SYDNEY, Aug. 8, 2017
/PRNewswire/ -- Benitec Biopharma Limited (ASX: BLT; NASDAQ:
BNTC; NASDAQ: BNTCW) is pleased to announce it has developed a new
single vector (gene therapy construct) system which uses DNA
directed RNA interference (ddRNAi) to silence expression of the
mutant gene associated with oculopharyngeal muscular dystrophy
(OPMD), while simultaneously adding back a copy of the normal
version of the same gene to restore gene function. This next
generation single vector system, termed BB-301, represents the
clinical candidate that Benitec intends to advance into human
clinical trials in the second half of calendar year 2018.
Simultaneous silence and replace modalities are required for an
effective gene therapy for OPMD and other orphan diseases. By
combining both 'silence and replace' functions into a single
vector, Benitec can focus its manufacturing efforts for the program
on a single product, which vastly simplifies the regulatory process
and reduces the complexity of the clinical strategy. The
innovative Benitec vector design which integrates both 'silence and
replace' modalities into a single vector is not readily achievable
with other gene therapy and gene editing technologies.
Greg West, Chief Executive
Officer, commented on today's news: "This is an important
development in our OPMD program. The single vector system shows the
same excellent activity as the earlier generation dual vector
system where the 'silence and replace' constructs were delivered in
separate vectors. Similar application of the single vector
technology may allow development of novel therapeutics to treat
other orphan diseases. OPMD is a significant commercial
opportunity for Benitec and we are working with the regulators and
key opinion leaders in this field to advance BB-301 into the clinic
as quickly as possible."
Background information
OPMD is a rare progressive,
muscle-wasting disease caused by mutation in the poly(A)-binding
protein nuclear 1 (PABPN1) gene, that is characterised by eyelid
drooping, swallowing difficulties, and proximal limb
weakness.
Since 2014, Benitec has been working on an OPMD collaboration
with research groups at Royal Holloway University of London and at the Myology Research Center
based in Paris. The previous
preclinical studies, conducted as part of this collaboration, used
the A17 mouse model of OPMD and used a two vector system, where one
vector silenced the production of the disease-causing mutant
protein and a second vector produced the wild type (normal) protein
to restore muscular function. A17 mice display many of the
clinical signs of OPMD including intranuclear inclusions (INIs),
fibrosis, and loss of muscle strength. Application of both
vectors resulted in improvement of many of these phenotypes
including a restoration of muscle strength to wild type
levels. These findings were central to Benitec receiving
Orphan Drug Designation in the European Union for the OPMD program
in January this year and were published in Nature Communications in
April 2017.
Latest development
The scientific team at Benitec has
now generated a single AAV vector system that uses a ddRNAi
approach combined with protein replacement to 'silence and replace'
the mutant PABPN1 protein. In a dose-dependent and
time-dependent manner, BB-301 treatment produced robust knockdown
of PABPN1 levels, including the mutant form of the protein, by up
to 88%, while simultaneously restoring wild type PABPN1 to levels
of up to 90% of normal. BB-301 treatment results in
substantial correction of INIs and fibrosis as well as muscle
strength. Importantly, treatment with the new clinical
candidate BB-301 restored the ratio of muscle weight to body weight
to wild type levels.
Benitec has engaged with a broad group of OPMD clinicians and
experts to assist us with defining the clinical development plan
that will be considered with the regulatory agencies later this
year. Benitec remains on track to be in the clinic by the
second half of calendar year 2018, contingent upon favourable
discussions with the regulatory agencies.
The OPMD data will be presented on October 4-6, 2017 at the Cell & Gene Meeting
on the Mesa conference in California. This is an annual
conference which is aimed at the significant progress of the
regenerative medicine sector in advancing transformational
therapeutics to patients.
For further information regarding Benitec and its activities,
please contact the persons below, or visit the Benitec website at
www.benitec.com
Australia
Investor Relations
|
United States
Investor Relations
|
Market Eye
Orla
Keegan
Director
Tel: +61 (2) 8097
1201
Email:
orla.keegan@marketeye.com.au
|
M Group Strategic
Communications
Jay
Morakis
Managing
Director
Tel: +1
212.266.0191
Email:
jmorakis@MGroupSC.com
|
About Benitec Biopharma Limited:
Benitec
Biopharma Limited (ASX: BLT; NASDAQ: BNTC; NASDAQ: BNTCW) is a
biotechnology company developing innovative therapeutics based on
its patented gene-silencing technology called ddRNAi or 'expressed
RNAi'. Based in Sydney, Australia
with laboratories in Hayward,
California (USA), and collaborators and licensees around the
world, the company is developing ddRNAi-based therapeutics for
chronic and life-threatening human conditions including OPMD, head
& neck squamous cell carcinoma, retinal based diseases such as
wet age-related macular degeneration, and hepatitis B. Benitec has
also licensed ddRNAi to other biopharmaceutical companies for
applications including HIV/AIDS, Huntington's Disease, chronic
neuropathic pain, cancer immunotherapy and retinitis
pigmentosa.
About OPMD:
OPMD is a rare inherited myopathy
characterized by dysphagia (difficulty in swallowing), the loss of
muscle strength, and weakness in multiple parts of the body.
Patients typically suffer from severe dysphagia, ptosis (eye lid
drooping), tongue atrophy, proximal lower limb weakness, dysphonia
(altered and weak voice), limitation in looking upward, as well as
facial muscle and proximal upper limb weakness. Progressing
throughout that patient's life, OPMD is not typically diagnosed
until the individuals reach their 50's or 60's. As the dysphagia
becomes more severe, patients become malnourished, lose significant
weight, become dehydrated and suffer from repeated incidents of
aspiration pneumonia. The last two symptoms are often the cause of
death. No cure is currently available for OPMD. The
cricopharyngeal myotomy is the only treatment available to improve
swallowing in these patients, but because the root cause of the
genetic disease has not been addressed, the pharyngeal musculature
still undergoes progressive degradation leading to the previously
mentioned complications.
Safe Harbor Statement:
This press release
contains "forward-looking statements" within the meaning of section
27A of the US Securities Act of 1933 and section 21E of the US
Securities Exchange Act of 1934. Any forward-looking statements
that may be in this ASX/Nasdaq announcement are subject to risks
and uncertainties relating to the difficulties in Benitec's plans
to develop and commercialise its product candidates, the timing of
the initiation and completion of preclinical and clinical trials,
the timing of patient enrolment and dosing in clinical trials, the
timing of expected regulatory filings, the clinical utility and
potential attributes and benefits of ddRNAi and Benitec's product
candidates, potential future out-licenses and collaborations, the
intellectual property position and the ability to procure
additional sources of financing. Accordingly, you should not rely
on those forward-looking statements as a prediction of actual
future results.
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SOURCE Benitec Biopharma Limited