEB wounds and specifically target larger and/or chronic 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 VIITALTM phase 3 trial. 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.
Current
Management of RDEB
At
present, there are no approved treatments for RDEB in the U.S. or Europe.
Wound
management currently consists of 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.
RDEB
patients also have periodic surgeries to relieve disease related issues such as narrowing of their esophagus, fusing of fingers
and corneal abrasions.
Program
Status
EB-101
is an autologous, gene-corrected 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.
EB-101
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”).
Results
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). To date, there have been no reported serious adverse events.
In
2020 Abeona initiated a pivotal Phase 3 clinical trial, referred to as VIITALTM, evaluating the potential of EB-101 for the
treatment of RDEB. VIITALTM is an ongoing randomized, control-matched Phase 3 clinical trial assessing treatment with EB-101
in 10 to 15 patients, comprising 35 large chronic wound sites treated in total. The co-primary endpoints of VIITALTM 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 endpoints and
other characteristics of the study.
ABO-102
and ABO-101 for the treatment of Mucopolysaccharidosis (MPS) III (Sanfilippo syndrome)
Disease
Overview
MPS
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.
Lysosomes
are intra-cellular structures responsible for a continuous process of replacing used materials and breaking them down for disposal.
Children with MPS III are missing a lysosomal enzyme that is essential in breaking down used 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.
In
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.
Program
Status
We
are 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.
ABO-102
for MPS IIIA
Preclinical
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.
On February 12, 2021, we reported updated
data from the ongoing Phase 1/2 gene transfer clinical trial of ABO-102 (scAAV9.U1a.hSGSH) for Mucopolysaccharidosis IIIA, or
MPS IIIA, (study ABT-001; NCT02716246). MPS IIIA is caused by the absence of functional SGSH gene. In the trial, 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. The results to-date
from the high dose cohort 3 (currently enrolling) showed evidence of preservation of neurocognitive development with continuous
cognitive gains within normal range of a non-afflicted child, for 2.5 years to 3 years after treatment with ABO-102 in the three
young patients treated before 30 months of age with relevant follow-up, 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.
Summary
of MPS IIIA ABO-102 Phase 1/2 Study Data:
● 19 patients treated as of January 2021
● Clear dose-response and sustained reduction of heparan sulfate levels in CSF
● Sustained reduction in liver volume
○ ABO-102 has been well tolerated to date
○ No deaths
○ No infusion-related adverse events
○ No serious drug-related adverse events
○ ELISpot negative for the SGSH enzyme
We
have initiated a second Phase 1/2 clinical trial with ABO-102 (study ABT-003; NCT04088734) to treat patients who do not qualify
for participation on study ABT-001 because of their more advanced cognitive impairment caused by MPS IIIA. The first patient in
study ABT-003 was enrolled in 2019 at Adelaide Women’s and Children’s Hospital in Australia and two more patients
were enrolled in Spain in 2020. We initiated this clinical trial in the U.S. in early 2021.
ABO-101
for MPSIIIB
Preclinical
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. In 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.
In
the ABO-101 (rAAV9.CMV.hNAGLU) program for Mucopolysaccharidosis IIIB (MPS IIIB), subjects in our ongoing Phase 1/2 gene transfer
clinical study (study ABT-002; 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 parameters. On February 12, 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 24 months in the patient in Cohort 1 that reached that timepoint. Longer follow-up in patients treated in cohorts 2 and
3 is needed to address cognitive changes. There 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.
As
of February 2021, the clinical trial is ongoing in the U.S., Spain, Germany, and France.
Summary
of MPS IIIB ABO-101 Phase 1/2 Study Data:
● 11 patients treated as of January, 2021
○ ABO-101 has been well tolerated to date
○ No deaths
○ No infusion-related adverse events
○ ELISpot negative for the NAGLU enzyme
ABO-50X
for the treatment of genetic eye disorders
Program
Overview
This
research program comprises several vectors being tested for different monogenic retinal disorders. Eighty percent of genetic eye
disorders affect the photoreceptor cells, and correction of mutations in the retina has been accomplished by several groups using
AAV gene therapy delivered through subretinal injection. We are exploring various routes of administration to deliver AAV to the
retina, including 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.
Program
Status
In
a preclinical study, we noted that intravitreal administration of the novel AIMTM AAV204 capsid in non-human primates resulted
in broad transgene expression in the peripheral retina as well as intense expression in the fovea 25 days post-administration.
AAV204 also transduced photoreceptor cells in retinal explants and transduced the outer retina, with positive green fluorescent
protein expression.
The
non-human primate data were complemented by findings from mice models, which identified AAV204 as one of three lead candidate
AIMTM capsids that demonstrate robust transduction of retinal cells. The data in mice demonstrated that intravitreal administration
resulted in broad retinal expression of AAV204 that penetrated to the photoreceptor and retinal pigmented epithelium layers.
ABO-201
for the treatment of CLN3 disease, also known as juvenile Batten disease (or Juvenile Neuronal Ceroid Lipofuscinosis) (“CLN3
Disease”)
Disease
Overview and Program Overview
CLN3
disease is a rare, fatal, autosomal recessive (inherited) disorder of the nervous system that typically begins between 4 and 8
years of age. Often the first noticeable sign of CLN3 disease is vision impairment, which tends to progress rapidly and eventually
result in blindness. 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 or sit. 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. Most people
with juvenile Batten disease live into their twenties or thirties. As of December 31, 2020, no specific treatment is known that
can halt or reverse the symptoms of CLN3 disease.
ABO-201
(scAAV9.CLN3) is an AAV-based gene therapy that has shown preclinical efficacy following delivery of a functioning copy of the
CLN3 gene to 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.
ABO-401
for the Treatment of Cystic Fibrosis
Disease
Overview and Program Overview
Cystic
Fibrosis (“CF”) is a progressive genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance
regulator (“CFTR”) gene. Malfunction of this gene affects cells that produce mucus, sweat and digestive juices. In
unaffected individuals, these secreted fluids are normally thin and slippery, but in cystic fibrosis, a defective gene causes
the secretions to become sticky and 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, and impaired pancreas function
and digestive abnormalities.
The preclinical ABO-401 program employs
the AAV204 AIMTM 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 CFTR transgene expression that has corrected the underlying chloride current
deficit in human CF donor derived nasal and bronchial epithelium cells grown at the air-liquid interface and treated with ABO-401.
Correction of chloride channel current following ABO-401 administration occurred regardless of underlying mutations of the CF
transmembrane conductance regulators, including the most common CF mutation, delta-F508.
Next-Generation
Gene Therapy Treatments anchored in AIMTM Vector Platform
In
2016, we licensed a library of first-generation novel AAV capsids from the University of North Carolina at Chapel Hill. 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, 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 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.
Establishing
Leadership Position in Commercial-Scale Gene and Cell-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 QA/QC scientists
with expertise in gene and cell therapy, particularly in cell culture, formulation, upstream, downstream and purification manufacturing.
We 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 gene and
cell 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 and process development, and assay development teams. The second phase
also included nearly 2,000 square feet of cGMP Inventory Control space. The last phase of our manufacturing build-out plan would
be a clinical/commercial AAV facility to support manufacturing to meet anticipated product demand globally.
We
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. It is 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. We have developed the cGMP manufacturing process for the LZRSE-Col7A1 retroviral vector and have produced three
GMP lots for analytical and clinical comparability. We have developed a GMP master cell bank and a working cell bank to support
the GMP production of the retroviral vector.
We
are developing 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 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, then purified and filtered
in a multi-step process. We continue to maintain focus on cGMP compliance and ensuring adequate supply to support our future clinical
activity.
We
have established and maintained strong and collaborative relationships with third-party companies specializing in the testing
of gene and cell 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 EB-101 and AAV-based vector therapies, including:
● sufficient scale to support commercial manufacturing requirements for EB-101
● processes related to product release testing for EB-101
● processes related to the manufacture of retroviral supernatant
● AAV serum-free suspension technology that is readily scalable
We
believe that these improvements and our continued investment in our manufacturing platform will enable us to develop best-in-class,
next-generation gene and cell therapy products. As we look to commercialize EB-101, we are working towards filing a Biologics
License Application (“BLA”) to support commercial manufacturing of EB-101 from our Cleveland facility.
Maintain
a Strong Intellectual Property Portfolio
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 gene and cell therapy. We may also
rely on regulatory protection afforded through data exclusivity, market exclusivity, and patent term extensions where available.
Our
success may depend in part on our ability to obtain and maintain patent 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 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 for a variety of technologies, including the following: research
tools and methods, methods for transferring genetic material into cells, AAV-based biological products, methods of designing novel
AAV constructs, methods for treating diseases of interest and methods for manufacturing, packaging, and transporting our product
candidates. 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. Mucopolysaccharidosis (“MPS”) IIIA and IIIB
We
have secured an exclusive license through Nationwide Children’s Hospital to a family of patent applications for AAV-based
treatments for patients with MPS IIIA and IIIB. The family includes three pending applications in the United States. United States
patent(s) that may grant from this family would be expected to expire in approximately 2031 and 2032.
2. CLN3 Disease (Juvenile Batten Disease)
We
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 well as U.S. Patent No. 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. The ‘134 Patent is expected to expire in December 2035 absent any future grant of patent term
extension.
3. Recessive Dystrophic Epidermolysis Bullosa
To
support our EB franchise, we have licensed a patent family from Stanford University covering technology for the treatment of RDEB.
National stage patent applications are pending in the United States, Canada, Europe, Israel, Japan, South Korea, China, New Zealand,
Australia, Russia, Mexico, South Africa, and Brazil. United States patent(s) that may grant from this portfolio would be expected
to expire in approximately 2037. We have also filed a United States provisional patent application directed to packaging and transport
of the EB product.
4. AIMTM Capsids
We
have an exclusive license to an international patent family from UNC at Chapel Hill covering novel adeno-associated virus (“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, Australia, Brazil, China, Hong Kong, Europe, Canada, Israel, India, Japan, South Korea, Mexico, New Zealand, Russia, and
South Africa. The first patent in this patent family, U.S. Patent No. 10,532,110 (the “‘110 Patent”), 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 patent in this patent family, U.S. Patent No. 10,561,743 (the “‘743 Patent”),
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.
5. CLN1 Disease (Infantile Batten Disease)
We
have also licensed from UNC at Chapel Hill 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 grant from this portfolio would be expected to expire approximately in 2037. In August 2020, we entered
into an agreement exclusively sublicensing the CLN1 patent portfolio to Taysha Gene Therapies.
6. Rett Syndrome
We
have licensed rights to patent applications from both UNC at Chapel Hill 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 Edinburgh patent rights to Taysha Gene Therapies.
We
will explore in due course strategies to support patent term extensions for all of our licensed 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. Moreover, in light of the COVID-19 pandemic,
the FDA has issued a number of guidance documents to assist companies navigating COVID-19, product development, and manufacturing,
including guidance specific to gene therapies.
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 chemistry, manufacturing, and control (“CMC”), clinical investigations and other areas of gene therapy