IND-Enabling Study Data Published in Human Gene Therapy Clinical Development Support Clinical Development of AGTC-402 for the...
June 15 2017 - 7:00AM
Applied Genetic Technologies Corporation (NASDAQ:AGTC), a
biotechnology company conducting human clinical trials of
adeno-associated virus (AAV)-based gene therapies for the treatment
of rare diseases, today announced the publication of IND-enabling
preclinical data demonstrating the safety and efficacy of AGTC-402
in the treatment of achromatopsia (ACHM) due to mutations in the
CNGA3 gene.
The study, “Safety and Efficacy Evaluation of
rAAV2tYF-PR.1-hCNGA3 Vector Delivered by Subretinal Injection in
CNGA3 Mutant Achromatopsia Sheep” appears in the June issue of
Human Gene Therapy Clinical Development and was led by researchers
at the Volcani Center and Hebrew University in Israel. The
gene-based therapy used in this study, AGTC-402, utilizes AGTC’s
proprietary AAV technology to deliver a functional copy of the
human CNGA3 gene.
“These data, which were included in our
Investigational New Drug application filed with the U.S. Food and
Drug Administration in October 2016, provide compelling evidence
that AGTC-402 has potential as a treatment for achromatopsia due to
CNGA3 mutations,” said Sue Washer, President and CEO of AGTC. “We
are currently scheduling patients for enrollment in our Phase I/II
trial in this patient population, and we continue enrollment in our
clinical trial for patients with CNGB3 achromatopsia.”
Patients and caregivers interested in
participating in or learning more about AGTC’s clinical trials for
patients with ACHM caused by mutations in the CNGB3 and CNGA3 genes
may find more information
at www.agtc.com/patients-and-caregivers or by
contacting advocacy@agtc.com.
Achromatopsia results from mutations in one of
several genes. Two of these genes, CNGA3 and CNGB3, encode the
alpha and beta subunits, respectively, of an ion channel that is
essential for proper function of cone cells within the retina.
About 75 percent of ACHM patients have mutations in one of these
two genes; the remainder of cases result from mutations in one of
several other genes.
The study was conducted in 13 sheep with
day-blindness due to mutations in the CNGA3 gene. This large animal
model has been used successfully in the evaluation of other
AAV-based gene therapies for ACHM. Nine animals received a low
(n=4) or high (n=5) dose of AGTC-402 administered as a single
subretinal injection to the right eye. A positive efficacy control
group of four animals received a different AAV-CNGA3 vector shown
to be effective in a previous study. Four animals distributed
across the three experimental groups received an injection of
carrier vehicle in the left eye. Animals were followed for 13 weeks
post-injection.
Key findings from the study include:
- Electroretinography (ERG) testing (30 Hz and CFFF) showed a
significant increase in cone responses in treated eyes at Weeks 6
and 12 compared with pre-treatment responses (P<0.05) in all
groups. ERG responses were also significantly higher at Weeks 6 and
12 when comparing treated and untreated eyes in animals receiving
AGTC-402 (P<0.05). Animals receiving the positive efficacy
control vector had significant increases in the 30 Hz response at
Weeks 6 and 12 and in the CFFF response at 12 Weeks
(P<0.05).
- Maze navigation tests showed significantly shorter navigation
times (P<0.05) and reduced obstacle collisions in the
vector-treated eye for all groups.
- Immunohistochemical analysis showed expression of the human
CNGA3 gene in all 13 vector-treated eyes but not in untreated or
vehicle treated eyes.
- No serum antibodies against the human CNGA3 protein were
detected in any vector-treated animal.
- Subretinal injections were generally well tolerated and were
not associated with any systemic toxicity. Most animals had mild to
moderate side effects thought to be related to the surgical
procedure, including inflammation, swelling and bleeding, which
generally resolved without further intervention.
The authors conclude that the study results
support the evaluation of AGTC-402 in clinical trials in
individuals affected by ACHM due to CNGA3 mutations, and add that
study participants should be carefully monitored for possible
inflammatory responses. The planned Phase I/II trial of AGTC-402
includes the prophylactic administration of oral and topical
corticosteroids to minimize inflammation at the time of
administration.
“These results add to the growing body of
preclinical evidence that support the safety and efficacy of
AAV-based delivery of the CNGA3 gene for the treatment of
achromatopsia,” said Michael Goldstein, M.D., Chief Medical Officer
of AGTC. “The significant improvements in ERG results and maze
navigation times demonstrate that AGTC-402 provided a functional
benefit in these animals. We believe that similar benefits may be
achievable in achromatopsia patients, and are excited to be
screening for enrollment in two clinical trials for this
condition.”
About AGTC
AGTC is a clinical-stage biotechnology company that uses its
proprietary gene therapy platform to develop products designed to
transform the lives of patients with severe diseases, with an
initial focus in ophthalmology. AGTC's lead product candidates are
designed to treat inherited orphan diseases of the eye, caused by
mutations in single genes that significantly affect visual function
and currently lack effective medical treatments.
AGTC's product pipeline includes ophthalmology programs in
X-linked retinoschisis (XLRS), X-linked retinitis pigmentosa
(XLRP), achromatopsia, wet age-related macular degeneration, and an
optogenetics program with Bionic Sight. AGTC's non-ophthalmology
programs include its adrenoleukodystrophy program and its otology
program, which is in pre-clinical development, and the company
expects to advance several otology product candidates into clinical
development in the next few years. Each of AGTC's XLRS, XLRP and
adrenoleukodystrophy programs is partnered with Biogen. AGTC
employs a highly-targeted approach to selecting and designing its
product candidates, choosing to develop therapies for indications
having high unmet medical need that it believes are clinically
feasible and present commercial opportunities. AGTC has a
significant intellectual property portfolio and extensive expertise
in the design of gene therapy products including capsids, promoters
and expression cassettes, as well as, expertise in the formulation,
manufacture and physical delivery of gene therapy products.
Forward Looking Statements
This release contains forward-looking statements that reflect
AGTC's plans, estimates, assumptions and beliefs. Forward-looking
statements include information concerning possible or assumed
future results of operations, business strategies and operations,
preclinical and clinical product development and regulatory
progress, potential growth opportunities, potential market
opportunities and the effects of competition. Forward-looking
statements include all statements that are not historical facts and
can be identified by terms such as "anticipates," "believes,"
"could," "seeks," "estimates," "expects," "intends," "may,"
"plans," "potential," "predicts," "projects," "should," "will,"
"would" or similar expressions and the negatives of those terms.
Actual results could differ materially from those discussed in the
forward-looking statements, due to a number of important factors.
Risks and uncertainties that may cause actual results to differ
materially include, among others: no gene therapy products have
been approved in the United States and only two such products have
been approved in Europe; AGTC cannot predict when or if it will
obtain regulatory approval to commercialize a product candidate;
uncertainty inherent in the regulatory review process; risks and
uncertainties associated with drug development and
commercialization; factors that could cause actual results to
differ materially from those described in the forward-looking
statements are set forth under the heading "Risk Factors" in the
Company's Annual Report on Form 10-K for the fiscal year ended June
30, 2016, as filed with the SEC. Given these uncertainties, you
should not place undue reliance on these forward-looking
statements. Also, forward-looking statements represent management's
plans, estimates, assumptions and beliefs only as of the date of
this release. Except as required by law, we assume no obligation to
update these forward-looking statements publicly or to update the
reasons actual results could differ materially from those
anticipated in these forward-looking statements, even if new
information becomes available in the future.
IR/PR CONTACTS:
David Carey (IR) or Danielle Lewis (PR)
Lazar Partners Ltd.
T: (212) 867-1768 or (212) 843-0211
dcarey@lazarpartners.com or dlewis@lazarpartners.com
CORPORATE CONTACTS:
Larry Bullock
Chief Financial Officer
Applied Genetic Technologies Corporation
T: (386) 462-2204
lbullock@agtc.com
Stephen Potter
Chief Business Officer
Applied Genetic Technologies Corporation
T: (617) 413-2754
spotter@agtc.com
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