ROCKVILLE, Md., Jan. 5, 2021 /PRNewswire/ -- REGENXBIO Inc.
(Nasdaq: RGNX) today provided an update on the RGX-314 programs,
including the announcement that the pivotal program for RGX-314 for
the treatment of wet age-related macular degeneration (wet AMD) is
now active. In addition, REGENXBIO announced a new program,
RGX-202, a novel, potentially best-in-class, one-time gene therapy
for the treatment of Duchenne Muscular Dystrophy (DMD).
"2020 was a very productive year at REGENXBIO, and we are
excited to move into 2021, which we expect to be another year of
clinical execution. The initiation of our first pivotal program for
RGX-314 for the treatment of wet AMD is a great step forward for
the field as we look to broaden the applicability of gene therapy
to larger patient populations. In addition, we are excited to
announce RGX-202, a potential one-time gene therapy for the
treatment of DMD. RGX-202 is the first gene therapy program in the
REGENXBIO pipeline to be developed under the leadership of our
Chief Scientific Officer, Olivier
Danos. We look forward to filing an IND for this program
later this year," said Kenneth T.
Mills, President and Chief Executive Officer of REGENXBIO.
"We continue to advance our pipeline of innovative therapies in the
clinic as well as our manufacturing capabilities. I would also like
to express my deep gratitude to our employees and clinical partners
as well as patients and their families for their ongoing commitment
and support despite the challenges posed by the global COVID-19
pandemic."
Pivotal Program for RGX-314 for the Treatment of wet
AMD
REGENXBIO today announced that
ATMOSPHERE™, the first of two planned
pivotal trials to evaluate RGX-314, is active and patient screening
is ongoing. RGX-314 is a potential best-in-class, one-time gene
therapy for the treatment of wet AMD.
REGENXBIO completed an End of Phase 2 meeting with the FDA to
discuss the details of a pivotal program to support a Biologics
License Application (BLA). Based on discussions with the FDA,
REGENXBIO plans to conduct two randomized, well-controlled clinical
trials to evaluate the efficacy and safety of RGX-314 in patients
with wet AMD, enrolling approximately 700 patients total. In
addition, REGENXBIO and the FDA aligned on a clear path to support
manufacturing plans in the pivotal program. REGENXBIO expects to
submit a BLA based on these trials in 2024.
"We are pleased to have reached alignment with the FDA on key
elements of our pivotal program for the treatment of wet AMD. Our
plan allows us to further accelerate the clinical development of
RGX-314 towards the goal of a BLA filing in 2024 and we have
already begun site activation and patient screening for our first
planned pivotal trial," said Steve
Pakola, M.D., Chief Medical Officer of REGENXBIO. "We have
strengthened the key design elements for the planned trials based
on the long-term data from our dose-escalation Phase I/IIa trial of
RGX-314 and believe that we are well-positioned to execute on this
pivotal program."
- ATMOSPHERE will evaluate the efficacy and safety of RGX-314 in
patients with wet AMD.
-
- The trial will enroll approximately 300 patients across two
RGX-314 dose arms versus ranibizumab. The primary endpoint of the
trial is non-inferiority to ranibizumab based on change from
baseline in Best Corrected Visual Acuity (BCVA) at one year.
- Site activation is ongoing and REGENXBIO expects to begin
dosing patients in this trial in the first quarter of 2021.
- The second pivotal trial is expected to be similar in design to
ATMOSPHERE and REGENXBIO plans to initiate the trial in the second
half of 2021.
-
- The trial is expected to have two RGX-314 dose arms versus
aflibercept, and the planned primary endpoint is non-inferiority to
aflibercept based on the change from baseline in BCVA at one
year.
- In addition, based on discussions with FDA, REGENXBIO believes
it has a clear path to support cGMP commercial-ready manufacturing
plans in the pivotal program.
-
- REGENXBIO has initiated its pivotal program using cGMP material
produced from its existing manufacturing process and has agreement
with the FDA to incorporate its scalable suspension cell culture
manufacturing process to support future commercialization, upon
completion of a bridging study and the pivotal trials. The bridging
study is expected to initiate in the first half of 2021.
Suprachoroidal Delivery of RGX-314 for the Treatment of Wet
AMD and Diabetic Retinopathy (DR)
- REGENXBIO has completed enrollment of patients in Cohort 1 of
AAVIATE™, a Phase II trial for the
treatment of wet AMD.
-
- REGENXBIO plans to report interim data from Cohort 1 in the
third quarter of 2021.
- Enrollment of patients in Cohort 2 is expected to begin in the
first quarter of 2021.
- Enrollment of patients continues in Cohort 1 for
ALTITUDE™, a Phase II trial for the
treatment of DR. REGENXBIO expects to report initial data from this
trial in 2021.
- As of December 31, 2020,
suprachoroidal delivery of RGX-314 in AAVIATE and ALTITUDE is
reported to be generally well-tolerated, with no evidence of
inflammation.
New Program for the Treatment of Duchenne Muscular
Dystrophy
REGENXBIO also announced today the development of a potential
one-time gene therapy for the treatment of DMD, which is based on a
novel microdystrophin construct.
"DMD is a severe, degenerative disease affecting thousands of
children worldwide. It is caused by mutations of the gene which
encodes dystrophin, a protein necessary for muscle cell strength
and function, and innovation and development of potential new
treatment options for patients with DMD has been a goal for the
gene therapy field for many years," said Olivier Danos, Ph.D., Chief Scientific Officer
of REGENXBIO. "Since I joined REGENXBIO, we have been working to
develop this gene therapy candidate using our proprietary AAV8
vector, with a focus on including the C-Terminal Domain of
dystrophin, which may potentially bolster the key cell signaling
pathways and muscle membrane integrity, leading to improved muscle
strength and resistance. We look forward to completing the
IND-enabling studies and bringing this program into the
clinic."
- RGX-202 is designed to deliver a novel microdystrophin
transgene which includes an extended coding region of the
C-Terminal (CT) domain found in naturally occurring dystrophin, as
well as other fundamental improvements.
-
- Presence of the CT domain has been shown to recruit several key
proteins to the muscle cell membrane, leading to improved muscle
resistance to contraction-induced muscle damage in dystrophic
mice.1
- Additional design features, including codon optimization and
reduction of CpG content, may potentially improve gene expression,
increase translational efficiency and reduce immunogenicity.
- RGX-202 is designed to use the NAV AAV8 vector, a vector used
in numerous clinical trials, and a well-characterized muscle
specific promoter (Spc5-12) to support the delivery and targeted
expression of genes throughout skeletal and heart muscle.
- Proof of concept data from preclinical studies of RGX-202 in
the mdx mouse model of DMD demonstrates broad and robust
expression of microdystrophin in muscle, recruitment of key
proteins to the muscle cells, improvements in muscle histology, as
well as meaningful increases in muscle strength and function.
- Commercial-scale cGMP material has already been produced at
1000L capacity using REGENXBIO's suspension cell culture
manufacturing process and will be used in the clinical development
of RGX-202.
- Investigational New Drug (IND) application enabling studies are
being completed and REGENXBIO expects to submit an IND to the FDA
in mid-2021.
The design of the new RGX-202 microdystrophin transgene is based
on innovative vector engineering by REGENXBIO scientists and
incorporates learnings from the laboratory of George Dickson, Emeritus Professor of Molecular
Cell Biology at Royal Holloway, University of London, a pioneering figure in dystrophin
research.
"The data from dystrophic laboratory trials suggest that a gene
therapy delivering a microdystrophin gene incorporating an extended
coding region from the C-Terminal Domain such as RGX-202 may
provide substantial added muscle function for patients with DMD. A
blend of the innovative science applied to microdystrophin gene
design, and an AAV vector that is well-established, makes this new
approach very promising," said Professor George Dickson from Royal Holloway. "I am
pleased to see this important science developing from Royal
Holloway's research is now being advanced under the leadership and
gene therapy expertise of Olivier
Danos and the team from REGENXBIO. I look forward to seeing
this program enter the clinic."
Financial Guidance
REGENXBIO expects to report that as of December 31, 2020, it had between $515 million and $530
million in cash, cash equivalents and marketable securities,
including the $200 million upfront
payment from REGENXBIO's royalty monetization agreement with
entities managed by Healthcare Royalty Management, LLC. REGENXBIO
expects these resources to fund its operations, including the
completion of its internal manufacturing capabilities and clinical
advancement of its product candidates, until late 2022.
About REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company
seeking to improve lives through the curative potential of gene
therapy. REGENXBIO's NAV Technology Platform, a proprietary
adeno-associated virus (AAV) gene delivery platform, consists of
exclusive rights to more than 100 novel AAV vectors, including
AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO and its third-party NAV
Technology Platform Licensees are applying the NAV Technology
Platform in the development of a broad pipeline of candidates in
multiple therapeutic areas.
About Wet AMD
Wet AMD is characterized by loss of vision due to new, leaky
blood vessel formation in the retina. Wet AMD is a significant
cause of vision loss in the United
States, Europe and
Japan, with up to 2 million people
living with wet AMD in these geographies alone. Current anti-VEGF
therapies have significantly changed the landscape for treatment of
wet AMD, becoming the standard of care due to their ability to
prevent progression of vision loss in the majority of patients.
These therapies, however, require life-long intraocular injections,
typically repeated every four to 12 weeks in frequency, to maintain
efficacy. Due to the burden of treatment, patients often
experience a decline in vision with reduced frequency of treatment
over time.
About RGX-314
RGX-314 is being developed as a potential one-time treatment for
wet AMD, diabetic retinopathy, and other chronic retinal
conditions. RGX-314 consists of the NAV AAV8 vector, which encodes
an antibody fragment designed to inhibit vascular endothelial
growth factor (VEGF). RGX-314 is believed to inhibit the VEGF
pathway by which new, leaky blood vessels grow and contribute to
the accumulation of fluid in the retina.
REGENXBIO is advancing two separate routes of administration of
RGX-314 to the eye, through a standardized subretinal delivery
procedure as well as delivery to the suprachoroidal space.
REGENXBIO has licensed certain exclusive rights to the SCS
Microinjector® from Clearside Biomedical, Inc. to deliver gene
therapy treatments to the suprachoroidal space of the eye.
About ATMOSPHERE™
ATMOSPHERE is a multi-center, randomized, active-controlled
trial to evaluate the efficacy and safety of a
single-administration of RGX-314 versus standard of care in
patients with wet AMD. The trial is designed to enroll 300 patients
at a 1:1:1 ratio across two RGX-314 dose arms (6.4x1010
genome copies (GC)/eye and 1.3x1011 GC/eye delivered
subretinally) and an active control arm of monthly intravitreal
injections of ranibizumab (0.5 mg/eye). The primary endpoint of the
trial is non-inferiority to ranibizumab based on change from
baseline in Best Corrected Visual Acuity (BCVA) at 54 weeks.
Secondary endpoints of the trial include safety and tolerability,
change in central retinal thickness (CRT) and need for supplemental
anti-VEGF injections. Patient selection criteria will include
patients with wet AMD who are responsive to anti-VEGF treatment and
will be independent of preexisting neutralizing antibody status.
Patients will not receive prophylactic immune suppressive
corticosteroid therapy before or after administration of RGX-314.
The trial will be conducted at approximately 60 clinical sites
based in the United States, with
over 100 retinal surgeons.
About AAVIATE™
AAVIATE is a multi-center, open-label, randomized,
active-controlled, dose-escalation trial that will evaluate the
efficacy, safety and tolerability of suprachoroidal delivery of
RGX-314 using the SCS Microinjector, a targeted, in-office route of
administration. The trial is expected to enroll approximately 40
patients with severe wet AMD across two cohorts. Patients in each
cohort will be randomized to receive RGX-314 versus monthly 0.5 mg
ranibizumab intravitreal injection at a 3:1 ratio, and two dose
levels of RGX-314 will be evaluated:
2.5x1011 GC/eye and 5x1011 GC/eye.
Patients will not receive prophylactic immune suppressive
corticosteroid therapy before or after administration of RGX-314.
The primary endpoint of the trial is mean change in vision in
patients dosed with RGX-314, as measured by best corrected visual
acuity (BCVA), at Week 40 from baseline, compared to patients
receiving monthly injections of ranibizumab. Other endpoints
include mean change in central retinal thickness (CRT) and number
of anti-VEGF intravitreal injections received following
administration of RGX-314.
About ALTITUDE™
ALTITUDE is a multi-center, open label, randomized, controlled
dose-escalation trial that will evaluate the efficacy, safety and
tolerability of suprachoroidal delivery of RGX-314. The trial is
expected to enroll approximately 40 patients with DR across two
cohorts. Patients will be randomized to receive RGX-314 versus
observational control at a 3:1 ratio, and two dose levels of
RGX-314 will be evaluated: 2.5x1011 GC/eye and
5.0x1011 GC/eye. Patients will not receive
prophylactic immune suppressive corticosteroid therapy before or
after administration of RGX-314. The primary endpoint of the trial
is the proportion of patients that improve in DR severity based on
the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy
Severity Scale (ETDRS-DRSS) at 48 weeks. Other endpoints include
safety and development of DR-related ocular complications.
About Duchenne Muscular Dystrophy
DMD is a severe, progressive, degenerative muscle disease,
affecting 1 in 3,500 to 5,000 boys born each year worldwide. DMD is
caused by mutations in the DMD gene which encodes for
dystrophin, a protein involved in muscle cell structure and
signaling pathways. Without dystrophin, muscles throughout the body
degenerate and become weak, eventually leading to loss of movement
and independence, required support for breathing, cardiomyopathy
and premature death.
About RGX-202
RGX-202 is designed to deliver a novel microdystrophin transgene
which retains key elements of the dystrophin protein, including an
extended coding region of the C-Terminal (CT) domain found in
naturally-occurring dystrophin, as well as other fundamental
improvements to the transgene. Presence of the CT domain has been
shown to recruit several key proteins to the muscle cell membrane,
leading to improved muscle resistance to contraction-induced muscle
damage in dystrophic mice. Additional design features, including
codon optimization and reduction of CpG content, may potentially
improve gene expression, increase translational efficiency and
reduce immunogenicity. RGX-202 is designed to use the NAV AAV8
vector, a vector used in numerous clinical trials, and a
well-characterized muscle specific promoter (Spc5-12) to support
the delivery and targeted expression of genes throughout skeletal
and heart muscle.
Forward-Looking Statements
This press release includes "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. These statements express a belief, expectation or
intention and are generally accompanied by words that convey
projected future events or outcomes such as "believe," "may,"
"will," "estimate," "continue," "anticipate," "design," "intend,"
"expect," "could," "plan," "potential," "predict," "seek,"
"should," "would" or by variations of such words or by similar
expressions. The forward-looking statements include statements
relating to, among other things, REGENXBIO's future operations and
clinical trials. REGENXBIO has based these forward-looking
statements on its current expectations and assumptions and analyses
made by REGENXBIO in light of its experience and its perception of
historical trends, current conditions and expected future
developments, as well as other factors REGENXBIO believes are
appropriate under the circumstances. However, whether actual
results and developments will conform with REGENXBIO's expectations
and predictions is subject to a number of risks and uncertainties,
including the timing of enrollment, commencement and completion and
the success of clinical trials conducted by REGENXBIO, its
licensees and its partners, the timing of commencement and
completion and the success of preclinical studies conducted by
REGENXBIO and its development partners, the timely development and
launch of new products, the ability to obtain and maintain
regulatory approval of product candidates, the ability to
accurately predict how long REGENXBIO's existing cash resources
will be sufficient to fund its anticipated operating expenses, the
ability to obtain and maintain intellectual property protection for
product candidates and technology, trends and challenges in the
business and markets in which REGENXBIO operates, the size and
growth of potential markets for product candidates and the ability
to serve those markets, the rate and degree of acceptance of
product candidates, the impact of the COVID-19 pandemic or similar
public health crises on REGENXBIO's business, and other factors,
many of which are beyond the control of REGENXBIO. Refer to the
"Risk Factors" and "Management's Discussion and Analysis of
Financial Condition and Results of Operations" sections of
REGENXBIO's Annual Report on Form 10-K for the year ended
December 31, 2019, and comparable
"risk factors" sections of REGENXBIO's Quarterly Reports on Form
10-Q and other filings, which have been filed with the U.S.
Securities and Exchange Commission (SEC) and are available on the
SEC's website at www.sec.gov. All of the forward-looking statements
made in this press release are expressly qualified by the
cautionary statements contained or referred to herein. The actual
results or developments anticipated may not be realized or, even if
substantially realized, they may not have the expected consequences
to or effects on REGENXBIO or its businesses or operations. Such
statements are not guarantees of future performance and actual
results or developments may differ materially from those projected
in the forward-looking statements. Readers are cautioned not to
rely too heavily on the forward-looking statements contained in
this press release. These forward-looking statements speak only as
of the date of this press release. REGENXBIO does not undertake any
obligation, and specifically declines any obligation, to update or
revise any forward-looking statements, whether as a result of
new information, future events or otherwise.
SCS Microinjector® is a trademark of Clearside Biomedical, Inc.
All other trademarks referenced herein are registered trademarks of
REGENXBIO.
Preliminary Financial Information
REGENXBIO reports its financial results in accordance with U.S.
generally accepted accounting principles. All financial data in
this press release for the year ended December 31, 2020 is preliminary, as financial
close procedures for the year ended December
31, 2020 are not yet complete. These estimates are not a
comprehensive statement of the financial position of REGENXBIO for
the year ended December 31, 2020.
Actual results may differ materially from these estimates as a
result of the completion of normal year-end accounting procedures
and adjustments, including the execution of REGENXBIO's internal
control over financial reporting, the completion of the preparation
and management's review of REGENXBIO's financial statements for the
year ended December 31, 2020 and the
subsequent occurrence or identification of events prior to the
filing of the financial results for the year ended December 31, 2020 on Form 10-K with the SEC.
Contacts:
Tricia Truehart
Investor Relations and Corporate Communications
347-926-7709
ttruehart@regenxbio.com
Investors:
Eleanor Barisser, 212-600-1902
eleanor@argotpartners.com
Media:
David Rosen, 212-600-1902
david.rosen@argotpartners.com
1 Koo, Taeyoung et al. "Delivery of
AAV2/9-microdystrophin genes incorporating helix 1 of the
coiled-coil motif in the C-terminal domain of dystrophin improves
muscle pathology and restores the level of α1-syntrophin and
α-dystrobrevin in skeletal muscles of mdx mice." Human gene therapy
vol. 22,11 (2011): 1379-88. doi:10.1089/hum.2011.020
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