AGTC Announces Publication of Preclinical Data that Support the Ongoing Clinical Development of Its XLRP Gene Therapy Program
Preclinical
studies validate the transgene and dosing used in the ongoing Phase 1/2
clinical trial in patients with XLRP due to mutations in the RPGR gene
| Source:Applied Genetic Technologies Corporation
GAINESVILLE,
Fla., and CAMBRIDGE, Mass., Aug. 25, 2020 (GLOBE NEWSWIRE) -- 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 that preclinical data validating the transgene (hRPGRco) that
is being evaluated in the Company’s ongoing Phase 1/2 clinical trial in
patients with X-lined retinitis pigmentosa (XLRP) have been published in
the July 15, 2020 print issue of Human Gene Therapy.
The studies, which evaluated the safety and efficacy of hRPGRco and
another XLRP transgene in a canine model of XLRP, demonstrated stronger
expression of hRPGRco than the other transgene at all dose levels
evaluated. Following subretinal administration in AGTC’s proprietary
rAAV2tYF vector, each of the XLRP transgenes corrected rod-cone opsin
mislocalization, which are early markers of the disease, but the hRPGRco
transgene demonstrated a broader therapeutic index. Study results also
helped to guide the initial dosing in ongoing Phase 1/2 trial. As previously announced, AGTC expects to begin a Phase 2/3 clinical trial of its XLRP gene therapy candidate in the first quarter of 2021.
“Gene-based
therapies contain multiple elements, and small differences in any one
of those elements can have a significant impact on safety and efficacy,”
said Mark Shearman, PhD, Chief Scientific Officer of AGTC and an author
on the publication. “We have shown our commitment to gene therapy
through almost 20 years of experience and multiple clinical programs;
this commitment demands that we conduct rigorous preclinical development
work to ensure that we advance gene-therapy candidates that are
optimized for safety and efficacy. These newly published preclinical
data not only further validate the safety of our therapy but our choice
of XLRP transgene for our clinical program.”
The publication
reports data from studies conducted in the RPGR-mutant canine model
(XLRPA2), which has been validated as a model for human XLRP due to
mutations in the RPGR gene. AAV vectors contained a “stabilized” version
of the human RPGR gene (hRPGRstb), which is shorter than the wildtype
DNA sequence, or a full-length version of the RPGR gene that has been
codon optimized for improved expression and stability (hRPGRco). Both
transgenes have previously been evaluated in the XLRPA2 model using an
AAV5 vector. The current studies were conducted using AGTC’s proprietary
AAV2tYF vector, which is optimized for delivery to target cells within
the retina. Safety was similar for the two transgenes. A key finding
from the studies is that the AAV2tYF-hRPGRco vector resulted in higher
RPGR gene expression compared with AAV2tYF-hRPGRstb and with
AAV5-GRK1-hRPGRco. Additionally, the studies showed that while the
mid-dose led to optimal correction of disease phenotypes, structural and
functional rescue of photoreceptors was also achieved when treating at
mid-stage disease with rAAV2tYFGRK1-hRPGRco at the lowest dose. This
significantly expands therapeutic index and guided a starting dose for
the ongoing Phase 1/2 clinical trial.
“Our focus
on optimizing every aspect of gene therapy – including vector elements,
routes of administration and manufacturing - differentiates AGTC from
competitors,” said Sue Washer, President and CEO of AGTC. “Our rigorous
approach to developing best-in-class therapies is, we believe, the
reason that our XLRP trial data to date, based on publicly released
information, compares favorably with that reported by our competitors.
With more than 100 patients enrolled in our collective clinical trials,
studies have shown that each of our therapies have been generally safe
and well-tolerated with no serious adverse events reported. We are
currently enrolling additional patients into our expanded Phase 1/2
trial and look forward to initiating a Phase 2/3 trial in the first
quarter of 2021.”
About AGTC AGTC
is a clinical-stage biotechnology company developing genetic therapies
for people with rare and debilitating ophthalmic, otologic and central
nervous system (CNS) diseases. AGTC is a leader in designing and
constructing all critical gene therapy elements and bringing them
together to develop customized therapies that address real patient
needs. The Company’s most advanced clinical programs leverage its
best-in-class technology platform to potentially improve vision for
patients with an inherited retinal disease. AGTC has active clinical
trials in X-linked retinitis pigmentosa and achromatopsia (ACHM CNGB3
& ACHM CNGA3). Its pre-clinical programs build on the Company’s
industry leading AAV manufacturing technology and scientific expertise.
AGTC is advancing multiple important pipeline candidates to address
substantial unmet clinical need in larger ophthalmology indications,
optogenetics, otology and CNS disorders.
About X-linked Retinitis Pigmentosa (XLRP) XLRP
is an inherited condition that causes progressive vision loss in boys
and young men. Characteristics of the disease include night blindness in
early childhood and progressive constriction of the visual field. In
general, XLRP patients experience a gradual decline in visual acuity
over the disease course, which results in legal blindness around the 4th
decade of life. AGTC was granted U.S. Food and Drug Administration
(FDA) orphan drug designation in 2017, as well as European Commission
orphan medicinal product designation in 2016, for its gene therapy
product candidate to treat XLRP caused by mutations in the RPGR gene.
Forward-Looking Statements This
release contains forward-looking statements that reflect AGTC's plans,
estimates, assumptions and beliefs, including statements regarding the
expected commencement of its Phase 2/3, the timing for reporting trial
data and AGTC’s ability to enroll patients in its ongoing clinical
trials, effectively design and successfully complete clinical trials.
Forward-looking statements include information concerning possible or
assumed preclinical and clinical product development and regulatory
progress, future results of operations, financial guidance, business
strategies and operations, potential growth opportunities, potential
market opportunities, the effects of competition and the impact of the
COVID-19 pandemic. 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: gene therapy is still novel with only
a few approved treatments so far; AGTC cannot predict when or if it
will obtain regulatory approval to commercialize a product candidate or
receive reasonable reimbursement; uncertainty inherent in clinical
trials and the regulatory review process; risks and uncertainties
associated with drug development and commercialization; the direct and
indirect impacts of the ongoing COVID-19 pandemic on our business,
results of operations, and financial condition; 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 our most recent annual or quarterly report and in other
reports we have 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 Glenn Silver (PR) Lazar FINN Partners T: (212) 867-1768 or (646) 871-8485 [email protected] or [email protected]
BioFlorida is the voice of Florida's life sciences industry, representing 8,600 establishments and research organizations in the BioPharma, MedTech, Digital Health and Health Systems that collectively employ nearly 107,000 Floridians. Source: TEConomy/BIO (released 2022)
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