Item 8.01. Other Events.
On October 13, 2022, Avidity Biosciences, Inc. ("Avidity" or the "Company")
announced its planned EXPLORE44 trial of AOC 1044 in healthy volunteers and
participants with Duchenne muscular dystrophy ("DMD"). The EXPLORE44 trial is a
randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial to
evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects
of single and multiple ascending doses of AOC 1044 administered intravenously,
with the primary objective being the safety and tolerability of AOC 1044 in
adult healthy volunteers and pediatric and adult participants with DMD mutations
amenable to exon 44 skipping ("DMD44"). The EXPLORE44 trial will assess exon
skipping and dystrophin protein levels in participants with DMD44 and will also
explore measures of muscle function, patient-reported outcomes and quality of
life. DMD44 is ultra rare, constituting approximately 7% of DMD patients,
approximately 900 of which are in the United States.
Participants with DMD44 will have the option to enroll in an extension study at
the end of the treatment period in the EXPLORE44 trial. The overall development
program for AOC 1044, which includes the EXPLORE44 trial and the extension study
is designed to potentially support accelerated approval in the United States. In
the second half of 2023, the Company plans to present results from the healthy
volunteer portion of the EXPLORE44 trial.
Preclinical studies showed that an antibody oligonucleotide conjugate ("AOC")
approach targeting exon 23 in a murine model of DMD demonstrated exon skipping,
dystrophin restoration and improved muscle function and serum biomarkers of
muscle damage. Additionally, data from a preclinical study of AOC 1044 in
patient-derived myotubes showed dose-dependent dystrophin restoration, and a
preclinical study in non-human primate ("NHP") observed dose-dependent exon
skipping in skeletal and heart muscle with AOC 1044.
In addition to the preclinical studies described above, Avidity completed an
IND-enabling good laboratory practice ("GLP") toxicology study of AOC 1044 in
NHP. Results from the IND-enabling study showed that AOC 1044 was generally well
tolerated and supported advancement into the clinic, with no dose limiting
toxicity observed in NHP at the highest dose tested. The study did not observe
any treatment-related histopathologic toxicity, platelet or renal toxicity or
any changes in safety pharmacology parameters (cardiac, respiratory and
neurological). The highest dose tested in both NHP and murine models was the
maximum feasible dose and was the no-observed adverse effect level ("NOAEL").
Results of a nine-month chronic toxicology study of AOC 1044 in NHPs was
consistent with the results of the IND-enabling study.
Forward-Looking Statements
Avidity cautions readers that statements contained in this report 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 progression of the Company's clinical program for AOC 1044; the
anticipated design of the EXPLORE44 trial;the potential for the overall
development program for AOC 1044 to support accelerated approval in the United
States; the estimated prevalence of DMD44; and AOC 1044's potential to treat the
underlying biological cause of DMD. 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 report
due to the risks and uncertainties inherent in the business, including, without
limitation: 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
and completion of preclinical studies or clinical trials; the success of its
preclinical studies and clinical trials for the Company's product candidates;
the results of preclinical studies and early clinical trials are not necessarily
predictive of future results; unexpected adverse side effects or inadequate
efficacy of its product candidates that may delay or limit their development,
regulatory approval and/or commercialization, or may result in clinical holds,
recalls or product liability claims; 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, including
acceptance of INDs and similar foreign regulatory filings and the proposed
design of future clinical trials; disruption to its operations from the COVID-19
pandemic or the war in Ukraine; and other risks described in prior press
releases and in filings with the Securities and Exchange Commission. 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 exist 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.
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