AOC 1044 delivered up to 50-times greater
concentrations of PMO in skeletal muscle following a
single dose compared to peptide conjugated PMOs in healthy
volunteers
AOC 1044 was well tolerated, demonstrated
statistically significant exon 44 skipping compared to placebo of
up to 1.5% in healthy volunteers after a single dose of 10 mg/kg
and increased exon skipping in all participants
Avidity plans to provide first look at AOC
1044 data in people living with DMD44 in 2H 2024
SAN
DIEGO, Dec. 13, 2023 /PRNewswire/ -- Avidity
Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company
committed to delivering a new class of RNA therapeutics called
Antibody Oligonucleotide Conjugates (AOCs™), today announced
positive AOC 1044 data in healthy volunteers from the Phase 1/2
EXPLORE44™ clinical trial for the treatment of Duchenne muscular
dystrophy mutations amenable to exon 44 skipping (DMD44). AOC 1044
delivered unprecedented concentrations of phosphorodiamidate
morpholino oligomers (PMO) in skeletal muscle with up to 50-times
greater concentrations of PMO in skeletal muscle following a single
dose compared to peptide conjugated PMOs in healthy volunteers. AOC
1044 was well tolerated, demonstrated statistically significant
exon 44 skipping compared to placebo of up to 1.5% in healthy
volunteers after a single dose of 10 mg/kg AOC 1044 and increased
exon skipping in all participants. Avidity plans to provide a first
look at AOC 1044 data in people living with DMD44 in 2H 2024.
AOC 1044 is designed to deliver PMO to skeletal muscle and heart
tissue to specifically skip exon 44 of the dystrophin gene to
enable dystrophin production. AOC 1044 has been granted Orphan
Designation by the U.S. Food and Drug Administration (FDA) and the
European Medicines Agency (EMA), and Fast Track Designation by the
FDA. AOC 1044 is the first of multiple AOCs the company is
developing for DMD.
"We are excited with the early data set of AOC 1044
demonstrating unprecedented delivery of therapeutic oligonucleotide
in skeletal muscle and consistent exon skipping in healthy
volunteers," said Sarah Boyce,
president and chief executive officer. "We are rapidly advancing
AOC 1044 and look forward to sharing data in people living with
DMD44 in 2024. Data from our clinical programs continue to
reinforce the broad and disruptive potential of our AOC platform
for the treatment of high burden muscle diseases like DMD, DM1 and
FSHD."
Phase 1/2 EXPLORE44 Healthy Volunteer Data
- AOC 1044 delivered unprecedented, dose-dependent increases in
PMO concentrations in skeletal muscle following a single dose of 5
mg/kg or 10 mg/kg, providing up to 50-times greater concentrations
of PMO in skeletal muscle when compared to a single dose of peptide
conjugated PMOs in healthy volunteers.
- AOC 1044 produced statistically significant exon 44 skipping
compared to placebo of up to 1.5% in healthy volunteers after a
single dose of 10 mg/kg AOC 1044 at Day 29. AOC 1044 increased exon
skipping in all participants.
- AOC 1044 was well tolerated in healthy volunteers. All
treatment-emergent adverse events in participants dosed with AOC
1044 were mild to moderate. There were no symptomatic hemoglobin
changes, no hypomagnesemia and no renal events.
In addition to AOC 1044, Avidity is also advancing AOC 1001 in
the MARINA open-label extension (MARINA-OLE™) study for people
living with myotonic dystrophy type 1 (DM1) and AOC 1020 in the
Phase 1/2 FORTITUDE™ trial for the treatment of facioscapulohumeral
muscular dystrophy (FSHD).
The EXPLORE44™ Phase 1/2 Trial of AOC 1044
The
EXPLORE44 trial is a randomized, placebo-controlled, double-blind,
Phase 1/2 clinical trial to evaluate AOC 1044 in healthy volunteers
and participants with DMD mutations amenable to exon 44 skipping
(DMD44). EXPLORE44 will evaluate the safety, tolerability,
pharmacokinetics, and pharmacodynamic effects of single and
multiple ascending doses of AOC 1044 administered intravenously.
EXPLORE44 is expected to enroll approximately 40 healthy volunteers
and 24 participants with DMD44, ages seven to 27 years old. The
EXPLORE44 trial will assess exon skipping and dystrophin protein
levels in participants with DMD44. Participants with DMD44 will
have the option to enroll into an extension study. For more
information about the EXPLORE44 trial, visit the EXPLORE44
study website or
visit http://www.clinicaltrials.gov and search for
NCT05670730.
About Duchenne muscular dystrophy (DMD)
Duchenne
muscular dystrophy (DMD) causes a lack of functional dystrophin
that leads to stress and tears of muscle cell membranes, resulting
in muscle cell death and the progressive loss of muscle function.
The dystrophin protein maintains the integrity of muscle fibers and
acts as a shock absorber through its role as the foundation of a
group of proteins that connects the inner and outer elements of
muscle cells. People living with DMD suffer from progressive muscle
weakness that typically starts at a very young age. Over time,
people with Duchenne will develop problems walking and breathing,
and eventually, the heart and respiratory muscles will stop
working. Those living with the condition often require special aid
and assistance throughout their lives and have significantly
shortened life expectancy. While there are treatments approved to
treat people with DMD, there remains a very high unmet need. DMD is
a monogenic, X-linked, recessive disease that primarily affects
males, with one in 3,500 to 5,000 boys born worldwide having
Duchenne.
About AOC 1044
AOC 1044 is designed to deliver
phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle
and heart tissue to specifically skip exon 44 of the dystrophin
gene to enable dystrophin production in people living with Duchenne
muscular dystrophy with mutations amenable to exon 44 skipping
(DMD44). DMD is characterized by progressive muscle degeneration
and weakness due to alterations of a protein called dystrophin that
protects muscle cells from injury during contraction. AOC 1044
consists of a proprietary monoclonal antibody that binds to the
transferrin receptor 1 (TfR1) conjugated with a PMO targeting exon
44. In a preclinical model of DMD, a murine active AOC produced
durable exon skipping and functional dystrophin protein in skeletal
muscle and heart tissue following a single intravenous dose. AOC
1044 is currently in Phase 1/2 development as part of the
EXPLORE44™ trial for the treatment of DMD mutations amenable to
exon 44 skipping.
About Avidity
Avidity Biosciences, Inc.'s mission is
to profoundly improve people's lives by delivering a new class of
RNA therapeutics - Antibody Oligonucleotide Conjugates (AOCs™).
Avidity is revolutionizing the field of RNA with its proprietary
AOCs, which are designed to combine the specificity of monoclonal
antibodies with the precision of oligonucleotide therapies to
address targets and diseases previously unreachable with existing
RNA therapies. Utilizing its proprietary AOC platform, Avidity
demonstrated the first-ever successful targeted delivery of RNA
into muscle and is leading the field with clinical development
programs for three rare muscle diseases: myotonic dystrophy type 1
(DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral
muscular dystrophy (FSHD). Avidity is broadening the reach of AOCs
with its advancing and expanding pipeline including programs in
cardiology and immunology through internal discovery efforts and
key partnerships. Avidity is headquartered in San Diego, CA. For more information about our
AOC platform, clinical development pipeline and people, please
visit www.aviditybiosciences.com and engage with us on LinkedIn and
X.
Forward-Looking Statements
Avidity cautions readers
that statements contained in this press release regarding matters
that are not historical facts are forward-looking statements. These
statements are based on the company's current beliefs and
expectations. Such forward-looking statements include, but are not
limited to, statements regarding: the characterization of data
associated with AOC 1044 in healthy volunteers; the impact of such
data on the advancement of AOC 1044; the pipeline of AOCs Avidity
is developing for DMD; the goals of the EXPLORE44™ trial and the
dosages of AOC 1044 to be administered therein; the number and type
of participants to enroll in the EXPLORE44 trial; an extension
study for EXPLORE44 participants; expectations related to the
EXPLORE44 trial and AOC 1044; the anticipated timing of release of
data from the EXPLORE44 trial; the need for treatments for
people with DMD; plans for the progression of clinical programs for
AOC 1001, AOC 1044 and AOC 1020 and the timing thereof; the
potential of Avidity's product candidates to treat rare diseases
and Avidity's efforts to bring them to people suffering from
applicable diseases; the potential of AOCs to target a range of
different cells and tissues beyond the liver, and to treat cardiac
and immunological diseases; Avidity's position in the RNA field;
and Avidity's plans to expand its AOC platform and to invest in its
pipeline programs.
The inclusion of forward-looking statements should not be
regarded as a representation by Avidity that any of these plans
will be achieved. Actual results may differ from those set forth in
this press release due to the risks and uncertainties inherent in
Avidity's business and beyond its control, including, without
limitation: additional healthy volunteer data related to AOC 1044
that continues to become available may be inconsistent with the
data produced as of the date hereof, and further analysis of
existing data and analysis of new data may lead to conclusions
different from those established as of the date hereof; AOC 1044
data in people living with DMD44 may not meet Avidity's
expectations; unexpected adverse side effects to, or inadequate
efficacy of, Avidity's product candidates that may delay or limit
their development, regulatory approval and/or commercialization, or
may result in clinical holds which may not be timely lifted (if at
all), recalls or product liability claims; Avidity is early in its
development efforts; Avidity's approach to the discovery and
development of product candidates based on its AOC platform is
unproven, and the company does not know whether it will be able to
develop any products of commercial value; potential delays in the
commencement, enrollment, data readouts and completion of
preclinical studies or clinical trials; the success of its
preclinical studies and clinical trials for the company's product
candidates; Avidity's dependence on third parties in connection
with preclinical and clinical testing and product manufacturing;
Avidity may not realize the expected benefits of its
collaborations; regulatory developments in the United
States and foreign countries; Avidity could exhaust its
available capital resources sooner than it currently expects and
fail to raise additional needed funds; and other risks described in
Avidity's Annual Report on Form 10-K for the fiscal year
ended December 31, 2022, filed with the Securities and
Exchange Commission (SEC) on February 28, 2023, and in
subsequent filings with the SEC. Avidity cautions readers not to
place undue reliance on these forward-looking statements, which
speak only as of the date hereof, and the company undertakes no
obligation to update such statements to reflect events that occur
or circumstances that arise after the date hereof. All
forward-looking statements are qualified in their entirety by this
cautionary statement, which is made under the safe harbor
provisions of the Private Securities Litigation Reform Act of
1995.
Investor Contact:
Geoffrey
Grande, CFA
(619) 837-5014
investors@aviditybio.com
Media Contact:
Navjot Rai
(619) 837-5016
media@aviditybio.com
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SOURCE Avidity Biosciences, Inc.