Delpacibart zotadirsen (AOC 1044) delivered
unsurpassed muscle concentrations of PMO of 200 nM after three
doses of 5 mg/kg
Statistically significant 37% increase in exon
44 skipping and up to 66% skipping with delpacibart zotadirsen 5
mg/kg at four months
Statistically significant increase of 25% of
normal in dystrophin production and restored total dystrophin up to
54% of normal with delpacibart zotadirsen 5 mg/kg at four
months
Creatine kinase levels reduced to near normal
with greater than 80% reduction compared to
baseline with delpacibart zotadirsen 5 mg/kg at four
months
Delpacibart zotadirsen data
demonstrated favorable safety and tolerability
Volume 10 of virtual investor and analyst
series today, Friday, Aug. 9 at 8:00 a.m. ET
SAN
DIEGO, Aug. 9, 2024 /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 5 mg/kg data demonstrated unsurpassed delivery of
phosphorodiamidate morpholino oligomers
(PMO) concentrations to skeletal muscle, statistically
significant increase of 25% of normal in dystrophin production
and statistically significant increase of 37% in exon 44
skipping in people living with Duchenne muscular dystrophy
mutations amenable to exon 44 skipping (DMD44) in the Phase 1/2
EXPLORE44™ clinical trial. In addition, AOC 1044 5
mg/kg reduced creatine kinase levels to near normal with
greater than 80% reduction compared to baseline. AOC 1044
demonstrated favorable safety and tolerability. Avidity also
announced delpacibart zotadirsen as the approved
international nonproprietary name of AOC 1044, abbreviated as
del-zota.
"This is an exciting moment as these data suggest
del-zota has the potential to change the treatment paradigm
and course of disease for patients with Duchenne muscular dystrophy
mutations amenable to exon 44 skipping. We have not seen this level
of dystrophin production and reduction in creatine kinase with
other PMO exon-skipping treatments," said Diana Castro, M.D., Board Certified Neurologist
and Neuromuscular Physician, Founder and Director Neurology and
Neuromuscular Care Center, Founder and Director Neurology Rare
Disease Center and EXPLORE44 trial program investigator.
"These del-zota data are very encouraging as children
and adults living with Duchenne muscular dystrophy mutations
amenable to exon 44 skipping are still in need of targeted
treatment options to address this debilitating disease."
Del-zota is designed to deliver PMO to skeletal
muscle and heart tissue to specifically skip exon 44 of the
dystrophin gene to enable dystrophin
production. Del-zota has been granted Orphan
designation by the U.S. Food and Drug Administration (FDA) and the
European Medicines Agency (EMA). The FDA has also granted
del-zota Rare Pediatric and Fast Track
designations. Del-zota is the first of multiple
AOCs the company is developing for DMD.
"The robust exon skipping, significant dystrophin production,
and profound reduction of creatine kinase reinforce our belief in
the potential of del-zota to be an effective treatment for
people living with DMD44. These data support expediting the
regulatory path for del-zota as quickly as possible," said
Sarah Boyce, president and chief
executive officer. "Del-zota is the first AOC in development
from our DMD franchise and with this data, we are also advancing
additional exon-skipping DMD candidates."
This initial assessment from the randomized, double-blind,
placebo-controlled Phase 1/2 EXPLORE44 trial of del-zota
provides a look at the safety and tolerability for 25 participants
across two dose levels (5 mg/kg and 10 mg/kg). For the four-month
assessment in the 5 mg/kg cohort, participants received three doses
of 5 mg/kg del-zota (PMO dose), or placebo every six weeks.
Data on muscle delivery, exon skipping, dystrophin production and
creatine kinase were assessed from 10 participants in the 5 mg/kg
cohort.
In the Phase 1/2 EXPLORE44 study, del-zota
demonstrated:
- Unsurpassed delivery of PMO of 200 nM in skeletal
muscle
- Statistically significant 37% increase in exon 44 skipping and
up to 66% exon 44 skipping
- Statistically significant increase of 25% of normal in
dystrophin production and restored total dystrophin up to 54% of
normal
- Reduction in creatine kinase levels to near normal with greater
than 80% reduction compared to baseline
- Favorable safety and tolerability with most treatment emergent
adverse events (AEs) mild or moderate in participants with
DMD44.
Video Webcast Information
The company is hosting
Volume 10 of its investor and analyst event series on August
9, 2024, beginning at 8:00 a.m. ET to discuss the initial
data from the EXPLORE44TM trial of del-zota in
people living with DMD44. The virtual event will be available via a
live video webcast and can be accessed here or from the
"Events and Presentations" page in the "Investors" section of
Avidity's website. A replay of the webcast will be archived on
Avidity's website following the event.
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 del-zota in
healthy volunteers and participants with DMD mutations amenable to
exon 44 skipping (DMD44). EXPLORE44 has completed enrollment and is
evaluating the safety, tolerability, pharmacokinetics, and
pharmacodynamic effects of single and multiple ascending doses of
del-zota administered intravenously. The EXPLORE44
trial is assessing exon skipping and dystrophin protein levels in
participants with DMD44. Participants with DMD44 have the option to
enroll into an open-label extension study, EXPLORE44-OLE. For more
information about the EXPLORE44 trial, visit the EXPLORE44
study website or
visit https://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 Del-zota (AOC
1044)
Del-zota (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.
Del-zota 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. Del-zota 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 safety,
tolerability and efficacy data associated with del-zota from
the Phase 1/2 EXPLORE44™ trial; the standards against which the
del-zota data are being measured; the impact of such data on
the advancement of del-zota; the plans and timing and
advancement of the EXPLORE44 trial; the design and goals of the
EXPLORE44 trial and individual cohorts therein; Avidity's DMD
franchise; the potential of Avidity's product candidates to treat
rare diseases and Avidity's efforts to bring them to people
suffering from applicable diseases; and the potential of AOCs
to target a range of different cells and tissues beyond the liver,
and to treat cardiac and immunological diseases. This press release
also contains estimates and other statistical data made by
independent parties and by us. This data involves a number of
assumptions and limitations, and the reader is cautioned not to
give undue weight to such estimates.
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 those beyond its control, including, without
limitation: preliminary results of a clinical trial are not
necessarily indicative of final results and additional data related
to del-zota 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
cutoff; 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 additional clinical holds which may not be timely lifted,
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; Avidity's dependence on
third parties in connection with preclinical and clinical testing
and product manufacturing; regulatory developments in the United States and foreign countries; and
other risks described in Avidity's Annual Report on Form 10-K for
the fiscal year ended December 31,
2023, filed with the Securities and Exchange Commission
(SEC) on February 28, 2024, 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:
Mike MacLean
(619) 837-5014
investors@aviditybio.com
Media Contact:
Navjot Rai
(619) 837-5016
media@aviditybio.com
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SOURCE Avidity Biosciences, Inc.